Development of a new dispenser for microbiological control agents and evaluation of dissemination by bumblebees in greenhouse strawberries.
To date, in modern agriculture, biological control strategies are increasingly becoming the preferred pest management approach. However, the success of microbiological control agents (MCAs) largely depends on efficient dissemination into the crop. The pollinator-and-vector technology employs pollinating insects like bees for a better dissemination. In this study, a new dispenser for bumblebee workers of Bombus terrestris L. was developed. Binab-T-vector and Prestop-Mix were used as two typical MCA products for dissemination. In a first series of experiments in the laboratory for optimisation, the newly developed dispenser was a two-way type dispenser, 20 cm long, with two rectangular compartments and different entrance and exit holes. In addition, the amounts of MCA loaded on the workers were 10 times higher with the new dispenser as compared with the side-by-side passageway (SSP) dispenser. Typically, the highest amounts were recovered from the thorax and legs of the workers. In a second series of experiments under greenhouse conditions with the use of queen-right B. terrestris hives, successful dissemination in strawberry flowers was obtained at different distances from the hive (0-8 m, 8-18 m and 18-21 m), and the workers inoculated the first, second and third flowers that were consecutively visited. In addition, the new dispenser caused no adverse effects on worker foraging intensity, whereas a dramatic reduction was scored with an SSP dispenser. Finally, the data suggested that it is necessary to refill the newly developed dispenser at 3 day intervals. The results demonstrated that, with the use of the newly developed dispenser, bumblebee workers carried high amounts of MCA, and this resulted in a successful dissemination of MCA into strawberry flowers.


Activation of c-Jun NH2-terminal kinase is required for gemcitabine's cytotoxic effect in human lung cancer H1299 cells.
Although gemcitabine is a potent therapeutic agent in the treatment of human non-small cell lung cancer (NSCLC), resistance to gemcitabine is common. In this study, we investigated the molecular mechanisms involved in acquired gemcitabine resistance against NSCLC cells. Gemcitabine-resistant NSCLC H1299 cells (H1299/GR) were selected by long-term exposure of parental H1299 cells to gemcitabine. The median inhibitory concentrations of gemcitabine in H1299 and H1299/GR cells were 19.4 and 233.1 nM, respectively. Gemcitabine induced activation of c-Jun NH2-terminal kinase (JNK) in parental H1299 cells but not in H1299/GR cells after 48 h. Blocking JNK activation by pretreatment with SP600125, a specific JNK inhibitor, or by transfection with dominant-negative JNK vectors abrogated gemcitabine-induced apoptosis in parental H1299 cells as evidenced by interruption of caspase activation. Transient transfection with a JNKK2-JNK1 plasmid expressing constitutive JNK1 partially restored the effect of gemcitabine in H1299/GR cells. Our results indicate that gemcitabine-induced apoptosis in human NSCLC H1299 cells requires activation of the JNK signaling pathway. Attenuated JNK activation may contribute to development of acquired gemcitabine resistance in cancer cells.


Salt Weakens Intermicellar Interactions and Structuring in Bulk Solutions and Foam Films.
Drainage via stratification in micellar foam films formulated with ionic surfactants shows dramatic changes on salt addition: both the step size and the number of steps in their stepwise thinning diminish. As the stratification process is governed by supramolecular oscillatory structural forces that arise due to confinement-induced structuring of micelles, it is apparent that salt addition reduces the magnitude, periodicity, and decay length of the oscillatory forces. In this contribution, we characterize the changes in micellar size, shape, and interactions on salt addition in bulk solutions using small-angle X-ray scattering (SAXS) to understand and elucidate the influence of salt on stratification in micellar foam films and, more broadly, on the oscillatory structural forces. Adding salt leads to a significant reduction in long-range correlations between micelles and smaller intermicellar distances. These effects manifest as a weakening of the primary peak of the structure factor, ascertained from SAXS spectra, accompanied by its shift to higher wave vectors. Weakened long-range correlations diminish the magnitude and periodicity of the oscillatory disjoining pressure leading to smaller step sizes, fewer steps, and a rich nanoscopic topography, due to the influence of disjoining pressure on the deformable interfaces. The step sizes in stratifying thin films and intermicellar distances in bulk solutions present incongruous values, implying an imperfect analogy with studies on charged nanoparticles with matched and salt concentration-independent values of measured interparticle distances that equal the periodicity of force-distance curves. We anticipate that our findings are significant for multicomponent soft and biological matter containing self-assembled supramolecular structures wherein screened Coulomb interactions govern the self-assembly, interfacial adsorption, interactions, dynamics, and stability.


Portal hypertension and nodular regenerative hyperplasia in a patient with celiac disease.
Nodular regenerative hyperplasia (NRH) is an uncommon cause of portal hypertension. The disease is often associated with rheumatological or lymphoproliferative disorders. We report the case of a 19-year old patient with celiac disease and portal hypertension. Biopsy of the liver revealed NRH as the underlying cause. There were no signs of autoimmune diseases or defects in the coagulation system that might cause NRH. Celiac disease is often associated with liver abnormalities, but the association with NRH has rarely been described. We discuss the possible relationship of celiac disease and NRH.


Patient-provider relationships, HIV, and adherence: requisites for a partnership.
This paper analyzes data collected through focus groups of patients at an outpatient AIDS clinic at a New York medical center. Seven focus groups were conducted with 42 HIV+ patients, and verbatim transcripts of focus group sessions were analyzed through a combination of ethnographic and content analysis. We examined patients' reports of interactions with and attitudes toward their providers and attempted to define what elements in the provider-patient relationship are necessary to enable patients to become more integrally involved in the management of their illness. Participants' statements emerged as consistent with three themes: (a) dynamics of provider-to-patient communication; (b) dynamics of patient-to-provider communication; and (c) dynamics of collaboration. Each of these themes is discussed in terms of its implications for creating patient-provider relationships based on mutual-participation, and requisites for effecting meaningful patient-provider partnerships are outlined.


Oscillometric evaluation of the effects of cardiotoxic chemotherapeutic agents on vascular stiffness.
Several clinical studies have demonstrated that arterial stiffness is an early indicator of cardiovascular events. Our study aimed to detect the potential cardiovascular changes using arterial stiffness parameters and compare these changes with echocardiographic aortic stiffness parameters, in cancer patients treated with cardiotoxic chemotherapeutics. Our study is a prospective case-control study. A total of seventy subjects between the ages of 18 and 50 years were included into our study. Thirty of them were newly diagnosed cancer patients and forty constituted the age- and sex-matched control group. Baseline oscillometric arterial and echocardiographic aortic stiffness parameters were measured in all patients. In cancer patients, all of these parameters were measured again, 1 month after chemotherapy protocol was completed. Mean age of the cancer patients was 41.4 ± 5.9 years and mean age of the control group was 39.6 ± 6.6 years (P = 0.258). Before chemotherapy, arterial and aortic stiffness parameters were similar between the study and the control group. After chemotherapy, the oscillometric pulse wave velocity parameter increased compared with the control group and to the prechemotherapy values (P = 0.004 and P < 0.001, respectively). After chemotherapy, the augmentation index parameter increased compared with the control group (P = 0.013). On the other hand, no difference was detected between the groups in terms of echocardiographic aortic stiffness parameters. In newly diagnosed cancer patients treated with cardiotoxic chemotherapeutics, considerable impairment occurs in some of the oscillometric arterial stiffness parameters, while there is no substantial effect on echocardiographic aortic stiffness. Arterial stiffness parameters in these patients might be useful in evaluating subclinical cardiovascular damage.


Embarrassment and Shame in People With Parkinson's Disease: A New Tool for Self-Assessment.
Shame and embarrassment related to Parkinson's disease (PD) are rarely addressed in clinical practice nor studied in neuroscience research, partly because no specific tool exists to detect them in PD. Objective: To develop a self-applied assessment tool of shame and embarrassment specifically related to PD or its treatment, to promptly identify the presence and severity of these two emotions in PD. Methods: Identification and selection of relevant items were obtained from the collection of PD patients' opinions during support groups and interviews. Several further items were added following a literature review. Subsequently, a two-phase pilot study was performed for identification of ambiguous items and omissions, and to obtain preliminary data on acceptability, reliability, validity and relevance of the new scale (SPARK). Results: A total of 105 PD patients were enrolled in the study. Embarrassment was reported in 85% of patients, while shame was present in 26%. Fifteen percent of patients did not describe any shame or embarrassment. On average, the intensity of these two emotions was low with a marked floor effect in SPARK items and subscales. However, SPARK total score inter-individual variability was important (range 1-84 out of 99). Acceptability and quality of data were satisfactory with no floor or ceiling effects (2.9% each) or missing data. Internal consistency (Cronbach's alpha) was 0.94 for total score and 0.73-0.87 for subscales. The scale correlated ≥0.60 with instruments measuring related constructs. Content validity was satisfactory. SPARK total score strongly correlated with impaired health-related quality of life (rS = 0.81), the propensity to feel embarrassed or ashamed (rS = 0.68 and 0.66, respectively), and anxiety (rS = 0.72) and depression (rS = 0.63) levels. Moderate to high correlations were observed between SPARK total score and apathy (rS = 0.46) and a more pronounced personality trait directed toward harm avoidance (rS = 0.46). No significant differences in SPARK scores were found by sex, education level, PD duration, Hoehn and Yahr stages or PD phenotype. Conclusion: Preliminary analysis of psychometric properties suggests that SPARK could be an acceptable and reliable instrument for assessing shame and embarrassment in PD. SPARK could help healthcare professionals to identify and characterize PD-induced shame and embarrassment.


Production of beams from solid materials at Center for Nuclear Study electron cyclotron resonance ion source.
Two methods for the feed of vapor from solid materials in the Center for Nuclear Study ECR ion source are described. A rod placed near the wall of the plasma chamber, operating up to a melting point of 2600 °C, has been used for CaO, SiO2, and FeO. An oven with a number of openings, operating up to 800 °C, has been used for P2O5, Li, and S. Typical ion beam intensities of (7)Li(2+), (6)Li(3+), (40)Ca(12+), and (56)Fe(15+) are achieved 280, 75, 28, and 7 eμA, respectively. High intensity heavy ion beams are stably supplied into the azimuthally varying field cyclotron.


Phase I/II study of dose-intense doxorubicin/paclitaxel/cyclophosphamide with peripheral blood progenitor cells and cytokine support in patients with metastatic breast cancer.
Relapse following complete remission achieved with a single course of high-dose chemotherapy continues to be the main cause of treatment failure in patients with metastatic breast cancer. A phase I/II trial was initiated that combined the two most active drugs against breast cancer, doxorubicin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), with cyclophosphamide, and delivered four cycles of these drugs with peripheral blood progenitor cells (PBPCs) and granulocyte colony-stimulating factor support in an outpatient setting. Patients with untreated metastatic breast cancer received two cycles of doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2. During recovery from the second cycle, PBPCs were harvested. Responding patients were then admitted for a day to receive escalating-dose doxorubicin, paclitaxel, and cyclophosphamide followed by PBPC reinfusion on day 3 as outpatients. Seventeen patients have been enrolled to date. Ten patients completed treatment and received 34 cycles of high-dose chemotherapy every 21 days (range, 21 to 28 days). The median age was 47 years (range, 26 to 56 years) and the median number of metastatic sites was two (range, one to three). Five patients had received adjuvant chemotherapy (four cyclophosphamide/methotrexate/5-fluorouracil and one mitoxantrone-based). The most common toxic reactions were nausea and vomiting (75% of courses) and neurosensory (50% of courses). No patients had a decreased ejection fraction or overt congestive heart failure. Ten patients underwent cardiac biopsy (median doxorubicin, 253 mg/m2; range, 120 to 312 mg/m2); only one showed grade 1 cytotoxic changes with doxorubicin 240 mg/ m2. Six patients were admitted for neutropenic fever. Eight of 10 patients responded (two pathologically confirmed complete remissions in liver). At these doses, four cycles of doxorubicin, paclitaxel, and cyclophosphamide with PBPC and granulocyte colony-stimulating factor support every 21 days was well tolerated and showed evidence of activity. Enrollment at higher dose levels continues so that maximum tolerated dose can be defined.


Deletion of neural tube defect-associated gene Mthfd1l causes reduced cranial mesenchyme density.
Periconceptional intake of supplemental folic acid can reduce the incidence of neural tube defects by as much as 70%, but the mechanisms by which folic acid supports cellular processes during neural tube closure are unknown. The mitochondrial 10-formyl-tetrahydrofolate synthetase MTHFD1L catalyzes production of formate, thus generating one-carbon units for cytoplasmic processes. Deletion of Mthfd1l causes embryonic lethality, developmental delay, and neural tube defects in mice. To investigate the role of mitochondrial one-carbon metabolism during cranial neural tube closure, we have analyzed cellular morphology and function in neural tissues in Mthfd1l knockout embryos. The head mesenchyme showed significantly lower cellular density in Mthfd1l nullizygous embryos compared to wildtype embryos during the process of neural tube closure. Apoptosis and neural crest cell specification were not affected by deletion of Mthfd1l. Sections from the cranial region of Mthfd1l knockout embryos exhibited decreased cellular proliferation, but only after completion of neural tube closure. Supplementation of pregnant dams with formate improved mesenchymal density and corrected cell proliferation in the nullizygous embryos. Deletion of Mthfd1l causes decreased density in the cranial mesenchyme and this defect is improved with formate supplementation. This study reveals a mechanistic link between folate-dependent mitochondrially produced formate, head mesenchyme formation and neural tube defects.


Linkage of the murine steroid sulfatase locus, Sts, to sex reversed, Sxr: a genetic and molecular analysis.
We present genetic and molecular data demonstrating linkage of the gene for steroid sulfatase (Sts) to the mutation sex reversed (Sxr) definitively showing the existance of a functional allele for Sts mapping to the pseudoautosomal region of the mouse Y chromosome. Thus, in mouse, functional Sts genes are present in the pseudoautosomal region of both the X and Y chromosomes. This is in contrast to man where Sts has been mapped to the short arm of the X just centromeric to the pseudoautosomal region. Only a single recombinant separating Sts and Sxr was found out of 103 male meioses analyzed; double recombinants were not found between sex (Tdy), Sts and Sxr. If the rate of recombination in the pseudoautosomal region in male mice is equivalent to that in man and thus 7-10X higher than normal, then our data suggest that the distance between Sts and Sxr (or the telomere of the Y) is approximately 100-200 kb in length. Our data is in contrast to a recent report of a recombination frequency separating Sts and Sxr of as high as 6.2-9.8%.


Rescue of defective T cell development and function in Atm-/- mice by a functional TCR alpha beta transgene.
The Atm-/- mice recapitulate most of the defects observed in ataxia-telangiectasia (A-T) patients, including a high incidence of lymphoid tumors and immune defects characterized by defective T cell differentiation, thymus hypoplasia, and defective T-dependent immune responses. To understand the basis of the T cell developmental defects in Atm-/- mice, a functional TCR alpha beta transgene was introduced into these mutant mice. Analysis of the Atm-/-TCR alpha beta+ mice indicated that the transgenic TCR alpha beta can rescue the defective T cell differentiation and partially rescue the thymus hypoplasia in Atm-/- mice, indicating that thymocyte positive selection is normal in the Atm-/- mice. In addition, cell cycle analysis of the thymocytes derived from Atm-/-TCR alpha beta+ and control mice suggested that Atm is involved in the thymocyte expansion. Finally, evaluation of the T-dependent immune responses in Atm-/-TCR alpha beta+ mice indicated that Atm is dispensable for normal T cell function. Therefore, the defective T-dependent immune responses in Atm-/- mice must be secondary to greatly reduced T cell numbers in these mutant mice.


Behavioral and modeling studies of sound localization in cats: effects of stimulus level and duration.
Sound localization accuracy in elevation can be affected by sound spectrum alteration. Correspondingly, any stimulus manipulation that causes a change in the peripheral representation of the spectrum may degrade localization ability in elevation. The present study examined the influence of sound duration and level on localization performance in cats with the head unrestrained. Two cats were trained using operant conditioning to indicate the apparent location of a sound via gaze shift, which was measured with a search-coil technique. Overall, neither sound level nor duration had a notable effect on localization accuracy in azimuth, except at near-threshold levels. In contrast, localization accuracy in elevation improved as sound duration increased, and sound level also had a large effect on localization in elevation. For short-duration noise, the performance peaked at intermediate levels and deteriorated at low and high levels; for long-duration noise, this "negative level effect" at high levels was not observed. Simulations based on an auditory nerve model were used to explain the above observations and to test several hypotheses. Our results indicated that neither the flatness of sound spectrum (before the sound reaches the inner ear) nor the peripheral adaptation influences spectral coding at the periphery for localization in elevation, whereas neural computation that relies on "multiple looks" of the spectral analysis is critical in explaining the effect of sound duration, but not level. The release of negative level effect observed for long-duration sound could not be explained at the periphery and, therefore, is likely a result of processing at higher centers.


[The development of a C1q-solid-phase immunoenzyme method for determining circulating immune complexes].
The method of quantitative enzyme immunoassay (EIA) for the determination of circulating immune complexes (CIC) was developed on the basis of solid-phase human C1q. The calibration curve was plotted with the use of aggregated human gamma-globulin (AHGG), the optimum range of concentration being 15-500 microg/ml. In the process of approbation on clinical material the method revealed an elevated level of CIC in the sera of patients in comparison with their level in the sera of healthy donors. Out of 40 studied serum samples from patients with Yersinia infection, in 3 serum samples the levels of CIC was 26, 65 and 94 microg of AHGG equivalents per ml. In 4 out of 46 studied serum samples obtained from patients with diagnosed Yersinia arthritis the level of CIC was 12, 27, 46 and 186 microg of AHGG per ml, and in serum samples from healthy donors this level was 8.6 microg/ml [corrected].


Translocations between two specific human chromosomes detected by three-color "chromosome painting".
Translocations between two specific chromosomes are important markers for many human malignancies. Previously, the detection of translocations involving random breakpoints between two specific chromosomes could only be accomplished by banding techniques, which are severely labor intensive and require highly trained technicians. The three-color chromosome painting approach described in this paper was developed in our laboratory to detect translocations between two specific human chromosomes rapidly and accurately, while simultaneously revealing the nonhybridized chromosomes. Because this method efficiently detects translocations involving breakpoints anywhere on the targeted chromosomes, it is ideal as a screening tool for chromosome-specific translocations.


Extracellular K+ in the supraoptic nucleus of the rat during reflex bursting activity by oxytocin neurones.
1. We have investigated changes in extracellular potassium concentration [K+]o in the supraoptic nucleus of lactating rats and in particular those that occur during the intense burst of firing by the oxytocin neurones involved in the milk ejection reflex. 2. Double-barrelled K(+)-selective microelectrodes containing a highly selective sensor based on valinomycin were lowered through the exposed cortex towards the supraoptic nucleus (SON) of female rats anaesthetized with urethane. The mean resting [K+]o in the hypothalami of five rats was 2.4 mM, S.D. = 0.3 mM. 3. Where the reference barrel recorded extracellular action potentials from an oxytocin cell, the reflex burst of firing (4 s, typical maximum 50 Hz) was accompanied by a mean increase in [K+]o (delta[K+]o) of 0.22 mM (S.E.M. = 0.02 mM, fifty-seven bursts in eight cells in seven rats). The rise in [K+]o did not begin more than 0.1 s before the onset of the burst, and began to fall from its maximum during the burst. Slow field potentials, indicative of spatial buffering of K+, were undetectable (less than 50 microV). When the electrode was advanced in steps, the amplitudes of both delta[K+]o and the action potential declined steeply to about 10% over a distance of 20 microns: K+ from oxytocin cells appears to be prevented from dispersing freely through the extracellular space of the SON. 4. When the electrode recorded action potentials from a vasopressin cell, delta[K+]o during an oxytocin cell burst was very small: 0.021 mM (S.E.M. = 0.005 mM). At other sites in the SON, where antidromic stimulation evoked a field potential but no action potential, delta[K+]o was 0.047 +/- 0.005 mM. We conclude that the reason oxytocin bursts do not affect vasopressin cells is that [K+]o rises very little around vasopressin cells. A fortiori, since the increases in [K+]o were very small except where action potentials from oxytocin cells were recorded, they can make no significant contribution to synchronizing the onsets of bursts in oxytocin cells that are not contiguous. 5. A standard antidromic stimulation from the pituitary stalk, at 40 Hz for 4 s, which stimulated both oxytocin neurones and vasopressin neurones, caused a delta[K+]o of 0.17-1.8 mM, the variation being mainly from rat to rat. The larger delta[K+]o values were accompanied by slow negative potentials of up to 1.5 mV, there was a gradient in delta[K+]o decreasing towards the pia at the inferior limit of the SON, and there was a slow increase in [K+] in the subarachnoid space.(ABSTRACT TRUNCATED AT 400 WORDS)


DKT Memorial Fund v. Agency for International Development, 13 February 1987.
The plaintiffs, domestic and foreign nongovernmental organizations, challenged the lawfulness of the Agency for International Development's implementation of Government policy not to contribute funds to foreign nongovernmental organizations that perform or actively promote abortion as a method of family planning abroad. The Court reversed a lower court decision and held that the plaintiffs had standing to bring their suit. It ruled that the plaintiffs were not attempting to litigate a political question since they did not seek to litigate the political and social wisdom of the policy, but only its legality. It also allowed the plaintiffs to amend their complaint to state that, but for the policy, they would be qualified to receive funds. In a similar case, the United States District Court, S.D. New York, held that AID was acting within its statutory and administrative authority in withholding federal assistance to organizations that perform or actively promote abortions as a method of family planning and that the plaintiffs' constitutional challenge of this policy presented a nonjusticiable political question (Planned Parenthood Federation of America, Inc. vs. Agency for International Development, 29 September 1987, [670 F.Supp. 538]).


High efficiency single-mode-multimode-single-mode fiber laser with diffraction-limited beam output.
We designed and tested an all-fiber, high efficiency Yb-doped laser operating at 1088 nm with a single-mode-multimode-single-mode (SMS) structure. A larger-mode-area gain fiber of 1.5 m length, with 20/130 μm core/cladding diameters was used to increase the absorption, and a diffraction-limited Gaussian output beam was obtained from the single-mode output fiber. Using a 976 nm laser diode as the pump source, the laser generated an output power up to 38.5 W with a slope efficiency of 70%. The output beam qualities, with and without SMS structure, were compared and showed that the fiber laser with the SMS structure can achieve high gain, short fiber length, and excellent beam quality.


Effectiveness of skill-based substance abuse intervention among male adolescents in an Islamic country: case of the Islamic Republic of Iran.
The prevalence of substance abuse among adolescents from low- and middle-income countries is increasing drastically and requires immediate intervention. The objective of this longitudinal quasi-experimental panel study was to design and implement a skill-based intervention to prevent and reduce substance use among urban adolescents who attended 2 randomly selected high-schools in Tehran, Iran. One-year post intervention data show that substance abuse, knowledge, attitudes, peer resistance skills, level of self-control, self-efficacy, and perceived susceptibility among intervention group were significantly improved, whereas level of self control and attitudes against substance abuse among the control group deteriorated. To efficiently prevent substance abuse among youth primary preventive interventions should be implemented before onset of substance abuse to improve resistance skills and provide adolescents with information and skills needed to develop anti-drug norms.


Sinistral portal hypertension associated with pancreatic pseudocysts - ultrasonography findings: A case report.
Sinistral portal hypertension associated with pancreatic pseudocysts is rare, often caused by extrinsic compression of splenic vein, the follow-up examinations by ultrasonography for early diagnosis are quietly necessary since haematemesis, a life-threatening condition. Few studies have reported the ultrasonography findings of sinistral portal hypertension. A 52-year-old man presented with acute abdominal pain after drinking, steatorrhea, weight loss and accidentally melena in the past 2 mo. He underwent ultrasound-guided fine needle aspiration in other hospital and diagnosed with pancreatic pseudocysts. Ultrasonography imaging, in our department, appeared as cystic heterogeneous hypoechoic area with the size of 4.7 cm × 3.8 cm that located posterior to the body and tail of pancreas, adjacent to splenic vein associated with thrombosis resulted from compression. Spleen incrassated to approximately 7.3 cm, but no dilation of main portal vein was presented. Color Doppler Flow Imaging demonstrated the formation of splenic venous collateral, nevertheless no significantly flow signals was observed in splenic vein. Pulsed Doppler revealed that the peak velocity of splenic venous collateral was 18.4 cm/s with continuous waveform. Laparotomy confirmed sinistral portal hypertension associated with pancreatic pseudocysts, subsequently distal pancreatectomy combined with splenectomy and partial gastrectomy was performed. It's important clinically to know the ultrasound appearance of sinistral portal hypertension associated with pancreatic pseudocysts for sonographer and physician.


Influence of PNA containing 8-aza-7-deazaadenine on structure stability and binding affinity of PNA·DNA duplex: insights from thermodynamics, counter ion, hydration and molecular dynamics analysis.
This paper describes the synthesis of a novel 8-aza-7-deazapurin-2,6-diamine (DPP)-containing peptide nucleic acid (PNA) monomer and Boc protecting group-based oligomerization of PNA, replacing adenine (A) with DPP monomers in the PNA strand. The PNA oligomers were synthesized against the biologically relevant SV40 promoter region (2494-AATTTTTTTTATTTA-2508) of pEGFP-N3 plasmid. The DPP-PNA·DNA duplex showed enhanced stability as compared to normal duplex (A-PNA·DNA). The electronic distribution of DPP monomer suggested that DPP had better electron donor properties over 2,6-diamino purine. UV melting and thermodynamic analysis revealed that the PNA oligomer containing a diaminopyrazolo(3,4-d)pyrimidine moiety (DPP) stabilized the PNA·DNA hybrids compared to A-PNA·DNA. DPP-PNA·DNA duplex showed higher water activity (Δnw = 38.5) in comparison to A-PNA·DNA duplex (Δnw = 14.5). The 50 ns molecular dynamics simulations of PNA·DNA duplex containing DPP or unmodified nucleobase-A showed average H-bond distances in the DPP-dT base pair of 2.90 Å (OH-N bond) and 2.91 Å (NH-N bond), which were comparably shorter than in the A-dT base pair, in which the average distances were 3.18 Å (OH-N bond) and 2.97 Å (NH-N bond), and there was one additional H-bond in the DPP-dT base pair of around 2.98 Å (O2H-N2 bond), supporting the higher stability of DPP-PNA·DNA. The analysis of molecular dynamics simulation data showed that the system binding free energy increased at a rate of approximately -4.5 kcal mol(-1) per DPP base of the PNA·DNA duplex. In summary, increased thermal stability, stronger hydrogen bonding and more stable conformation in the DPP-PNA·DNA duplex make it a better candidate as antisense/antigene therapeutic agents.


Cardiac rehabilitation services: what are they and are they worth it?
The objectives of cardiac rehabilitation include lowering mortality but, more importantly, increasing functional capacity so reducing disability and potentially improving quality of life. The data suggest that cardiac rehabilitation services are worth the patient's costs and efforts and as such, they should be considered an integral component of comprehensive cardiovascular care by cardiologists and primary care physicians. While there is considerable agreement on the roles of exercise testing and training in the three position stands, there are also substantiated, and important, differences in their recommendations on other cardiac rehabilitation services, such as counseling and risk factor management. The challenge for the 1990's is not only to continue to better define the effectiveness of cardiac rehabilitation services, but more urgently, how to deliver effective services most efficiently. This will help physicians provide optimum care for their patients, will improve the patient's likelihood of regaining for themselves an active and productive life, and should generate a more equitable and accountable reimbursement system for quality health care.


Non-invasive prenatal diagnosis for single gene disorders: experience of patients.
The aim of this study is to explore women's experiences of using newly developed non-invasive prenatal diagnosis (NIPD) for single gene disorders. Methods used in this study include qualitative one-to-one interviews with eight women with pregnancies at risk of achondroplasia, Apert syndrome, thanatophoric dysplasia or a neuromuscular condition. The results of the study show that the women were positive about an accurate, safe, and early test. Where the foetus was at increased risk of inheriting a genetic condition, the benefits of NIPD over invasive testing were that it reduced the period of uncertainty and worry by being conducted within the first trimester. For those women for whom there was a low recurrence risk, the period of uncertainty could be reduced and pregnancy 'normalized' earlier. For women who would not have risked invasive testing, NIPD enabled them to have an early diagnostic test that was more accurate than ultrasound. Where ultrasound abnormalities were detected, NIPD ended the 'diagnostic odyssey', enabling women to make practical and psychological preparations for the birth. NIPD conducted through specialist services was considered most appropriate. NIPD for these particular single gene disorders was appreciated by women and appears to be satisfactory. Further exploration of stakeholder views may be required to inform more widespread implementation of NIPD for a broader range of genetic conditions.


Fertility, pregnancies and offspring complications after bone marrow transplantation.
Hormonal assessment including luteotropic hormone (LH), follicle stimulating hormone (FSH), testosterone (T), oestradiol and sex hormone binding globulin was performed 1-6 years after allogeneic, syngeneic and autologous bone marrow transplantation in nine patients with severe aplastic anaemia (SAA) and 14 patients with haematological malignancy (HM). Among nine allografted SAA patients, seven aged less than 26 years showed normal gonadal function while two women above 26 years had premature ovarian failure. All eight female patients transplanted for HM had premature ovarian failure. Among six male patients transplanted for HM, four have elevated FSH but normal LH and T levels, while two have normal LH, FSH and T levels or elevated LH and FSH levels but decreased T levels, respectively. Three patients transplanted for SAA (two female, one male), but none of those transplanted for HM, parented four healthy children. A high incidence of offspring complications was noticed, including (i) persistence of fetal circulation syndrome, (ii) erythroblastosis fetalis, and (iii) prolonged newborn icterus. One female patient transplanted for SAA had an abortion in the 25th week of gestation. These observations confirm previous reports on recovery of fertility, mainly in younger patients transplanted for SAA; there was, however, an unexpectedly high incidence of pre-, peri- and postpartum complications in the offspring of bone marrow graft recipients.


Wnt7a regulates multiple steps of neurogenesis.
Although Wnt7a has been implicated in axon guidance and synapse formation, investigations of its role in the early steps of neurogenesis have just begun. We show here that Wnt7a is essential for neural stem cell self-renewal and neural progenitor cell cycle progression in adult mouse brains. Loss of Wnt7a expression dramatically reduced the neural stem cell population and increased the rate of cell cycle exit in neural progenitors in the hippocampal dentate gyrus of adult mice. Furthermore, Wnt7a is important for neuronal differentiation and maturation. Loss of Wnt7a expression led to a substantial decrease in the number of newborn neurons in the hippocampal dentate gyrus. Wnt7a(-/-) dentate granule neurons exhibited dramatically impaired dendritic development. Moreover, Wnt7a activated β-catenin and its downstream target genes to regulate neural stem cell proliferation and differentiation. Wnt7a stimulated neural stem cell proliferation by activating the β-catenin-cyclin D1 pathway and promoted neuronal differentiation and maturation by inducing the β-catenin-neurogenin 2 pathway. Thus, Wnt7a exercised critical control over multiple steps of neurogenesis by regulating genes involved in both cell cycle control and neuronal differentiation.


Optimizing the Protein Fluorescence Reporting System for Somatic Embryogenesis Regeneration Screening and Visual Labeling of Functional Genes in Cotton.
Protein fluorescence reporting systems are of crucial importance to in-depth life science research, providing systematic labeling tools for visualization of microscopic biological activities in vivo and revolutionizing basic research. Cotton somatic cell regeneration efficiency is low, causing difficulty in cotton transformation. It is conducive to screening transgenic somatic embryo using the fluorescence reporting system. However, available fluorescence labeling systems in cotton are currently limited. To optimize the fluorescence reporting system of cotton with an expanded range of available fluorescent proteins, we selected 11 fluorescent proteins covering red, green, yellow, and cyan fluorescence colors and expressed them in cotton. Besides mRuby2 and G3GFP, the other nine fluorescent proteins (mCherry, tdTomato, sfGFP, Clover, EYFP, YPet, mVenus, mCerulean, and ECFP) were stably and intensely expressed in transgenic callus and embryo, and inherited in different cotton organs derive from the screened embryo. In addition, transgenic cotton expressing tdTomato appears pink under white light, not only for callus and embryo tissues but also various organs of mature plants, providing a visual marker in the cotton genetic transformation process, accelerating the evaluation of transgenic events. Further, we constructed transgenic cotton expressing mCherry-labeled organelle markers in vivo that cover seven specific subcellular compartments: plasma membrane, endoplasmic reticulum, tonoplast, mitochondrion, plastid, Golgi apparatus, and peroxisome. We also provide a simple and highly efficient strategy to quickly determine the subcellular localization of uncharacterized proteins in cotton cells using organelle markers. Lastly, we built the first cotton stomatal fluorescence reporting system using stomata-specific expression promoters (ProKST1, ProGbSLSP, and ProGC1) to drive Clover expression. The optimized fluorescence labeling system for transgenic somatic embryo screening and functional gene labeling in this study offers the potential to accelerating somatic cell regeneration efficiency and the in vivo monitoring of diverse cellular processes in cotton.


The role of the growth and lactogenic hormone family in immune function.
The influence of various members of the growth and lactogenic hormone family on the immune system is reviewed. A general hypothesis is proposed for growth control in higher animals. It is suggested that immune reactions, which are based on lymphocyte proliferation, obey the general rules of growth control in vertebrate animals. Growth and lactogenic hormones (GLH) are required for the development and function of the immune system and are suggested to deliver the first signal that prepares the cell for proliferation, differentiation and function. This signal has already been designated by other as the competence signal which initiates the cell cycle. Second signals are delivered through the antigen receptor, and/or by some other cell surface receptors (adhesion molecules) and always involve cell-to-cell ('bridging') and/or cell-to-matrix interaction. This category of signals is designated as stromal or adherence signals. The lymphocyte adhesion molecules that mediate second signals have evolved form organ- and tissue-specific recognition/regulatory molecules. The antigen receptors have been perfected during evolution from self recognition to specific-antigen recognition. Apart from this exquisitely specific mechanism of immune recognition, there is evidence for other less specific means of recognition by adherence molecules that mediate the activation of the immune system during nonspecific injury and also play a role in the elimination of degenerated and neoplastic cells. Signals delivered through adhesion molecules have the power to commit the cell to a given activity which is executed by the delivery of third signals in the form of soluble cytokines, usually, but not always, by the same cell delivering the second signal(s). The combination of these three groups of signals will ultimately determine whether or not the cell will proliferate, differentiate, maintain function or, perhaps, be committed to apoptosis. Therefore, GLH maintain immunocompetence which enables the immune system to respond to specific antigenic and tissue-derived stimuli in a self-regulated fashion. The adrenocorticotropic hormone-adrenal axis antagonizes the immunostimulatory effect of GLH. This basic pattern of lymphocyte regulation is influenced further by additional hormones, neurotransmitters and neuropeptides, mostly by the modulation of signal delivery. The constant interaction of neuroendocrine and internal immunoregulatory mechanisms assures the fine tuning of the immune system, so that it is able to function in homeostasis and harmony with the organism.


Long-Proboscid Flies as Pollinators of Cretaceous Gymnosperms.
The great evolutionary success of angiosperms has traditionally been explained, in part, by the partnership of these plants with insect pollinators. The main approach to understanding the origins of this pervasive relationship has been study of the pollinators of living cycads, gnetaleans, and basal angiosperms. Among the most morphologically specialized living pollinators are diverse, long-proboscid flies. Early such flies include the brachyceran family Zhangsolvidae, previously known only as compression fossils from the Early Cretaceous of China and Brazil. It belongs to the infraorder Stratiomyomorpha, a group that includes the flower-visiting families Xylomyidae and Stratiomyidae. New zhangsolvid specimens in amber from Spain (ca. 105 mega-annum [Ma]) and Myanmar (100 Ma) reveal a detailed proboscis structure adapted to nectivory. Pollen clumped on a specimen from Spain is Exesipollenites, attributed to a Mesozoic gymnosperm, most likely the Bennettitales. Late Mesozoic scorpionflies with a long proboscis have been proposed as specialized pollinators of various extinct gymnosperms, but pollen has never been observed on or in their bodies. The new discovery is a very rare co-occurrence of pollen with its insect vector and provides substantiating evidence that other long-proboscid Mesozoic insects were gymnosperm pollinators. Evidence is thus now gathering that visitors and probable pollinators of early anthophytes, or seed plants, involved some insects with highly specialized morphological adaptations, which has consequences for interpreting the reproductive modes of Mesozoic gymnosperms and the significance of insect pollination in angiosperm success.


Broadly wavelength tunable acousto-optically Q-switched Tm:Lu2SiO5 laser.
A broadly wavelength tunable acousto-optically Q-switched Tm:Lu2SiO5 (Tm:LSO) laser is presented for the first time, to our best knowledge. The emission wavelength was tuned in a broad spectral region over 111 nm ranging from 1959 to 2070 nm. A shortest pulse duration of 345 ns with beam quality of M(2)≤1.65 was obtained at pulse repetition frequency (PRF) of 1 kHz, corresponding to a maximum single pulse energy of 0.26 mJ and peak power of 0.75 kW. The experimental results indicated that Tm:LSO crystal has outstanding potential for obtaining broadly wavelength tunable and low-PRF laser pulses at 2 μm.


Hallmarks in the history of orthopaedic implants for trauma and joint replacement.
This manuscript represents an attempt to review orthopaedic implants and reconstructive orthopaedic surgery for lower limbs lesions or trauma mainly in the 20th century. We emphasized on the type of implants, the biomaterials and their evolution, and we also engaged in a special reference for the pioneers of orthopaedic implant surgery and the innovative designers of those implants, in such a way to understand the ways and the stages through which they evolved to their present forms, as well as the scientific principles that affected their design and progress. A correlation between the evolution of implants and several relevant disciplines (biomaterial chemists and engineers, biomechanics) that developed simultaneously with orthopaedic reconstructive joint surgery is present since the first attempts to reconstruct a damaged joint. In the future, further progress is anticipated in the use of biomaterials, more compatible towards human biology, with minimally invasive applications and a perpetually increased life span. This progress depicts a phenomenon directly related to a multilevel, multifactorial and interdisciplinary scientific and technological field with many expectations.


Drug interaction after ritonavir discontinuation: considerations for antiretroviral therapy changes in renal transplant recipients.
Organ transplantation among people living with human immunodeficiency virus (PLHIV) is increasing. Guidelines recommend any changes in antiretroviral therapy (ART) prior to transplantation, but there are limited data regarding ART changes post transplantation. We report a case where an ART switch from a protease inhibitor-based regimen to dolutegravir plus emtricitabine/tenofovir alafenamide in a renal transplant recipient led to subtherapeutic tacrolimus concentrations and an increased serum creatinine (SCr). A workup for graft rejection was performed (including kidney biopsy and cytomegalovirus and BK virus polymerase chain reaction) following the rise in SCr, which was higher than expected from dolutegravir initiation (via organ cation transporter 2 inhibition). This case highlights the potential challenges of switching ART regimens in PLHIV post transplantation.


Investigation of the aging clock's intermittent-light responses uncovers selective deficits to green millisecond flashes.
The central pacemaker of flies, rodents, and humans generates less robust circadian output signals across normative aging. It is not well understood how changes in light sensitivity might contribute to this phenomenon. In the present study, we summarize results from an extended data series (n = 5681) showing that the locomotor activity rhythm of aged Drosophila can phase-shift normally to intermittently spaced episodes of bright polychromatic light exposure (600 lx) but that deficits emerge in response to 8, 16, and 120-millisecond flashes of narrowband blue (λm, 452 nm) and green (λm, 525 nm) LED light. For blue, phase-resetting of the activity rhythm of older flies is not as energy efficient as it is in younger flies at the fastest flash-exposures tested (8 milliseconds), suggesting there might be different floors of light duration necessary to incur photohabituation in each age group. For green, the responses of older flies are universally crippled relative to those of younger flies across the slate of protocols we tested. The difference in green flash photosensitivity is one of the most salient age-related phenotypes that has been documented in the circadian phase-shifting literature thus far. These data provide further impetus for investigations on pacemaker aging and how it might relate to changes in the circadian system's responses to particular sequences of light exposure tuned for wavelength, intensity, duration, and tempo.


Calcium signal communication between glial and vascular brain cells.
The brain is composed of neurons that communicate electrical signals over neurites and chemical signals across synapses, and non-neuronal cells like glial and vascular cells that communicate calcium signals among each other Calcium ions have an important signaling function in the cytoplasm that depends on their amplitude, time course of change and subcellular localisation. Work over the last decade has added an additional dimension to this rich repertoire by including the possibility that calcium signals can be communicated between cells. In astrocytes and endothelial cells, connexins appear to be at the crossroad of calcium signal communication pathways, because they are the building blocks of gap junction channels that functionally connect cells, and because they can arrange as hemichannels that act as a conduit for cellular ATP release, thus initiating paracrine purinergic signaling. The two pathways appear to be operational in astrocytes and endothelial cells and we review in this paper possible functions of astrocyte-to-blood vessel calcium signaling at the level of arterioles where blood flow is controlled, at the level of capillaries where the blood-brain barrier is located and at the level of blood immune cells.


Tuberculosis--immunopathogenesis and therapy.
Infection with Mycobacterium tuberculosis (TB) has returned to the forefront of public and medical concern because of the recent sharp increase in the number of cases. Major strides have been made in understanding the pathogenesis of TB, and some of these basic advances are being applied clinically. This review focuses on current concepts of the host response to TB, the changing epidemiology of TB, and optimal treatment strategies.


Rapid method for isolation and staining of bacterial lipopolysaccharide.
Classically bacterial lipopolysaccharide (LPS) purification and silver staining take several days. We designed a simple and fast method for LPS isolation which when combined with silver staining using Pharmacia PhastSystem both can be completed in few hours. The purity of LPS isolated by this simple method may not be comparable to that by the phenol-water method hence we recommend this rapid isolation and staining procedures for simple and fast study of LPS patterns in gels.


The New Generation from Biomembrane with Green Technologies for Wastewater Treatment.
A biopolymer of polylactic acid (PLLA)/polypropylene carbonate (PPC)/poly (3-hydroxybutrate) (PHB)/triethyl citrate (TEC) blends was prepared by the solution-casting method at different proportions. The thermal characteristics were studied by differential scanning calorimetry (DSC) and thermogravimetry (TG). PHB and TEC were added to improve the interfacial adhesion, crystallization behavior, and mechanical properties of the immiscible blend from PLLA and PPC (20%). The addition of more than 20% of PPC as an amorphous part hindered the crystallization of PLLA. PPC, PHB, and TEC also interacted with the PLLA matrix, which reduced the glass transition temperature (Tg), the cold crystallization temperature (Tcc), and the melting point (Tm) to about 53, 57 and 15 °C, respectively. The Tg shifted from 60 to 7 °C; therefore, the elongation at break improved from 6% (pure PLLA) to 285% (PLLA blends). In this article, biomembranes of PLLA with additives were developed and made by an electrospinning process. The new generation from biopolymer membranes can be used to absorb suspended pollutants in the water, which helps in the purification of drinking water in the household.


[Patient Reported Outcome(PRO)in Oncology].
In recent years, the importance of patient-reported outcomes(PRO)in addition to clinician-outcome assessment has been particularly recognized in clinical trials and routine clinical care of practice. PRO is defined as "any report of the status of a patient's health condition that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else". For example, in oncology field, NCI-CTCAE has conventionally been used for adverse event assessment. However, it has been pointed out that the adverse event reported by medical staffs tends to underestimate as compared by patients themselves. Hence, PRO version of the Common Terminology Criteria for Adverse Events(PRO-CTCAE), is expected to play an important role. In this article, the background of importance of PRO in oncology, the role of PRO in clinical outcome assessments, the difference between PRO and QOL, significance that PRO evaluation brings to patients and clinical practice, PRO-CTCAE and recent methodology of PRO research will be overviewed.


The chronically critically ill: to save or let die?
Critically ill patients admitted to an intensive care unit (ICU) are rapidly evaluated, and aggressive management is immediately instituted. They are intubated and placed on mechanical ventilation, and invasive monitoring is begun. Many patients are successfully treated and discharged from the ICU, but unfortunately a large percentage of the critically ill do not improve and become chronically critically ill. A high percentage of these patients do not survive in spite of extraordinary life support for weeks to months. The ICU health care team and the patient's family use their collective judgment to determine which patients are salvageable and which patients have no realistic chance to regain a good quality of life and therefore should have extraordinary life support withdrawn. This article examines why chronically critically ill patients die. We present a management strategy for improving the prognosis of the chronically critically ill patient by concentrating on exercise, nutrition, fluid management, emotional support, and adequate sleep. We address issues dealing with withholding and withdrawing extraordinary life support. We conclude by demonstrating how these concepts were applied in the case of a chronically critically ill young man with the acquired immunodeficiency syndrome (AIDS).


Differential induction of hepatic drug-metabolizing enzymes by fenvaleric acid in male rats.
Racemic fenvaleric acid [2-(4-chlorophenyl)-3-methyl-butanoic acid], the principal metabolite of fenvalerate, was administrated orally at 0.75, 1.5, and 3.0 mmol/kg body weight/day to Fisher-344 male rats for 7 days. Both pure enantiomers of fenvaleric acid were administered at 1.5 mmol/kg body weight/day; the clofibric acid at the same concentration was used as a positive control. Hepatic enzyme activities were measured. Results obtained clearly show that fenvaleric acid induced numerous hepatic drug metabolism enzymes in F344 rats. The (R) enantiomer of this compound induces a proliferation of peroxisomes, whereas the (S) enantiomer induces CYP2B and mEH activities. Therefore, high exposure to pyrethroid insecticides could interact with the normal metabolism of drugs or xenobiotics.


Expression of E-cadherin catenin and C-erbB-2 gene products in invasive ductal-type breast carcinomas.
Special attention has focused on E-cadherin and the invasiveness of breast carcinoma because E-cadherin was suggested to be the major cell adhesion molecule in the mammary gland. In the cytoplasm, E-cadherin is linked to beta-catenin and alpha-catenin which mediate the connection of the cytoskeleton. In addition, c-erbB-2 oncoprotein causes disruption of this cell adhesion system through beta-catenin phosphorylation. We investigated the expression of E-cadherin, alpha-catenin and c-erbB-2 gene products in 66 invasive ductal carcinomas by immuno-histochemistry to examine the relation between the E-cadherin mediated cell adhesion system and histological subtypes used in Japan as well as histological grading. The series included 21 papillotubular carcinomas, 16 solid-tubular carcinomas and 29 scirrhous carcinoma. There were 33 cases of grade I, 20 cases of grade II and 13 cases of grade III. We defined P&P&N as E-cadherin positive and alpha-catenin positive and c-erbB-2 negative cases to evaluate the preservation of the E-cadherin mediated cell adhesion system. There were only 13 cases (19.7%) of P&P&N in total. As for the frequency of E-cadherin/alpha-catenin/c-erbB-2 expression and P&P&N, no significant difference between histological subtypes was found. However, those in the grade I group tended to be higher than in the other two grade groups. Regarding the rates of alpha-catenin positive cases and P&P&N cases, there were significant differences between the grade I group and a combination group consisting of the grade II and grade III groups. These results suggest that the E-cadherin-mediated cell adhesion system is frequently lost in invasive ductal-type breast cancers by random loss of E-cadherin/catenins or c-erbB-2 overexpression, and that the preservation of this system correlates with well differentiated morphological features.


Brefeldin A activates CHOP promoter at the AARE, ERSE and AP-1 elements.
Brefeldin A induces apoptosis in PC-3 and MCF-7 cells at a concentration of 30 ng/ml. RT-PCR analyses showed up-regulation of CHOP/GADD153 and splicing of XBP-1 mRNA in brefeldin A-treated cells. CHOP promoter-luciferase reporter assays demonstrated activation of AARE, ERSE, and AP-1 elements of CHOP promoter by brefeldin A treatment. The activation of these elements was not affected by preincubation of cells with N-acetyl-cysteine (NAC), L: -buthionine-(S,R)-sulfoximine (BSO), and c-Jun N-terminal kinase (JNK) inhibitor (SP600125), suggesting that activation of CHOP promoter by brefeldin A may not involve oxidative stress or JNK signaling pathway. On the other hand, brefeldin A-induced apoptosis was not affected by NAC and BSO pretreatment, but was completely suppressed by JNK inhibitor pretreatment. Our results suggest that although CHOP is up-regulated by brefeldin A, it is not a major mediator of brefeldin A-induced apoptosis.


Non-saphenofemoral venous reflux in the groin in patients with varicose veins.
To investigate the incidence, clinical significance, anatomical variation and physiology of non-saphenofemoral venous reflux (non-SF reflux) in the groin. Prospective study. A total of 1072 vascular diagnostic workups in 680 patients with possible venous diseases to the legs were included. Duplex scanning and air plethysmography. A total of 1022 legs had venous diseases. Of these, 101 (9.9%) had non-SF reflux in the groin. Such reflux occurred in recurrent varicose veins (RVV) in 16.3%, in primary varicose veins (PVV) in 6.1% and in deep venous thrombosis (DVT) in 8.0%. Two patterns of reflux were distinguished: epigastric reflux from lower abdominal wall veins (71 legs) and pudendal reflux from perineal and/or gluteal veins (30 legs). Pudendal reflux was almost exclusive to women and did not occur with DVT. If there was only non-SF reflux at the groin the venous filling indices (VFI) were close to normal (1.7+/-1.0 ml/s for RVV, 1.9+/-1.2 for PVV, 1.7+/-1.0 for DVT) and no active ulcers were observed. However, if non-SF reflux was associated with saphenofemoral or other reflux the VFIs (3.3+/-2.3 ml/s for RVV, 3.8+/-1.5 ml/s for PVV) were abnormal (p <0.05) and ulcers occurred in 11/32. Non-SF reflux in the groin is common. Such reflux may be missed at initial surgery and lead to recurrence of varicose veins. However, the venous physiological disturbance of such reflux is mild and it is not associated with ulcers unless combined with reflux at other sites in the leg.


Female genital schistosomiasis of the lower genital tract: prevalence and disease-associated morbidity in northern Tanzania.
Female genital schistosomiasis (FGS) is a neglected disease manifestation of schistosomiasis. A cross-sectional study was carried out to assess in a schistosomiasis-endemic area the proportion of women affected by FGS of the lower reproductive tract and to compare the frequency of symptoms and signs possibly associated with FGS between women with proven FGS (n=134), endemic referents (n=225, women living in an endemic site), and referents (n=75, women living in a nonendemic site). Urinary schistosomiasis was diagnosed in 36% (239/657) and FGS in 37% (134/359) of the women. Cervical lesions occurred in 75% of the FGS cases, in 48% of endemic referents, and in 36% of nonendemic referents. The high prevalence of FGS in all age groups and the high levels of pathologic cervical alterations such as swollen and disrupted epithelium support the hypothesis that FGS might be a risk factor for the transmission of human immunodeficiency virus.


Arthroscopic Latarjet With Cortical Buttons Versus Open Latarjet With Screws: A Short-Term Comparative Study.
The arthroscopic bone block procedure according to Latarjet remains a controversial subject, and few comparative studies have demonstrated the benefit of arthroscopy over open surgery. The objective of this study was to compare both procedures by analyzing the short-term clinical results. The hypothesis was that the arthroscopic procedure is superior to the standard open procedure. Cohort study; Level of evidence, 3. This was a retrospective comparative study. Patients treated for chronic anterior instability by arthroscopic Latarjet with double cortical buttons (group A) or open Latarjet with screws (group O) with a minimum follow-up of 12 months were included. Intraoperative (duration, complications) and postoperative (complications, pain, mobility, functional scores, resumption of sport, Patient and Observer Scar Assessment Scale scar aesthetics, satisfaction) data were compared. In total, 50 patients were included (n = 24 in group A, n = 26 in group O). Operating time was longer in group A (103 vs 61 min; P = .001). The average number of days on analgesics was higher in group A (8.9 vs 5.3 days; P = .04). The complication rate was similar for the 2 groups (12.5% vs 27%; P = .46). At 3 months, the loss of external rotation was greater in group A (-33° vs -18°; P = .01), and resumption of sports was less frequent (11% vs 48%; P = .01). At 12 months, the average scores were excellent, with no significants differences between the 2 groups: Walch-Duplay average, 90 points; Rowe, 94 points; Subjective Shoulder Value (SSV), 92.5%; sport SSV, 85%; and Patient and Observer Scar Assessment Scale score, 17.2 points. Over the short term, this comparative study did not prove the superiority of the cortical-button arthroscopic Latarjet procedure over the open Latarjet procedure. A delay in the resumption of sports, longer time to recover range of motion, and no benefit regarding postoperative pain or the aesthetic aspect of the scar were observed in this study with the arthroscopic procedure.


Extended prophylaxis against venous thromboembolism following total hip and knee replacement.
The recently reported reductions in the incidence of post-operative venous thromboembolism (VTE) are related to the widespread use of prophylactic anticoagulants. Many uncertainties remain with regard to the most effective ways to use thromboprophylaxis, however. The trend towards shorter hospital stays means that patients may receive less than the recommended 7-10 days of prophylaxis. Prolonged periods of thromboprophylaxis may be beneficial for patients at high risk of post-operative VTE, such as those undergoing major orthopaedic surgery. The relative rarity of symptomatic deep vein thrombosis and pulmonary embolism means that very large patient populations are required for studies that rely on clinical endpoints, but studies using venographic endpoints have shown 28-35 days of prophylaxis with low-molecular-weight heparin to be more effective than 10-14 days. Other factors that may influence the efficacy of thromboprophylaxis include the timing of the first injection and the choice of agent.


The rH index for quality and environmental controls: standards and application procedures.
The quantity rH, an index of the reducing power of a redox system is, in conceptual and operational terms, coordinatively linked with the two familiar electroanalytical quantities: redox potential (EO/R) and pH, and has recently become important in quality and environmental controls (hydrographic network, human consumption waters, industrial effluents, etc.). It has some significant problems of standardization and methodological applications, especially on passing from pure water medium to aqueous-organic media, and the results of the most recent researches are here presented.


Adherence to antihypertensive therapy and its determinants among patients attending primary care hospitals of Kashmir, India.
Adherence to antihypertensive therapy is an important factor in determining the clinical course of hypertension. This study was planned to estimate adherence to antihypertensive therapy and its determinants among OPD patients attending two primary care hospitals in Kashmir valley. This study employed a cross-sectional study design. All subjects who reported to OPD between October and December 2020 and had been prescribed antihypertensive medications for at least 1 year were included. Sociodemographic information was collected on a pretested schedule and adherence to medications was assessed by using the-14 item Hill-Bone HBP Compliance to High Blood Pressure Therapy Scale (HB-HBP). Mann-Whitney test and Spearman's rank correlation coefficient were used. A total of 406 subjects were included in the final analysis with a mean age of 58 years for women and 56 years for men. The sample comprised 54% women. More than 60% of subjects were currently married, urban area residents, and belonged to middle strata of social class. The mean score obtained in the HB-MAS (maximum score 56) was 19.26 (SD ± 4.3). Subjects aged 60 years and above, those belonging to lower socioeconomic class, and subjects prescribed three or more drugs with more than once-daily dosing regimen had higher odds of having poor adherence. There is suboptimal adherence among OPD patients at primary care level. There is a need for enhanced counselling regarding medication adherence particularly for elderly, poor, illiterate persons and those prescribed multiple medicines with more than once-daily dosing.


Vagally mediated heart rate variability and heart rate entropy as predictors of treatment outcome in flight phobia.
In the present study a computer-assisted exposure-based treatment was applied to 54 flight phobics and the predictive role of vagally mediated heart rate (HR) variability (high frequency, 0.15-0.4 Hz band power) and heart rate entropy (HR time series sample entropy) on treatment outcome was investigated. Both physiological measures were taken under controlled breathing at 0.2 Hz and during exposure to a fearful sequence of audiovisual stimuli. Hierarchical regression analyses were conducted to assess the predictive power of these variables in these conditions on treatment self-report measures at the end of treatment and at 6 months follow-up, as well as on the behavioral treatment outcome (i.e. flying at the end of treatment). Regression models predicting significant amounts of outcome variance could be built only when HR entropy was added to the HR variability measure in a second step of the regression analyses. HR variability alone was not found to be a good predictor of neither self-reported nor behavioral treatment outcomes.


Synthesis and Biological Evaluation of 1-(2-(6-Methoxynaphthalen-2-yl)-6-methylnicotinoyl)-4-Substituted Semicarbazides/Thiosemicarbazides as Anti-Tumor Nur77 Modulators.
Nur77 is an orphan nuclear receptor that participates in the occurrence and development of a variety of tumors. Many agonists of Nur77 have been reported to have significant anticancer effects. Our previous studies have found that the introduction of bicyclic aromatic rings, such as naphthalyl and quinoline groups, into the N'-methylene position of indoles' Nur77 modulators can effectively improve the anti-tumor activity of the target compounds. Following our previous studies, a series of novel 1-(2-(6-methoxynaphthalen-2-yl)-6-methylnicotinoyl)-4-substituted semicarbazide/thiosemicarbazide derivatives 9a-9w were designed and synthesized in four steps from 6-methoxy-2-acetonaphthone and N-dimethylformamide dimethylacetal. All compounds were characterized by 1H-NMR, 13C-NMR and HRMS, and their anti-tumor activity on various cancer cell lines such as A549, HepG2, HGC-27, MCF-7 and HeLa are also evaluated. From the series of compounds, 9h exhibited the most potent anti-proliferative activity against several cancer cells. Colony formation and cell cycle experiments showed that compound 9h inhibited cell growth and arrested the cell cycle. Additionally, 9h leads to the cleavage of PARP. We initially explored the mechanism of 9h-induced apoptosis and found that compound 9h can upregulate Nur77 expression and triggered Nur77 nuclear export, indicating the occurrence of Nur77-mediated apoptosis. These results suggested that 9h may be a promising anti-tumor leading compound for the further research.


Green Tides in the Yellow Sea Promoted the Proliferation of Pelagophyte Aureococcus anophagefferens.
Harmful algal blooms formed by fast-growing, ephemeral macroalgae have expanded worldwide, yet there is limited knowledge of their potential ecological consequences. Here, we select intense green tides formed by Ulva prolifera in the Yellow Sea, China, to examine the ecological consequences of these blooms. Using 28-isofucosterol in the surface sediment as a biomarker of green algae, we identified the settlement region of massive floating green algae in the area southeast of the Shandong Peninsula in the southern Yellow Sea. The responses of the phytoplankton assemblage from the deep chlorophyll-a maximum layer were then resolved using high-throughput sequencing. We found striking changes in the phytoplankton community in the settlement region after an intensive green tide in 2016, characterized by a remarkable increase in the abundance of the pelagophyte Aureococcus anophagefferens, the causative species of ecosystem disruptive brown tides. Our study strongly suggests that the occurrence of massive macroalgal blooms may promote blooms of specific groups of microalgae through alteration of the marine environment.


Roles of ROS/TACE in neutrophil elastase-induced mucus hypersecretion in NCI-H292 airway epithelial cells.
Complications arise in chronic obstructive pulmonary diseases (COPD) with excessive mucus production, especially during the exacerbation period, which contributes to airway blockage and bacterial infection. Neutrophil elastase (NE) is detected at high levels in airway secretions, and is the primary inducer of mucin production. Understanding the mechanism of NE-induced overproduction of mucin may lead to new therapies for COPD. It is known that activation of epidermal growth factor receptor (EGFR) and its downstream signaling cascade are involved in mucin production. However, the mechanism of NE-induced EGFR activation remains unclear. Tumor necrosis factor-α-converting enzyme (TACE) cleaves pro-transforming growth factor (TGF)-α in airway epithelial cells to release the mature, soluble TGF-α form, which subsequently binds to and activates EGFR. In this investigation, we demonstrate that NE-induced mucin production requires reactive oxygen species (ROS) production, which activates TACE, resulting in TGF-α shedding, and EGFR phosphorylation in NCI-H292 epithelial cells.


Association Between State Limits on Opioid Prescribing and the Incidence of Persistent Postoperative Opioid Use Among Surgical Patients.
To examine whether laws limiting opioid prescribing have been associated with reductions in the incidence of persistent postoperative opioid use. In an effort to address the opioid epidemic, 26 states (as of 2018) have passed laws limiting opioid prescribing for acute pain. However, it is unknown whether these laws have achieved their reduced the risk of persistent postoperative opioid use. We identified 957,639 privately insured patients undergoing one of 10 procedures between January 1, 2004 and September 30, 2018. We then estimated the association between persistent postoperative opioid use, defined as having filled ≥10 prescriptions or ≥120 days supply of opioids during postoperative days 91-365, and whether opioid prescribing limits were in effect on the day of surgery. States were classified as having: no limits, a limit of ≤7 days supply, or a limit of >7 days supply. The regression models adjusted for observable confounders such as patient comorbidities and also utilized a difference-in-differences approach, which relied on variation in state laws over time, to further minimize confounding. The adjusted incidence of persistent postoperative opioid use was 3.5% (95%CI 3.3%-3.7%) for patients facing a limit of ≤7 days supply, compared with 3.3% (95%CI 3.3%-3.3%) for patients facing no prescribing limits ( P = 0.13 for difference compared to no prescribing limits) and 3.4%, (95%CI 3.2%-3.6%) for patients facing a limit of >7 days supply ( P = 0.43 for difference compared to no prescribing limits). Laws limiting opioid prescriptions were not associated with subsequent reductions in persistent postoperative opioid use.


Disease progression, adherence, and response to protease inhibitor therapy for HIV infection in an Urban Veterans Affairs Medical Center.
Indinavir therapy has demonstrated promise in the treatment of HIV-1 infection in clinical trials; however, its efficacy in a U.S. Veterans Affairs Medical Center, where access to therapy is generally unimpeded, is unknown. A review of the Miami cohort was conducted for the year beginning May 1996 to evaluate response to indinavir plus two nucleoside analogues. Of 483 HIV-1-positive patients (97% male; mean age, 46.7+/-9.7 years), 266 were offered indinavir based on their having CD4 counts <200 cells/microl or viral loads >10,000 copies/ml. Of these patients, 36% were adherent and experienced significant reductions in viral loads (-93,325+/-147,911 copies/ml) and elevations in CD4+ (111+/-103 cells/microl) and CD8+ (225+/-338 cells/microl) T cell counts. Adherent patients with baseline CD4 counts <100 cells/microl were 4.5 times more likely to have follow-up viral loads >10,000 copies/ml than those with CD4 >200 cells/microl. Adherent patients with CD4 counts <100 cells/microl did not show evidence of immune "exhaustion" because they were equal to those with CD4 counts >200 cells/microl in their capacity to replenish CD4 cells. Nonadherence to the regimen resulted in loss of therapeutic benefit and suggested that strategies to enhance adherence may become an essential component of treatment.


Transforming social perspectives with cognitive maps.
Growing evidence suggests that cognitive maps represent relations between social knowledge similar to how spatial locations are represented in an environment. Notably, the extant human medial temporal lobe literature assumes associations between social stimuli follow a linear associative mapping from an egocentric viewpoint to a cognitive map. Yet, this form of associative social memory does not account for a core phenomenon of social interactions in which social knowledge learned via comparisons to the self, other individuals or social networks are assimilated within a single frame of reference. We argue that hippocampal-entorhinal coordinate transformations, known to integrate egocentric and allocentric spatial cues, inform social perspective switching between the self and others. We present evidence that the hippocampal formation helps inform social interactions by relating self vs other social attribute comparisons to society in general, which can afford rapid and flexible assimilation of knowledge about the relationship between the self and social networks of varying proximities. We conclude by discussing the ramifications of cognitive maps in aiding this social perspective transformation process in states of health and disease.


[Participate of nitric oxide participate in hypoxic regulation of cerebrovascular tension].
Making use of nitric oxide synthesase (NOS) inhibitor Nw-nitric-oxide-L-arginine (L-NNA), the effect of NO and the pressence of endothelial cell on hypoxia-induced vascular dilatation was studied with new-born calve basilar artery. The experimental results show that L-NNA can attenuate the hypoxia-induced vascular dilatation, but the magnitude of attenuation is smaller than that of constriction caused by L-NNA on normoxic calve basilar artery. Under hypoxia, the vascular dilatation of endothelial cell denuded artery is smaller than that of endothelial cell intact artery; the difference between them is approximate by the same as the change caused by L-NNA on endothelial call intact artery. After destroying the endothelial cell, L-NNA has no obvious effect on the vascular tension. These results suggest that NO and endothelial cell are involved in hypoxia-induced vascular dilaxation.


Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial.
In the phase 3 CELESTIAL trial, cabozantinib improved overall survival (OS) and progression-free survival (PFS) compared with placebo in patients with previously treated advanced hepatocellular carcinoma (HCC). This subgroup analysis evaluated cabozantinib in patients who had received sorafenib as the only prior systemic therapy. CELESTIAL randomised (2:1) patients with advanced HCC and Child-Pugh class A liver function to treatment with cabozantinib (60 mg daily) or placebo. Eligibility required prior treatment with sorafenib, and patients could have received ≤2 prior systemic regimens. The primary endpoint was OS. Outcomes in patients who had received sorafenib as the only prior therapy were analysed by duration of prior sorafenib (<3 months, 3 to <6 months and ≥6 months). Of patients who had received only prior sorafenib, 331 were randomised to cabozantinib and 164 to placebo; 136 patients had received sorafenib for <3 months, 141 for 3 to <6 months and 217 for ≥6 months. Cabozantinib improved OS relative to placebo in the overall second-line population who had received only prior sorafenib (median 11.3 vs 7.2 months; HR=0.70, 95% CI 0.55 to 0.88). This improvement was maintained in analyses by prior sorafenib duration with longer duration generally corresponding to longer median OS-median OS 8.9 vs 6.9 months (HR=0.72, 95% CI 0.47 to 1.10) for prior sorafenib <3 months, 11.5 vs 6.5 months (HR=0.65, 95% CI 0.43 to 1.00) for 3 to <6 months and 12.3 vs 9.2 months (HR=0.82, 95% CI 0.58 to 1.16) for ≥6 months. Cabozantinib also improved PFS in all duration subgroups. Safety data were consistent with the overall study population. Cabozantinib improved efficacy outcomes versus placebo in the second-line population who had received only prior sorafenib irrespective of duration of prior sorafenib treatment, further supporting the utility of cabozantinib in the evolving treatment landscape of HCC. NCT01908426.


The art of prescribing. Antidepressants in late-life depression: prescribing principles.
Ms. Antai-Otong, I am a psychiatric nurse practitioner currently employed in a large primary care clinic. My greatest challenge with older adults suspected of being depressed is their hesitancy to admit they are depressed or unwillingness to take antidepressants. I have started some of these patients on antidepressants and had mixed results. Please provide some guidelines for treating depression in older adults with coexisting medical conditions. Depression is a common companion of chronic medical illnesses and frequently goes unrecognized and untreated, resulting in high morbidity and mortality. Depression is unrecognized and underdiagnosed in approximately 16% of older patients seen in primary care settings (Unutzer, 2002). Typically, older adults deny being depressed, minimize symptom severity, fail to recognize common subjective experiences, such as anhedonia, fatigue, and concentration difficulties associated with this disorder, and hesitate to accept their illness due to social stigma and effects of stoicism. Cultural and generational influences also impact how older adults perceive mental health services. Due to the growing number of individuals 65 and older with coexisting medical and psychiatric conditions, particularly depression, seeking health care in vast practice settings, advanced practice psychiatric nurses must collaborate with primary care providers and develop holistic care that addresses coexisting chronic medical and psychiatric conditions.


A Novel Glutamine Metabolism-Related Gene Signature in Prognostic Prediction of Osteosarcoma.
Metabolic reprogramming, as one of the hallmarks of cancer, shows promising translational potential for cancer diagnosis, treatment and prognostic prediction. This study aims to construct and validate a prognostic prediction model for osteosarcoma based on glutamine metabolism-related genes. A group of glutamine metabolism-related genes was identified from a public database and intersected with a list of osteosarcoma survival-related genes, and a risk score model based on sixteen glutamine metabolism-related genes was developed by using LASSO penalized Cox regression analysis. The prognosis of patients in the high-risk group was significantly worse than that of patients in the low-risk group in the training dataset (high- vs low-risk, 5-year overall survival: 11% vs 88%, p < 0.0001) and in two other external validation cohorts (high- vs low-risk, 5-year overall survival: 39% vs 81%, p = 0.015; 50% vs 94%, p = 0.011).In addition, a novel nomogram was constructed by integrating the risk score and clinical characteristics, including age, sex, metastasis status and chemotherapy response. This nomogram had superior predictive power compared with a nomogram composed of only conventional factors. Gene set enrichment analysis indicated that several well-known malignancy-associated gene sets, including MYC targets V1, DNA repair, and unfolded protein response, were enriched in the high-risk subgroup. A novel glutamine metabolism-related prognostic prediction model and nomogram for osteosarcoma was developed and validated in the present study, which could predict the survival of patients with osteosarcoma and may facilitate individualized clinical decision-making for patients.


Long-term survivors of glioblastoma: a closer look.
Glioblastoma has a poor prognosis with median survival of 12-14 months. Long-term survivors (LTS), alive at least 2 years from diagnosis, comprise 13% of this population. This study aims to provide a clinical profile of LTS at two institutions in Melbourne, Australia. Histological diagnosis of glioblastoma from 1st January 2006 to 31st December 2012 were identified from pathology/oncology databases. Demographic, treatment and survival characteristics were recorded (follow-up to 31st December 2015). Relevant inter-group statistics were used to identify differences between LTS and those surviving less than 2 years. Survival estimated by Kaplan-Meier. 776 patients were identified with 154 surviving > 2 years. Compared with patients surviving < 2 years, LTS were more likely to be younger (median age 56 vs. 65 years, p < .001), have ECOG 0-2 (97 vs. 65%, p < .001), gross tumour resection (91 vs. 61%, p < .001), and receive chemoradiotherapy (94 vs. 40%, p < .001). Most common presenting symptoms amongst LTS were headache (42%), seizure (28%) and speech disturbance (16%). Of LTS, 111 patients (72%) progressed at a median of 20.1 months from diagnosis, with 46% undergoing a second craniotomy. The most common non-surgical second line treatments were temozolomide (41%), followed by radiotherapy (12%). One-third of LTS received three or more lines of treatment, and 10% underwent three or more craniotomies. LTS of glioblastoma (20%) are more likely to be younger, have unilateral tumours, good performance status and undergo multimodality treatment. These data may assist in predicting LTS at diagnosis and understanding their clinical journey to facilitate planning of treatment and supportive care.


The Chitty effect: a consequence of dynamic energy allocation in a fluctuating environment.
An important biological feature of cyclic populations of voles and lemmings is phase-related changes in average body mass, with adults in high-density phases being 20-30% heavier than those in low-density phases of a cycle. This observation, called the "Chitty effect," is considered to be a ubiquitous feature of cyclic populations. It has been argued that understanding the Chitty effect is fundamental to unraveling the enigma of population cycles. However, there exists no agreement among biologists regarding the causes of the Chitty effect. Here, I propose a simple hypothesis to explain the Chitty effect, based on phase-related, dynamic allocation of energy between reproductive and somatic effort. The essence of the hypothesis is that: (1) reproduction is suppressed in animals born or raised in the later part of the increase phase by environmental factors, including social influences; (2) suppression of reproduction limits the amount of energy that is diverted for reproductive effort, and forces a disproportionately greater amount of surplus power (the energy left after the energetic costs of standard and active metabolism are met) to be allocated for somatic effort; (3) the surplus energy, above and beyond what is required for routine biological activities, will allow continuous growth and deposition of additional body mass, which causes an increase in body mass; and (4) animals grow to a larger size as a population enters the peak density phase, causing an increase in the average body mass. The Chitty effect is predicted to be most pronounced at the late increase or peak phase of a population cycle. Possible causes of reproductive suppression include direct or indirect influences of the environmental factors. The Chitty effect may be a consequence, not a cause, of population cycles in small mammals.


Threatened or Threatening? How Ideology Shapes Asylum Seekers' Immigration Policy Attitudes in Israel and Australia.
Can different political ideologies explain policy preferences regarding asylum seekers? We focus on attitudes regarding governmental policy towards out-group members and suggest that perceptions of threat help to shape these policy attitudes. Study 1 compared public opinion regarding asylum policy in Israel (N = 137) and Australia (N = 138), two countries with restrictive asylum policies and who host a large number of asylum seekers; Study 2, a longitudinal study, was conducted during two different time periods in Israel-before and during the Gaza conflict. Results of both studies showed that threat perceptions of out-group members drive the relationship between conservative political ideologies and support for exclusionary asylum policies among citizens. Perceptions of threat held by members of the host country (the in-group) towards asylum seekers (the out-group) may influence policy formation. The effect of these out-groups threats needs to be critically weighed when considering Israeli and Australian policies towards asylum seekers.


History of the Food and Drug Administration's total diet study--1961 to 1987.
The Total Diet Study provides the Food and Drug Administration with baseline information on the levels of pesticide residues, contaminants, and nutrient elements in the food supply and in the diets of specific age-sex groups. The study also identifies trends and changes in the levels of these substances in the food supply and in diets over time and thereby assists in identifying potential public health problems. This paper describes the evolution of the Total Diet Study from 1961 to 1987. Food collections, sites of analysis, diets, food commodity groups, analytes, analytical methodologies, data transfer, publication of results, notable results, resources, and advantages of the study are discussed.


Prevention and reversal of cartilage degradation in rheumatoid arthritis by interleukin-10 and interleukin-4.
Inflammation-induced articular cartilage degradation is a major problem in rheumatoid arthritis (RA). Type 1 T cell activity (characterized by interferon-gamma/interleukin-2 [IL-2] production), and consequently, the production of the proinflammatory cytokines IL-1 and tumor necrosis factor alpha (TNF alpha), have been reported to play a major role in cartilage damage. IL-10 and IL-4, both produced by type 2 T cells, are cytokines with the capacity to down-regulate proinflammatory responses. The present study was undertaken to investigate the way in which these cytokines affect activated mononuclear cells (MNC) of RA patients in relation to human articular cartilage degradation in vitro. MNC from synovial fluid and peripheral blood of RA patients were stimulated with bacterial antigen and treated with IL-10 and/or IL-4. Bacterial antigen is known to activate type 1 T cells and to induce proinflammatory IL-1/TNF alpha-dependent cartilage damage. Cytokine production and effects of conditioned media, as well as effects of IL-10 and IL-4 on proteoglycan (PG) turnover (as a measure for cartilage damage), were determined. IL-10 and IL-4 inhibited proinflammatory cytokine production of stimulated RA MNC and completely reversed inhibition of cartilage PG synthesis induced by these stimulated RA MNC. IL-10 was more potent than IL-4 in this respect, and the combination of IL-10 and IL-4 had an additive effect. In addition, IL-10 directly stimulated cartilage PG synthesis. IL-10 reverses the cartilage degradation induced by antigen-stimulated MNC, and IL-4 has an additive effect on this process. Furthermore, IL-10 has a direct stimulatory effect on PG synthesis, and IL-4, as a growth factor for type 2 T cells, can reduce the ratio of type 1 to type 2 T cell activity. These results provide evidence in favor of the use of a combination of the two cytokines in the treatment of RA.


Dearomatization and functionalization of terpyridine by lutetium(III) alkyl complexes.
Lutetium(III)-bis(alkyl) and -tris(alkyl) fragments supported by either 2,2':6',2' '-terpyridine or 4,4',4' '-tri-tert-butyl-2,2':6',2' '-terpyridine are not stable and undergo facile 1,3-alkyl migration under ambient conditions resulting in dearomatization and ortho (2' or 6') functionalization of the terpyridyl ligand, clearly demonstrating that the terpyridyl ligand framework is not as innocent as previously thought.


[Trends in polymer-grade L-lactic acid fermentation by non-food biomass].
Lactic acid has a wide range of uses in the chemical, pharmaceutical and food industry. With rapid development of poly (lactic acid) industry, the demand for polymer-grade L-lactic acid is continuously increasing. Developing low-cost, non-food-biomass-lactic-acid fermentation process and the fermentation-separation coupled technology are trends to reduce polymer-grade L-lactic acid production cost. This review summarized the most recent advances in low-cost L-lactic acid fermentation based on the use of non-food biomass, followed by addressing the key issue that might be strategically important for future development of polymer-grade L-lactic acid production in industry.


Short report: geographic distribution of different genetic types of Ehrlichia chaffeensis.
The 120-kD protein gene of Ehrlichia chaffeensis was used to characterize ehrlichial DNA from seven pools of adult Amblyomma americanum ticks. Ticks from Missouri, Kentucky, and North Carolina contained E. chaffeensis DNA of the Arkansas strain genotype. Ticks from North Carolina also contained ehrlichiae of the Sapulpa strain genotype, originally identified in Oklahoma.


An enzyme-free electrochemiluminescence insulin probe based on the regular attachment of ZnO nanoparticles on a 3-D nickel foam and H2O2 as an efficient co-reactant.
In this study, a highly sensitive, fast, and enzyme-free electrochemiluminescence (ECL) probe based on the decoration of zinc oxide nanoparticles on nickel foam is proposed for insulin determination. A silica film was employed as a size adjusting agent for the modification of the nickel foam surface with ZnO nanoparticles (ZnO NPs). The ECL of the ZnO NP/Ni foam was investigated in a natural medium in the presence of hydrogen peroxide (H2O2) as an efficient co-reactant. With increasing insulin concentration, a remarkable improvement in ECL signal was observed, which proved the enhancing effect of insulin on the ECL emission. The characterization of the ZnO-NP/Ni-foam electrode was performed via electrochemical impedance spectroscopy, Brunauer-Emmett-Teller (BET) surface area measurement, X-ray diffraction, field emission scanning electron microscopy (FESEM), and energy-dispersive X-ray analysis techniques. The fabricated electrode was applied for the trace analysis of insulin using the ultrasensitive ECL method in a phosphate buffer solution. Under the optimal conditions, the results showed excellent performance during insulin determination with a wide linear range of 3.57 × 10-15 M to 2.94 × 10-9 M, a low detection limit of 1.00 × 10-16 M, and a relative standard deviation of 1.03%. The proposed ECL sensor with excellent reproducibility, long-term stability, and high selectivity was used for insulin determination in real serum samples with acceptable outcomes.


Multidimensional Adaptive Testing with Optimal Design Criteria for Item Selection.
Several criteria from the optimal design literature are examined for use with item selection in multidimensional adaptive testing. In particular, it is examined what criteria are appropriate for adaptive testing in which all abilities are intentional, some should be considered as a nuisance, or the interest is in the testing of a composite of the abilities. Both the theoretical analyses and the studies of simulated data in this paper suggest that the criteria of A-optimality and D-optimality lead to the most accurate estimates when all abilities are intentional, with the former slightly outperforming the latter. The criterion of E-optimality showed occasional erratic behavior for this case of adaptive testing, and its use is not recommended. If some of the abilities are nuisances, application of the criterion of A(s)-optimality (or D(s)-optimality), which focuses on the subset of intentional abilities is recommended. For the measurement of a linear combination of abilities, the criterion of c-optimality yielded the best results. The preferences of each of these criteria for items with specific patterns of parameter values was also assessed. It was found that the criteria differed mainly in their preferences of items with different patterns of values for their discrimination parameters.


Atrial fibrillation predicts cognitive impairment in patients with ischemic stroke.
Atrial fibrillation (AF) is considered as a risk factor for cognitive impairment. This retrospective chart review study was conducted in a patient stroke rehabilitation ward of a university-affiliated referral hospital. The participants were 707 patients admitted for a standard rehabilitation course after an ischemic stroke. Cognitive status was assessed by the Mini-Mental State Examination (MMSE), and scores lower than 24 points were considered as suggestive of cognitive impairment. Atrial fibrillation, age, gender, diabetes, and dementia emerged as the only statistically significant parameters differing between those with MMSE score lower than 24 or higher. In a multiple logistic regression analysis, AF (odds ratio 1.6, 95% confidence interval 1.03-2.47, P = .03) was associated with an increased risk of cognitive impairment. Our findings suggest that atrial fibrillation upon admission is independently associated with lower MMSE scores in patients with ischemic stroke.


Disability and inclusive education in an Italian region: analysis of the data for the school year 2012-2013.
In Italy, pupils with disabilities enroll in mainstream schools and attend the ordinary classes at all educational levels. For the past twelve years, the Region Emilia Romagna has witnessed an increase in the number of children who need special support. The aim of the study was to identify the causes of disability in children attending public schools during the school year 2012-2013. The study was designed as a cross-sectional survey. Data were obtained from the Regional Education Department and divided into categories based on clinical diagnoses. Statistical analyses were performed to analyze the distribution of the diagnostic categories among Provinces and school grades. The most recurrent combinations of illnesses were identified. Intellectual disability was the most common cause of impairment (38.5%), often associated with epilepsy and autism. Hyperkinetic disorder associated with specific disorders of scholastic skills was the most recurrent combination of diagnoses. Rare diseases were diagnosed in 4.1%, whereas 5.0% of cases were affected by psychopathological disorders. Our study is the first in Italy for its focus on the causes of children's disabilities in an Italian region. Being familiar with the causes of disability affecting the children of a territory is important to allocate the available resources efficiently, and to ensure all children's effective social integration.