Giant cell tumor of the distal femur associated with complete tumor necrosis.
Giant cell tumor is a benign tumor of bone with a predilection for juxta-articular locations. Although not malignant, giant cell tumor often exhibits unpredictable and locally aggressive behavior, and in rare cases can metastasize in the absence of histologic malignancy. Partial tumor necrosis has been infrequently reported within typical giant cell tumor. A 17-year-old girl presented with a right distal femur giant cell tumor associated with complete tumor necrosis on histopathologic analysis. The etiology, prevalence, and implications of complete necrosis in previously untreated giant cell tumor of bone remain unclear, as there are no previously published reports. Despite the complete necrosis evident in our patient, she nonetheless presented with pain. There were no radiographic signs of the necrotic tumor space remodeling with new bone. The patient was treated with standard extended intralesional curetting through a generous cortical window permitting visualization of the entire lesion, and systematic high speed burring and thermal electrocautery ablation of the periphery, followed by micro particulate allogenic bone grafting. At short-term follow-up, she had healed well with no evidence of tumor recurrence. This article presents the first case, to our knowledge, of complete spontaneous tumor necrosis in a previously untreated bone giant cell tumor. Increased understanding of spontaneous tumor necrosis associated with giant cell tumor may help guided future targeted medical and surgical treatment modalities.


Four years' experience of maternal alpha-fetoprotein screening and its effect on the pattern of antenatal care.
Estimation of alpha-fetoprotein (A.F.P.) in maternal serum was used as a screening method for the detection of fetal neural tube defect (N.T.D.) in 7315 women over a four year period. Of these, 5668 pregnancies were tested between 15 and 21 weeks. Action was advised in 129 patients (2.3 per cent). In 74 patients, the only action required was reviewing the notes, including the report of any ultrasound examination, and repeating the blood A.F.P. Detailed ultrasound including scanning the fetal spine was requested in 47 patients and amniocentesis was advised in 19 of these (0.33 per cent). In practice the incidence of amniocentesis was 0.28 per cent as three patients declined our advise. The programme gave detection rates between 15 and 21 weeks of 100 per cent and 75 per cent respectively for anencephaly and open spina bifida. A high fetal mortality was associated with persistently elevated blood A.F.P. levels whether amniocentesis was performed or not.


Vaccination of dogs with Duramune DAPPi+LC protects against pathogenic canine parvovirus type 2c challenge.
In this study, we determined whether vaccination with Duramune DAPPi+LC containing canine parvovirus (CPV) type 2b protects against challenge with virulent CPV antigenic type 2c. Seven healthy dogs, seronegative for CPV2, were enrolled into two treatment groups; five were vaccinated twice, 21 days apart, with minimum titre vaccine, and two were given saline. Dogs were challenged with CPV 2c three weeks later. Clinical observations, body weight and rectal temperature measurements, blood samples for serology and white blood cell counts and faecal samples for virus excretion were collected. Control dogs remained seronegative until challenge; vaccinated dogs seroconverted and were positive for antibodies to CPV2 from day 21. Four days after challenge, clinical signs associated with parvovirus infection (vomiting, paroxysmal shivering, depression, loose stools) were observed in the control dogs. Both animals were withdrawn from the study for welfare reasons one day later. On day 47, leucopenia was observed in controls, with white blood cell counts less than 50 per cent prechallenge values. No specific clinical sign of parvovirus infection were observed in the vaccinated dogs, nor was (detectable) challenge virus shed in faeces suggesting that antibodies generated contributed sterilising immunity. We conclude that vaccination of dogs with Duramune DAPPi+LC protects against challenge with a virulent field strain of CPV 2c.


Constructing a World Wide Web site for disaster management and humanitarian assistance.
There is a huge need for access to information in the areas of disaster relief, disaster medicine, and humanitarian assistance. The extraordinarily rapid increase in the literature in these subject areas attests to this need. However, use of the printed word has substantial limitations that are even more profound in the developing world. Currently, the information available tends to be fragmented and sequestered by the specific interests of the organizations and governments involved. The evolving electronic methods for the storage, organization, and retrieval of information makes coordination between organizations concerned with disasters within our grasp. This paper discusses the Center of Excellence in Disaster Management and Humanitarian Assistance and describes the World Wide Web and the implications it has in disaster management and medicine. It describes methods for obtaining user input to the techniques used for the development of the world wide web for the areas of disaster management and disaster medicine. The implementation of an on-line Internet reference desk that will provide: 1) a list of "experts;" 2) a searchable disaster database; and 3) on-line simulation courses and training exercises also is discussed.


Identification of a new hominin bone from Denisova Cave, Siberia using collagen fingerprinting and mitochondrial DNA analysis.
DNA sequencing has revolutionised our understanding of archaic humans during the Middle and Upper Palaeolithic. Unfortunately, while many Palaeolithic sites contain large numbers of bones, the majority of these lack the diagnostic features necessary for traditional morphological identification. As a result the recovery of Pleistocene-age human remains is extremely rare. To circumvent this problem we have applied a method of collagen fingerprinting to more than 2000 fragmented bones from the site of Denisova Cave, Russia, in order to facilitate the discovery of human remains. As a result of our analysis a single hominin bone (Denisova 11) was identified, supported through in-depth peptide sequencing analysis, and found to carry mitochondrial DNA of the Neandertal type. Subsequent radiocarbon dating revealed the bone to be >50,000 years old. Here we demonstrate the huge potential collagen fingerprinting has for identifying hominin remains in highly fragmentary archaeological assemblages, improving the resources available for wider studies into human evolution.


Comparative molecular dynamics study of dimeric and monomeric forms of HIV-1 protease in ligand bound and unbound state.
Human immunodeficiency virus type 1 protease is a viral-encoded enzyme and it is essential for replication and assembly of the virus. Inactivation of HIV-1 protease causes production of immature, noninfectious viral particles and thus HIV-1 protease is an attractive target in anti-AIDS drug design. In our current work, we performed molecular dynamics (MD) calculations (500 ns) for two different ligands (COM5 - designed in our previous study, and Darunavir) and made effort to understand dynamics behaviour of our designed compound COM5. An apo form of HIV-1 protease as monomer and dimer form was also studied in order to analyze response of protein to the ligand. MD results suggest that presence of ligand in hinders the stability of HIV-1 protease and one monomer from dimer systems is dominant on other monomer in terms of interaction made with ligands. We were able to trace functional residues as well as continuous motion of opening and closing (clapping) of flap region in HIV-1 protease (apo form) during entire 1000 ns of MD simulation. COM5 showed almost similar behaviour towards HIV-1 protease enzyme as Darunavir and propose as promising lead compound for the development of new inhibitor for HIV-1 protease.


[HIV transmission from mother to child--can the epidemic be stopped?].
HIV (human immunodeficiency virus) may be transmitted from mother to child during pregnancy, delivery and breast-feeding. Transmission can be prevented, and efficient methods have caused vertical transmission to become rare in Europe and the USA. The article discusses the global HIV epidemic among children and challenges in reducing transmission from HIV-positive mothers. The article is based on literature retrieved through a non-systematic search in Medline and experience from working as a paediatrician in Botswana. HIV transmission from mother to child can be reduced from about 30 % to 4 % with relatively simple measures. In many high-endemic areas in Sub-Saharan Africa, little is done to prevent HIV transmission to neonates. Major challenges exist in identifying pregnant women with HIV, especially in areas which lack pregnancy surveillance programmes. To prevent neonatal transmission, safe feeding practices should be encouraged and retroviral drugs should be available. The increasing focus and investments in HIV prevention are possible explanations for the decline of the epidemic.


Mid-term follow-up of aortic valve replacement for bicuspid aortic valve.
The purpose of this study was to evaluate the mid-term outcome of aortic valve replacement for bicuspid aortic valve and tricuspid aortic valve and the related risk factors. From January 2014 to June 2019, 177 tricuspid aortic valve patients and 101 bicuspid aortic valve patients who underwent aortic valve replacement in our hospital were collected. 1:1 propensity score matching analysis was used to control the bias in patient selection. The perioperative and follow-up data between the two groups were compared. Independent risk factors which were associated with the continued dilatation of the ascending aorta were identified by univariate or multivariate logistic regression analysis. After the matching procedure, 160 patients were included in the analysis (80 in each group). Baseline characteristics, intraoperative, and perioperative outcomes were similar between the two groups (all p > 0.05). Moreover, 67 patients in the tricuspid aortic valve group and 70 in the bicuspid aortic valve group completed the follow-up. The ascending aorta change, annual change rate, and the proportion of continuous dilation of ascending aorta in bicuspid aortic valve group were significantly higher than those in the tricuspid aortic valve group (p < 0.05). Multivariate logistic regression analysis showed that type 1 in bicuspid aortic valve (OR 5.173; 95% CI 1.772, 15.101; p = 0.003), aortic regurgitation (OR 3.673; 95% CI 1.133, 11.908; p = 0.030), and aortic valve stenosis with regurgitation (OR 6.489; 95% CI 1.726, 24.404; p = 0.006) were independent risk factors for the continued dilatation of the ascending aorta in all AV patients. Furthermore, the multivariate logistic regression analysis showed that type 1 in bicuspid aortic valve (OR 5.157; 95% CI 1.053, 25.272; p = 0.043), age ≥ 40 years (OR 6.956; 95% CI 1.228, 39.410; p = 0.028), and aortic regurgitation (OR 4.322; 95% CI 1.174, 15.911; p = 0.028) were independent risk factors for the continued dilatation of the ascending aorta in bicuspid aortic valve patients. Compared with tricuspid aortic valve patients, the ascending aorta of bicuspid aortic valve patients is more likely to continue to enlarge after aortic valve replacement. Type 1 in bicuspid aortic valve, age ≥ 40 years, and aortic regurgitation were the independent risk factors.


Effect of RU486 on development and implantation of rat embryos.
This study evaluated the effects of postcoital treatment with the antiprogestin RU486 on transport, development and implantation of rat embryos. Doses of 0.1, 0.5, 1.0, 2.0, or 3.0 mg/rat of RU486 were injected subcutaneously on days 1, 1 + 2, or 4 of pregnancy. Autopsies were carried out on days 5 or 12 of pregnancy. RU486 provoked a significant dose-related reduction in the number of recovered embryos and inhibited their development (day 5) and decreased the number and size of implanted embryos (day 12). Treatment on day 4 was the least effective. Blastocysts recovered from RU486-treated rats exhibited comparable rate of trophoblastic outgrowth in vitro as the controls. Blastocysts transferred from RU486-treated rats to synchronous untreated pseudopregnant recipients yielded implanted embryos 12 days later in all recipients, although at a significantly lower rate than the controls. Blastocysts transferred from control pregnant rats to RU486-treated pseudopregnant recipients failed to implant completely when the dose was greater than or equal to 1.0 mg. The interceptive mechanism of postcoital treatment with RU486 in the rat involves loss of embryos from the reproductive tract and altered development prior to implantation. Endometrial receptivity or the ability of the uterus to retain the embryos until the time of implantation are also impaired by RU486. The embryos that survive these effects may experience delayed implantation in their mothers.


Effect of exercise on circulating adipokine levels in obese young women.
We studied the effect of exercise on circulating adipokine, high sensitivity C-reactive protein (hs-CRP), and metabolic parameters in obese young women. Ninety-six healthy Japanese young female students aged 18-23 years were studied. The longitudinal intervention study of a 7-month exercise training program (30-60 min/day, 60-70% HR-reserve, 200-400 kcal, 4-5 days/week) was performed in eight obese female students (BMI > or =25 kg/m(2)). Eight control female students (mean BMI = 22 kg/m(2)) were included in the follow-up study. Body weight, body mass index (BMI), percentage of body fat (%Fat), body fat mass, lean body mass, health-promoting lifestyle profile-scale (L-scale), VO(2)max (maximal oxygen uptake), hs-CRP, lipids, insulin homeostasis model assessment (HOMA-R), fasting levels for circulating adiponectin, leptin, and TNF-alpha, were measured before and after the exercise program. In obese subjects, body weight, BMI, %Fat, body fat mass, lean body mass, hs-CRP, leptin, and TNF-alpha were significantly higher, and L-scale and adiponectin were lower than those in control subjects. In obese subjects, exercise decreased body weight, BMI, %Fat, body fat mass, lean body mass, hs-CRP, leptin, and TNF-alpha, and increased L-scale, VO(2)max, HDL-cho, and adiponectin. It was concluded that changes in circulating adipokine levels are involved in the improvement of the metabolic state by exercise and may be useful markers for evaluation and prescription of exercise.


[Immunology in clinical practice. VII. Psoriasis].
A new hypothesis of the pathogenesis of psoriasis holds that psoriasis is an epidermal hyperproliferative disorder resulting from abnormal interaction between T cells and basal layer stem cell keratinocytes. New therapies aimed at reducing T cell activity are most successful, as exemplified by the efficacy of systemic cyclosporine in severe cases of psoriasis. New developments in immunogenetics and immunodermatology are anticipated and it is expected that they will fully explain the chain of pathological events.


Effect of serial subculturing on the genetic composition and cytotoxic activity of Mycobacterium tuberculosis.
Continuous subculture has been observed to produce changes in the virulence of micro-organisms, e.g. rabies virus, poliovirus and Mycobacterium bovis BCG. The latter has been used as a vaccine for tuberculosis for the last 100 years; however, in some instances its efficacy has been observed to be very low. In order to determine whether similar changes can be produced in Mycobacterium tuberculosis, we selected four isolates, M. tuberculosis H37Rv, a Beijing strain (DR-689), and two more isolates with deletion of the phospholipase C locus (plcA-plcB-plcC ), and subjected them to serial culturing on Middlebrook 7H9 medium, with or without ox bile. After 100 passages, we performed RFLP-IS6110 analysis to determine whether genomic changes were produced. We also checked their genomic composition by microarray analysis. Changes in virulence were studied by measuring the cytotoxic effect of parental and subcultured isolates on a THP-1 macrophage monolayer. The most visible change was the change of position of an IS6110 band of approximately 1400 bp to approximately 1600 bp in the Beijing isolate subcultured in the ox bile medium. Analysis by microarray and PCR confirmation did not reveal any genomic changes. Cytotoxic activity was decreased in the isolates at levels close to that of BCG, and more consistently in those subcultured in the presence of ox bile.


Clinicopathological Characteristics of Primary Ovarian Adenomyoma: A Single-institutional Experience.
Adenomyoma is a benign neoplasm composed of endometrial-type glands, specialized endometrial-type stroma, and well-formed smooth muscle bundles. This tumor typically originates within the uterus, whereas extrauterine adenomyoma is an unusual presentation. The ovary is the most common site of extrauterine adenomyoma. In this study, we describe the clinical and pathological features and immunohistochemical findings of primary ovarian adenomyoma in patients at our Institution. In addition, we provide a thorough review of previously published cases of primary ovarian adenomyoma and clarify their clinicopathological characteristics. The most common clinical presentations of ovarian adenoma were abdominopelvic pain and abnormal menstruation. Imaging features of ovarian adenomyoma varied, showing mixed solid and cystic, solid, or cystic masses. Frequently associated conditions included congenital anomalies of the urinary tract and endometriosis. Although most cases of ovarian adenomyoma exhibit benign histopathological features, we observed one case of endometrioid carcinoma arising in ovarian adenomyoma. Clinical follow-up data indicated that simple excision of the mass is curative for ovarian adenomyoma, but certain patients underwent unnecessary surgical procedures due to lack of awareness of primary ovarian adenomyoma and high index of suspicion for malignancy in patients with solid ovarian masses. Although ovarian adenomyoma is rare, awareness of this tumor type aids pathologists in making correct diagnoses and clinicians in avoiding unwarranted therapeutic procedures.


Efficacy of probenecid for a patient with juvenile dermatomyositis complicated with calcinosis.
Calcinosis of juvenile dermatomyositis (JDM) is a crucial problem because it is refractory to various therapies. An 11-year-old boy who had been treated for JDM with interstitial pneumonia developed calcinosis of both legs despite treatment with corticosteroid and cyclosporin A. Images of his knees showed massive calcinosis with restricted range of motion. Probenecid was used to reduce calcinosis, resulting in remarkable improvement of calcinosis accompanied by normalization of serum phosphorus level and disability after 17 months of administration. We suggest that probenecid is useful for the treatment of calcinosis of JDM.


[Nerve-blocking properties of antibiotics].
Comparative data on the neuroblocking activity of antibiotics of various groups in acute experiments on albino mice and narcotized cats are presented. It was found that according to the impairments in the neuro-muscle conductivity the drugs were arranged in the following descending order: polymyxin B, neomycin, gentamicin, streptomycin, lincomycin and kanamycin. The streptomycin derivatives were approximately 2 times less toxic than streptomycin. The problems of the mode of action of the antibiotics on conductivity of excitation in the neuro-muscle synapses are discussed.


tRNA ADENOSINE DEAMINASE 3 is required for telomere maintenance in Arabidopsis thaliana.
KEY MESSAGE: tRNA Adenosine Deaminase 3 helps to sustain telomere tracts in a telomerase-independent fashion, likely through regulating cellular metabolism. Telomere length maintenance is influenced by a complex web of chromatin and metabolism-related factors. We previously reported that a lncRNA termed AtTER2 regulates telomerase activity in Arabidopsis thaliana in response to DNA damage. AtTER2 was initially shown to partially overlap with the 5' UTR of the tRNA ADENOSINE DEAMINASE 3 (TAD3) gene. However, updated genome annotation showed that AtTER2 was completely embedded in TAD3, raising the possibility that phenotypes ascribed to AtTER2 could be derived from TAD3. Here we show through strand-specific RNA-Seq, strand-specific qRT-PCR and bioinformatic analyses that AtTER2 does not encode a stable lncRNA. Further examination of the original tad3 (ter2-1/tad3-1) mutant revealed expression of an antisense transcript driven by a cryptic promoter in the T-DNA. Hence, a new hypomorphic allele of TAD3 (tad3-2) was examined. tad3-2 mutants showed hypersensitivity to DNA damage, but no deregulation of telomerase, suggesting that the telomerase phenotype of tad3-1 mutants reflects an off-target effect. Unexpectedly, however, tad3-2 plants displayed progressive loss of telomeric DNA over successive generations that was not accompanied by alteration of terminal architecture or end protection. The phenotype was exacerbated in plants lacking the telomerase processivity factor POT1a, indicating that TAD3 promotes telomere maintenance through a non-canonical, telomerase-independent pathway. The transcriptome of tad3-2 mutants revealed significant dysregulation of genes involved in auxin signaling and glucosinolate biosynthesis, pathways that intersect the stress response, cell cycle regulation and DNA metabolism. These findings indicate that the TAD3 locus indirectly contributes to telomere length homeostasis by altering the metabolic profile in Arabidopsis.


Extreme Thouless effect in a minimal model of dynamic social networks.
In common descriptions of phase transitions, first-order transitions are characterized by discontinuous jumps in the order parameter and normal fluctuations, while second-order transitions are associated with no jumps and anomalous fluctuations. Outside this paradigm are systems exhibiting "mixed-order" transitions displaying a mixture of these characteristics. When the jump is maximal and the fluctuations range over the entire range of allowed values, the behavior has been coined an "extreme Thouless effect." Here we report findings of such a phenomenon in the context of dynamic, social networks. Defined by minimal rules of evolution, it describes a population of extreme introverts and extroverts, who prefer to have contacts with, respectively, no one or everyone. From the dynamics, we derive an exact distribution of microstates in the stationary state. With only two control parameters, N(I,E) (the number of each subgroup), we study collective variables of interest, e.g., X, the total number of I-E links, and the degree distributions. Using simulations and mean-field theory, we provide evidence that this system displays an extreme Thouless effect. Specifically, the fraction X/(N(I)N(E)) jumps from 0 to 1 (in the thermodynamic limit) when N(I) crosses N(E), while all values appear with equal probability at N(I)=N(E).


Comparison of 99mTc-DTPA and 51Cr-EDTA for glomerular filtration rate measurement with the continuous infusion method.
In late 2018, the production of 51Chromium-labelled ethylenediamine tetra-acetic acid (51Cr-EDTA), a validated and widely used radio-isotopic tracer for measuring glomerular filtration rate, was halted. Technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) has been validated for GFR measurement with a single bolus injection, a procedure not suitable in patients with extracellular compartment hyperhydration. In such cases, a bolus followed by continuous infusion of the tracer is required. The aim of this study was to evaluate whether 99mTc-DTPA with the infusion protocol can replace 51Cr-EDTA for GFR measurement. We conducted a prospective single centre study during February and March 2019. All patients referred for GFR measurement received both radiotracers simultaneously: 51Cr-EDTA and 99mTc-DTPA bolus and continuous infusion were administered concomitantly through the same intravenous route. Over four and a half hours, plasma and urine samples were collected to calculate urinary and plasma clearance. Twenty-two patients were included (mean age 63.4 ± 17.5 years; 68% men). Mean urinary clearance of 51Cr-EDTA and 99mTc-DTPA was 52.4 ± 22.5 mL/min and 52.8 ± 22.6 mL/min, respectively (p = 0.47), with a mean bias of 0.39 ± 2.50 mL/min, an accuracy within 10% of 100% (95% CI 100; 100) and a Pearson correlation coefficient of 0.994. Mean plasma clearance of 51Cr-EDTA and 99mTc-DTPA was 54.8 ± 20.9 mL/min and 54.4 ± 20.9 mL/min, respectively (p = 0.61), with a mean bias of - 0.43 ± 3.89 mL/min, an accuracy within 10% of 77% (95% CI 59; 91) and a Pearson correlation coefficient of 0.983. Urinary and plasma clearance of 99mTc-DTPA can be used with the infusion protocol to measure GFR.


The role of signal averaged P wave duration and serum magnesium as a combined predictor of atrial fibrillation after elective coronary artery bypass surgery.
To investigate the role of low serum magnesium as a trigger for atrial fibrillation in patients with a substrate for the arrhythmia (assessed by signal averaged P wave duration). A case-control study. A regional referral cardiac centre. 105 consecutive patients undergoing elective coronary artery bypass surgery had signal averaged P wave recordings before operation. Serum electrolytes were analysed preoperatively and on days 1, 2, and 5 after surgery. Any episode of electrocardiographically recorded atrial fibrillation was taken as a study end point. Of 102 patients discharged, 27 (26%) had documented episodes of atrial fibrillation at a mean of 2.7 days after surgery. A combination of P wave duration > 155 ms and serum magnesium on the first postoperative day of < 0.7 mmol/l had a sensitivity of 75% and specificity of 80% for predicting atrial fibrillation. Duration of hospital stay (7.9 v 6.8 days) was longer in the atrial fibrillation group (P < 0.01). Stepwise regression showed age, serum magnesium < 0.7 mmol/l on the first postoperative day (both P < 0.001), angiotensin converting enzyme inhibitor withdrawal (P < 0.02), and signal averaged P wave duration (P = 0.04) to be independent predictors. The combination of signal averaged P wave duration and low serum magnesium on the first postoperative day identified the majority of patients with atrial fibrillation after coronary artery bypass surgery. Early identification and pharmacological treatment for selected patients may reduce the incidence of postoperative atrial fibrillation.


The impact of beak tissue sloughing and beak shape variation on the behavior and welfare of infrared beak-treated layer pullets and hens.
This research examined how infrared beak treatment (IRBT), sloughing of the treated beak tissue, and the variations in beak shape that can occur post-IRBT impact the welfare and mortality of Lohmann LSL-Lite (LW) and Lohmann Brown (LB) pullets and hens. Two experiments were conducted and birds for both experiments were treated on the day of hatch. IRBT equipment settings were adjusted to create 4 specific beak shapes: shovel (SHV), step (STP), standard (STAN), and an untreated sham control (C). Experiment 1 pullets (n = 80 per strain) were reared in bioassay cages from 1 to 29 D of age (4 replicates per treatment). Data collected included time and presence of beak sloughing, pecking force, behavioral expression, and mortality. Experiment 2 pullets (n = 320 per strain) were reared in floor pens from 1 D to 18 wk of age (2 replicates per treatment) and then conventional cages from 18 to 60 wk of age (6 replicates per treatment). Data collected for Experiment 2 included behavioral expression, feather cover, comb damage, and mortality. Data were analyzed using PROC MIXED (SAS® 9.4) with Tukey's test to separate means. Differences were significant when P ≤ 0.05. IRBT and sloughing had no effect on pecking force or mortality throughout rearing. The variations in post-IRBT beak shape had minor effects on behavior. During rearing, STAN pullets were more active than C pullets but STP and STAN pullets performed less exploratory pecking. During the laying period, SHV and STP hens preened more than C hens. The IRBT treatments, regardless of beak shape, reduced feather loss, comb damage, and cannibalism-related mortality during the laying period. Overall, the results indicate that LW and LB pullets and hens can cope with the change in beak shape that occurs with IRBT, and that welfare is not negatively impacted if some variation in beak shape occurs.


Changes in hospital costs after introducing an intermediate care unit: a comparative observational study.
The high cost of critical care resources has resulted in strategies to reduce the costs of ruling out low-risk patients by developing intermediate care units (IMCs). The aim of this study was to compare changes in total hospital costs for intensive care patients before and after the introduction of an IMC at the University Hospital Maastricht. The design was a comparative longitudinal study. The setting was a university hospital with a mixed intensive care unit (ICU), an IMC, and general wards. Changes in total hospital costs were measured for patients who were admitted to the ICU before and after the introduction of the IMC. The comparison of interest was the opening of a six-bed mixed IMC. The mean total hospital cost per patient increased significantly. Before the introduction of the IMC, the total hospital cost per patient was n12,961 (+/- n14,530) and afterwards it rose to n16,513 (+/- n17,718). Multiple regression analysis was used to determine to what extent patient characteristics explained these higher hospital costs using mortality, type of stay, diagnostic categories, length of ICU and ward stay, and the Therapeutic Intervention Scoring System (TISS) as predictors. More surgical patients, greater requirements of therapeutic interventions on the ICU admission day, and longer ICU stay in patients did explain the increase in hospital costs, rather than the introduction of the IMC. After the introduction of the IMC, the higher mean total hospital costs for patients with a high TISS score and longer ICU stay explained the cost increase.


[Urgent problems of occupational diseases in Georgia in the junction of XX-XXI centuries].
The radical reform of health care system in Georgia after the collapse of the Soviet Union negatively affected the occupational medicine, environmental medicine, occupational health services, and preventive measures. The level of medical assistance to people suffering from harmful industrial factors decreased, which is a serious danger for the health of the workers and for the next generations. The aim of the article is to protect the right to means for adequate health and suggest effective ways for health care improvement. In order to reconstruct the system of Occupational and Environmental Medicine, it is necessary to create a network of occupational healthcare. We strongly believe investment in preventive health is vital to safeguard and improve the health of the community. The Center of Occupational Medicine and the Institute of Labor Medicine and Ecology with corresponding financing, educational programs for medical students and continuous practice of physicians in occupational medicine, enhancing the number of the scientific research designed to discover the early forms of occupational pathologies and timely prevention of the disease is vital to protect the right to means for adequate health, to advance the professional development of physicians, nurses, research scientists, and allied health professionals in order to diminish general and occupational diseases in Georgia.


A Two-Filter Approach for State Estimation Utilizing Quantized Output Data.
Filtering and smoothing algorithms are key tools to develop decision-making strategies and parameter identification techniques in different areas of research, such as economics, financial data analysis, communications, and control systems. These algorithms are used to obtain an estimation of the system state based on the sequentially available noisy measurements of the system output. In a real-world system, the noisy measurements can suffer a significant loss of information due to (among others): (i) a reduced resolution of cost-effective sensors typically used in practice or (ii) a digitalization process for storing or transmitting the measurements through a communication channel using a minimum amount of resources. Thus, obtaining suitable state estimates in this context is essential. In this paper, Gaussian sum filtering and smoothing algorithms are developed in order to deal with noisy measurements that are also subject to quantization. In this approach, the probability mass function of the quantized output given the state is characterized by an integral equation. This integral was approximated by using a Gauss-Legendre quadrature; hence, a model with a Gaussian mixture structure was obtained. This model was used to develop filtering and smoothing algorithms. The benefits of this proposal, in terms of accuracy of the estimation and computational cost, are illustrated via numerical simulations.


The Role of Age in Change in Unmet Supportive Care Needs in Hepatocellular Carcinoma Patients During Transition From Hospital to Home.
Age might affect the change in care needs in patients with hepatocellular carcinoma after treatment during their transition process from hospital to home. However, there have been no studies that focus on this. The aim of this study is to examine changes in unmet supportive care needs in young (<65 years old) and elderly (≥65 years old) groups of patients with hepatocellular carcinoma from before discharge to 2 months after discharge. A longitudinal prospective study design was used with recruited participants at a teaching hospital in Taiwan. Data were collected 3 times: within 3 days before discharge and at 1 and 2 months after discharge. A set of questionnaires was used to assess participants' levels of supportive care needs, symptom distress, anxiety, and depression. A total of 104 patients completed the data collection process. Supportive care needs decreased monthly after discharge, with health system and information being the domain with the highest level of unmet needs in the 2 groups. The young group had a higher level of overall unmet needs before discharge, but they had a lower level of overall needs compared with the elderly group after 2 months of discharge. Age could be a significant potential factor to affect change in unmet needs during transition. Comprehensive assessment in care needs especially in the health system and information and physical and daily living domains before discharge is recommended to design personalized education programs before discharge.


The effect of miotics on the intraocular pressure of conscious owl monkeys.
The intraocular pressure of conscious, unsedated owl monkeys (Aotus trivirgatus) was measured with an applanation tonometer. Untreated eyes of the conscious animals were found to have higher values than those reported for owl monkeys anesthetized with pentobarbitone. Locally applied pilocarpine, carbachol, and oxotremorine gave concentration-related reduction in pressure, oxotremorine being the most potent and having longer duration of effect than the other compounds. Slight reductions were also observed with aceclidine and R. S. 86. These results are discussed in relation to the effects of miotics in man.


Hair Follicle Plasticity with Complemented Immune-modulation Following Follicular Unit Extraction.
During hair transplantation as an effective therapy for androgenetic alopecia, hair follicles were typically trans-located from the nonaffected occipital to the balding frontal or vertex region of the scalp. Although this is an autologous intervention, the donor and recipient hair follicle tissue differ in composition and local environment. In two case studies, we investigated the changes in hair follicle morphology and the immune status of scalp and body hair follicles from different origins transplanted to the eyebrows and the frontal scalp using follicular unit extraction. Quantitative histomorphometry and immunohistochemistry revealed a transformation in hair follicle length and dermal papilla size of the scalp, chest and beard hair follicles, which had been re-extracted after a 6-month period posttransplantation. Furthermore, a significant infiltration of B and T lymphocytes as well as macrophages could be observed most prominently in the infundibulum of transplanted hair follicles. The presented results demonstrate that hair follicle units from different body sites are capable to replace miniaturized or degraded hair follicles in different recipient areas like scalp or eyebrows as they keep their intrinsic capability or acquire the potential to readjust plastically within the beneficiary skin region. The essential secretory crosstalk underlying the observed tissue remodeling is possibly mediated by the infiltrating immune cells.


Naphthenic acids in athabasca oil sands tailings waters are less biodegradable than commercial naphthenic acids.
Naphthenic acids (NAs) are natural constituents in many petroleum sources, including bitumen in the oil sands of Northern Alberta, Canada. Bitumen extraction processes produce tailings waters that cannot be discharged to the environment because NAs are acutely toxic to aquatic species. However, aerobic biodegradation reduces the toxic character of NAs. In this study, four commercial NAs and the NAs in two oil sands tailings waters were characterized by gas chromatography-mass spectrometry. These NAs were also incubated with microorganisms in the tailings waters under aerobic, laboratory conditions. The NAs in the commercial preparations had lower molecular masses than the NAs in the tailings waters. The commercial NAs were biodegraded within 14 days, but only about 25% of the NAs native to the tailings waters were removed after 40-49 days. These results show that low molecular mass NAs (C < or =17) are more readily biodegraded than high molecular mass NAs (C > or =18). Moreover, the results indicate that biodegradation studies using commercial NAs alone will not accurately reflect the potential biodegradability of NAs in the oil sands tailings waters.


Association of fibre degradation with ruminal dissolved hydrogen in growing beef bulls fed with two types of forages.
The present study investigated the association between fibre degradation and the concentration of dissolved molecular hydrogen (H2) in the rumen. Napier grass (NG) silage and corn stover (CS) silage were compared as forages with contrasting structures and degradation patterns. In the first experiment, CS silage had greater 48-h DM, neutral-detergent fibre (NDF) and acid-detergent fibre degradation, and total gas and methane (CH4) volumes, and lower 48-h H2 volume than NG silage in 48-h in vitro incubations. In the second experiment, twenty-four growing beef bulls were fed diets including 55 % (DM basis) NG or CS silages. Bulls fed the CS diet had greater DM intake (DMI), average daily gain, total-tract digestibility of OM and NDF, ruminal dissolved methane (dCH4) concentration and gene copies of protozoa, methanogens, Ruminococcus albus and R. flavefaciens, and had lower ruminal dH2 concentration, and molar proportions of valerate and isovalerate, in comparison with those fed the NG diet. There was a negative correlation between dH2 concentration and NDF digestibility in bulls fed the CS diet, and a lack of relationship between dH2 concentration and NDF digestibility with the NG diet. In summary, the fibre of CS silage was more easily degraded by rumen microorganisms than that of NG silage. Increased dCH4 concentration with the CS diet presumably led to the decreased ruminal dH2 concentration, which may be helpful for fibre degradation and growth of fibrolytic micro-organisms in the rumen.


Effects of STAT3 gene silencing and rapamycin on apoptosis in hepatocarcinoma cells.
The PI3K/Akt/mTOR and JAK/STAT3 signaling pathways are important for regulating apoptosis, and are frequently activated in cancers. In this study, we targeted STAT3 and mTOR in human hepatocellular carcinoma Bel-7402 cells and examined the subsequent alterations in cellular apoptosis. The expression of STAT3 was silenced with small interfering RNA (siRNA)-expressing plasmid. The activity of mTOR was inhibited using rapamycin. Following treatment, Annexin V/propidium iodide staining followed by flow cytometry and Hoechst33258 immunofluorescence staining was used to examine cellular apoptosis. JC-1 staining was used to monitor depolarization of mitochondrial membrane (ΔΨm). Furthermore, the expression of activated caspase 3 protein was analyzed by Western blotting. Compared to non-treated or control siRNA-transfected cells, significantly higher levels of apoptosis were detected in siSTAT3-transfected or rapamycin-treated cells (P < 0.05), which was further enhanced in cells targeted for both molecules (P < 0.05). The pro-apoptotic effects were accompanied with concomitant depolarization of mitochondrial membrane and up-regulation of activated caspase 3. Combined treatments using rapamycin and STAT3 gene silencing significantly increases apoptosis in Bel-7402 cells, displaying more dramatic effect than any single treatment. This study provides evidence for targeting multiple molecules in cancer therapy.


Comparison of Procedure-Based and Diagnosis-Based Identifications of Severe Sepsis and Disseminated Intravascular Coagulation in Administrative Data.
Diagnoses recorded in administrative databases have limited utility for accurate identification of severe sepsis and disseminated intravascular coagulation (DIC). We evaluated the performance of alternative identification methods that use procedure records. We obtained data for adult patients admitted to intensive care units in three hospitals during a 1-year period. Severe sepsis and DIC were identified by three means: laboratory data, diagnoses, and procedures. Using laboratory data as a reference, the sensitivity and specificity of procedure-based methods and diagnosis-based methods were compared. Of 595 intensive care unit admissions, 212 (35.6%) and 81 (13.6%) were identified as severe sepsis and DIC, respectively, using laboratory data. The sensitivity of procedure-based methods for identifying severe sepsis was 64.2%, and the specificity was 65.3%. Two diagnosis-based methods -the Angus and Martin algorithms- exhibited sensitivities of 21.7% and 14.6% and specificities of 98.7% and 99.5%, respectively, for severe sepsis. For DIC, the sensitivity of procedure-based methods was 55.6%, and the specificity was 67.1%, and the sensitivity and specificity of diagnosis-based methods were 35.8% and 98.2%, respectively. Procedure-based methods were more sensitive and less specific than diagnosis-based methods in identifying severe sepsis and DIC. Procedure records could improve disease identification in administrative databases.


Charnley low-friction arthroplasty in the young patient.
One thousand three hundred forty-two Charnley low-friction arthroplasties (LFAs) were reviewed at an average of ten years four months after surgery. Patients' average age at surgery was 41 years. The clinical results at follow-up review remained excellent: 79% were pain free and 11% had no more than occasional discomfort. One hundred forty-one (10.5%) LFAs have been revised so far. Stem fracture has been completely eliminated. Revision for stem loosening has been reduced to below 1% and revision for socket loosening has also been reduced. The long-term problem remains socket wear--and with it--an increasing incidence of socket migration. Failure of component fixation is a short- and medium-term problem that has been improved by better component design and surgical technique.


Endoscopic resection of upper neck masses via retroauricular approach is feasible with excellent cosmetic outcomes.
In this study, the authors introduce and evaluate the feasibility of endoscopic resection using the retroauricular approach for various benign lesions of the upper neck. A retrospective comparative analysis was performed on the clinical outcomes of patients who underwent surgery for upper neck masses as endoscopic resection using the retroauricular approach or conventional transcervical resection at the authors' center from January 2010 through August 2011. The primary outcome was the cosmetic satisfaction of the patients in each group. In addition, the feasibility of the procedure was evaluated by comparing the operation time; hospital stay; amount and duration of drainage; complications such as marginal mandibular nerve, lingual, or hypoglossal nerve palsy; paresthesia of the ear lobe; and wound problems such as hematoma and skin necrosis. Statistical analysis was performed by independent-samples t test and the Fisher exact test, and a P value less than .05 was considered statistically significant. Thirty-six patients underwent endoscopic resection (endo group; 15 men, 21 women; mean age, 38.8 ± 15.0 years) and 40 patients underwent conventional transcervical resection (conventional group; 18 men, 22 women; mean age, 45.1 ± 14.1 years). The operating time in the endo group was longer than in the conventional group (P = .003). No significant difference was observed in the overall perioperative complications between the 2 groups. Cosmetic satisfaction evaluated with a graded scale showed much better results in the endo group (P < .001). Endoscopic resection using the retroauricular approach is feasible for various benign upper neck masses when conducted by an experienced endoscopic surgeon, with excellent cosmetic results.


A nationwide survey of methods and barriers to adverse drug reaction monitoring and reporting among hospital pharmacists in Thailand.
To explore the methods of adverse drug reaction identification and monitoring used by hospital pharmacists in all regions of Thailand, to explore barriers to and pharmacists' attitudes towards adverse drug reaction monitoring and reporting, and to assess the factors related to these aspects. Pharmacists in 480 hospitals in Thailand were selected by stratified sampling. Self-administered questionnaires were sent by post and pharmacists returned completed questionnaires via QR code. In total, pharmacists at 286 hospitals returned the questionnaire (response rate = 59.6%). The most common adverse drug reaction (ADR) monitoring methods were the spontaneous reporting system (SRS), which was used by 100% of respondents, followed by high alert drug lists (73.1%) and routine adverse drug reaction monitoring (64.0%). The most frequently used methods of adverse drug reaction prevention were providing drug allergy card and recording allergy history in database. The major barrier to adverse drug reaction monitoring and reporting among respondents was uncertainty about whether the suspected drug caused the reaction (49.3%). Pharmacists had a good attitude towards adverse drug reaction monitoring and reporting (60.5%). Longer work experience (≥10 years) was negatively related with good attitudes towards adverse drug reaction monitoring and reporting (OR = 0.535, P = 0.040), whereas higher education level was positively related (OR = 2.201, P = 0.025). Spontaneous reporting system is the main method used for adverse drug reaction monitoring and reporting among hospital pharmacists in Thailand. Pharmacists had good attitudes towards adverse drug reaction monitoring and reporting, however, barriers remain.


Sensitivity of quantitative sensory models to morphine analgesia in humans.
Opioid analgesia can be explored with quantitative sensory testing, but most investigations have used models of phasic pain, and such brief stimuli may be limited in the ability to faithfully simulate natural and clinical painful experiences. Therefore, identification of appropriate experimental pain models is critical for our understanding of opioid effects with the potential to improve treatment. The aim was to explore and compare various pain models to morphine analgesia in healthy volunteers. The study was a double-blind, randomized, two-way crossover study. Thirty-nine healthy participants were included and received morphine 30 mg (2 mg/mL) as oral solution or placebo. To cover both tonic and phasic stimulations, a comprehensive multi-modal, multi-tissue pain-testing program was performed. Tonic experimental pain models were sensitive to morphine analgesia compared to placebo: muscle pressure (F=4.87, P=0.03), bone pressure (F=3.98, P=0.05), rectal pressure (F=4.25, P=0.04), and the cold pressor test (F=25.3, P<0.001). Compared to placebo, morphine increased tolerance to muscle stimulation by 14.07%; bone stimulation by 9.72%; rectal mechanical stimulation by 20.40%, and reduced pain reported during the cold pressor test by 9.14%. In contrast, the more phasic experimental pain models were not sensitive to morphine analgesia: skin heat, rectal electrical stimulation, or rectal heat stimulation (all P>0.05). Pain models with deep tonic stimulation including C fiber activation and and/or endogenous pain modulation were more sensitive to morphine analgesia. To avoid false negative results in future studies, we recommend inclusion of reproducible tonic pain models in deep tissues, mimicking clinical pain to a higher degree.


Geriatric drug therapy.
Elderly Americans make up 11 percent of the population but consume 25 percent of all prescription medications. The incidence of adverse drug effect is 1.5 to 3 times higher in older patients and accounts for numerous hospitalizations. The basic pharmacokinetic parameters of absorption, distribution, metabolism, and excretion are all significantly altered in geriatric patients. Certain specific drug side effects, such as orthostatic hypotension and anticholinergic effects, can be particularly hazardous in older patients. This paper describes general therapeutic principles for geriatric patients. Commonly used drug categories are considered separately. A thorough knowledge of these principles will allow the physician to prescribe drugs more effectively, improve patient compliance, and minimize adverse drug effects.


Genetic Mapping of Behavioral Traits Using the Collaborative Cross Resource.
The complicated interactions between genetic background, environment and lifestyle factors make it difficult to study the genetic basis of complex phenotypes, such as cognition and anxiety levels, in humans. However, environmental and other factors can be tightly controlled in mouse studies. The Collaborative Cross (CC) is a mouse genetic reference population whose common genetic and phenotypic diversity is on par with that of humans. Therefore, we leveraged the power of the CC to assess 52 behavioral measures associated with locomotor activity, anxiety level, learning and memory. This is the first application of the CC in novel object recognition tests, Morris water maze tasks, and fear conditioning tests. We found substantial continuous behavioral variations across the CC strains tested, and mapped six quantitative trait loci (QTLs) which influenced these traits, defining candidate genetic variants underlying these QTLs. Overall, our findings highlight the potential of the CC population in behavioral genetic research, while the identified genomic loci and genes driving the variation of relevant behavioral traits provide a foundation for further studies.


Objective structured assessment of technical skill in upper extremity surgery.
Objective assessment of technical skills in hand surgery has been lacking. This article reports on an Objective Structured Assessment of Technical Skills format of a multiple bench-station evaluation of orthopedic surgery residents' technical skills for 3 common upper extremity surgeries. Twenty-seven residents (6 postgraduate year [PGY] 2, 8 PGY 3, 8 PGY 4, and 5 PGY 5) participated in the examination. Each resident performed surgery on a cadaveric specimen at 3 stations, trigger finger release (TFR), open carpal tunnel release, and distal radius fracture fixation. A board-certified hand surgeon evaluated trainee performance at each station, using a procedure-specific detailed checklist, a validated global rating scale, and pass/fail assessment. A resident post-testing evaluation was collected. Construct validity with correlation between year in training and detailed checklist scores was demonstrated for TFR and carpal tunnel release; between year in training and global rating scores for TFR and distal radius fracture fixation; and between year in training and pass/fail assessment for TFR. Criterion validity was demonstrated by the correlation between global rating scale scores, detailed checklist scores, and pass/fail assessment for TFR, carpal tunnel release, and distal radius fracture fixation. Time to complete the surgery was not correlated with surgical performance. Residents rated the multiple-station Objective Structured Assessment of Technical Skills format as highly educational. This study reports that a surgeon's ability to release a trigger finger does not correlate specifically to his or her ability to perform a carpal tunnel release or to perform plate fixation of a radius fracture. The results of this study would indicate that, for 3 different surgical simulations representing procedures of varying complexity, assessments by a single assessment tool is not adequate. To completely understand a resident's abilities, assessment by checklist (understanding the steps of the surgery), global rating scales (assessment of basic surgical skills in light of lesser or greater complexity surgeries), and pass/fail assessment (examination of adverse events) are all necessary components. Therapeutic II.


The impact of physical load on duration estimation in sport.
We investigated whether physical load has an influence on the accuracy of duration estimation of sporting activities presented in real time and slow motion. 86 participants were studied in two single sessions of 45 min each. Our results showed no general effects for physical load, when comparing physical load versus rest. However, we could replicate findings of past research (Schütz et al., 2021), showing that the duration of sports performance is estimated more accurately when presented in real time compared to slow motion. Further we found, that under physical load, participants perceiving the physical exercise as hard (RPE ≥15) estimated time significantly shorter and more accurately compared to participants perceiving the physical exercise as light or moderate (RPE <15). Thus, our results suggest that using slow motion may worsen the assessment of sports performance. Additionally, we could show that intense physical exertion contributes to reducing the overestimation of time.


A 100,000 Scale Factor Radar Range.
The radar cross section of an object is an important electromagnetic property that is often measured in anechoic chambers. However, for very large and complex structures such as ships or sea and land clutters, this common approach is not practical. The use of computer simulations is also not viable since it would take many years of computational time to model and predict the radar characteristics of such large objects. We have now devised a new scaling technique to overcome these difficulties, and make accurate measurements of the radar cross section of large items. In this article we demonstrate that by reducing the scale of the model by a factor 100,000, and using near infrared wavelength, the radar cross section can be determined in a tabletop setup. The accuracy of the method is compared to simulations, and an example of measurement is provided on a 1 mm highly detailed model of a ship. The advantages of this scaling approach is its versatility, and the possibility to perform fast, convenient, and inexpensive measurements.


CKA, a novel multidomain protein, regulates the JUN N-terminal kinase signal transduction pathway in Drosophila.
The Drosophila melanogaster JUN N-terminal kinase (DJNK) and DPP (decapentaplegic) signal transduction pathways coordinately regulate epithelial cell sheet movement during the process of dorsal closure in the embryo. By a genetic screen of mutations affecting dorsal closure in Drosophila, we have now identified a multidomain protein, connector of kinase to AP-1 (cka), that functions in the DJNK pathway and controls the localized expression of dpp in the leading-edge cells. We have also investigated how CKA acts. This unique molecule forms a complex with HEP (DJNKK), BSK (DJNK), DJUN, and DFOS. Complex formation activates BSK kinase, which in turn phosphorylates and activates DJUN and DFOS. These data suggest that CKA represents a novel molecule regulating AP-1 activity by organizing a molecular complex of kinases and transcription factors, thus coordinating the spatial-temporal expression of AP-1-regulated genes.


Synthesis of a gene for rat liver fatty-acid-binding protein and its expression in Escherichia coli.
A gene coding for rat liver fatty-acid-binding protein (FABP) has been constructed by the single-step ligation of ten synthetic oligonucleotides. The gene has been cloned into the bacterial expression vector pKK223-3. Induction of protein synthesis from this gene results in over expression of an FABP that is indistinguishable in its structure and binding properties with that isolated from rat liver.


Evaluation of direct infusion-multiple reaction monitoring mass spectrometry for quantification of heat shock proteins.
Protein quantification with liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM) has emerged as a powerful platform for assessing panels of biomarkers. In this study, direct infusion, using automated, chip-based nanoelectrospray ionization, coupled with MRM (DI-MRM) is used for protein quantification. Removal of the LC separation step increases the importance of evaluating the ratios between the transitions. Therefore, the effects of solvent composition, analyte concentration, spray voltage, and quadrupole resolution settings on fragmentation patterns have been studied using peptide and protein standards. After DI-MRM quantification was evaluated for standards, quantitative assays for the expression of heat shock proteins (HSPs) were translated from LC-MRM to DI-MRM for implementation in cell line models of multiple myeloma. Requirements for DI-MRM assay development are described. Then, the two methods are compared; criteria for effective DI-MRM analysis are reported on the basis of the analysis of HSP expression in digests of whole cell lysates. The increased throughput of DI-MRM analysis is useful for rapid analysis of large batches of similar samples, such as time course measurements of cellular responses to therapy.


A review of antimycobacterial drugs in development.
The needs of newly developed antitubercular agents are required for the control of tuberculosis in the present time. In the discovery of new antitubercular drugs, the emergence of multidrug-resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis (Mtb) has encouraged the researchers to intensify the efforts to discover novel antitubercular drugs. These novel drugs will predominantly target the persistent state of mycobacterium strains, which are resistant to conventional drugs including non resistant mycobacterium strains. In the last three to four decades no new effective drug has been developed for the treatment of resistant tuberculosis. However, in recent years, the research and development programs for the control of TB, there is a lot works is going on to enhancement of the anti-TB activity of new drugs particularly against resistant mycobacterium strains. Simultaneously, practical usefulness of some new targets is being identified and validated for the treatment of TB. Some compounds are presently in clinical trials, while others are being investigated in an attempt to explore new compounds for the target based treatment. The present review provides an overview of the new anti-TB agents with different molecular structures that are being clinically used and advanced stages of preclinical as well as clinical stages and also attempted to highlight the efforts that are being made in the development of new drug molecules as lead anti-TB agents.


Rheo-optical Near-infrared (NIR) Analysis of Binary Amorphous Polymer Blend Consisting of Polyvinyl Chloride (PVC) and Polymethyl Methacrylate (PMMA).
A binary amorphous polymer blend consisting of polyvinyl chloride (PVC) and polymethyl methacrylate (PMMA) was studied with a rheo-optical characterization technique based on the combination of a near-infrared (NIR) spectrometer and a tensile testing machine. In rheo-optical NIR spectroscopy, tensile deformations were applied to polymers to induce the displacement of molecular chains while being probed by NIR light. The application of this technique was extended to a partially miscible amorphous polymer blend consisting of PVC and PMMA to demonstrate how it can be utilized to detect subtle but important deformation behavior. A change in the NIR spectral feature revealed that the initial deformation of the blend induces the reorientation of the PVC chains. A part of the PMMA connected to the PVC was tagged during the PVC deformation. Further deformation of the sample eventually resulted in necking propagation to the surrounding area.


Fermi resonance controlled product branching in the H + HOD reaction.
Accurate full-dimensional quantum state-to-state reaction probabilities and integral cross sections are calculated for the title reaction. Product vibrational state distributions are studied for the HOD reactant in various vibrational states. The correlation of initial reactant vibrational excitation with product channel branching and product vibrational state distribution is analyzed in detail. In particular, the effect of bending vibrational excitation on the reactivity is studied. While results for the HOD reactant in the fundamentally excited bending vibrational state confirm intuitive expectation with minor enhancement for both product channels, a surprising effect is found for HOD in the first overtone of bending vibration. Here, the reactivity towards breaking the OD bond is significantly enhanced. This finding can be explained by the state-mixing caused by a 1 : 2 Fermi resonance between the fundamental OD stretch and the first overtone of the bend. The results highlight the importance of a proper analysis of the initial vibrational state.


Reduced heme levels underlie the exponential growth defect of the Shewanella oneidensis hfq mutant.
The RNA chaperone Hfq fulfills important roles in small regulatory RNA (sRNA) function in many bacteria. Loss of Hfq in the dissimilatory metal reducing bacterium Shewanella oneidensis strain MR-1 results in slow exponential phase growth and a reduced terminal cell density at stationary phase. We have found that the exponential phase growth defect of the hfq mutant in LB is the result of reduced heme levels. Both heme levels and exponential phase growth of the hfq mutant can be completely restored by supplementing LB medium with 5-aminolevulinic acid (5-ALA), the first committed intermediate synthesized during heme synthesis. Increasing expression of gtrA, which encodes the enzyme that catalyzes the first step in heme biosynthesis, also restores heme levels and exponential phase growth of the hfq mutant. Taken together, our data indicate that reduced heme levels are responsible for the exponential growth defect of the S. oneidensis hfq mutant in LB medium and suggest that the S. oneidensis hfq mutant is deficient in heme production at the 5-ALA synthesis step.


Brief, Web-Based Interventions to Motivate Smokers With Schizophrenia: Randomized Trial.
In-person motivational interventions increase engagement with evidence-based cessation treatments among smokers with schizophrenia, but access to such interventions can be limited because of workforce shortages and competing demands in mental health clinics. The use of digital technology to deliver interventions can increase access, but cognitive impairments in schizophrenia may impede the use of standard digital interventions. We developed an interactive, multimedia, digital motivational decision support system for smokers with schizophrenia (Let's Talk About Smoking). We also digitalized a standard educational pamphlet from the National Cancer Institute (NCI Education). Both were tailored to reduce cognitive load during use. We conducted a randomized trial of Let's Talk About Smoking versus NCI Education to test whether the interactive motivational intervention was more effective and more appealing than the static educational intervention for increasing use of smoking cessation treatment, quit attempts, and abstinence among smokers with schizophrenia, accounting for the level of cognitive functioning. Adult smokers with schizophrenia (n=162) were enrolled in the study from 2014 to 2015, randomly assigned to intervention condition, and assessed in person at 3- and 6-month follow-ups. Interventions were delivered on a laptop computer in a single session. All participants had access to standard, community-delivered cessation treatments during follow-up. Multivariate models were used to evaluate outcomes. Treatment initiation outcomes were not different between intervention conditions (27/84 [32%] for Let's Talk About Smoking vs 36/78 [46%] for NCI Education; odds ratio [OR] 0.71 [95% CI 0.37-1.33]); 38.9% (63/162) of participants initiated treatment. Older age (OR 1.03 [95% CI 1.00-1.07]; P=.05), higher education (OR 1.21 [95% CI 1.04-1.41]; P=.03), and fewer positive symptoms (OR 0.87 [95% CI 0.80-0.96]; P=.01) predicted cessation treatment initiation, whereas level of cognition did not. The mean satisfaction and usability index score was higher for Let's Talk About Smoking versus NCI Education (8.9 [SD 1.3] vs 8.3 [SD 2.1]; t120.7=2.0; P=.045). Quit attempts (25/84, 30% vs 36/78, 46%; estimate [Est]=-0.093, SE 0.48; P=.85) and abstinence (1/84, 1% vs 6/78, 7%; χ21=3.4; P=.07) were not significantly different between intervention conditions. Cognitive functioning at baseline (Est=1.47, SE 0.47; P=.002) and use of any behavioral or medication cessation treatment (Est=1.43, SE 0.47; P=.003) predicted quit attempts with self-reported abstinence over the 6-month follow-up. The interactive, multimedia intervention was not more effective than the static, text-based intervention among smokers with schizophrenia. Both tailored digital interventions resulted in levels of treatment engagement and quit attempts that were similar to findings from previous studies of in-person interventions, confirming the potential role of digital interventions to educate and motivate smokers with schizophrenia to use cessation treatment and to quit smoking. These findings indicate that additional cessation treatment is needed after brief education or motivational interventions, and that cessation treatment should be adjusted for people with cognitive impairment. ClinicalTrials.gov NCT02086162; https://clinicaltrials.gov/show/NCT02086162.


PU box-binding transcription factors and a POU domain protein cooperate in the Epstein-Barr virus (EBV) nuclear antigen 2-induced transactivation of the EBV latent membrane protein 1 promoter.
Expression of the Epstein-Barr virus (EBV) latent membrane protein (LMP1) is regulated by virus- and host cell-specific factors. The EBV nuclear antigen 2 (EBNA2) has been shown to transactivate a number of viral and cellular gene promoters including the promoter for the LMP1 gene. EBNA2 is targeted to at least some of these promoters by interacting with a cellular DNA binding protein, RBP-J kappa. In the present report we confirm and extend our previous observation that the LMP1 promoter can be activated by EBNA2 in the absence of the RBP-J kappa-binding sequence in the LMP1 promoter regulatory region (LRS). We show that two distinct LRS regions, -106 to +40 and -176 to -136, contribute to EBNA2 responsiveness. Site-directed mutagenesis analysis of the upstream -176/-136 EBNA2 responsive element revealed that two critical cis-acting elements are required for full promoter function. These same elements analysed by electrophoretic mobility shift assays define two binding sites recognized by nuclear factors derived from B cells. An octamer-like sequence (-147 to -139) contained overlapping binding sites for an unidentified transcriptional repressor on the one hand and a factor(s) belonging to the POU domain family but distinct from Oct-1 and Oct-2 on the other. An adjacent purine tract (-171 to -155) held a PU.1 binding site, which was also recognized by a related factor. The results suggest that the POU domain protein and either of two PU box-binding factors bind simultaneously to LRS, creating a ternary complex that might be in part responsible for mediating the transactivation of the LMP1 promoter by EBNA2. There were no qualitative differences between EBV-negative and EBV-positive cells with regard to transcription factor binding to the octamer-like sequence and the PU.1 recognition site, as revealed by electrophoretic mobility shift assays.


Latent cytomegalovirus infection in blood donors.
Twenty-one out of 32 apparently healthy blood donors aged 21 to 65 years yielded positive complement fixation tests with a cytomegalovirus antigen, at titres ranging from 1:8 to 1:64. Virus was present in leucocyte cultures of fresh peripheral blood of two seropositive subjects from a total of 35 donors examined. Plasma and 48-hour stored blood specimens failed to disclose virus in culture. Viruria could not be demonstrated, and there was no evidence of recent illness in the study group. These findings suggest that subclinical viraemia is not uncommon in blood donors.


Antiviral activity of prostaglandin A on encephalomyocarditis virus-infected cells: a unique effect unrelated to interferon.
Antiviral effects of prostaglandins of the A series (PGAs) on Sendai, vaccinia and vesicular stomatitis viruses have previously been reported and a relationship between the antiviral actions of PGAs and interferons has been suggested. We have investigated the antiviral activity of PGAs on encephalomyocarditis (EMC) virus. Using single-cycle assays of virus replication our results indicate that PGAs only inhibit when present in the culture medium after the cells are infected, and that they are most effective during incubation periods including from 3 to 5 h post-infection. Furthermore, viral RNA synthesis is blocked in infected cells treated with PGA and, as a result, viral antigens are greatly reduced in the cytoplasm of the cells 5 h post-infection. Since the antiviral effect of PGAs is unperturbed by actinomycin D, when cellular RNA synthesis is greatly reduced, it appears unlikely that induction of new cellular proteins is the reason for the antiviral activity of PGAs. In separate experiments we were unable to demonstrate directly the induction of interferon, or of the two dsRNA-dependent enzymes, 2',5'-oligoadenylate synthetase and protein kinase, which are greatly increased in interferon-treated cells. Thus, we conclude that the antiviral activity of PGAs is unrelated to the antiviral action of interferons and involves a unique mechanism independent of cellular protein synthesis.


Examining functional content in widely used Health-Related Quality of Life scales.
Assess extent to which generic Quality of Life (QOL) and Health-Related Quality of Life (HRQOL) scales include function in assessment of health, and identify health assessment items that are free of functional content. An expert panel on measurement of health and disability reached consensus on definitions of health, disability, and function. They assessed all items of all generic (non-condition-specific) scales in the 2006 ProQolid database for being important to measuring health as distinct from function. Ratings were summarized as content validity ratios. Retained items were written into standard format and reviewed again by the expert panel and a validity panel with expertise in specific disabilities. Of 85 scales, 21 were retained as containing items important for assessing health. Scales ranged from 100% (BRFSS HRQOL, WHO-5) to only 4% of items rated as important. In further review of "important" items, functional content was identified in many of the items, particularly with regard to mental functioning. Popular generic scales of QOL and HRQOL vary greatly in the degree to which they include content on function. A pool of items can be identified that are relatively free of function. Distinguishing measurement of function and health is particularly important for people with long-standing functional limitations and for assessing the relationship of health with function.


[Endoscopic electromyographic study on upper gastrointestinal tract (author's transl)].
Recently we made the electromyographic study on human gastrointestinal tract using the endoscopic method is useful for the clinical studies of the patho-physiological aspects on human gastrointestinal tract. The silver bipolar needle electrode which was 0.2 mm in diameter, 10 mm in length and 1.0 mm in interpolar distance and the electroencephalography recorder provided with pen-writer were used for this research. The endoscopy was done to the volunteer anesthetized his pharynx with xylocaine spray. 20 cases of gastro-electromyograms, 35 cases of duodeno-electromyograms and 5 cases of the electromyograms of duodenal papilla were recorded. On these endoscopic electromygorams, the typical rhythms and patterns of electrical activities were disturbed by various kinds of factors; that is, on the endoscopic manipulation, the sticking of needle electrode into the shallow layer of gastrointestinal wall and automatical pouring of water into canal through the endoscope. On volunteers' condition, his deep breathing, electrocardiogram and vasotonic condition were important factors. Typical duodeno-electromyograms showed the grouped spikes synchronizing with the duodenal peristalsis observed endoscopically. The electromyograms of the duodenal papilla showed the similar patterns and rhythms to those of duodeno-electromyograms on active phase. In the clinical study on the correlation and propagation between gastric and duodenal motility, the rhythms of electrical activities on duodeno-electromyograms were not similar to the rhythms of gastric peristalsis at the prepyloric region. The propagation of gastric movement to duodenal bulb were not able to be clarified. We assumed that the gastric and duodenal motility occurred each other on the different rhythms.


Light alcohol drinking and cancer: a meta-analysis.
There is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day). We evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010. We included 222 articles comprising ∼92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06-1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09-1.56) and female breast cancer (RR = 1.05; 95% CI 1.02-1.08). We estimated that ∼5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors. Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast.


Efficacy of pudendal nerve block for alleviation of catheter-related bladder discomfort in male patients undergoing lower urinary tract surgeries: A randomized, controlled, double-blind trial.
Catheter-related bladder discomfort (CRBD) to an indwelling urinary catheter is defined as a painful urethral discomfort, resistant to conventional opioid therapy, decreasing the quality of postoperative recovery. According to anatomy, the branches of sacral somatic nerves form the afferent nerves of the urethra and bladder triangle, which deriving from the ventral rami of the second to fourth sacral spinal nerves, innervating the urethral muscles and sphincter of the perineum and pelvic floor; as well as providing sensation to the penis and clitoris in males and females, which including the urethra and bladder triangle. Based on this theoretical knowledge, we formed a hypothesis that CRBD could be prevented by pudendal nerve block. To evaluate if bilateral nerve stimulator-guided pudendal nerve block could relieve CRBD through urethra discomfort alleviation. Single-center randomized parallel controlled, double blind trial conducted at West China Hospital, Sichuan University, China. One hundred and eighty 2 male adult patients under general anesthesia undergoing elective trans-urethral resection of prostate (TURP) or trans-urethral resection of bladder tumor (TURBT). Around 4 out of 182 were excluded, 178 patients were randomly allocated into pudendal and control groups, using computer-generated randomized numbers in a sealed envelope method. A total of 175 patients completed the study. Pudendal group received general anesthesia along with nerve-stimulator-guided bilateral pudendal nerve block and control group received general anesthesia only. Incidence and severity of CRBD; and postoperative VAS score of pain. CRBD incidences were significantly lower in pudendal group at 30 minutes (63% vs 82%, P = .004), 2 hours (64% vs 90%, P < .000), 8 hours (58% vs 79%, P = .003) and 12 hours (52% vs 69%, P = .028) also significantly lower incidence of moderate to severe CRBD in pudendal group at 30 minutes (29% vs 57%, P < .001), 2 hours (22% vs 55%, P < .000), 8 hours (8% vs 27%, P = .001) and 12 hours (6% vs 16%, P = .035) postoperatively. The postoperative pain score in pudendal group was lower at 30 minutes (P = .003), 2 hours (P < .001), 8 hours (P < .001), and 12 hours (P < .001), with lower heart rate and mean blood pressure. One patient complained about weakness in levator ani muscle. General anesthesia along with bilateral pudendal nerve block decreased the incidence and severity of CRBD for the first 12 hours postoperatively.


Independent prognostic value of coronary artery calcium score and coronary computed tomography angiography in an outpatient cohort of low to intermediate risk chest pain patients.
Limited studies report on the additional prognostic value of coronary computed tomography angiography (CCTA) and the coronary artery calcium score (CACS). For a median of 637 days, 1551 outpatients with chest pain, without known coronary artery disease (CAD) and low or intermediate pre-test probability of CAD, were followed for major adverse cardiac events (MACE), defined as death, myocardial infarction or late revascularisation. Cox proportional hazard regression was used to evaluate the independent prognostic value of CCTA and CACS. MACE occurred in 23 patients (1.5 %): death (3, 0.2 %), myocardial infarction (4, 0.3 %) and late revascularisation (16, 1.3 %). Multivariate analysis showed an independent prognostic value of CCTA (p < 0.001), CACS of 100-400 (p = 0.035) and CACS of > 400 (p = 0.021). CCTA showed obstructive CAD in 3.1 % of patients with CACS = 0. No events occurred in patients with CACS = 0 without obstructive CAD at CCTA, whereas 2/23 patients (9 %) with CACS = 0 with obstructive CAD had a MACE. Our study shows that both CCTA and higher CACS categories have independent prognostic value in chest pain patients with low to intermediate pre-test probability of obstructive CAD, in which CCTA is appropriate. Furthermore a non-negligible amount of patients with CACS = 0 have obstructive CAD at CCTA. CCTA can be used in these patients to identify those at risk for MACE.


Survey of patients' responses to breast reconstruction.
Patients' responses to single-stage breast reconstruction were evaluated in 100 cases using a questionnaire. The availability of breast reconstruction did not influence the decision to have a mastectomy in 63% of patients but did serve as an incentive in 24%. The reconstruction was acceptable for 92% of patients; increased sexual expressiveness in 45% of patients was another benefit of reconstruction. Multiple-stage reconstruction was acceptable for 65% of patients; however, 56% favored the one-stage operation. Given the same opportunity, 91% of the patients would consider undergoing breast reconstruction.


The use of Xenopus oocytes in drug screening.
The physiological roles of ion channels are receiving increased interest in both basic research and drug discovery, and a demand for pharmacological approaches that can characterize or screen ion channels and their ligands with higher throughput has emerged. Traditionally, screening of compound libraries at ion channel targets has been performed using assays such as binding assays, fluorescence-based assays and flux assays that allow high-throughput, but sacrifice high data quality. The use of these assays with ion channel targets can also be problematic, emphasizing the usefulness of automated Xenopus oocyte electrophysiological assays in drug screening. This review summarizes the use of Xenopus oocytes in drug screening, presents the advantages and disadvantages of the use of Xenopus oocytes as expression system, and addresses the options available for automated two-electrode voltage-clamp recordings from Xenopus oocytes. Automated and manual Xenopus oocyte two-electrode voltage-clamp recordings are useful and important techniques in drug screening. Although they are not compatible with high-throughput experimentation, these techniques are excellent in combination or as alternatives to fluorescence-based assays for hit validation, screening of focused compound libraries and safety screening on ion channels with their high flexibility for the choice of molecular targets, quality of data and reproducibility.


The Utility of Fallopian Tube Cytology in the Early Detection of Extrauterine Serous Gynecological Malignancies: A Narrative Literature Review.
The aim of the study was to analyze the published evidence for the use of fallopian tube brush cytology for the early detection of extrauterine serous gynecological cancer. We systematically searched the literature and, additionally, cross-checked on the bibliographies of selected articles. The inclusion criteria involved studies assessing the utility of fallopian tube brush cytology and its applications in the diagnosis, screening, or follow-up of extrauterine serous gynecological cancer. The search strategy resulted in 21 abstracts or full-text articles, 5 of which met the inclusion criteria. The year of publication ranged from 2016 to 2022, and a total of 193 fallopian tube samples were investigated. Cytobrush, Tubebrush©, and Cytuity™ were used to obtain salpingeal samples for liquid-based cytology evaluation. Our findings indicate that, at present, there is a lack of satisfying evidence-based data in the literature which would support the implementation of fallopian tube brush cytology as an adjunctive tool for early detection of extrauterine serous gynecological cancer. Thus, we believe that there is need for well-designed clinical studies to assess the effectiveness and diagnostic accuracy of the method as well as to validate the cytological criteria for the diagnosis and prediction of gynecological malignancies.


Characteristics of clinical trials assessing antimicrobial treatment of bovine respiratory disease, 1970-2005.
To evaluate reporting of key study design features and study outcomes in trials of antimicrobial treatment of bovine respiratory disease (BRD) in North American feedlots. Systematic review. 29 manuscripts (41 studies) reporting antimicrobial treatment of BRD in North American feedlot cattle. A search of the electronic citation databases AGRICOLA, Commonwealth Agricultural Bureau, and PubMed was conducted to identify relevant manuscripts published between 1970 and 2005. Key study design features were extracted by 2 reviewers. 12 of 29 (41%) manuscripts did not disclose a funding source, and 21 (72%) had an author clearly identified as an employee of a pharmaceutical company. At the study level, 36 of 41 (88%) studies reported a random method of treatment allocation, 9 (22%) described the method of allocation sequence generation, 20 (49%) reported that study investigators were blinded to treatment, and 3 (7%) included a study size justification. No studies described the null hypothesis to be tested. Thirty-seven (90%) studies reported at least 3 outcomes; the largest number of outcomes reported was 14. It was not possible to conduct the statistical analysis as originally planned because it was not possible to discern the primary outcome for the majority of studies. Many studies did not report key study design features that would assist critical evaluation by readers. It was not clear whether the studies failed to use the design features or failed to report them. Several nondesign features, such as reporting of the null hypothesis, a primary outcome, and sample size rationale, represent relatively new standards for reporting; however, reporting these features would substantially clarify the study objective.


Magnetic Field Generation in Plasma Waves Driven by Copropagating Intense Twisted Lasers.
We present a new magnetic field generation mechanism in underdense plasmas driven by the beating of two, copropagating, Laguerre-Gaussian orbital angular momentum laser pulses with different frequencies and also different twist indices. The resulting twisted ponderomotive force drives up an electron plasma wave with a helical rotating structure. To second order, there is a nonlinear rotating current leading to the onset of an intense, static axial magnetic field, which persists over a long time in the plasma (ps scale) after the laser pulses have passed by. The results are confirmed in three-dimensional particle-in-cell simulations and also theoretical analysis. For the case of 300 fs duration, 3.8×10^{17} W/cm^{2} peak laser intensity we observe magnetic field of up to 0.4 MG. This new method of magnetic field creation may find applications in charged beam collimation and microscale pinch.


Current knowledge on pathogenesis and immunodiagnosis of paracoccidioidomycosis.
Host-parasite relationship and immunodiagnostic testing in paracoccidioidomycosis have been extensively investigated in recent years. We review the major advances in the understanding of pathogenesis of the disease with emphasis on the sequential steps in granuloma formation and the envolvement of immunological mechanisms in host defenses against the parasite. In addition, the several immunodiagnostic tests used for diagnosis and in the follow-up of patients are commented upon and critically analysed.


Involvement of Nrf2 in Ocular Diseases.
The human body harbors within it an intricate and delicate balance between oxidants and antioxidants. Any disruption in this checks-and-balances system can lead to harmful consequences in various organs and tissues, such as the eye. This review focuses on the effects of oxidative stress and the role of a particular antioxidant system-the Keap1-Nrf2-ARE pathway-on ocular diseases, specifically age-related macular degeneration, cataracts, diabetic retinopathy, and glaucoma. Together, they are the major causes of blindness in the world.


Human Periosteal Derived Stem Cell Potential: The Impact of age.
There is a great deal of interest in the understanding of possible age-related changes in Mesenchymal Stem Cells in view of their use for regenerative medicine applications. Given to the outmost standing of periosteum in bone biology and to probe data for a cell-based therapy promoting graft osseointegration in the elderly, we tried to identify specific aging markers or pattern of expression in human periosteal precursor cells. Immunohistochemical detection of Ki67 and p53, Nitric Oxide production and qRT- PCR of a selected gene panel for osteoblastic differentiation, bone remodeling and stemness were evaluated. We confirmed that both Ki67 and p53 are noteworthy indicators of senescence in human periosteal precursor cells and their expression significantly correlate with cell NO production. Moreover, cell age affects genes involved in bone remodeling, with a significant increase in interleukin-6 mRNA expression and receptor activator of nuclear factor kappa-B ligand/osteoprotegerin ratio. The analysis of mRNAs of genes involved in pluripotency regulation and self-renewal of stem cells, evidenced changes at least in part related to bone remodeling. We believe that this is the first study taking on age-related changes in human periosteal precursor cells, and paving the way toward new regenerative medicine strategies in bone aging and/or bone metabolic diseases.


Estimation of indoor (220)Rn progeny concentrations with (220)Rn measurements.
For estimating indoor thoron ((220)Rn) progeny concentrations with (220)Rn measurements, both theoretical studies and field measurements were carried out in this work. Based on the theoretical study, it was found that the exhalation rate of (220)Rn (E(Tn)) could be optimally assessed with the (220)Rn concentration measured at a point of 50 cm far from the source wall, and the equilibrium equivalent thoron concentration (EETC) could be further estimated with the E(Tn) and the area of wall surface as well as the room volume. Field measurements testified that the estimated EETCs were in general agreement with the directly measured results with an average ratio of 0.87 ± 0.12. The new method developed in this study is thought to be preferable for long-term and large-scale surveys of indoor EETC.


Model complexity has a significant effect on the numerical value and interpretation of metabolic sensitivity coefficients.
Logarithmic sensitivity coefficients were promulgated for the analysis of metabolic regulation about 20 years ago. Interest in their use has risen significantly since their introduction. However, no comprehensive evaluation of the utility of these metabolic sensitivity coefficients is available for realistic metabolic models. In this study, logarithmic sensitivity coefficients calculated from three progressively simpler metabolic models of red blood cell metabolism were compared. Two simpler models were obtained from a comprehensive red cell model by first removing volume regulation, and second by removing two pathways. The comparisons of sensitivity coefficients obtained for these three models showed that model complexity has significant effects on the numerical values and interpretation of the metabolic sensitivity coefficients. Additionally, it was found that the physiochemical volume regulatory mechanism, namely electroneutrality and osmotic balances, play an important role in the red cell metabolic flux control. In general, there is no proportionate relationship between sensitivity coefficients calculated from the three different red cell metabolic models or other simple red cell models reported in the early literature. Some sensitivity coefficients determined by different models even have opposite signs. Thus, analysis of incomplete metabolic models can be seriously misleading and produce inappropriate indicators of the characteristics of a full model for the same metabolic network.


Geographical distribution, host associations, and vector roles of ticks (Acari: Ixodidae, Argasidae) in Sweden.
This review covers the geographic distribution and host relationships of the tick species in Sweden. Ixodes uriae White, I. caledonicus Nuttall, I. unicavatus Neumann, I. arboricola Schulze & Schlottke, and I. lividus Koch are ornithophagous species. I. trianguliceps Birula, I. canisuga Johnston, I. hexagonus Leach, and Argas vespertilionis (Latreille) are mammalophagous. I. ricinus (L.) and Haemaphysalis punctata Canestrini & Fanzago feed on both birds and mammals. All these tick species may be considered to be permanently present in Sweden. I. persulcatus Schulze, Hyalomma marginatum Koch, and the brown dog tick, Rhipicephalus sanguineus (Latreille), may be regarded as not indigenous to Sweden although they may be regularly introduced by spring-migrating birds or imported dogs, respectively. The first European record of the American dog tick, Dermacentor variabilis (Say), is reported. There are several records of Hyalomma aegyptium (L.) from imported tortoises in Sweden. Excluding other ticks imported on exotic pets and zoo animals, another 13 tick species are listed that may occur, at least occasionally, in Sweden. Because of its wide geographic distribution, great abundance, and wide host range, I. ricinus is medically the most important arthropod in northern Europe. I. ricinus is common in southern and south-central Sweden and along the coast of northern Sweden and has been recorded from 29 mammal species, 56 bird species, and two species of lizards in Sweden alone. The potential introduction to Sweden of exotic pathogens with infected ticks (e.g., I. persulcatus and H. marginatum on birds or Dermacentor spp. and R. sanguineus on mammals) is evident.


Gastrointestinal delivery of baculovirus displaying influenza virus hemagglutinin protects mice against heterologous H5N1 infection.
The recent outbreaks of influenza A H5N1 virus in birds and humans have necessitated the development of potent H5N1 vaccines. In this study, we evaluated the protective potential of an immediate-early promoter-based baculovirus displaying hemagglutinin (BacHA) against highly pathogenic avian influenza (HPAI) H5N1 virus infection in a mouse model. Gastrointestinal delivery of BacHA significantly enhanced the systemic immune response in terms of HA-specific serum IgG and hemagglutination inhibition (HI) titers. In addition, BacHA vaccine was able to significantly enhance the mucosal IgA level. The inclusion of recombinant cholera toxin B subunit as a mucosal adjuvant along with BacHA vaccine did not influence either the systemic or mucosal immunity. Interestingly, an inactivated form of BacHA was able to induce only a negligible level of immune responses compared to its live counterpart. Microneutralization assay also indicated that live BacHA vaccine was able to induce strong cross-clade neutralization against heterologous H5N1 strains (clade 1.0, clade 2.1, and clade 8.0) compared to the inactivated BacHA. Viral challenge studies showed that live BacHA was able to provide 100% protection against 5 50% mouse lethal doses (MLD(50)) of homologous (clade 2.1) and heterologous (clade 1) H5N1. Moreover, histopathological examinations revealed that mice vaccinated with live BacHA had only minimal bronchitis in lungs and regained their body weight more rapidly postchallenge. Furthermore, immunohistochemistry results demonstrated that the live BacHA was able to transduce and express HA in the intestinal epithelial cells in vitro and in vivo. We have demonstrated that recombinant baculovirus with a white spot syndrome virus (WSSV) immediate-early promoter 1 (ie1) acted as a vector as well as a protein vaccine and will enable the rapid production of prepandemic and pandemic vaccines without any biosafety concerns.


Winter severity predicts the timing of host shifts in the mosquito Culex erraticus.
In temperate regions, seasonal epidemics of many mosquito-borne viruses are triggered when mosquito populations shift from feeding on avian to mammalian hosts. We investigated effects of temperature on the timing of bird-to-mammal shifts using an 8 year dataset of blood-meals from a mosquito (Culex erraticus) in Alabama, USA. As expected, Cx. erraticus shifted from avian to mammalian hosts each year. The timing of the shift, however, varied considerably among years. Harshness of the preceding winter (chill accumulation) explained 93 per cent of the variation in the timing of bird-to-mammal shifts, with shifts occurring later in years following harsher winters. We hypothesize that winter temperatures drive the timing of bird-to-mammal shifts through effects on host reproductive phenology. Because mosquitoes target birds during the nesting season, and bird nesting occurs later in years following colder winters, later nesting dates result in a concomitant delay in the timing of bird-to-mammal host shifts. Global increases in winter temperatures could cause significant changes in the timing of seasonal host shifts by mosquitoes, with prolonged periods of epidemic transmission of mosquito-borne diseases.


The micro-RNA 199b-5p regulatory circuit involves Hes1, CD15, and epigenetic modifications in medulloblastoma.
Micro-RNA (miR) 199b-5p targets Hes1 in medulloblastoma, one of the downstream effectors of both the canonical Notch and noncanonical Sonic Hedgehog pathways. In medulloblastoma patients, expression of miR-199b-5p is significantly decreased in metastatic cases, thus suggesting a downregulation mechanism. We studied this mechanism, which is mediated mostly by Hes1 and epigenetic promoter modifications. The miR-199b-5p promoter region was characterized, which identified a Hes1 binding site, thus demonstrating a negative feedback loop of regulation. MiR-199b-5p was shown to be downregulated in several medulloblastoma cell lines and in tumors by epigenetic methylation of a cytosine-phosphate-guanine island upstream of the miR-199b-5p promoter. Furthermore, the cluster of differention (CD) carbohydrate antigen CD15, a marker of medulloblastoma tumor-propagating cells, is an additional direct target of miR-199b-5p. Most importantly, regulation of miR-199b-5p expression in these CD15+/CD133+ tumor-propagating cells was influenced by only Hes1 expression and not by any epigenetic mechanism of regulation. Moreover, reverse-phase protein array analysis showed both the Akt and extracellular-signal-regulated kinase pathways as being mainly negatively regulated by miR-199b-5p expression in several medulloblastoma cell lines and in primary cell cultures. We present here the finely tuned regulation of miR-199b-5p in medulloblastoma, underlining its crucial role by its additional targeting of CD15.