Influence of gait mode and body orientation on following a walking avatar.
Regulating distance with a moving object or person is a key component of human movement and of skillful interpersonal coordination. The current set of experiments aimed to assess the role of gait mode and body orientation on distance regulation using a cyclical locomotor tracking task in which participants followed a virtual leader. In the first experiment, participants moved in the backward-forward direction while the body orientation of the virtual leader was manipulated (i.e., facing towards, or away from the follower), hence imposing an incongruence in gait mode between leader and follower. Distance regulation was spatially less accurate when followers walked backwards. Additionally, a clear trade-off was found between spatial leader-follower accuracy and temporal synchrony. Any perceptual effects were overshadowed by the effect of one's gait mode. In the second experiment we examined lateral following. The results suggested that lateral following was also constrained strongly by perceptual information presented by the leader. Together, these findings demonstrated how locomotor tracking depends on gait mode, but also on the body orientation of whoever is being followed.


[Methods of suicide in an autopsy sample of the Institute of Forensic Medicine of the Hannover Medical School].
Between 1978 and 1987 513 cases of suicide were examined at the Institute of Legal Medicine of the Medical School of Hannover (337 males (65.7%) and 176 females (34.3%). The greatest share of the suicides was found in the age group 18 to 30. 42.1% of the cases showed positive alcohol concentrations with men accounting for a relatively higher share. The most frequently used methods for committing suicide were intoxications (28.1%), hanging (25.3%), firearms (17.2%), falling from great height (9.7%) and drowning (7.6%). The incidence in terms of sex showed marked differences in distribution, however. Women mostly used the following methods for committing suicide: Intoxication (37.4%), falling (17.6%) and hanging (17%). With men we found the following order: Hanging (29.7%), firearms (24.3%) and intoxications (23.1%). Compared with other institutes of legal medicine the five most frequent suicide methods showed similar distributions, but with a higher rate of intoxications. On the other hand there were distinct differences as to the relative frequency of the individual suicide methods in the total population and the respective number of autopsies performed. Especially in cases of gunshot wounds the number of autopsies performed to rule out homicide was higher. Of 2390 case of suicide registered in Greater Hannover an autopsy was ordered by the court in only 6.7%. According to our experience the autopsy rate seems too low, because homicide in the form of pretended suicide is not too rare.


Does patient-prosthesis mismatch have a negative impact on outcomes following mitral valve replacement?
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether patient-prosthesis mismatch (PPM) has a negative impact on patients undergoing mitral valve replacement in terms of postoperative mortality, incidence of postoperative pulmonary hypertension (PH) and higher transmitral gradients. Altogether 103 papers were found using the reported search, 18 of which represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Overall, 8 studies with a total of 4812 patients reported that PPM has a significantly negative impact on long-term mortality, whereas 5 studies with a total of 1558 patients reported no effect on mortality. One study with a total of 2440 patients reported preoperative PH as the risk factor for increased mortality in the presence of moderate or severe PPM. Three studies evaluated the effect of PPM on postoperative PH and reported that PPM was associated with significantly increased postoperative PH. The majority of the studies reported that PPM was associated with higher peak or mean transmitral gradient and systolic pulmonary artery pressure. The results presented in these studies suggest that PPM in patients undergoing mitral valve replacement was associated with increased postoperative mean and peak transmitral gradient and higher postoperative systolic pulmonary artery pressure. PPM may be associated with increased long-term mortality. Severe PPM was directly associated with increased long-term mortality when compared with moderate or no PPM. Evidence suggests that PPM is associated with increased incidence of postoperative PH.


Physical properties of rabbit articular cartilage after transection of the anterior cruciate ligament.
The effect of unilateral transection of the anterior cruciate ligament on the confined compression and swelling properties of the distal femoral articular cartilage of skeletally mature rabbits at 9 weeks after surgery was determined. Gross morphological grading of the transected and contralateral control distal femora stained with India ink confirmed that cartilage degeneration had been induced by ligament transection. Osteochondral cores, 1.8 mm in diameter, were harvested from the medial femoral condyles. The modulus, permeability, and electrokinetic (streaming potential) coefficient of the articular cartilage of the osteochondral cores were assessed by confined compression creep experiments. The properties (mean +/- SD) of control cartilage were: confined compression modulus, 0.75 +/- 0.28 MPa; hydraulic permeability, 0.63 +/- 0.28 x 10(-15) m2/Pa*sec; and electrokinetic coefficient, 0.16 +/- 0.31 x 10(-9) V/Pa. In transected knees, the modulus was reduced by 18% (p = 0.04), while the permeability and electrokinetic coefficient were not detectably altered. The change in modulus was accompanied by a trend (p = 0.07) toward a decrease (-11%) in the glycosaminoglycan density within the tissue, a significant increase (p < 0.001) in the water content of the cartilage after equilibration in 1 x phosphate buffered saline from 70.3 +/- 4.1% in control knees to 75.2 +/- 4.0% in transected knees, and little further swelling after tissue equilibration in hypotonic saline. The compressive modulus of the cartilage from both control and transected knees was positively correlated with the density of tissue glycosaminoglycan. The alterations in the physical properties of the articular cartilage after transection of the anterior cruciate ligament in the rabbit show trends similar to those observed in human and other animal models of osteoarthritis and provide further support for the use of this model in the study of cartilage degeneration.


Imaging of carbonic anhydrase IX with an 111In-labeled dual-motif inhibitor.
We developed a new scaffold for radionuclide-based imaging and therapy of clear cell renal cell carcinoma (ccRCC) targeting carbonic anhydrase IX (CAIX). Compound XYIMSR-01, a DOTA-conjugated, bivalent, low-molecular-weight ligand, has two moieties that target two separate sites on CAIX, imparting high affinity. We synthesized [111In]XYIMSR-01 in 73.8-75.8% (n = 3) yield with specific radioactivities ranging from 118 - 1,021 GBq/μmol (3,200-27,600 Ci/mmol). Single photon emission computed tomography of [111In]XYIMSR-01 in immunocompromised mice bearing CAIX-expressing SK-RC-52 tumors revealed radiotracer uptake in tumor as early as 1 h post-injection. Biodistribution studies demonstrated 26% injected dose per gram of radioactivity within tumor at 1 h. Tumor-to-blood, muscle and kidney ratios were 178.1 ± 145.4, 68.4 ± 29.0 and 1.7 ± 1.2, respectively, at 24 h post-injection. Retention of radioactivity was exclusively observed in tumors by 48 h, the latest time point evaluated. The dual targeting strategy to engage CAIX enabled specific detection of ccRCC in this xenograft model, with pharmacokinetics surpassing those of previously described radionuclide-based probes against CAIX.


Primary care service use by end-of-life cancer patients: a nationwide population-based cohort study in the United Kingdom.
End of life (EoL) care becomes more complex and increasingly takes place in the community, but there is little data on the use of general practice (GP) services to guide care improvement. This study aims to determine the trends and factors associated with GP consultation, prescribing and referral to other care services amongst cancer patients in the last year of life. A retrospective cohort study of cancer patients who died in 2000-2014, based on routinely collected primary care data (the Clinical Practice Research DataLink, CPRD) covering a representative sample of the population in the United Kingdom. Outcome variables were number of GP consultations (primary), number of prescriptions and referral to other care services (yes vs no) in the last year of life. Explanatory variables included socio-demographics, clinical characteristics and the status of palliative care needs recognised or not. The association between outcome and explanatory variables were evaluated using multiple-adjusted risk ratio (aRR). Of 68,523 terminal cancer patients, 70% were aged 70+, 75% had comorbidities and 45.5% had palliative care needs recognised. In the last year of life, a typical cancer patient had 43 GP consultations (Standard deviation (SD): 31.7; total = 3,031,734), 71.5 prescriptions (SD: 68.0; total = 5,074,178), and 21(SD: 13.0) different drugs; 58.0% of patients had at least one referral covering all main clinical specialities. More comorbid conditions, prostate cancer and having palliative care needs recognised were associated with more primary care consultations, more prescriptions and a higher chance of referral (aRRs 1.07-2.03). Increasing age was related to fewer consultations (aRRs 0.77-0.96), less prescriptions (aRR 1.09-1.44), and a higher chance of referral (aRRs 1.08-1.16) but less likely to have palliative care needs recognised (aRRs 0.53-0.89). GPs are very involved in end of life care of cancer patients, most of whom having complex care needs, i.e. older age, comorbidity and polypharmacy. This highlights the importance of enhancing primary palliative care skills among GPs and the imperative of greater integration of primary care with other healthcare professionals including oncologists, palliative care specialists, geriatricians and pharmacists. Research into the potential of deprescribing is warranted. Older patients have poorer access to both primary care and palliative care need to be addressed in future practices.


Six Sesamoid Bones on Both Feet: Report of a Rare Case.
There is a variation of the total number of distinct bones in the human in the literature. This difference is mainly caused by the variable existence of sesamoid bones. Sesamoid bones at the first MTP are seen regularly. In contrast additional sesamoid bones at the second to fifth MTP are rare. We report a case of additional sesamoid bones at every metatarsophalangeal joint (MTP) of both feet. A 22-year-old female Caucasian presented with weight-dependent pain of the second MTP of the left foot. In the radiographs of both feet additional sesamoid bones at every MTP could be seen. This case reports a very rare variation in human anatomy. A similar case has not been displayed to the academic society and therefore should be acknowledged.


Effects of antibiotic use in sows on resistance of E. coli and Salmonella enterica Typhimurium in their offspring.
To determine effects of exposure of parental animals to antibiotics on antibiotic resistance in bacteria of offspring, sows were either treated or not treated with oxytetracycline prior to farrowing and their pigs were challenged with Salmonella enterica Typhimurium and treated or not treated with oxytetracycline and apramycin. Fecal Escherichia coli were obtained from sows, and E. coli and salmonella were recovered from pigs. Antibiotic resistance patterns of isolates were determined using a minimum inhibitory concentration (MIC) analysis. Polymerase chain reaction (PCR) and electroporation were used to characterize the genetic basis for the resistance and to determine the location of resistance genes. Treatments had little effect on resistance of the salmonella challenge organism. The greatest resistance to apramycin occurred in E. coli from pigs treated with apramycin and whose sows had earlier exposure to oxytetracycline. Resistance to oxytetracycline was consistently high throughout the study in isolates from all pigs and sows; however, greater resistance was noted in pigs nursing sows that had previous exposure to that drug. The aac(3)-IV gene, responsible for apramycin resistance, was found in approximately 90% of apramycin-resistant isolates and its location was determined to be on plasmids. Several resistant E. coli bio-types were found to contain the resistance gene. These results indicate that resistance to apramycin and oxytetracycline in E. coli of pigs is affected by previous use of oxytetracycline in sows.


Phytohormone Behavior in the Model Environment of Plant and Human Lipid Membranes.
Interactions between three auxins (indole-3-acetic acid (IAA), 2-naphthoxyacetic acid (BNOA), and 2,4-dichlorophenoxyacetic acid (2,4-D)) and model two-dimensional lipid systems mimicking plant and human cell membranes were investigated in monolayers formed at the air/water solution interface. The analysis was based on the recorded π-A isotherm characteristics complemented with Brewster angle microscopy. The influence of auxins on model membranes was discussed on the basis of condensation changes, modification of mutual lipid-lipid interactions in the mixed films, and morphological alteration of the surface domains on the microscopic scale. It was demonstrated that the lipid composition and mutual proportion of the artificial membranes together with sterol to main the phospholipid ratio play a crucial role in the context of auxin behavior in the membrane-mimicking environment. Apart from specific molecular interactions between studied phytohormones represented by auxins and lipids, the condensation of the investigated monolayers was found to be a regulative factor of model systems' susceptibility toward auxin action. Two effects were recognized: fluidizing of monolayers being in the liquid state (model membranes) and initialization of the three-dimensional structure formation in ordered sterol films at high surface pressure. The influence of auxin molecules on lipid interactions in the monolayer and diminishing of the film condensation was the largest for BNOA, due to the presence of the most bulky nonpolar, aromatic fragment in the molecule. It was also demonstrated that auxins interact with model plant membranes more selectively, stronger, and at markedly lower concentration than with the human membrane models.


Oral contraceptive use and fibrocystic breast disease among pre- and postmenopausal women.
The association between use of oral contraceptives and fibrocystic breast disease was assessed among women aged 20-74 years in a hospital-based case-control study conducted between November 1979 and November 1981 in Connecticut. The study groups comprised 633 women with biopsy-proven fibrocystic breast disease and 1,062 controls who had been admitted, as inpatients or outpatients, to general surgical services. For the premenopausal women, there was no evidence that long-term use of oral contraceptives was associated with a decreased frequency of fibrocystic breast disease among either current or past users. For the postmenopausal women, previous oral contraceptive exposure was associated with an increased occurrence of cystic disease. These findings contradict previous investigations reporting a negative association between oral contraceptive use and the development of fibrocystic breast disease.


Risperidone versus haloperidol and amitriptyline in the treatment of patients with a combined psychotic and depressive syndrome.
In a multicenter, double-blind, parallel group trial, the efficacy of risperidone (RIS) was compared with a combination of haloperidol and amitriptyline (HAL/AMI) over 6 weeks in patients with coexisting psychotic and depressive symptoms with either a schizoaffective disorder, depressive type, a major depression with psychotic features, or a nonresidual schizophrenia with major depressive symptoms according to DSM-III-R criteria. A total of 123 patients (62 RIS; 61 HAL/AMI) were included; the mean daily dosage at endpoint was 6.9 mg RIS versus 9 mg HAL combined with 180 mg AMI. Efficacy results for those 98 patients (47 RIS; 51 HAL/AMI) who completed at least 3 weeks of double-blind treatment revealed in both treatment groups large reductions in the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale (RIS 37%; HAL/AMI 51%) and the Bech-Rafaelsen Melancholia Scale total scores (RIS 51%; HAL/AMI 70%). The reductions in the Brief Psychiatric Rating Scale and the Bech-Rafaelsen Melancholia Scale scores in the total group were significantly larger in the HAL/AMI group than in the RIS group (p < 0.01), mostly because of significant differences in the subgroup of patients suffering from depression with psychotic features, whereas treatment differences in the other diagnostic subgroups were not significant. The incidence of extrapyramidal side effects as assessed by the Extrapyramidal Symptom Rating Scale was slightly higher under RIS (37%) than under HAL/AMI (31%). Adverse events were reported by 66% of RIS and 75% of HAL/AMI patients. The results of this trial suggest that the therapeutic effect of HAL/AMI is superior to RIS in the total group of patients with combined psychotic and depressive symptoms. However, subgroup differences have to be considered.


Digitomyces, a new genus of hyphomycetes with cheiroid conidia.
The new anamorphic genus Digitomyces, based on Dictyosporium verrucosum, is proposed. It is characterized by micronematous or semimacronematous conidiophores, integrated or discrete, holoblastic, determinate conidiogenous cells, and olivaceous to pale brown, verrucose, cheiroid conidia, with a truncate basal cell and (2-)3 arms. The new taxon is compared with morphologically similar anamorph genera.


Reducing methane production by supplementation of Terminalia chebula RETZ. containing tannins and saponins.
This study investigates the effects of Terminalia chebula Retz. meal supplementation on rumen fermentation and methane (CH4 ) production by using an in vitro gas technique. The experimental design was a completely randomized design (CRD) and the dietary treatments were T. chebula supplementation at 0, 4, 8, 12, 16 and 20 mg with 0.5 g of roughage and concentrate ratio at 60:40. The results revealed that cumulative gas production (96 h of incubation) were higher (P < 0.01) with T. chebula supplementation at 12, 16 and 20 mg than other treatments. However, in vitro dry matter degradability (IVDMD) and in vitro organic matter digestibility (IVOMD) were not significantly different among treatments (P > 0.05). The NH3 -N concentrations tended to quadratically increase with increasing levels of T. chebula in the diet. In addition, total volatile fatty acids (VFA) and propionate concentrations were increased (P < 0.01), while acetate concentration, acetate-to-propionate ratio, CH4 production and protozoal populations were decreased (P < 0.01) when supplemented with T. chebula at 8, 12 and 16 mg, respectively. Based on this study, it could be concluded that supplementation of T. chebula at 12 mg could improve rumen fermentation by reducing CH4 production and protozoa populations, thus improving in vitro gas production and VFA profiles.


Monoclonal antibodies in the treatment of hematopoietic malignancies.
The development of practical methods for producing specific, highly purified monoclonal antibodies (MoAbs) targeted to specific tumor-cell antigens has opened new vistas in therapy for both hematologic malignancies and solid tumors. Numerous phase I trials with first-generation MoAbs have revealed both the broad therapeutic promise of MoAbs in anticancer therapy and the obstacles that must be overcome before they can be utilized fully in the clinical setting. MoAbs can be used to activate or manipulate the patient's immune system to destroy malignant cells. They also can be used as carriers for antitumor agents such as chemotherapeutic compounds, radiation, and toxins. Because many MoAbs are prepared from mouse cells, a common problem has been the development of resistance to the heterologous mouse protein. Strategies to circumvent this resistance include the use of human MoAbs, the production of chimeric mouse-human MoAbs, and the induction of tolerance to the mouse MoAbs. The possibility of combination therapy using MoAbs in conjunction with chemotherapy, lymphokines, or other biological response modifiers also is being explored.


Comment on "On the security of a spatiotemporal chaotic cryptosystem" [Chaos 17, 033117 (2007)].
This paper comments on a recent paper by R. Rhouma and B. Safya [Chaos 17, 033117 (2007)]. They claimed to find some security weakness of the spatiotemporal chaotic cryptosystem suggested by G. Tang et al. [Phys. Lett. A 318, 388 (2003)] and proposed a chosen-plaintext attack to analyze this system. We find that in their analysis, called a "chosen-plaintext attack," they actually act as a legal receiver (with a machine in their hands during the entire decryption process) rather than an attacker and, therefore, the whole reasoning is not valid.


Cryo-electron microscopy in the fight against COVID-19-mechanism of virus entry.
Cryogenic electron microscopy (cryo-EM) and electron tomography (cryo-ET) have become a critical tool for studying viral particles. Cryo-EM has enhanced our understanding of viral assembly and replication processes at a molecular resolution. Meanwhile, in situ cryo-ET has been used to investigate how viruses attach to and invade host cells. These advances have significantly contributed to our knowledge of viral biology. Particularly, prompt elucidations of structures of the SARS-CoV-2 spike protein and its variants have directly impacted the development of vaccines and therapeutic measures. This review discusses the progress made by cryo-EM based technologies in comprehending the severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2), the virus responsible for the devastating global COVID-19 pandemic in 2020 with focus on the SARS-CoV-2 spike protein and the mechanisms of the virus entry and replication.


The Menstrual Cycle Influences Emotion but Has Limited Effect on Cognitive Function.
From a psychological perspective, the menstrual cycle has been a research topic for more than 50 years. The most recent menstrual cycle research has been driven by an increased interest in sex differences in neuroscience, and the urge to understand sex disparities in prevalence, clinical presentation, and treatment response in psychiatric or neurologic disorders. Indeed, the menstrual cycle is an excellent model of ovarian steroid influence on emotion, behavior, and cognition. This review summarizes the emotion-related and cognitive findings of methodologically sound menstrual cycle studies. In particular, the review is devoted to the sex hormone-induced emotional disturbances in women with premenstrual dysphoric disorder, a subgroup of women responding with enhanced sensitivity to the normal fluctuations in endogenous hormone levels during the menstrual cycle. In addition, emotion processing and cognitive findings across the menstrual cycle in healthy women are also discussed. The overall conclusion is that that menstrual cycle differences in sexually dimorphic cognitive tasks are small and difficult to replicate. Emotion-related changes are more consistently found and are better associated with progesterone and the luteal phase, than with estradiol.


Childhood myelodysplasia.
The clinical data and hematological features of 29 children, under the age of 12 years, with primary myelodysplasia are presented. The diagnosis was made using the FAB (French-American-British) Cooperative Group criteria. There were 24 males and 5 females aged 4 months to 12 years (median 2.5 years) with marked male preponderance. Childhood myelodysplasia constituted 16% of all hematological malignancies and 36.7% of acute myeloid leukemias. The median duration of symptoms prior to diagnosis was 3 months. There were 15 cases of refractory anemia, one of refractory anemia with excess blasts, 3 of refractory anemia with excess blasts in transformation and 10 cases of chronic myelomonocytic leukemia. Five patients evolved to acute myeloid and 4 to acute lymphatic leukemia. The median duration of preleukemic phase in these patients was 7 months (range 4-29 months). The overall mean survival was short (5-9 months) in all the subgroups. Besides supportive therapy in most patients, two patients were treated with etoposide, one with alfa interferon 2b and one with high dose methylprednisolone. Our results show that myelodysplasia is not infrequent in children. The disease has an aggressive clinical course and may evolve into acute leukemia.


A systematic literature review of the effect of different prosthetic components on human functioning with a lower-limb prosthesis.
A correct prosthetic prescription can be derived from adapting the functional benefits of a prosthesis to the functional needs of the prosthetic user. For adequate matching, the functional abilities of the amputees are of value, as well as the technical and functional aspects of the various prosthetic components. No clear clinical consensus seems to be given on the precise prescription criteria. To obtain information about different prosthetic components and daily functioning of amputees with a prosthesis, we performed a systematic literature search. The quality of the studies was assessed with the use of predetermined methodological criteria. Out of 356 potentially relevant studies, 40 studies eventually qualified for final methodological analysis and review. Four satisfied all the criteria and were classified as A-level studies, 26 as B-level, and 10 studies as C-level studies. Despite a huge amount of literature, our formal clinical knowledge had considerable gaps concerning the effects of different prosthetic components and their mechanical characteristics on human functioning with a lower-limb prosthesis. Therefore, with regard to prosthetic guideline development, we must still largely rely on clinical consensus among experts. The integration of knowledge from research with the expert opinion of clinical professionals and the opinions and wishes of consumers can form a solid base for a procedure on guideline development for prosthetic prescription.


Evaluation of evacuated blood-collection tubes: effects of three types of polymeric separators on therapeutic drug-monitoring specimens.
The potential of three types of separator materials found in conventional blood-collection tubes for interference in therapeutic drug measurements was assessed. None of the separators (based on acrylic, silicone, or polyester polymers) had any significant effect on the concentrations of seven drugs (theophylline, digoxin, phenytoin, phenobarbital, gentamicin, ethanol, and cyclosporine) in blood specimens that were processed and analyzed promptly. Storage of specimens for 24 h resulted in an average 2.4% increase in theophylline values in specimens collected in tubes with the acrylic separator (P = 0.024); an average 8.1% decrease in phenytoin in specimens collected in tubes with the polyester-based separator (P < 0.001); and an average 4.2% decrease in phenobarbital in specimens collected in tubes with the polyester-based separator (P = 0.02). All other drug concentrations were not significantly affected. A small decrease in phenytoin (7.9%; P < 0.01) was seen when the specimen volume in 7-mL tubes containing polyester-based separator was reduced to 1.0 mL; all other drug concentrations were unaffected by partial filling of tubes. Paired blood specimens from pediatric patients, when collected in plain tubes and tubes containing acrylic separator, yielded no significant differences for theophylline, digoxin, tobramycin, phenytoin, or phenobarbital concentrations. The three commercially available separators had only small effects on therapeutic drug concentrations, and a newly developed separator based on an acrylic resin was suitably inert.


Characterization of yolk DNA from Xenopus laevis oocytes ovulated in vitro.
High molecular weight DNA was isolated from the yolk platelets of Xenopus laevis oocytes ovulated in vitro. Yolk DNA has the same buoyant density in CsCl gradients as mitochondrial and nuclear DNAs, and, like them, it is double-stranded. Yolk DNA behaves like nuclear DNA, and not like mitochondrial DNA, upon renaturation after denaturation. The molecules are always linear. Cytochemical and biochemical controls preclude the possibility that the yolk DNA might be contaminated by nuclear or mitochondrial DNA. We conclude that the yolk DNA is an endogenous component of the yolk platelets.


Early Detection of Pressure Injury Using a Forensic Alternate Light Source.
This study aimed to determine if an alternate light source (ALS) can be used to detect tissue trauma before visible manifestations of tissue injury are evident with the naked eye. Ten participants were recruited and gave consent, and 7 completed the study. Researchers examined and photographed participants' heels in ambient light to establish baseline. A series of photographs using ALS and camera were taken as follows: violet wavelength at 415 nm to 445 nm with yellow lens; blue wavelength at 455 nm to 515 nm with orange lens; and green wavelength at 535 nm to 575 nm with red lens. Participants were examined weekly for 6 consecutive weeks to ascertain skin changes in ambient light and through the ALS. Overt tissue changes were noted when viewed with the ALS and camera compared with visual screens in ambient light. Descriptive statistics were calculated for all wavelengths. Two chi-square tests of independence were run to look for relationships between wavelength and the number of detected injuries (absorption). Participants presenting with nonblanching erythema in ambient light showed significant tissue absorption under ALS and camera, depicting the actual scope and magnitude of the tissue trauma. Participants with scars, areas of previous injury, and pigmentary changes also showed significant absorption at those sites. These combined findings indicate that ALS can detect tissue trauma and areas at risk not readily visible by the naked eye. This noninvasive tool could help identify patients in the early stages of tissue trauma as well as screen for sites of previous injury that are at risk for subsequent breakdown, saving significant health care dollars and improving outcomes and quality of life.


Site-specific phosphorylation of L-form starch phosphorylase by the protein kinase activity from sweet potato roots.
A 78-amino acid insertion (L78) is found in the low-affinity type (L-form) of starch phosphorylase (L-SP, EC 184.108.40.206). This insertion blocks the starch-binding site on the L-SP molecule, and it decreases the binding affinity of L-SP toward starch. The computational analysis of the amino acid sequence on L78 predicts several phosphorylation sites at its Ser residues. Indeed, from the immunoblotting results using antibodies against phosphoamino acids, we observed that the purified L-SP from mature sweet potato (Ipomoea batatas) roots is phosphorylated. This observation led us to the detection of a protein kinase activity in the protein fraction of the crude extract from the sweet potato roots. The kinase was partially purified by liquid chromatography, and its native molecular mass was estimated as 338 kDa. An expressed peptide (L78P) containing the essential part of L78 was intensively phosphorylated by the kinase. However, H-SP (the high-affinity isomer of SP lacking the L78 insertion) and the proteolytic modified L-SP, which lost its L78 fragment, could not be phosphorylated. Furthermore, using L78P mutants by site-directed mutagenesis at Ser residues on L78, we demonstrate that only one Ser residue on L78 is phosphorylated by the kinase. These results imply that this kinase is specific to L-SP, or more precisely, to the L78 insertion. The in vitro phosphorylated L-SP shows higher sensitivity to proteolytic modification, but has no change in its kinetic parameters.


Does c-erbB-2 play a role in the first steps of lung carcinogenesis?
The 1999 WHO/IASLC histological classification of preneoplastic bronchial lesions has been shown to be reproducible, but little is known about its biological significance. The EGFR expression rate increases from normal epithelium to carcinoma in situ (CIS) with a significant difference between mild versus severe dysplasia. C-erbB-2, another member of the erbB family, is overexpressed in lung carcinomas, suggesting that this mechanism may play a role in carcinogenesis. We evaluated the correspondence between the morphological changes of the bronchial epithelium and the c-erbB-2 expression. Nine normal bronchial epithelia, 16 hyperplasia, 12 metaplasia, 12 mild dysplasia, 8 severe dysplasia, 11 CIS and 6 microinvasive tumours were evaluated. Immunostaining was performed using anti-c-erbB-2 antibodies (clone CBI ). No immunostaining was found whatever the bronchial lesions evaluated. C-erbB-2 does not seem to be involved in the first step of carcinogenesis of squamous cell carcinoma. These findings suggest that there is no place for chemoprevention by anti-c-erbB-2 drugs such as trastuzumab in lung cancer.


A simple test system for the separation of staphylococci from micrococci.
A simple test system for the separation of staphylococci from micrococci is described, which is based on the ability of staphylococci to produce acid aerobically from glycerol in the presence of 0.4 mug of erythromycin per ml and on their sensitivity to lysostaphin.


A framework for longitudinal data analysis via shape regression.
Traditional longitudinal analysis begins by extracting desired clinical measurements, such as volume or head circumference, from discrete imaging data. Typically, the continuous evolution of a scalar measurement is estimated by choosing a 1D regression model, such as kernel regression or fitting a polynomial of fixed degree. This type of analysis not only leads to separate models for each measurement, but there is no clear anatomical or biological interpretation to aid in the selection of the appropriate paradigm. In this paper, we propose a consistent framework for the analysis of longitudinal data by estimating the continuous evolution of shape over time as twice differentiable flows of deformations. In contrast to 1D regression models, one model is chosen to realistically capture the growth of anatomical structures. From the continuous evolution of shape, we can simply extract any clinical measurements of interest. We demonstrate on real anatomical surfaces that volume extracted from a continuous shape evolution is consistent with a 1D regression performed on the discrete measurements. We further show how the visualization of shape progression can aid in the search for significant measurements. Finally, we present an example on a shape complex of the brain (left hemisphere, right hemisphere, cerebellum) that demonstrates a potential clinical application for our framework.


Paclitaxel-Loaded Mixed Micelles Enhance Ovarian Cancer Therapy through Extracellular pH-Triggered PEG Detachment and Endosomal Escape.
Although PEGylation allows a drug delivery vehicle to have prolonged blood circulation time, it faces the problem of reduced cellular uptake. Removal of the polyethylene glycol (PEG)-shell at the appropriate time through tumor-microenvironment triggers could be a feasible solution to this problem. Here, paclitaxel (PTX)-loaded mixed micelles (PTX-mM) self-assembled from stearate-modified hyaluronic acid (SHA), mPEG-b-poly(β-amino ester) (mPEG-b-PAE), and ethylene acetyl-b-poly(β-amino ester) (EA-b-PAE) were developed. In the preparation of PTX-mM, SHA micelles were coated with EA-b-PAE followed by coloading of PTX and mPEG-b-PAE. PTX-mM were capable of extracellular pH-triggered PEG-detachment and poly(β-amino ester) (PAE)-mediated endosomal escape. When the pH was changed from pH 7.4 to pH 6.8, the particle size of PTX-mM significantly decreased from 97.5 ± 4.4 to 71.5 ± 2.3 nm. It also resulted in rapid and complete release of mPEG-b-PAE from PTX-mM as monitored using quartz crystal microbalance (QCM) technology. PTX-mM capable of PEG detachment provided significant enhancement of PTX accumulation in SKOV-3 cells compared to PEG nondetachable PTX-mM. Interestingly, intracellular transport studies using confocal laser scanning microscopy (CLSM) showed that EA-b-PAE could promote the escape of micelles from endolysosomes. The half-maximal inhibitory concentration (IC50) of PTX-mM against SKOV-3 cells was 5.7 μg/mL, and PTX-mM containing 20 μg/mL of PTX induced apoptosis in 53.0% of the cell population. PTX-mM exhibited a highly prolonged elimination half-life (t1/2, 2.83 ± 0.37 h) and improved area under the curve (AUC, 7724.82 ± 1190.75 ng/mL/h) than the PTX-loaded SHA micelles (PTX-M). Furthermore, PTX-mM showed the highest tumor inhibition rate (64.9%) and the longest survival time (53 days) against the SKOV-3 ovarian cancer xenograft models among all formulations. Taken together, the results suggested that PTX-mM have potential as an efficient anticancer formulation in treatment of ovarian cancer.


A Modified Supine Position Facilitates Bladder Function in Patients Undergoing Percutaneous Coronary Intervention: A Randomized Controlled Clinical Trial.
Percutaneous coronary intervention (PCI) is currently the most common intervention for cardiovascular disease. Standard care after PCI typically involves a period of bed rest in the supine position, but this position creates voiding difficulties. This study aimed to determine whether a modified supine position could facilitate bladder emptying after PCI. A randomized controlled trial involving 300 patients was conducted. Patients in the intervention group were nursed in the supine position with the bed tilted 20° upright and with a pillow between their feet and the end of the bed. Patients in the control group received standard care, which was supine positioning. One hundred fifty patients were allocated to the intervention group (100 men, 50 women), and 150 were allocated to the control group (103 men, 47 women). Baseline data did not differ between the 2 groups. Patients in the intervention group had significantly better bladder function as evidenced by a shorter time to the first void (5 vs 15 minutes) and fewer patients requiring voiding assistance (8.6% vs 35.3%). Residual urinary volumes were also much lower in the intervention group (88.71 vs 248.22 mL, P < .001). This study demonstrates that a modified supine position can reduce the incidence of impaired micturition and the preservation of normal bladder function after PCI.


Folate Deficiency Facilitates Genomic Integration of Human Papillomavirus Type 16 DNA In Vivo in a Novel Mouse Model for Rapid Oncogenic Transformation of Human Keratinocytes.
Epidemiologic and in vitro studies suggest independent linkages between poor folate and/or vitamin B-12 nutrition, genomic human papillomavirus (HPV) type 16 viral integration, and cancer. However, there is no direct evidence in vivo to support the causative role of poor folate nutrition in HPV16 integration into the cellular genome. We tested the hypothesis that folate deficiency enables the integration of HPV16 into the genome of HPV16-harboring keratinocytes, and could thereby influence earlier transformation of these cells to cancer in an animal model. HPV16-harboring human keratinocytes [(HPV16)BC-1-Ep/SL] were differentiated into 3-dimensional HPV16-organotypic rafts under either folate-replete or folate-deficient conditions in vitro. These were then subcutaneously implanted in severely immunocompromised female Beige Nude XID (Hsd: NIHS-LystbgFoxn1nuBtkxid) mice (4-6 wk old, 16-18 g) fed either a folate-replete diet (1200 nmol folate/kg diet) or a progressively folate-deficient diet (600 or 400 nmol folate/kg diet) for 2 mo prior to raft-implantation surgery, and indefinitely thereafter. The tumors that subsequently developed were characterized for onset, pattern of growth, morphology, HPV16 oncogene expression, and HPV16-genomic integration. All HPV16-organotypic rafts developed in either folate-replete or physiologic low-folate media in vitro and subsequently implanted in folate-replete mice eventually transformed into aggressive malignancies within weeks. When compared to HPV16-high folate-organotypic raft-derived tumors from mice fed either a 1200 or 600 nmol folate/kg diet, those raft-derived cancers that developed in mice fed a 400 nmol folate/kg diet expressed significantly more HPV16 E6 (1.8-fold more) and E7 (2.8-fold more) oncogenic proteins (P = 0.001), and revealed significantly more HPV16-integration sites in genomic DNA (2-fold more), either directly into, or in the vicinity of, cellular genes (P < 0.05). This unprecedented animal model for the consistent rapid transformation of differentiated (HPV16)BC-1-Ep/SL-derived organotypic raft-keratinocytes to cancer in Beige Nude XID mice confirms that dietary folate deficiency can profoundly influence and modulate events leading to HPV16-induced carcinogenesis, and facilitates genomic integration of HPV16 DNA in vivo.


Dietary changes needed to reach nutritional adequacy without increasing diet cost according to income: An analysis among French adults.
To explore the dietary changes needed to achieve nutritional adequacy across income levels at constant energy and diet cost. Individual diet modelling was used to design iso-caloric, nutritionally adequate optimised diets for each observed diet in a sample of adult normo-reporters aged ≥20 years (n = 1,719) from the Individual and National Dietary Survey (INCA2), 2006-2007. Diet cost was estimated from mean national food prices (2006-2007). A first set of free-cost models explored the impact of optimisation on the variation of diet cost. A second set of iso-cost models explored the dietary changes induced by the optimisation with cost set equal to the observed one. Analyses of dietary changes were conducted by income quintiles, adjusting for energy intake, sociodemographic and socioeconomic variables, and smoking status. The cost of observed diets increased with increasing income quintiles. In free-cost models, the optimisation increased diet cost on average (+0.22 ± 1.03 euros/d) and within each income quintile, with no significant difference between quintiles, but with systematic increases for observed costs lower than 3.85 euros/d. In iso-cost models, it was possible to design nutritionally adequate diets whatever the initial observed cost. On average, the optimisation at iso-cost increased fruits and vegetables (+171 g/day), starchy foods (+121 g/d), water and beverages (+91 g/d), and dairy products (+20 g/d), and decreased the other food groups (e.g. mixed dishes and salted snacks), leading to increased total diet weight (+300 g/d). Those changes were mostly similar across income quintiles, but lower-income individuals needed to introduce significantly more fruit and vegetables than higher-income ones. In France, the dietary changes needed to reach nutritional adequacy without increasing cost are similar regardless of income, but may be more difficult to implement when the budget for food is lower than 3.85 euros/d.


Diagnosis of tuberculous lymphadenitis: combining cytomorphology, microbiology and molecular techniques - a study from Sri Lanka.
Fine needle aspiration is a simple technique to obtain material for early diagnosis of tuberculous lymphadenitis. To assess the value of fine needle aspiration cytology (FNAC) in the diagnosis of tuberculous lymphadenitis. A total of 43 aspirates from patients who were clinically suspected to have tuberculous lymphadenitis were included in the study. Apart from FNAC, aspirates were smeared for Ziehl Neelsen stain and cultured on Middlebrook 7H9 and 7H10 media. Culture was considered the gold standard. Positive and negative predictive values and agreement between the gold standard and five diagnostic criteria were assessed. Kappa value was used to calculate the agreement. The presence of epithelioid cells either with caseation or positive Ziehl Neelsen had the highest agreement (kappa value 0.84), with high positive and negative predictive values (85.71% and 96.55%). Positive Ziehl Neelsen alone and presence of epithelioid cells with positive Ziehl Neelsen had 100% positive predictive values, but the kappa values were lower (0.62 and 0.52) with lower negative predictive values (83.33% and 81.08%). Epithelioid cells alone had a high negative predictive value (93.35%), but the positive predictive value was lower (84.62%). When epithelioid cells were taken together with caseation, the positive predictive value reduced further (83.33%). The presence of epithelioid cells either with caseation or positive Ziehl Neelsen stain appears to be the best diagnostic criteria, with a very good agreement with the gold standard and high positive and negative predictive values.


Most basal I(SC) in Calu-3 human airway cells is bicarbonate-dependent Cl- secretion.
Serous cells secrete antibiotic-rich fluid, but secretion is impaired in cystic fibrosis. We are investigating Calu-3 cells as a serous cell model. Basal short-circuit current (I[SC]) in Calu-3 cells grown at air interface had a basal I(SC) approximately six times larger than submerged cultures (69 +/- 22 vs. 11 +/- 10 microA/cm2). Basal I(SC) in either condition was reduced only 7 +/- 5% by bumetanide and was unaffected by apical amiloride, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 4,4'-dinitrostilbene-2,2'-disulfonic acid (DNDS), or calixarene but was reduced 77 +/- 18% by N-phenylanthranilic acid. Three transport mechanisms accounted for almost all basal I(SC). The largest component is HCO3(-)-dependent Cl- secretion. Replacement of Krebs-Henseleit solution with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered solution and changing gassing from 95% O2-5% CO2 to air reduced the basal I(SC) by 61 +/- 10%. Acetazolamide decreased basal I(SC) by 33 +/- 6%, whereas acetazolamide + basolateral DNDS eliminated 42-58% of the bumetanide-insensitive basal I(SC). Neither DNDS nor acetazolamide had any effect when applied in HCO3(-)-free solution. Apical phlorizin, a blocker of Na+-glucose cotransport, eliminated one-half of the remaining I(SC). Cl- replacement with gluconate eliminated all I(SC) except the phlorizin-sensitive component. Unlike basal I(SC), 80 +/- 24% of stimulated I(SC) was inhibited by bumetanide. Thus basal and stimulated secretions are mediated by different mechanisms.


Stem-cell therapy for diabetes mellitus.
Curative therapy for diabetes mellitus mainly implies replacement of functional insulin-producing pancreatic beta cells, with pancreas or islet-cell transplants. However, shortage of donor organs spurs research into alternative means of generating beta cells from islet expansion, encapsulated islet xenografts, human islet cell-lines, and stem cells. Stem-cell therapy here implies the replacement of diseased or lost cells from progeny of pluripotent or multipotent cells. Both embryonic stem cells (derived from the inner cell mass of a blastocyst) and adult stem cells (found in the postnatal organism) have been used to generate surrogate beta cells or otherwise restore beta-cell functioning. Recently, Andreas Lechner and colleagues failed to see transdifferentiation into pancreatic beta cells after transplantation of bone-marrow cells into mice (Diabetes 2004; 53: 616-23). Last year, Jayaraj Rajagopal and colleagues failed to derive beta cells from embryonic stem cells (Science 2003; 299: 363). However, others have seen such effects. WHERE NEXT? As in every emerging field in biology, early reports seem confusing and conflicting. Embryonic and adult stem cells are potential sources for beta-cell replacement and merit further scientific investigation. Discrepancies between different results need to be reconciled. Fundamental processes in determining the differentiation pathways of stem cells remain to be elucidated, so that rigorous and reliable differentiation protocols can be established. Encouraging studies in rodent models may ultimately set the stage for large-animal studies and translational investigation.


Geriatric gynecology.
The quality of life of the postmenopausal woman can be significantly improved by active investigation and treatment of gynecologic disorders, such as postmenopausal osteoporosis, in this age group. Surgical intervention should never be excluded simply on the basis of chronologic age.


Calcium influx into dendrites of the leech Retzius neuron evoked by 5-hydroxytryptamine.
5-Hydroxytryptamine (5-HT) is a ubiquitous neurotransmitter and neuromodulator that affects neural circuits and behaviours in vertebrates and invertebrates. In the present study, we have investigated 5-HT-induced Ca(2+) transients in subcellular compartments of Retzius neurons in the leech central nervous system using confocal laser scanning microscopy, and studied the effect of 5-HT on the electrical coupling between the Retzius neurons. Bath application of 5-HT (50mM) induced a Ca(2+) transient in axon, dendrites and cell body of the Retzius neuron. This Ca(2+) transient was significantly faster and larger in dendrites than in axon and cell body, and was half-maximal at a 5-HT concentration of 5-12mM. The Ca(2+) transient was suppressed in the absence of extracellular Ca(2+) and by methysergide (100mM), a non-specific antagonist of metabotropic 5-HT receptors, and was strongly reduced by bath application of the Ca(2+) channel blocker Co(2+) (2mM). Injection of the non-hydrolysable GTP analogue GTPgammaS increased and prolonged the dendritic 5-HT-induced Ca(2+) transient. The non-selective protein kinase inhibitor H7 (100mM) and the adenylate cyclase inhibitor SQ22536 (500 mM) did not affect the Ca(2+) transient, and the membrane-permeable cAMP analogue dibutyryl-cAMP (500 mM) did not mimic the effect of 5-HT application. 5-HT reduced the apparent electrical coupling between the two Retzius neurons, whereas suppression of the Ca(2+) influx by removal of external Ca(2+) improved the transmission of action potentials at the electrical synapses which are located between the dendrites of the adjacent Retzius neurons. The results indicate that 5-HT induces a Ca(2+) influx through calcium channels located primarily in the dendrites, and presumably activated by a G protein-coupled 5-HT receptor. The dendritic Ca(2+) increase appears to modulate the excitability of, and the synchronization between, the two Retzius neurons.


Dabigatran and vitamin K antagonists' use in naïve patients with non-valvular atrial fibrillation: a cross-sectional study of primary care-based electronic health records.
The purpose of this study was to characterize the profile of patients with non-valvular atrial fibrillation who start an anticoagulant treatment after diagnosis with dabigatran and compare it with those who start with vitamin K antagonists (VKAs). We analysed primary health care-based electronic health records data from 15,075 people with new diagnosis of atrial fibrillation who initiated treatment with dabigatran or VKA spanning 2011-2013. Logistic regression analysis for determination of factors associated with initiation of dabigatran was performed. We identified 14,266 (94.6%) people who initiated VKA and 809 (5.4%) who initiated dabigatran. Mean age of people treated with dabigatran was lower than in VKA patients (73.7 vs 75.5 years, p < 0.001). People (90.5%) in VKA group and 83.6% in the dabigatran group had a high risk of stroke, according to CHA2DS2VASc score. There was higher proportion of people with hypertension, diabetes mellitus, dyslipidaemia, and chronic kidney disease among people treated with VKA. The proportion of people with a history of cerebral haemorrhage and stroke was higher among dabigatran patients compared with VKA patients (1.4 vs 0.6%, p = 0.015 and 14.0% vs 10.8%, p = 0.006, respectively). Multivariable logistic model showed that treatment with dabigatran was associated with male sex, history of stroke and Mortalidad en áreas pequeñas Españolas y Desigualdades Socioeconómicas index. Most patients recently diagnosed with non-valvular atrial fibrillation initiated treatment with VKA. Primary healthcare patients with non-valvular atrial fibrillation initiating dabigatran are younger, had a lower risk of stroke or bleeding, fewer comorbidity and more history of stroke and intracranial haemorrhage compared to those who were initiated on VKA.


Selective gastric hypersensitivity and reflex hyporeactivity in functional dyspepsia.
We have previously shown that patients with functional dyspepsia are hypersensitive to gastric distention. The aim of this study was to establish whether this sensory disturbance was confined to the stomach and whether it was associated with gut reflex dysfunction. In 10 selected patients with dyspepsia and 12 healthy controls, perception and gut reflex responses to gastric distention, duodenal distention, and somatic stimulation were measured. Standardized distentions at fixed pressures were performed by gastric and duodenal barostats. Perception was scored by a detailed symptom questionnaire; gut reflex responses were measured as isobaric volume changes by each barostat. Somatic transcutaneous electrical nerve stimulation was produced on the hand. Individual stimuli (2-minute duration) were randomly applied at 10-minute intervals in stepwise increments in search of the respective threshold for discomfort. Patients with dyspepsia had gastric hypersensitivity to distention (discomfort threshold at 6.4 +/- 0.4 mm Hg vs. 8.3 +/- 0.6 mm Hg in controls; mean +/- SE; P < 0.05), whereas duodenal and somatic sensitivity was normal. Furthermore, patients with dyspepsia explicitly recognized their clinical symptoms in all gastric but only in 58% +/- 12% of the duodenal distention trials. In addition, patients with dyspepsia showed defective gastric relaxatory responses to duodenal distention (68 +/- 30 mL gastric expansion vs. 239 +/- 12 mL in controls; P < 0.05). Patients with dyspepsia are selectively hypersensitive to gastric distention; this sensory dysfunction is associated with impaired reflex reactivity of the stomach.


The Atopic Dermatitis Quickscore (ADQ): validation of a new parent-administered atopic dermatitis scoring tool.
Atopic dermatitis (AD) severity is assessed using relatively elaborate scoring systems administered by health care practitioners; modification for parent assessment or self-assessment is limited. For ongoing home-based evaluation of pediatric AD treatment and outcomes, a quick, easy-to-use, parent-administered scoring tool is essential. To evaluate the validity and responsiveness to change of the Atopic Dermatitis Quickscore (ADQ) compared with the established, widely used Scoring Atopic Dermatitis Severity Index (SCORAD). The ADQ was developed for parent report and was validated against the SCORAD. The SCORAD assesses percentage of body surface area involved, intensity of a "representative area," pruritus, and insomnia. The ADQ assesses involvement and pruritus of 7 body parts. Sixty-eight children entering a pediatric day treatment program for moderate to severe AD were recruited. Skin severity was scored at admission by a physician assistant using the SCORAD and by a parent using the ADQ. Pearson correlations of the 2 scales were assessed. The ADQ total score correlates with the SCORAD total score (r = 0.64, P < .001). The ADQ pruritus score correlates with the SCORAD pruritus score (r = 0.62, P < .001). Correlation at the end of treatment was also seen for ADQ and SCORAD total and pruritus scores (r = 0.39, P = .02, and r = 0.66, P < .001, respectively). Responsiveness of both scales to change in skin condition was demonstrated, with significant decreases in total and pruritus scores (P < .001). The parent-administered ADQ takes 5 minutes to complete. Scores from the ADQ and the SCORAD are well correlated and are responsive to changes in skin condition, supporting the validity of the ADQ.


Effects of a nitric oxide synthesis inhibitor on renal sodium handling and diluting capacity in humans.
Inhibition of nitric oxide (NO) synthesis has antinatriuretic and antidiuretic effects. Limited information is available on the role of NO in tubular sodium transport in the human kidney. We studied nine healthy, sodium-replete males with clearance techniques during maximal diuresis. NG-monomethyl-L-arginine (L-NMMA, 3 mg/kg priming dose plus 3 mg/kg/h) was infused for 3 h, to achieve steady-state inhibition of NO synthesis. Data were compared with a time control study. The effects of L-NMMA were quickly established and persisted through the entire infusion period. Mean arterial pressure increased slightly from 85+/-3 to 91+/-3 mmHg (P<0.05). Renal plasma flow decreased substantially, and glomerular filtration rate slightly. Large decreases in absolute sodium excretion, from 79+/-10 to 34+/-5 micromol/min (P<0.01), and fractional sodium excretion, from 0.5+/-0.0 to 0.3+/-0.0% (P<0.01), were associated with significant reductions in fractional lithium excretion (P<0.05) and maximum urine flow (P<0.01). Minimal urine sodium concentration decreased from 5.8+/-0.04 to 3.9+/-0.4 mmol/l (P<0.01) whereas minimal urine osmolality increased (P<0.05). Plasma renin activity, aldosterone and atrial natriuretic peptide levels did not change, whereas urinary excretions of guanosine 3'5'-cyclic monophosphate and of nitrite plus nitrate decreased slightly. Inhibition of endogenous NO synthesis in humans to an extent that raises blood pressure only mildly causes antinatriuresis, that can be attributed to increases in sodium reabsorption both at proximal and distal nephron sites. In addition, renal diluting capacity decreases. The effects in the diluting segment have not been reported before, and may be due to medullary vasoconstriction, similar to that described for angiotensin II.


Distribution of the ribosome associated endonuclease Rae1 and the potential role of conserved amino acids in codon recognition.
We recently identified a novel ribonuclease in Bacillus subtilis called Rae1 that cleaves mRNAs in a translation-dependent manner. Rae1 is a member of the NYN/PIN family of ribonucleases and is highly conserved in the Firmicutes, the Cyanobacteria and the chloroplasts of photosynthetic algae and plants. We have proposed a model in which Rae1 enters the A-site of ribosomes that are paused following translation of certain sequences that are still ill-defined. In the only case identified thus far, Rae1 cleaves between a conserved glutamate and lysine codon during translation of a short peptide called S1025. Certain other codons are also tolerated on either side of the cleavage site, but these are recognized less efficiently. The model of Rae1 docked in the A-site allows us to make predictions about which conserved residues may be important for recognition of mRNA, the tRNA in the adjacent P-site and binding to the 50S ribosome subunit.


Androgen replacement therapy in the aging male.
Beginning around age 40 years, men experience a decrease in testosterone level-referred to as "andropause"-and the pathophysiologic changes that accompany this decrease. Androgen replacement therapy, typically used for the treatment of senile hypogonadism, is evolving as a potential treatment of various other conditions related to testosterone loss, such as osteoporosis, sarcopenia, and even psychological symptoms. As with any treatment modality, certain patient factors are more predictive of success with minimal adverse effects, and consideration must be given to concomitant conditions. This article will provide a review of recent studies examining the effects of androgen supplementation and evaluate the purported benefits and potential risks of this therapy. Further research is anticipated to elucidate the most appropriate candidates, as well as other potential indications, for this treatment.


An in vitro model for analysis of oxidative death in primary mouse astrocytes.
Astrocytes provide a vital protective function in the brain. These cells are also vulnerable to oxidative stress, thus their loss of function could contribute to neurodegeneration. The goal of this study is to develop a cell culture model to study oxidative stress in astrocytes. Enriched astrocytic cultures were generated from neonatal mice. tertiary-butyl hydroperoxide (t-bOOH) was used as an exogenous peroxide and lactate dehydrogenase (LDH) release as a measure of loss of viability. Exposure to t-bOOH resulted in a linear increase in astrocytic death reaching 91.2% after 4 h exposure. That cell death was due to oxidative injury, was shown by the ability of the antioxidant N,N'-diphenyl-1,4-phenylenediamine (DPPD) to protect the t-bOOH treated cells. The involvement of iron in cell toxicity was demonstrated by the ability of the iron specific chelator desferal (DF) to completely prevent t-bOOH induced LDH release. Cells treated with a lipid soluble iron compound 3,5, 5-trimethyl (hexanoyl) ferrocene (TMH-Ferrocene), were more vulnerable to t-bOOH whereas neither ferrous ammonium sulfate (FAS) nor ferric ammonium citrate (FAC) had an effect. The increased sensitivity of the cells exposed to TMHF was reversible with the iron chelator desferal. Addition of recombinant human heavy chain ferritin or human apo-transferrin (Tf) did not alter LDH release. Electron microscopic analysis indicated astrocytes exposed to t-bOOH exhibited mitochondrial swelling prior to cell death (lactate dehydrogenase release). Additional increases in mitochondrial swelling were seen when the astrocytes were exposed to the lipophilic iron compound TMH-ferrocene and t-bOOH. These studies show that astrocytes are exquisitely sensitive to oxidative stress and that their vulnerability is related to and enhanced by iron. Decreased mitochondrial function in response to oxidative stress may precede cell death.


Impact of hospitals' Referral Region racial and ethnic diversity on 30-day readmission rates of older adults.
Background: The Hospital Readmissions Reduction Program (HRRP) began decreasing Medicare payments to hospitals reporting high readmission rates for individuals over 65. Thus, financially incentivizing hospitals to improve quality performance on preventable readmissions. Well-established research indicates that minorities are more frequently readmitted to hospitals, but it is unknown if community diversity is associated with 30-day readmission rates. Objectives: To investigate the association between racial/ethnic diversity and hospitals' 30-day readmission rates. Methods: We linked the 2017 HRRP, American Hospital Association (AHA) database, Area Health Resource File, US Census Bureau Current Population Survey, and the Dartmouth Atlas HRR dataset to examine 30-day readmission rate for heart failure (HF), pneumonia (PN), acute myocardial infarction (AMI), and hip replacement (HR) surgery of 4,299 hospitals across 306 HRRs. Results: Our findings indicate a statistically significant negative relationship between diversity and 30-day readmission rates for HF, PN, AMI, and HR with a hospital referral region (HRR). Thus, hospitals located in HRRs with diverse populations are more likely to have higher 30-day readmission rates for all conditions under Medicare's HRRP Conclusion: Better discharge follow-up, interventions, and use of support staff aimed at meeting needs associated with differences in communities and cultures are likely to prove more fruitful than traditional one-size fits all approaches to care.


Insight into the characterization and digestion of lotus seed starch-tea polyphenol complexes prepared under high hydrostatic pressure.
Complex starch is gaining research attention due to its unique physicochemical and functional properties. In this study, the effects of green tea polyphenols on the properties and digestion of lotus seed starch under high hydrostatic pressure were investigated. The particle size, swelling power, solubility, crystallization, morphology and thermal properties of lotus seed starch were affected by green tea polyphenols. These may be due to the formation of non-inclusive complexes between lotus seed starch and green tea polyphenols. The morphology and green tea polyphenols distribution of the complexes were determined by scanning electron microscopy and confocal laser scanning microscopy. In addition, slow digestion properties of starch were realized under a dynamic in vitro rat stomach-duodenum model and the erosion of granules by amylase gradually decreased by scanning electron microscopy. Furthermore, green tea polyphenols were shown to be able to form V-type inclusion complex with amylose via high hydrostatic pressure.


HIF1A is Overexpressed in Medulloblastoma and its Inhibition Reduces Proliferation and Increases EPAS1 and ATG16L1 Methylation.
Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxiarelated genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions. Our study focused on evaluation the of CA9, CA12, HIF1A, EPAS1, SCL2A1 and VEGF genes in 41 pediatric fresh-frozen medulloblastoma sample. Additionally, we analyzed the effect of hypoxia and normoxia in the pediatric medulloblastoma cell-line UW402. Furthermore, we assessed the effects of HIF1A knockdown in cell-proliferation and methylation levels of genes related to hypoxia, apoptosis and autophagy. qPCR was performed to evaluate mRNA levels, and Western blot to confirm HIF1A silencing in both patient samples and cell line. Pyrosequencing was performed to asses the methylation levels after HIF1A knockdown in the UW402 cell line. A higher HIF1A mRNA level was observed in MB patients when compared to the cerebellum (non-tumor match). In UW402 MB cell-line, chemically induced hypoxic resulted in an increase of mRNA levels of HIF1A, VEGF, SCL2A1 and CA9 genes. Additionally, HIF1A knockdown induced a decrease in the expression of hypoxia related genes and a decrease of 30% in cell proliferation was also observed. Also, a significant increase in the methylation of ATG16L1 promoter and decrease in the methylation of EPAS1 promoter were observed after HIF1A knockdown. HIF1A knockdown in medulloblastoma cells lead to decreased cellular proliferation, suggesting that HIF1A can be a potential therapeutic target to be explored in the medulloblastoma. However, the mechanisms behind HIF1A protein stabilization and function are very complex and more data need to be generated to potentially use HIF1A as a therapeutical target.


Transcutaneous Electric Nerve Stimulation on ischemic rest pain in inpatients: randomised trial.
To investigate the efficacy of a short-term application of Transcutaneous Electric Nerve Stimulation to relieve rest pain in patients with chronic limb-threatening ischemia. In patients ³18 years old, with chronic limb-threatening ischemia and rest pain ³3 in the Visual Analogue Scale, without diabetic neuropathy were randomly assigned to 1) Transcutaneous Electric Nerve Stimulation (100 Hz, 200 μs) or 2) sham intervention, both during one or two 20 min treatment sessions. The primary outcome was pain intensity, assessed by the visual analogue scale (0-10 cm) and described by the McGill Pain Questionnaire. We used a t-test for difference of means. A total of 169 patients were assessed, 23 met the study criteria and were randomized. Thirty-four applications were performed in two days: in the 17 Transcutaneous Nerve Stimulation and 17 sham. The within-group analysis indicated a pain decrease in both groups (Transcutaneous Electric Nerve Stimulation, from 7-3.9 cm, p<0.0001, and sham from 5.8-3.2 cm, p<0.0001). No statistically significant difference was verified between-groups (p=0.5). Both groups showed a decrease in rest pain of 54 and 55%, respectively. However, there was no difference between short-term high-frequency Transcutaneous Electric Nerve Stimulation and sham intervention to relieve ischemic rest pain in chronic limb-threatening ischemia patients.


Acceptability and use of a patient-held communication tool for people living with dementia: a longitudinal qualitative study.
To assess the acceptability and use of a low-cost patient-held communication tool. Longitudinal qualitative interviews at three time points over 18 months and document content analysis. Primary and community services. Twenty-eight dyads: People living with dementia in Northern Ireland and their informal carers. A patient-held healthcare 'passport' for people living with dementia. Acceptability and use of the passport-barriers and facilitators to successful engagement. There was a qualified appreciation of the healthcare passport and a much more nuanced, individualistic or personalised approach to its desirability and use. How people perceive it and what they actually do with it are strongly determined by individual contexts, dementia stage and other health problems, social and family needs and capacities. We noted concerns about privacy and ambivalence about engaging with health professionals. Such tools may be of use but there is a need for demanding, thoughtful and nuanced programme delivery for future implementation in dementia care. The incentivisation and commitment of general practitioners is crucial. Altering the asymmetrical relationship between professionals and patients requires more extensive attention.


Improving hospital quality to reduce disparities in severe maternal morbidity and mortality.
Significant racial/ethnic disparities in maternal morbidity and mortality exist in the United States. Black women are 3-4 times more likely to die a pregnancy-related death as compared with white women. Growing research suggests that hospital quality may be a critical lever for improving outcomes and narrowing disparities. This overview reviews the evidence demonstrating that hospital quality is related to maternal mortality and morbidity, discusses the pathways through which these associations between quality and severe maternal morbidity generate disparities, and concludes with a discussion of possible levers for action to reduce disparities by improving hospital quality.


The LysE Superfamily of Transport Proteins Involved in Cell Physiology and Pathogenesis.
The LysE superfamily consists of transmembrane transport proteins that catalyze export of amino acids, lipids and heavy metal ions. Statistical means were used to show that it includes newly identified families including transporters specific for (1) tellurium, (2) iron/lead, (3) manganese, (4) calcium, (5) nickel/cobalt, (6) amino acids, and (7) peptidoglycolipids as well as (8) one family of transmembrane electron carriers. Internal repeats and conserved motifs were identified, and multiple alignments, phylogenetic trees and average hydropathy, amphipathicity and similarity plots provided evidence that all members of the superfamily derived from a single common 3-TMS precursor peptide via intragenic duplication. Their common origin implies that they share common structural, mechanistic and functional attributes. The transporters of this superfamily play important roles in ionic homeostasis, cell envelope assembly, and protection from excessive cytoplasmic heavy metal/metabolite concentrations. They thus influence the physiology and pathogenesis of numerous microbes, being potential targets of drug action.


Cyclooxygenase-2 inhibitors.
The purpose of this review is to summarize new information regarding the use of selective inhibitors of the cyclooxygenase-2 enzyme, emphasizing recent developments regarding cardiovascular risk. Selective cyclooxygenase-2 inhibitors are as effective as nonselective nonsteroidal antiinflammatory drugs in relieving pain and inflammation but are associated with significantly fewer gastric, duodenal, and intestinal ulcers and ulcer complications. Cyclooxygenase-2 inhibitors may also reduce colorectal polyp development or recurrence as well as reduce the risk of colorectal and esophageal cancer. Some, but not all, studies have suggested increased myocardial infarction with certain cyclooxygenase-2 inhibitors, in particular rofecoxib. It is unclear whether this is a class effect because there are inconclusive data to incriminate celecoxib despite a relatively large number of clinical trials enrolling a large number of patients. Rofecoxib was voluntarily withdrawn by the manufacturer. The European Medicines Agency concluded that cyclooxygenase-2 inhibitors are contraindicated in patients with established cardiovascular disease, should be used with caution in patients with risk factors, and were justified in patients at risk for serious gastrointestinal adverse events. Rofecoxib, but perhaps not all cyclooxygenase-2 inhibitors, may be associated with increased risk for myocardial infarction. It is unclear whether nonselective nonsteroidal antiinflammatory drugs increase or decrease the rate of myocardial infarction. The final truth awaits further studies.


Inorganic arsenic impairs proliferation and cytokine expression in human primary T lymphocytes.
Inorganic arsenic is a toxic environmental contaminant to which humans are mainly exposed through drinking water. This metalloid impairs functions of several key immune cells. Particularly, it reduces IL-2 secretion and proliferation of blood peripheral mononuclear cells stimulated by lectins that, however, do not mimic physiological T cell activation. The present study used isolated human T cells activated, in a more physiological manner, through stimulation with CD3/CD28 antibodies, to carefully analyze the impact of arsenic on T cell proliferation and cytokine expression. We demonstrate that non cytotoxic concentrations of sodium arsenite (As(III), 0.25-2μM) significantly reduce T cell proliferation by increasing the percentage of non dividing cells blocked in G1 phase and by preventing cyclin D3 and CDC25A expression. They also markedly, although not totally, reduces IL-2 expression at both mRNA and protein levels; however, metalloid-dependent inhibition of T cells could not be reversed by addition of recombinant IL-2. In addition, As(III) markedly reduces secretion of interferon-γ without impairing that of IL-4 and IL-13; it also decreases interferon-γ mRNA levels but increases those of IL-13. Finally, simultaneously to its immune effects, As(III) rapidly and potently increases expression of the redox-sensitive genes HMOX1, NQO1 and GCLM in activated T cells without altering the levels of reactive oxygen species. In conclusion, our results demonstrate that As(III) inhibits T cell proliferation, independently of IL-2, and alters the Th balance of cytokines secreted by co-stimulated T cells which thus constitute direct targets of this major environmental contaminant.


Evaluation of components of gingival crevicular fluid as diagnostic tests.
Gingival crevicular fluid (GCF) is an inflammatory exudate that can be collected at the gingival margin or within the gingival crevice. The biochemical analysis of the fluid offers a noninvasive means of assessing the host response in periodontal disease. In recent years, the relationship of measures of the inflammatory response in GCF to risk for development of active periodontal disease (defined as clinical attachment loss or radiographic bone loss) has been studied in longitudinal trials. The greatest interest has focused on prostaglandin E2, an arachidonic acid metabolite; beta-glucuronidase and neutrophil elastase, markers of lysosomal enzyme release from neutrophils; and aspartate aminotransferase, a cytoplasmic enzyme indicative of cellular necrosis. Analysis of the data allows a number of conclusions to be drawn concerning the potential diagnostic significance of GCF: 1) an exuberant host inflammatory response is associated with progressive disease in patients with periodontitis; 2) collection of GCF using small precut strips is a reproducible and reliable collection technique; 3) the total amount of the mediator and not concentration of the mediator in the GCF sample can be reported when timed samples are collected; and 4) technology exists for GCF-based diagnostic tests to be performed in the dental office. Nevertheless, many questions remain. Still to be determined are: 1) the relationship of test results to the development of periodontitis in patients with gingivitis; 2) the level of test accuracy needed to justify use of these tests; 3) the unit of observation (patient, site) that is being evaluated by the test; and 4) the need for such tests as perceived by clinicians. While these questions are formidable, introduction of GCF-based diagnostic tests will provide clinicians with an improved, quantitative means of evaluating patients and offer specific criteria to assess the effectiveness of treatment.


Electromyographic Evaluation of the Effect of Lined Dentures on Masticatory Muscle Activity in Edentulous Subjects.
The purpose of this study was to examine changes in relative electromyographic (EMG) activities of temporal and masseter muscles after relining the dentures with silicone and acrylic-resin based denture liners. Conventional complete dentures were fabricated for 20 edentulous patients. One month after completing adjustments of the dentures, electromyography of the masseter and temporalis muscle during maximum intercuspation was recorded. The dentures were then relined with a silicone denture liner and after an adaptation period of one month, were again subjected for electromyographic evaluation. Further, the dentures were relined with acrylic denture liner and subjected to electromyographic evaluation. Data was analysed using Statistical Package for Social Sciences (SPSS) version 15.0. Intergroup comparisons were done using ANOVA followed by post-hoc assessments using Tukey HSD test. Mean amplitude and duration with conventional dentures was found to be significantly lower as compared to silicone lined and acrylic lined dentures for all the comparisons. Statistically, no significant difference between silicone lined and acrylic lined dentures was observed for any of the comparisons. Within the limitations of this experimental design, it was concluded that relining significantly increases electromyographic activity of the masseter and temporalis muscles. Thus, resulting in an improved biting force, chewing efficiency and masticatory performance. There were no significant differences between silicone and acrylic based denture liners for both electromyographic variables.


Knowledge about cervical cancer screening and its practice among female health care workers in southern Ethiopia: a cross-sectional study.
Cervical cancer remains a major cause of morbidity and mortality among the women in the world. Early screening for cervical cancer is a key intervention in reduction of maternal deaths. Health care workers have a significant contribution to improve cervical cancer screening practice among women. Hence, this study aimed to assess the knowledge and practice of cervical cancer screening among female health care workers in southern Ethiopia. Institution-based cross-sectional study was conducted during March and April, 2015. All hospitals in Hawassa city administration and Sidama zone were purposively selected. A simple random sampling technique was used to draw the health centers. After proportional allocations to their respective health facilities, a total of 367 female health workers were selected by simple random sampling technique. A structured and pretested questionnaire was used to collect the data. Data were entered to SPSS version 20.0 for further analysis. Logistic regression analyses were used to see the association of different variables. Out of the total respondents, 319 (86.9%) had a good level of knowledge on cervical cancer. Similarly, a majority of them, 329 (89.6%), 321 (87.5%), and 295 (80.4%), knew about the risk factors, symptoms, and outcomes of cervical cancer, respectively. More than two thirds of the respondents, 283 (77.1%), knew that there is a procedure used to detect premalignant cervical lesions and 138 (37.6%) of them mentioned visual inspection with acetic acid as a screening method. In this study, only 42 (11.4%) of the respondents were screened for cervical cancer (confidence interval [CI]: 8.7, 13.9). Being a physician (adjusted odds ratio [AOR] =0.12, 95% CI: 0.02, 0.79) and working in a cervical cancer screening center (AOR =0.14, 95% CI: 0.03, 0.68) had a lower odds of cervical cancer screening practices. Significant numbers of health care workers were knowledgeable on cervical cancer. Cervical cancer screening among health care workers in southern Ethiopia was found to be low. Being a physician and working in a screening center had lower odds of cervical cancer screening practice. In spite of having adequate knowledge on cervical cancer the reasons for low practice of cervical cancer screening among health care workers needs to be investigated.


[Treatment of intrastent restenosis].
The use of stents has significantly reduced post PTCA restenosis rates. However, even with optimal stenting the rate of instant restenosis (ISR) is 8-15%. Thus, the extended use of stents (> or = 85% of angioplasty procedures) has made ISR a growing problem. We review the current interventional approach for treating ISR, where the strategy is dictated by the extent of the restenotic plaque. For focal lesions, redilation with balloon is the therapy of choice. For diffuse lesions, the Cutting Balloon offers good angiographic results with acceptable recurrence rates; in some selected cases, plaque removal can be helpful with a tendency for better results with rotablation. In centers where brachitherapy is available, this is considered the preferred approach for diffuse ISR. In all ISR cases, the alternatives of continuing medical therapy or surgical therapy should also be considered in the decision-making process.


Iron chelation equilibria, redox, and siderophore activity of a saccharide platform ferrichrome analogue.
A complete characterization of the aqueous solution Fe(III) and Fe(II) coordination chemistry of a saccharide-based ferrichrome analogue, 1-O-methyl-2,3,6-tris-O-[4-(N-hydroxy-N-ethylcarbamoyl)-n-butyryl]-alpha-D-glucopyranoside (H3LN236), is reported including relevant thermodynamic parameters and growth promotion activity with respect to both Gram-negative and Gram-positive bacterial strains. The saccharide platform is an attractive backbone for the design and synthesis of ferrichrome analogues because of its improved water solubility and hydrogen-bonding capabilities, which can potentially provide favorable receptor recognition and biological activity. The ligand deprotonation constants (pKa values), iron complex (FeIII(LN236) and FeII(LN236)1-) protonation constants (KFeHxL-236-N), overall Fe(III) and Fe(II) chelation constants (beta110), and aqueous solution speciation were determined by spectrophotometric and potentiometric titrations, EDTA competition equilibria, and cyclic voltammetry. Log betaIII110 = 31.16 and pFe = 26.1 for FeIII(LN236) suggests a high affinity for Fe(III), which is comparable to or greater than ferrichrome and other ferrichrome analogues. The E1/2 for the FeIII(LN236)/FeII(LN236)1- couple was determined to be -454 mV (vs NHE) from quasi-reversible cyclic voltammograms at pH 9. Below pH 6.5, the E1/2 shifts to more positive values and the pH-dependent E1/2 profile was used to determine the FeII(LN236)1- protonation constants and overall stability constant log betaII110 = 11.1. A comparative analysis of similar data for an Fe(III) complex of a structural isomer of this exocyclic saccharide chelator (H3LR234), including strain energy calculations, allows us to analyze the relative effects of the pendant arm position and hydroxamate moiety orientation (normal vs retro) on overall complex stability. A correlation between siderophore activity and iron coordination chemistry of these saccharide-hydroxamate chelators is made.


Impairment of primary hemostasis and platelet function after alcohol ingestion in man.
The effect of alcohol ingestion on primary hemostasis was investigated in fasting healthy humans. Primary hemostasis was measured with the template bleeding time and platelet aggregation assayed with the turbidometric method. Blood was collected to study coagulation and fibrinolysis. 1 h after ingestion of 2 ml/kg body weight of 40% alcohol the plasma alcohol concentration was 19.3 +/- 1.6 mmol/l. At this time there was a significant prolongation of the bleeding time accompanied by an impairment of platelet responsiveness to both collagen and ADP. A prolongation of the bleeding time and impairment of platelet function was also found 2 h after alcohol ingestion. Ingestion of this amount of alcohol did not affect parameters of coagulation or fibrinolysis. The data indicate that primary hemostasis is impaired in man after ingestion of moderate amounts of alcohol. This may explain the favorable effect of moderate alcohol consumption on ischemic heart disease but indicates an increased risk for patients with bleeding.


Link auxiliary field method in the extended Hubbard model.
The aim of this work is to generalize the method of Hubbard fields in fermion quantum Monte Carlo simulations to the case of link fields. The introduced Hubbard link fields play the role of the interaction fields responsible for the attraction and repulsion of electronic excitations at the nodes. Such improvements lead to a number of advantages concerning thermalization time, autocorrelations, metastable states, and probability distributions of the quantities. It is demonstrated that computations using five fields are more stable and reliable in the case of energy observables.


Effects of evocalcet on parathyroid calcium-sensing receptor and vitamin D receptor expression in uremic rats.
Little is known about the effect of the recently developed calcimimetic evocalcet (Evo) on parathyroid calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) expression. We examined the effects of Evo and cinacalcet (Cina) on CaSR and VDR expression in 5/6 nephrectomized Sprague-Dawley rats fed a high-phosphorus diet for 4 weeks to develop secondary hyperparathyroidism (SHPT). These uremic rats were divided into 4 groups-baseline control (Nx4W) and groups with additional treatment with either the Vehicle, Evo, or Cina for 2 weeks; normal rats were used as normal controls (NC). Blood parameters and parathyroid tissue were analyzed. CaSR and VDR expression levels were determined using immunohistochemistry. The degree of kidney injury and hyperphosphatemia was similar in the uremic groups (Nx4W, Vehicle, Cina, and Evo). Serum parathyroid hormone levels were significantly higher in the Nx4W and Vehicle groups than in the NC group. This increase was significantly suppressed in the Cina and Evo groups compared with that in the Vehicle group. Serum calcium levels were significantly and equally lower in the Cina and Evo groups relative to those in the Vehicle group. CaSR expression was significantly lower in the Nx4W and Vehicle groups than in the NC group. This downregulation was of an equally lesser magnitude in the Cina and Evo groups. A similar trend was observed for VDR expression. These results indicate that Evo and Cina treatment can increase parathyroid CaSR and VDR expression in uremic rats with SHPT, which could provide better control of mineral and bone disorder markers.


Delayed healthcare and secondary infections following freshwater stingray injuries: risk factors for a poorly understood health issue in the Amazon.
This study aimed to describe the profile of freshwater stingray injuries in the State of Amazonas, Brazilian Amazon, and to identify the associated risk factors for secondary infections. This cross-sectional study used surveillance data from 2007 to 2014 to identify factors associated with secondary infections from stingray injuries. A total of 476 freshwater stingray injuries were recorded, with an incidence rate of 1.7 cases/100,000 person/year. The majority of injuries were reported from rural areas (73.8%) and 26.1% were related to work activities. A total of 74.5% of patients received medical assistance within the first 3 hours of injury. Secondary infections and necrosis were observed in 8.9% and 3.8%, respectively. Work-related injuries [odds ratio (OR) 4.1, confidence interval (CI); 1.87-9.13] and >24 hours from a sting until receiving medical care (OR; 15.5, CI; 6.77-35.40) were independently associated with the risk of secondary bacterial infection. In this study, work-related injuries and >24 hours from being stung until receiving medical care were independently and significantly associated with the risk of secondary infection. The frequency of infection following sting injuries was 9%. The major factor associated with the risk of secondary bacterial infection was a time period of >24 hours from being stung until receiving medical care.


[Growth rate analysis of pulmonary metastases in giant cell tumor of bone].
We reviewed six cases with pulmonary metastases in giant cell tumor of bone. The growth rate and the doubling time of pulmonary metastases was measured and compared to the clinical course. The six cases were classified into two each of the following three types: 1) spontaneous remission, 2) continuously slow growing and 3) rapid growing. A favorable factor was a doubling time of more than 80 days in pulmonary metastases. A poor prognosis was indicated by a doubling time of around 30 days. Aggressive primary lesions should be excised widely.


Musculoskeletal complaints, absenteeism and associated factors among cytotechnologists: cross-sectional study.
Cytotechnologists are laboratory professionals who analyze cytology slides under optical microscopes. Static postures, speed and repetitive movements are associated with occurrence of musculoskeletal complaints. To establish the main musculoskeletal complaints among cytotechnologists at the National Cancer Institute, Brazil, test associations between absenteeism due to musculoskeletal complaints and individual and occupational variables, and characterize absenteeism related to diseases of the musculoskeletal system in 2016 and 2017. Cross-sectional study in which we administered the Nordic Musculoskeletal Questionnaire and tested associations between exposure variables and absenteeism. We also analyzed morbidity records kept at the Occupational Health Division (OHD) to establish the main disorders related to absenteeism. Associations were investigated by means of Fisher's test using SPSS version 20.0. The significance level was set to p<0.05. 34.4% of the sample required sick leave due to musculoskeletal complaints. The most affected body site was the neck (18%). As per the OHD records, sickness absenteeism was mainly due to diseases of the musculoskeletal system and connective tissue (25%). We found statistically significant association of absenteeism with length in the job and body mass index. Diseases of the musculoskeletal system and connective tissue were the main reason for missing work days. Absenteeism was associated with length in the job and high body mass index.


INTERMEDIATE UVEITIS ASSOCIATED WITH PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS, AND CERVICAL ADENITIS SYNDROME.
To report two novel cases of intermediate uveitis associated with Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis syndrome. Observational case reports and review of the literature. Both patients in this report had an established diagnosis of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis syndrome before the onset of ocular inflammation. Infectious and noninfectious systemic conditions known to be associated with intermediate uveitis were excluded. Intermediate uveitis was confirmed clinically in both patients by the presence of vitritis, snowballs, and peripheral snowbanks in the region of the pars plana. Both cases had a course characterized by recurrent inflammation; in which systemic steroid treatment, and in one case, immunomodulatory therapy was necessary. Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis syndrome is an auto-inflammatory fever disorder in childhood. Although other auto-inflammatory disorders such as, Blau syndrome, Muckle-Wells syndrome, and Behcets disease have been associated with various forms of uveitis, Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis has never been reported to be associated with any type of ocular inflammation. We describe for the first time, two cases of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis syndrome presenting with intermediate uveitis.


Beta-2-adrenoceptor agonists up-regulate the in vitro Fc epsilon receptor II/CD23 expression on, and release from, the promonocytic cell line U937 and human blood monocytes.
The possible regulatory role of beta 2-adrenoceptor agonists in the modulation of CD23 on the human promonocytic cell line U937 and on human monocytes was investigated. Incubation for 48 h in the presence of interleukin-4 (IL-4; 30 U/ml) induced optimal expression and release of CD23 on both U937 cells and human monocytes. When a beta 2-adrenoceptor agonist, either salbutamol or fenoterol, was added to U937 cells or monocytes both the IL-4-induced CD23 expression and release were markedly up-regulated. This effect was dose-dependent, starting at 10 nM and reaching a maximum at 1 microM final concentration of either salbutamol or fenoterol. The potentiating effect of salbutamol and fenoterol on CD23 expression and release was not observed when a beta-adrenoceptor antagonist, either D,L-propranolol (1 microM) or butoxamine (1 microM), was added to the incubation medium. The alpha-adrenoceptor agonist norepinephrine (1 microM) was ineffective in enhancing the IL-4-induced expression and release of CD23 from U937 cells or human monocytes, demonstrating the specificity of the beta 2-adrenoceptor-mediated effect. In the absence of IL-4, a moderate but significant increase in the CD23 expression on U937 cells and human monocytes by these drugs was observed, as compared to the basal values. These results indicate that, besides their bronchodilator effect, beta 2-adrenoceptor agonists may regulate IgE-dependent processes.


Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling.
Tight regulation of COX-2 expression is a key feature controlling eicosanoid production in atherosclerosis and other inflammatory syndromes. Adhesive interactions between platelets and monocytes occur in these conditions and deliver specific signals that trigger inflammatory gene expression. Using a cellular model of monocyte signaling induced by activated human platelets, we identified the central posttranscriptional mechanisms that regulate timing and magnitude of COX-2 expression. Tethering of monocytes to platelets and to purified P-selectin, a key adhesion molecule displayed by activated platelets, induces NF-kappaB activation and COX-2 promoter activity. Nevertheless, COX-2 mRNA is rapidly degraded, leading to aborted protein synthesis. Time-dependent signaling of monocytes induces a second phase of transcript accumulation accompanied by COX-2 enzyme synthesis and eicosanoid production. Here, generation of IL-1beta, a proinflammatory cytokine, promoted stabilization of COX-2 mRNA by silencing of the AU-rich mRNA decay element (ARE) in the 3'-untranslated region (3'UTR) of the mRNA. Consistent with observed mRNA stabilization, activated platelets or IL-1beta treatment induced cytoplasmic accumulation and enhanced ARE binding of the mRNA stability factor HuR in monocytes. These findings demonstrate that activated platelets induce COX-2 synthesis in monocytes by combinatorial signaling to transcriptional and posttranscriptional checkpoints. These checkpoints may be altered in disease and therefore useful as targets for antiinflammatory intervention.


Bovine miR-146a regulates inflammatory cytokines of bovine mammary epithelial cells via targeting the TRAF6 gene.
It has been reported previously that bovine miR-146a (bta-miR-146a) is significantly differentially expressed in mammary glands infected with mastitis, compared with healthy udders. This suggests that bta-miR-146a plays an important role in the regulation of mammary inflammation. However, the specifics of this function have yet to be elucidated. Bovine mammary epithelial cells (bMEC) represent the first line of defense against pathogens and have important roles in initiating and regulating inflammatory responses and innate immunity during infection. In this study, a double luciferase reporter assay was used to confirm that bta-miR-146a directly targets the 3' UTR of the tumor-necrosis factor receptor-associated factor 6 (TRAF6) gene. To elucidate the role of bta-miR-146a in innate immune responses, either a mimic or inhibitor of bta-miR-146a was transfected into bMEC stimulated with lipopolysaccharide, which activates the innate immune response through the toll-like receptor (TLR) 4/nuclear factor (NF)-κB signaling pathway. Forty-eight hours posttransfection, quantitative real-time PCR and Western blots were used to detect the expressions of the related genes and proteins, respectively. An ELISA was used to measure the quantity of inflammatory factors in culture supernatants. The results showed that bta-miR-146a significantly inhibits both mRNA and protein expression levels of bovine TRAF6, and ultimately suppresses downstream expression of NF-κB mRNA and protein. As a result, production of NF-κB-dependent inflammatory mediators such as tumor necrosis factor α, IL-6, and IL-8 are suppressed following lipopolysaccharide stimulation of bMEC. Thus, we concluded that bta-miR-146a acts as a negative feedback regulator of bovine inflammation and innate immunity through downregulation of the TLR4/TRAF6/NF-κB pathway. This study presents a potential regulatory mechanism of bta-miR-146a on immune responses in bovine mammary infection and may provide a potential therapeutic target for mastitis.