Cyanidin-3-O-Glucoside-Rich Haskap Berry Administration Suppresses Carcinogen-Induced Lung Tumorigenesis in A/JCr Mice.
In our previous study, we demonstrated that cyanidin-3-O-glucoside (C3G)-rich haskap (Lonicera caerulea L.) berry extracts can attenuate the carcinogen-induced DNA damage in normal lung epithelial cells in vitro. Here, the efficacy of lyophilized powder of whole haskap berry (C3G-HB) in lowering tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, (NNK)-induced lung tumorigenesis in A/JCr mice was investigated. Three weeks after daily oral administration of C3G-HB (6 mg of C3G in 0.2 g of C3G-HB/mouse/day), lung tumors were initiated by a single intraperitoneal injection of NNK. Dietary C3G-HB supplementation was continued, and 22 weeks later, mice were euthanized. Lung tumors were visualized through positron emission tomography (PET) and magnetic resonance imaging (MRI) 19 weeks after NNK injection. Dietary supplementation of C3G-HB significantly reduced the NNK-induced lung tumor multiplicity and tumor area but did not affect tumor incidence. Immunohistochemical analysis showed reduced expression of proliferative cell nuclear antigen (PCNA) and Ki-67 in lung tissues. Therefore, C3G-HB has the potential to reduce the lung tumorigenesis, and to be used as a source for developing dietary supplements or nutraceuticals for reducing the risk of lung cancer among high-risk populations.


Hydrogen-bonded one-dimensional networks in 1:1 complexes of N,N'-bis(2-pyridyl)aryldiamines with anilic acid.
The 1:1 complexes N,N'-bis(2-pyridyl)benzene-1,4-diamine-anilic acid (2,5-dihydroxy-1,4-benzoquinone) (1/1), C(16)H(14)N(4).C(6)H(4)O(4), (I), and N,N'-bis(2-pyridyl)biphenyl-4,4'-diamine-anilic acid (1/1), C(22)H(18)N(4).C(6)H(4)O(4), (II), have been prepared and their solid-state structures investigated. The component molecules of these complexes are connected via conventional N-H.O and O-H.N hydrogen bonds, leading to the formation of an infinite one-dimensional network generated by the cyclic motif R(2)(2)(9). The anilic acid molecules in both crystal structures lie around inversion centres and the observed bond lengths are typical for the neutral molecule. Nevertheless, the pyridine C-N-C angles [120.9 (2) and 120.13 (17) degrees for complexes (I) and (II), respectively] point to a partial H-atom transfer from anilic aicd to the bispyridylamine, and hence to H-atom disorder in the OHN bridge. The bispyridylamine molecules of (I) and (II) also lie around inversion centres and exhibit disorder of their central phenyl rings over two positions.


Crystallization and preliminary X-ray diffraction studies of cyanuric acid hydrolase from Azorhizobium caulinodans.
Cyanuric acid is synthesized industrially and forms during the microbial metabolism of s-triazine herbicides. Cyanuric acid is metabolized by some microorganisms via cyanuric acid hydrolase (CAH), which opens the s-triazine ring as a prelude to further metabolism. CAH is a member of the rare cyanuric acid hydrolase/barbiturase family. Here, the crystallization and preliminary X-ray diffraction analysis of CAH from Azorhizobium caulinodans are reported. CAH was cocrystallized with barbituric acid, a close analog of cyanuric acid that is a tight-binding competitive inhibitor. Crystals suitable for X-ray diffraction experiments were grown in conditions containing PEG 8K or magnesium sulfate as precipitants. An X-ray diffraction data set was collected from CAH-barbituric acid crystals to 2.7 Å resolution. The crystals were found to belong to space group I4₁22, with unit-cell parameters a = b = 237.9, c = 105.3 Å, α = β = γ = 90°.


Infectious waste management and laboratory design criteria.
Infectious waste management and laboratory design criteria are provided to help in recognizing what information needs to be included in an individual program and to develop an infectious waste management plan. Relevant engineering aspects of a containment laboratory are described in detail, and suggested equipment and operating procedures for collection, sterilization, and disposal of solid and liquid waste are discussed. The need for public awareness regarding infectious waste is discussed, including liability considerations associated with improper disposal. This study shows how proper management of infectious waste results in lower disposal cost, lower operating costs, reduction in liabilities, increased worker safety, and a cleaner environment.


To err is human: "abnormal" neuropsychological scores and variability are common in healthy adults.
Normative studies of variability in performance by healthy adults on neuropsychological batteries are reviewed. Regarding test score scatter, normative participants often have large discrepancies between best and worst scores. When "abnormality" was defined as a score more than one standard deviation below the mean, in test batteries with at least 20 measures, the great majority of normative participants had one or more abnormalities. Restricting samples to participants with above average IQ or educational levels and using more conservative definitions of abnormality, such as two standard deviations below the mean did not eliminate the presence of abnormal scores. We conclude that abnormal performance on some proportion of neuropsychological tests in a battery is psychometrically normal. Abnormalities do not necessarily signify the presence of acquired brain dysfunction because low scores and large intraindividual variability often are characteristic of healthy adults. We recommend that test battery developers provide data on the amount of variability in normal samples and also provide base rate tables with false positive rates that can be used clinically when interpreting test performance.


Sesquiterpene lactones and their derivatives inhibit high glucose-induced NF-κB activation and MCP-1 and TGF-β1 expression in rat mesangial cells.
Diabetic nephropathy (DN) is one of the most common and serious chronic complications of diabetes mellitus, however, no efficient clinical drugs exist for the treatment of DN. We selected and synthesized several sesquiterpene lactones (SLs), and then used the MTT assay to detect rat mesangial cells (MCs) proliferation, ELISA to measure the expression level of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta (TGF-β1) and fibronectin(FN), real-time fluorescent quantitative PCR analysis to measure the MCP-1 and TGF-β1 gene expression, western blot to detect the level of IκBα protein and EMSA to measure the activation of nuclear factor kappa B (NF-κB). We discovered that SLs, including parthenolide (PTL), micheliolide (MCL), arglabin, and isoalantolactone (IAL), as well as several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated activation of NF-κB, the degradation of IκBα, and the expression of MCP-1, TGF-β1 and FN in rat mesangial cells (MCs). These findings suggest that SLs and their derivatives have potential as candidate drugs for the treatment of DN.


Therapeutic embolization of the gastroduodenal artery in hepatic artery infusion chemotherapy.
Transcatheter embolization of the gastroduodenal artery with Gelfoam was performed in 12 patients undergoing percutaneous hepatic artery catheterization for infusion chemotherapy of metastatic liver disease. The purpose of the embolization was to prevent chemotherapeutic drugs from reaching the stomach and duodenum and thereby inducing gastrointestinal toxicity in patients in whom the catheter tip could not be satisfactorily positioned beyond the gastroduodenal origin. Embolization proved safe and effective in eight cases. Three other patients experienced clinical problems that may or may not have been related to embolization. The final patient had a significant complication (necrosis of the pancreatic head and gastric mucosa) that was felt to be directly related to the embolization. Transcatheter gastroduodenal occlusion may help reduce gastrointestinal toxicity of intraarterial infusion chemotherapy. However, it may on occasion be associated with significant complications, particularly in patients who are debilitated due to metastatic disease.


Methadone-associated Q-T interval prolongation and torsades de pointes.
The association of methadone with Q-T interval prolongation and torsades de pointes (TdP) is reviewed, and recommendations for preventing Q-T interval prolongation in methadone users are provided. Abnormalities in voltage-gated potassium channels have been shown to lead to prolonged action potentials that are expressed as long Q-T intervals, and methadone has been found to interact with the voltage-gated potassium channels of the myocardium. While cardiac arrhythmias in methadone users have been reported for several decades, specific reports of methadone-associated Q-T interval prolongation and TdP did not appear in the literature until the early part of the 21st century. Because not every patient experiences Q-T interval prolongation with methadone, recent research has elucidated risk factors that predispose patients to this adverse effect, including female sex, hypokalemia, high-dose methadone, drug interactions, underlying cardiac conditions, unrecognized congenital long Q-T interval syndrome, and predisposing DNA polymorphisms. Given the high mortality rates seen in untreated illicit opioid users and the clear efficacy of methadone in treating opioid addiction, the risk of using methadone, even in a patient with other risk factors for Q-T interval prolongation, may outweigh the alternative of no pharmacologic treatment. A baseline electrocardiogram (ECG), personal and family history of syncope, and a complete medication history should be obtained before a patient begins treatment with methadone. Given the apparent synergistic effects of parenteral methadone and chlorobutanol, oral methadone should be used whenever possible. Q-T interval prolongation and TdP associated with the use of methadone are potentially fatal adverse effects. A thorough patient history and ECG monitoring are essential for patients treated with this agent, and alterations in treatment options may be necessary.


The impact of carbon coating on the synthesis and properties of α''-Fe16N2 powders.
This paper presents the preparation of carbon composite Fe16N2 powders, and the influence of a protective carbon coating on the yield and magnetic properties of Fe16N2. Nanoparticle precursors with and without carbon were reacted under ammonia gas flow to produce Fe16N2. Neutron and X-ray powder diffraction indicate that the powders contain typically 40-60% Fe16N2, with the remaining phases being unreacted iron, Fe4N or Fe3N. Transmission electron microscopy demonstrates that the carbon coating is effective at reducing the level of sintering of Fe nanoparticles during the reduction stage prior to ammonolysis. XPS results support the retention of a carbon coating on the surface after ammonolysis, and that there is Fe-C bonding present at the particle surface. In situ TEM was used to observe loss of ordering in the nitrogen sublattice of carbon composite Fe16N2 powders in the range of 168 °C to 200 °C. Magnetic susceptibility measurements show maximum values for saturation magnetization in the range of 232 emu g(-1), and for coercivity near 930 Oe, for different samples measured up to 2 T applied field at 300 K.


Population growth rates decline in five provinces.
Natural population growth rates in Shandong, Zhejiang, Shaanxi, Jiangxi, and Henan provinces last year were much lower than the 1980 national average of less than 11/1000, according to provincial authorities. The population growth rate in Shandong province, which has 73 million people, dropped to 7.03/1000 last year, 3.76/1000 less than in 1979. Some 100,000 fewer babies were born in Zhejiang province last year, compared with the figure for 1979. That birth rate was the lowest achieved in the past 30 years. In Shaanxi province, the population growth rate in 1980 was 7.19/1000. More than 458,000 couples in the province who have 1 child have decided to bear no more children, the authorities said. The population growth rate in Jiangxi and Henan provinces fell from 13.74/1000 in 1979 to 9.11/1000 in 1980 and from 12.88/1000 in 1979 to 9.53/1000 last year. The decline of the population growth rate is attributed to late marriage, late childbearing, family planning education, and encouragement of 1-child families.


Dual actions of the metabolic inhibitor, sodium azide on K(ATP) channel currents in the rat CRI-G1 insulinoma cell line.
1. The effects of various inhibitors of the mitochondrial electron transport chain on the activity of ATP-sensitive K+ channels were examined in the Cambridge rat insulinoma G1 (CRI-G1) cell line using a combination of whole cell and single channel recording techniques. 2. Whole cell current clamp recordings, with 5 mM ATP in the pipette, demonstrate that the mitochondrial uncoupler sodium azide (3 mM) rapidly hyperpolarizes CRI-G1 cells with a concomitant increase in K+ conductance. This is due to activation of K(ATP) channels as the sulphonylurea tolbutamide (100 microM) completely reversed the actions of azide. Other inhibitors of the mitochondrial electron transport chain, rotenone (10 microM) or oligomycin (2 microM) did not hyperpolarize CRI-G1 cells or increase K+ conductance. 3. In cell-attached recordings, bath application of 3 mM sodium azide (in the absence of glucose) resulted in a rapid increase in K(ATP) channel activity, an action readily reversible by tolbutamide (100 microM). Application of sodium azide (3 mM), in the presence of Mg-ATP, to the intracellular surface of excised inside-out patches also increased K(ATP) channel activity, in a reversible manner. 4. In contrast, rotenone (10 microM) or oligomycin (2 microM) did not increase K(ATP) channel activity in either cell-attached, in the absence of glucose, or inside-out membrane patch recordings. 5. Addition of sodium azide (3 mM) to the intracellular surface of inside-out membrane patches in the presence of Mg-free ATP or the non-hydrolysable analogue 5'-adenylylimidodiphosphate (AMP-PNP) inhibited, rather than increased, K(ATP) channel activity. 6. In conclusion, sodium azide, but not rotenone or oligomycin, directly activates K(ATP) channels in CRI-G1 insulin secreting cells. This action of azide is similar to that reported previously for diazoxide.


Structural Basis of Transcription Inhibition by CBR Hydroxamidines and CBR Pyrazoles.
CBR hydroxamidines are small-molecule inhibitors of bacterial RNA polymerase (RNAP) discovered through high-throughput screening of synthetic-compound libraries. CBR pyrazoles are structurally related RNAP inhibitors discovered through scaffold hopping from CBR hydroxamidines. CBR hydroxamidines and pyrazoles selectively inhibit Gram-negative bacterial RNAP and exhibit selective antibacterial activity against Gram-negative bacteria. Here, we report crystal structures of the prototype CBR hydroxamidine, CBR703, and a CBR pyrazole in complex with E. coli RNAP holoenzyme. In addition, we define the full resistance determinant for CBR703, show that the binding site and resistance determinant for CBR703 do not overlap the binding sites and resistance determinants of other characterized RNAP inhibitors, show that CBR703 exhibits no or minimal cross-resistance with other characterized RNAP inhibitors, and show that co-administration of CBR703 with other RNAP inhibitors results in additive antibacterial activities. The results set the stage for structure-based optimization of CBR inhibitors as antibacterial drugs.


Enhancement of lymphocyte function and interleukin 1 beta transcription by recombinant bovine interleukin 1 beta.
Six nonpregnant, nonlactating Jersey cows, averaging 4 to 6 years old, were used to evaluate the immunomodulatory effects of recombinant bovine interleukin 1 beta (rBoIL-1 beta). Cows were given 166 ng of rBoIL-1 beta/kg of body weight at 8-hour intervals for 96 hours. Persistent leukocytosis was observed within 3 hours of rBoIL-1 treatment, peaking 24 hours after the first IL-1 beta injection and returning to baseline values within 72 hours after cessation of IL-1 beta treatment. Injection of cows with rBoIL-1 beta stimulated lymphocyte blastogenesis and mitochondrial methyl-thiazoltetrazolium cleavage activity in resting cell cultures. Increases in the aforementioned lymphocyte activities were also observed in stimulated blood mononuclear cell cultures during IL-1 beta administration. Change in IgM production in cell cultures was not observed during IL-1 beta treatment. Within 24 hours of the first IL-1 beta injection, IL-1 beta mRNA transcription in stimulated blood mononuclear cell cultures was markedly increased, suggesting that IL-1 beta upregulates its own production in mononuclear cells. These data provide evidence that administration of cytokines, such as rBoIL-1 beta, enhances immune cell function and, therefore, may be useful in alleviating immunosuppresion in cattle.


Determination of c-myc amplification and overexpression in breast cancer patients: evaluation of its prognostic value against c-erbB-2, cathepsin-D and clinicopathological characteristics using univariate and multivariate analysis.
C-myc and c-erbB-2 amplification and/or overexpression as well as total cathepsin-D (CD) concentration have been reported to be associated with poor prognosis in breast cancer. The prognostic significance, however, remains somewhat controversial, partly because of discrepancies among the different methodologies used. We determined the amplification and overexpression of c-myc oncogene in 152 breast cancer patients and examined its prognostic value in relation to c-erbB-2 amplification and overexpression, high concentration of CD (> or = 60 pmol mg(-1) protein) and standard clinicopathological prognostic factors of the disease. High CD concentration, as well as c-myc amplification and overexpression, proved to be the best of the new variables examined for prediction of early relapse (ER; before 3 years). After multivariate analysis only CD remained significant, which suggests that the prognostic power of these variables is similar. Using univariate analysis we proved that c-myc amplification and overexpression were highly significant for disease-free survival (DFS) (P = 0.0016 and P = 0.0001 respectively) and overall survival (OS) (P < 0.0001 and P = 0.0095 respectively), although by multivariate analysis c-myc overexpression was statistically significant only for DFS (P = 0.0001) and c-myc amplification only for OS (P = 0.0006). With regard to c-erbB-2, only its overexpression appeared to be significant for DFS and OS, although after multivariate analysis its prognostic power was weaker (P = 0.030 and P = 0.024 respectively). c-myc amplification and overexpression exhibited a tendency for locoregional recurrence (LRR) (P = 0.0024 and P = 0.0075 respectively), however, their prognostic value was lower after multivariate analysis and only CD remained significant.


An outbreak of penicillin-resistant Neisseria gonorrhoea in southern Israel.
Since the early 1980s the incidence of gonorrhea has been declining worldwide, as well as in Israel. This decline has been attributed to the fear of AIDS. We report an outbreak of penicillin-resistant Neisseria gonorrhoea that occurred in the last quarter of 1988 and throughout 1989 in southern Israel. During 1987 and the first three-quarters of 1988 only 13 new cases were diagnosed, all penicillin sensitive. During the epidemic, 94 new cases were diagnosed, 41% of them penicillin resistant. In March 1989, ceftriaxone was substituted for penicillin for the treatment of gonococcal urethritis. The number of cases of penicillin-resistant gonorrhea dropped dramatically. It is concluded that despite the AIDS panic, outbreaks of gonorrhea can still be encountered, as demonstrated in this study.


A Randomized, Placebo-Controlled Trial of Mirtazapine for the Treatment of Posttraumatic Stress Disorder in Veterans.
The aim of this study was to determine the efficacy of mirtazapine, a tetracyclic antidepressant, as monotherapy for the treatment of posttraumatic stress disorder (PTSD). This multisite, randomized, double-blind, placebo-controlled trial was conducted between April 2006 and November 2010 at the Tuscaloosa and Birmingham Veterans Affairs Medical Centers in Alabama. US military veterans who met DSM-IV criteria for PTSD were randomly assigned to placebo (n = 39) or mirtazapine (n = 39) titrated up to 45 mg/d for an 8-week double-blind period followed by an 8-week open-label phase of mirtazapine treatment. The primary outcome efficacy measure was the Structured Interview for Posttraumatic Stress Disorder (SIP). Secondary measures included other measures of PTSD, depression, and sleep. Analyses of treatment groups involved mixed-model procedures using a random intercept to test the hypotheses that mirtazapine would be more effective than placebo in reducing symptoms of PTSD and depression and improving quality of sleep. Seventy-eight participants were randomized with 61 completing the 8-week controlled phase and 48 completing the open-label phase. No significant differences were observed between groups on the primary outcome of SIP scores during the controlled phase (P = .418). In secondary outcomes, significant improvements per the Clinical Global Impressions-Improvement scale were found for the mirtazapine group compared to the placebo group (P = .041). The 8-week open-label phase demonstrated significant symptom improvement in SIP total score (P = .0003) and in scores on the SIP re-experiencing (P = .0007), avoidance (P = .0309), and hyperarousal (P = .0014) subscales. There were no significant differences in the occurrence of adverse events between groups. This study did not show efficacy of mirtazapine monotherapy in the treatment of PTSD. Identification of more effective treatments, either as monotherapy or adjunctive, for PTSD is imperative. ClinicalTrials.gov identifier: NCT00302107.


Clinicopathologic manifestations and outcome of dengue fever and dengue haemorrhagic fever.
During the peak period of outbreak from July through October, during the year 2000 through 2002, a total of 390 cases of either dengue fever (DF) or dengue haemorrhagic fever (DHF) were collected from medicine outpatient department (MOPD) of Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka to study their clinicopathologic manifestations and management outcome. Data were collected using a structured questionnaire. Almost all of the patients presented with fever (100%), headache (98.2%), bodyache (97.7%), anorexia (100%) and nausea (100%) and the vast majority had skin rash (78.5%), backache (78.2%) and retro-orbital pain (79.7%). Mean +/-SD of duration of total illness was 7.57 +/- 1.11 days and that of fever and skin rash were 5.40 +/- 0.86 and 3.02 +/- 0.78 days respectively. Mean +/-SD of platelet count was 69643.59 +/- 32043.97/mm3 of blood and that of haematocrit was 41.18 +/- 2.65%. Almost all of the patients (97.7%) developed thrombocytopenia but only 4.1% developed leucopenia at sometime during the course of the disease and anaemia was found in 49.4% of the patients. Both anti-dengue IgG and anti-dengue IgM were positive in 55.1% of patients and either anti-dengue IgG or anti-dengue IgM was positive in 23.6% and 21.3% of patients respectively. Management outcome of the patients was quite satisfactory without any case fatality.


Survival analysis of one versus two treatments of local delivery cisplatin in a biodegradable polymer for canine osteosarcoma.
The purpose of this study was to evaluate one versus two doses of local delivery cisplatin in a biodegradable polymer (OPLA-Pt) for the treatment of osteosarcoma (OSA) after amputation in dogs. Medical records were reviewed retrospectively, and 105 dogs were included in the study; 39% of dogs received one treatment (surgical implantation) of OPLA-Pt and 61% of dogs received two treatments of OPLA-Pt after amputation. Administration of two doses of OPLA-Pt did not have a significant effect on disease-free interval or survival time compared to one dose. The anatomic site of the tumour was identified as a prognostic factor, and dogs with proximal humeral OSA had the shortest disease-free interval and survival times. There was no advantage to giving a second dose of local delivery cisplatin following amputation for the treatment of OSA in dogs.


Evolving insights in the pathogenesis and therapy of cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome).
Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignancies derived from skin-homing T cells. The most common forms of CTCL are Mycosis Fungoides (MF) and Sezary Syndrome (SS). Accurate diagnosis remains a challenge due to the heterogeneity of presentation and the lack of highly characteristic immunophenotypical and genetic markers. Over the past decade molecular studies have improved our understanding of the biology of CTCL. The identification of gene expression differences between normal and malignant T-cells has led to promising new diagnostic and prognostic biomarkers that now need validation to be incorporated into clinical practice. These biomarkers may also provide insight into the mechanism of development of CTCL. Additionally, treatment options have expanded with the approval of new agents, such as histone deacetylase inhibitors. A better understanding of the cell biology, immunology and genetics underlying the development and progression of CTCL will allow the design of more rational treatment strategies for these malignancies. This review summarizes the clinical epidemiology, staging and natural history of MF and SS; discusses the immunopathogenesis of MF and the functional role of the malignant T-cells; and reviews the latest advances in MF and SS treatment.


[Dural arteriovenous malformation in the posterior fossa presenting with multiple intracerebral hematomas. Case report].
A 59-year-old female was hospitalized because of disturbance of consciousness and convulsive seizures. She had taken a hormonal drug for 15 months after breast cancer surgery. A computed tomography scan revealed multiple high-density areas in the left temporal and frontal and the right parietal lobes. Angiography showed a dural arteriovenous malformation (AVM) in the posterior fossa fed by the occipital and the middle meningeal arteries and draining into the transverse sinus. It also demonstrated occlusion of the left sigmoid sinus in the venous phase. She complained of headache in the occipital region and dizziness. On day 13, the left occipital artery was ligated and cut, and then abnormal arterial anastomoses around the lesion were coagulated. After surgery, clinical symptoms disappeared. The etiology of dural AVM is controversial, but in this case it is suspected that sinus thrombosis due to the drug caused the dural AVM. The authors discuss the etiology and treatment of dural AVM in the posterior fossa.


Screening guide for hepatitis C virus infection in Spain.
Since the Plan Estratégico para el Abordaje de la Hepatitis C (Strategic Plan for Tackling Hepatitis C - PEAHC) of the Spanish Health Service (SNS) was approved in 2015, the joint response to hepatitis C in Spain has made great progress. From 2015 to mid-2020, more than 135,000 people had access to direct-acting antiviral therapies. That same period saw advances in knowledge of the epidemiology of the active infection as well as heightened awareness and community participation in infection prevention.


Study of phosphoglucomutase polymorphism by isoelectric focusing: gene frequencies in the Gaddi tribe of Himachal Pradesh, India.
A total of 254 Rajputs and Brahmins of the Gaddi tribe from the regions of Kangra and Chamba in Himachal Pradesh, north-west India, were examined for red cell PGM1 phenotypes by isoelectric focusing (IEF). All the ten possible phenotypes from the four alleles of PGM1 described by IEF were found in this population. Comparison of gene frequencies in the present two ethnic groups and with the only other study available on Asians from London shows that IEF is another useful biochemical method for the study of population diversity.


Effectiveness of treatment to improve pregnancy outcomes among women with syphilis in Zhejiang Province, China.
To determine the effectiveness of treatment in improving pregnancy outcomes among women with syphilis. This is a retrospective study based on the provincial prevention of mother-to-child transmission of syphilis database. All women with syphilis with singleton pregnancies were recruited. We evaluated their pregnancy outcomes by group-specific analyses according to their treatment time and adequacy. The syphilis prevalence among pregnant women was 0.3% (4214/1 338 739) in Zhejiang Province, China, during 2013-2014, considering all live births and abortions. Women with singleton pregnancies (3767) were included in the study, including live births and stillbirths (≥28 weeks). The treatment coverage for all women with syphilis was 80.2% (3022/3767), and 68.2% (2062/3022) of the women were treated adequately. Of 745 infants born to untreated pregnant women with syphilis, 1.2% manifested pneumonia, 2.7% asphyxia, 1.6% birth defects, 3.8% congenital syphilis (CS), 14.2% were preterm, 10.1% had low birth weight (LBW) and 3.1% experienced perinatal death. The risks of asphyxia (OR=2.7), CS (OR=3.1), preterm birth (OR=1.5), LBW (OR=1.9) and perinatal death (OR=3.1) were much higher in infants born to mothers treated inadequately than from those treated adequately. Moreover, mothers with syphilis who initiated treatment in the third trimester suffered an increased risk for asphyxia (OR=3.0), CS (OR=6.0) and LBW (OR=1.7) compared with those who initiated treatment in the first trimester. Early and adequate treatment could improve the adverse pregnancy outcomes among women with syphilis.


Mitochondrial DNA sequence evolution in the Arctoidea.
Some taxa in the superfamily Arctoidea, such as the giant panda and the lesser panda, have presented puzzles to taxonomists. In the present study, approximately 397 bases of the cytochrome b gene, 364 bases of the 12S rRNA gene, and 74 bases of the tRNA(Thr) and tRNA(Pro) genes from the giant panda, lesser panda, kinkajou, raccoon, coatimundi, and all species of the Ursidae were sequenced. The high transition/transversion ratios in cytochrome b and RNA genes prior to saturation suggest that the presumed transition bias may represent a trend for some mammalian lineages rather than strictly a primate phenomenon. Transversions in the 12S rRNA gene accumulate in arctoids at about half the rate reported for artiodactyls. Different arctoid lineages evolve at different rates: the kinkajou, a procyonid, evolves the fastest, 1.7-1.9 times faster than the slowest lineage that comprises the spectacled and polar bears. Generation-time effect can only partially explain the different rates of nucleotide substitution in arctoids. Our results based on parsimony analysis show that the giant panda is more closely related to bears than to the lesser panda; the lesser panda is neither closely related to bears nor to the New World procyonids. The kinkajou, raccoon, and coatimundi diverged from each other very early, even though they group together. The polar bear is closely related to the spectacled bear, and they began to diverge from a common mitochondrial ancestor approximately 2 million years ago. Relationships of the remaining five bear species are derived.


Conducting Polymer Based Nanobiosensors.
In recent years, conducting polymer (CP) nanomaterials have been used in a variety of fields, such as in energy, environmental, and biomedical applications, owing to their outstanding chemical and physical properties compared to conventional metal materials. In particular, nanobiosensors based on CP nanomaterials exhibit excellent performance sensing target molecules. The performance of CP nanobiosensors varies based on their size, shape, conductivity, and morphology, among other characteristics. Therefore, in this review, we provide an overview of the techniques commonly used to fabricate novel CP nanomaterials and their biosensor applications, including aptasensors, field-effect transistor (FET) biosensors, human sense mimicking biosensors, and immunoassays. We also discuss prospects for state-of-the-art nanobiosensors using CP nanomaterials by focusing on strategies to overcome the current limitations.


Critical values in anatomic pathology.
Similar to critical values (CVs) in clinical pathology, occasional diagnoses in surgical pathology and cytology could require immediate notification of the physician to rapidly initiate treatment. However, there are no established CV guidelines in anatomic pathology. A retrospective review of surgical pathology reports was recently conducted to study the incidence of CVs in surgical pathology and to survey the perceptions of pathologists and clinicians about CVs in surgical pathology, with a similar analysis of CVs performed in cytology. The results indicated that CVs in surgical pathology and cytology are uncommon but not rare and that there is a wide range of opinion among pathologists and between pathologists and clinicians about the need for an immediate telephone call and about the degree of urgency. It was obvious from the study that there is a lack of consensus in identifying what constitutes surgical pathology and cytology CV cases. Since the Institute of Medicine's report on medical errors, there has been an increasing number of initiatives to improve patient safety. Having guidelines for anatomic pathology CVs could enhance patient safety, in contrast to the current practice in which CV cases are managed based on common sense and on personal experience. Therefore, a discussion involving the pathology community might prove useful in an attempt to establish anatomic pathology CV guidelines that could represent a practice improvement.


Characterization and genetic analysis of bovine alpha S1-casein I variant.
The aim of this study was to identify the molecular genetic origin underlying the I variant of alpha(s1)-casein and to develop a DNA-based test for this polymorphism as a tool for genetic analyses independent of milk sample testing. All coding exons and flanking regions of the alpha(s1)-casein gene were sequenced in DNA samples from cattle of known alpha(s1)-casein genotypes (BI, CI, II, CC), determined by isoelectric focusing of milk samples. A nucleotide substitution (A>T) in exon 11 (g.19836A>T) leads to the exchange of Glu with Asp at amino acid position 84 of the mature protein (p.Glu84Asp) and perfectly co-segregated with the presence of the alpha(s1)-casein I variant in the milk of the analysed animals. Genotyping of a total of 680 DNA samples from 31 Bos taurus and Bos indicus cattle breeds and from Bos grunniens, Bison bison and Bison bonasus by restriction fragment length polymorphism analysis revealed the occurrence of Asp at position 84 at low frequencies in Bos taurus and Bos indicus breeds and established its origin from the alpha(s1)-casein C variant (p.Glu192Gly). Ten different intragenic haplotypes in the gene region from intron 8 to intron 12 were observed by sequencing, of which two occurred in Bison bison and one in Bison bonasus only. Using available casein gene complex information, an association of Asp at position 84 to beta-casein A(2) and kappa-casein B was shown in the Bos indicus breed Banyo Gudali. Taken together, we can postulate that the alpha(s1)-casein variant I is caused by a non-synonymous nucleotide substitution in exon 11 of the gene and that it originated within Bos indicus and spread to Bos taurus subsequently.


Identification of key serum biomarkers for the diagnosis and metastatic prediction of osteosarcoma by analysis of immune cell infiltration.
The role of circular RNAs (circRNAs) and microRNAs (miRNAs) in osteosarcoma (OS) development has not been fully elucidated. Further, the contribution of the immune response to OS progression is not well defined. However, it is known that circRNAs and miRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of many cancers. Thus, the aim of this study was to identify novel key serum biomarkers for the diagnosis and metastatic prediction of OS by analysis of immune cell infiltration and associated RNA molecules. Human OS differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified by analysis of microarray data downloaded from Gene Expression Omnibus (GEO) datasets. Further, characteristic patterns of OS-infiltrating immune cells were analyzed. On this basis, we identified statistically significant transcription factors. Moreover we performed pathway enrichment analysis, constructed protein-protein interaction networks, and devised competitive endogenous RNA (ceRNA) networks. Biological targets of the ceRNA networks were evaluated and potential OS biomarkers confirmed by RT-qPCR analysis of the patients' serum. Seven differentially expressed circRNAs, 166 differentially expressed miRNAs, and 175 differentially expressed mRNAs were identified. An evaluation of cellular OS infiltration identified the highest level of infiltration by M0 macrophages, M2 macrophages, and CD8+ T cells, with M0 macrophages and CD8+ T cells as the most prominent. Significant patterns of tumor-infiltrating immune cells were identified by principal component analysis. Moreover, 185 statistically significant transcription factors were associated with OS. Further, in association with immune cell infiltration, hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A were identified as potential novel biomarkers for OS diagnosis. Of these, FAM98A had the most promise as a diagnostic marker for OS and OS metastasis. Most importantly, a novel diagnostic model consisting of these four biomarkers (hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A) was established with a 0.928 AUC value. In summary, potential serum biomarkers for OS diagnosis and metastatic prediction were identified based on an analysis of immune cell infiltration. A novel diagnostic model consisting of these four promising serum biomarkers was established. Taken together, the results of this study provide a new perspective by which to understand immunotherapy of OS.


Selective uptake of cytosolic, peroxisomal, and plasma membrane proteins into the yeast lysosome for degradation.
When glucose-starved cells are replenished with glucose, the key gluconeogenic enzyme, fructose-1,6-bisphosphatase (FBPase), is selectively targeted from the cytosol to the yeast lysosome (vacuole) for degradation. The glucose-induced targeting of FBPase to the vacuole for degradation occurs in cells grown under a variety of metabolic conditions. Immunoelectron microscopic studies demonstrate that the uptake of FBPase by the vacuole is mediated in part by an autophagic process. FBPase can be found on the vacuolar membrane and also at the sites of membrane invaginations. Furthermore, FBPase is associated with different forms of vesicles, which are induced to accumulate inside the vacuole. We have identified peroxisomes as the organelles that are delivered to the vacuole for degradation when cells are replenished with glucose. Ultrastructural studies indicate that peroxisomes are engulfed by the vacuole by an autophagic process, leading to the destruction of whole organelles in the vacuole. Furthermore, the galactose transporter (Gal2p) is also delivered from the plasma membrane to the vacuole for degradation in response to glucose. Gal2p is delivered to the vacuole through the endocytic pathway, as mutants defective in receptor-mediated endocytosis fail to degrade Gal2p in response to glucose.


Ventricular arrhythmogenesis following slowed conduction in heptanol-treated, Langendorff-perfused mouse hearts.
Arrhythmogenic effects of slowed action potential conduction produced by the gap junction and sodium-channel inhibitor heptanol (0.1-2 mM) were explored in Langendorff-perfused mouse hearts. Monophasic action potential recordings showed that 2 mM heptanol induced ventricular tachycardia in the absence of triggered activity arising from early or after-depolarizations during regular 8 Hz pacing and programmed electrical stimulation (PES). It also increased activation latencies and ventricular effective refractory periods (VERPs), but did not alter action potential duration (APD), thereby reducing local critical intervals for re-excitation given by APD(90) - VERP. Bipolar electrogram recordings showed that 2 mM heptanol increased electrogram duration (EGD) and ratios of EGDs obtained at the longest to those obtained at the shortest S1S2 intervals studied during PES, suggesting increased dispersion of conduction velocities. These findings show, for the first time in the mouse heart, that slowed conduction induces reversible arrhythmogenic effects despite repolarization abnormalities expected to reduce arrhythmogenicity.


Reasons for not participating in scleroderma patient support groups: a comparison of results from the North American and European scleroderma support group surveys.
Many people with scleroderma rely on peer-led support groups as a coping resource. Reasons for not attending support groups in scleroderma have been investigated only in North American participants. This study assesses reasons for nonattendance in European countries and compares results with previously published North American findings. The same 21-item survey as used in the North American sample assessed possible reasons for not attending scleroderma support groups. Proportions of items rated Important or Very Important were compared between samples. Consistent with the North American survey findings (N = 242), the two items most commonly rated as (Very) Important reasons for nonattendance among 228 European participants were (1) already having enough support (57%), and (2) not knowing of any local scleroderma support groups (58%). Compared to North American non-attenders, European patients were significantly more likely to rate not knowing enough about what happens at support groups (46% vs 19%), not having reliable ways to get to meetings (35% vs 17%), and being uncomfortable sharing experiences with a group (22% vs 11%) as (Very) Important reasons for nonattendance. Improving access to European support groups, providing education about support groups and group leader training may encourage participation.IMPLICATIONS FOR REHABILITATIONRehabilitation professionals might help develop local support groups for people with systemic sclerosis (scleroderma) to address the lack of access to these groups for many patients.The need for transportation and limited local accessibility may also be addressed by implementing online systemic sclerosis support groups.Professionals in the field of rehabilitation may work with people with systemic sclerosis and patient organizations to provide education about support groups to improve support group attendance in Europe.


Oral administration of synthetic retinoid Am80 (Tamibarotene) decreases brain beta-amyloid peptides in APP23 mice.
The purpose of this study is to investigate whether a synthetic retinoid Am80 (tamibarotene) exhibits any improving effects on amyloid precursor protein (APP)23 mice, a model of Alzheimer's disease. Am80 was orally administered in feed to 20-week (5-month)-old APP23 mice at a dose of 0 (control) or 0.5 mg/kg/d for 14 weeks. The Am80 treatment reduced significantly the insoluble Abeta levels in brain, in particular Abeta(42), while it gave no apparent effects on the soluble Abeta levels. The results suggest that oral administration of Am80 may have potency to reduce the extracellular Abeta(42) of insoluble and possibly oligomeric or protofibril forms, which are related to the cause and/or progression of Alzheimer's disease. The Am80 treatment showed no significant effect on spatial learning and memory of APP23 mice by Morris water maze analysis. The main reason for the absence of significance seems based on the large deviation and some mice both in the treated and the non-treated groups would neither swim nor make efforts to reach the platform.


Ctf1, a transcriptional activator of cutinase and lipase genes in Fusarium oxysporum is dispensable for virulence.
Cutinolytic enzymes are secreted by fungal pathogens attacking the aerial parts of the plant, to facilitate penetration of the outermost cuticular barrier of the host. The role of cutinases in soil-borne root pathogens has not been studied thus far. Here we report the characterization of the zinc finger transcription factor Ctf1 from the vascular wilt fungus Fusarium oxysporum, a functional orthologue of CTF1alpha that controls expression of cutinase genes and virulence in the pea stem pathogen Fusarium solani f. sp. pisi. Mutants carrying a Deltactf1 loss-of-function allele grown on inducing substrates failed to activate extracellular cutinolytic activity and expression of the cut1 and lip1 genes, encoding a putative cutinase and lipase, respectively, whereas strains harbouring a ctf1(C) allele in which the ctf1 coding region was fused to the strong constitutive Aspergillus nidulans gpdA promoter showed increased induction of cutinase activity and gene expression. These results suggest that F. oxysporum Ctf1 mediates expression of genes involved in fatty acid hydrolysis. However, expression of lip1 during root infection was not dependent on Ctf1, and virulence of the ctf1 mutants on tomato plants and fruits was indistinguishable from that of the wild-type. Thus, in contrast to the stem pathogen F. solani, Ctf1 is not essential for virulence in the root pathogen F. oxysporum.


The views of U.S. medical school deans toward academic primary care.
To understand the views of U.S. medical school deans about their primary care faculties. In 2000, the authors mailed a questionnaire containing 43 multipart items to deans of 130 U.S. allopathic medical schools. The questionnaire assessed the deans' attitudes about and evaluation of primary care at their school and their school's efforts to strengthen it. Deans were asked to compare family medicine, general internal medicine, and general pediatrics with nonprimary care clinical departments at their schools. Of the 83 (64%) deans who responded, 82% reported their school had departments or divisions of family medicine, general internal medicine, and general pediatrics. Deans rated general internal medicine and general pediatrics higher than nonprimary care faculty on clinical expertise and productivity (p < .001) and family medicine equivalent to nonprimary care faculty. Deans rated all three primary care faculties superior to nonprimary care faculty for teaching skills (p < .001) and programs (p < .05), but lower than nonprimary care disciplines for research productivity (p < .01) and revenues (p < .001). They rated family medicine and general pediatrics lower for research skills (p < .001), but 73% of deans stated research was equally important for primary care and nonprimary care departments. Deans considered overall financial resources to be equivalent for primary care and nonprimary care departments, but 77% of deans felt primary care departments or divisions needed financial support from the medical school to survive. Most deans attempted to strengthen primary care by changing the curriculum to promote primary care and by providing financial support. Deans ranked primary care faculty high on clinical and teaching measures. Although they considered research to be an important activity for primary care faculty, they evaluated it low relative to nonprimary care departments.


Prevalence of Multiple Sclerosis (MS) in Zanjan Province of Iran.
The prevalence of multiple sclerosis (MS) varies in different geographical regions and has dramatically increased in Iran. Revealing the high prevalence rate draws the attention of policymakers and helps them allocate necessary resources. The aim of this study is to determine the prevalence of MS in Zanjan province of Iran. We included all registered residents of Zanjan province with MS on the prevalence day (July 31, 2019). All cases met the McDonald criteria. All registered cases in Zanjan MS society were identified as index cases. Data regarding patient's national code, gender, age, age at the first symptom onset, city of residence, marital status, education level, occupation, ethnicity, family history of MS and the time span between symptom's onset and disease diagnosis were recorded. We identified 758 patients, 551 of whom (72.7%) were female. The mean age at the first symptom onset was 28.9 ±8.7 years old. The crude prevalence was 71.6 per 100,000 population (95% CI 66.6-76.9). The disease was most prevalent in Zanjan city (100.5 per 100,000). The gender-specific prevalence per 100,000 population was 105.4 for women (95% CI: 96.8-114.6) and 38.7 for men (95% CI: 33.6-44.1), with female to male ratio of 2.6. The standardized mortality ratio (SMR) was calculated as expected/observed for both men and women as 2.3 (207/88.2) (551/234.1). Our data confirm that the MS prevalence rate is high in Zanjan province of Iran.


Increasing self-efficacy and knowledge through a seizure education program for special education teachers.
Since the passage of the 1975 Education for All Handicapped Children Act and the 1986 PL99-457 amendment, many children aged birth to 3 years with special health care needs are enrolled in early intervention programs. Educators working in early intervention services often need to respond to and manage seizure activity and medical emergencies for special needs children. To do so, they need to have knowledge and confidence in their ability to intervene effectively. This intervention study was designed to address the knowledge and self-efficacy of 28 special needs educators on seizure management. The intervention resulted in increased knowledge, skills, and self-efficacy related to seizure management and their ability to interact supportively with families.


Hypervirulent Klebsiella pneumoniae serotype K1 clinical isolates form robust biofilms at the air-liquid interface.
The prevalence of a new hypervirulent and hypermucoviscous K. pneumoniae phenotype (Hmv) is increasing worldwide, mainly linked to serotypes K1 and K2. Since capsular thickness can directly affect the capability to form biofilms, we aimed to evaluate the association between the Hmv phenotype with adhesion and biofilm formation in a collection of clinical K. pneumoniae isolates. We selected 38 Hmv clinical isolates [15 serotype K1; 9 serotype K2; 3 non-K1/K2 (rmpA+); 11 non-K1/K2 (rmpA-)] and 7 non-Hmv clinical isolates. The Hmv phenotype was assessed through the mucoviscosity test. Serum resistance was determined by bacterial viability tests in pooled human serum. Adhesion was evaluated with the Biofilm Ring Test®, and biofilm formation was identified by crystal violet staining (Solid-Liquid, SLI-biofilm) or visual examination (Air-Liquid, ALI-biofilm). This study linked for the first time the formation of robust ALI-biofilm plugs by K. pneumoniae to the capsular serotype K1, a group of hypervirulent strains which are generally highly susceptible to the antimicrobial agents. Among all the studied isolates, the capsular serotype K1 presented lower initial adhesion despite having the adhesins mrkD and fimH but higher ALI-biofilm formation than isolates with other capsular serotypes (K2 or non-K1/K2). This structure might confer increased resistance to a group of hypervirulent K. pneumoniae serotype K1.


Toward Better Accuracy-Efficiency Trade-Offs: Divide and Co-Training.
The width of a neural network matters since increasing the width will necessarily increase the model capacity. However, the performance of a network does not improve linearly with the width and soon gets saturated. In this case, we argue that increasing the number of networks (ensemble) can achieve better accuracy-efficiency trade-offs than purely increasing the width. To prove it, one large network is divided into several small ones regarding its parameters and regularization components. Each of these small networks has a fraction of the original one's parameters. We then train these small networks together and make them see various views of the same data to increase their diversity. During this co-training process, networks can also learn from each other. As a result, small networks can achieve better ensemble performance than the large one with few or no extra parameters or FLOPs, i. e., achieving better accuracy-efficiency trade-offs. Small networks can also achieve faster inference speed than the large one by concurrent running. All of the above shows that the number of networks is a new dimension of model scaling. We validate our argument with 8 different neural architectures on common benchmarks through extensive experiments.


Abnormal diffusion-weighted magnetic resonance images in Creutzfeldt-Jakob disease.
Traditional imaging methods, including computed tomography, routine magnetic resonance imaging (MRI), and magnetic resonance spectroscopy, have not been particularly useful in the diagnosis of Creutzfeldt-Jakob disease (CJD). Although abnormalities can be seen using these methods, the findings are evident only late in the disease or lack specificity or sensitivity. To describe abnormalities on diffusion-weighted MRIs in 4 patients with proven CJD. Diffusion-weighted MRIs were obtained on 4 patients with CJD as part of a routine MRI brain examination. In all 4 patients, diffusion-weighted MRIs of the brain demonstrated bilateral hyperintensity in the basal ganglia. In 1 patient, the most conspicuous abnormality seen in diffusion-weighted images was in the thalamus. Two patients also demonstrated hyperintensity in the cerebral cortex on diffusion-weighted images. Only 2 of 4 patients demonstrated clear abnormalities on routine (non-diffusion-weighted) MRIs. Diffusion abnormalities were visible in 1 patient within 1 month of symptom onset. The findings were most conspicuous and extensive in the patient with the longest duration of symptoms (7 months). Diffusion-weighted MRI might provide a noninvasive method of identifying patients with CJD. However, further investigations must be performed to determine the specificity of these findings for CJD.


Muscle differentiation: how two cells become one.
A key feature of myogenesis is the fusion of myoblasts to form multinucleate myotubes. Recent work in Drosophila has uncovered a collection of genes that operate at different stages of this process. Some interactions between them have been described that begin to define links from outside the cell via the plasma membrane to the cytoskeleton. Future studies will establish the extent to which the molecular mechanisms of myoblast fusion are conserved between Drosophila and other animals, as found in other aspects of myogenesis.


Epiphrenic Diverticulum in an Infant with Congenital Esophageal Stenosis Associated with Esophageal Atresia.
Congenital esophageal stenosis (CES) is a rare congenital disorder which may be isolated or associated with esophageal atresia (EA). It courses with esophageal outflow tract obstruction. Esophageal epiphrenic diverticulae are esophageal outpouchings above diaphragm which develop because of an underlying esophageal motor disorder. We present an infant who had CES associated with EA detected during the course of routine follow-up. She underwent several sessions of esophageal balloon dilatations for CES with some symptomatic improvement. However, an epiphrenic diverticulum (ED) developed during the course of treatment which was detected by further investigations. A surgical excision was performed with a successful outcome. An ED developed secondary to CES has not been previously reported. We have highlighted the diagnostic modalities employed, treatment options, and clinical follow-up for these two rare conditions in children.


Genetic polymorphisms and transcriptional pattern analysis of CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes in breast cancer.
In order to detect the contribution of cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), glutathione S-transferases M1 (GSTM1), P1 (GSTP1), and T1 (GSTT1) genes in breast cancer, genetic analysis was performed, as well as transcriptional analysis in sporadic primary tumours and corresponding adjacent normal tissues from the same patient. CYP1A1 3'-untranslated region (3'-UTR) termed as m1 (MspI) polymorphism and the null(-) deletions of both GSTM1 and GSTT1 genes were examined in genomic DNA from blood samples of 207 female breast cancer patients and 171 age and sex matched controls. The frequencies of the m1 genotype of the CYP1A1 gene in cases and controls were 0.13 and 0.15, while the frequencies of homozygotes with GSTM1(-) were 0.52, in each, and for homozygotes with GSTT1(-) were 0.14 and 0.10, respectively. Statistical analysis of these genotypes in combinations did not reveal any significant difference between the breast cancer population and the control group. Expression of mRNA levels of CYP1A1, GSTM1, GSTP1, GSTT1 and AhR genes in 31 breast cancer patients, revealed inter-individual variation in an independent manner to patient age, genotype, or tumour stage. Eighty-seven percent of the tumour specimens tested were deregulated, compared to their normal counterparts, in at least one locus. Up-regulation of CYP1A1 was observed only when one of the GSTM1 or GSTP1 was down-regulated while the other remained constant. Genotyping analysis did not show any correlation to breast cancer risk. However, RT-PCR analysis provided evidence that CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes are frequently deregulated in breast cancer and could be used as molecular biomarkers for better clinical management of such patients, with respect to chemotherapy.


Regeneration of the lung: Lung stem cells and the development of lung mimicking devices.
Inspired by the increasing burden of lung associated diseases in society and an growing demand to accommodate patients, great efforts by the scientific community produce an increasing stream of data that are focused on delineating the basic principles of lung development and growth, as well as understanding the biomechanical properties to build artificial lung devices. In addition, the continuing efforts to better define the disease origin, progression and pathology by basic scientists and clinicians contributes to insights in the basic principles of lung biology. However, the use of different model systems, experimental approaches and readout systems may generate somewhat conflicting or contradictory results. In an effort to summarize the latest developments in the lung epithelial stem cell biology, we provide an overview of the current status of the field. We first describe the different stem cells, or progenitor cells, residing in the homeostatic lung. Next, we focus on the plasticity of the different cell types upon several injury-induced activation or repair models, and highlight the regenerative capacity of lung cells. Lastly, we summarize the generation of lung mimics, such as air-liquid interface cultures, organoids and lung on a chip, that are required to test emerging hypotheses. Moreover, the increasing collaboration between distinct specializations will contribute to the eventual development of an artificial lung device capable of assisting reduced lung function and capacity in human patients.


Semicarbazide-sensitive amine oxidase and kidney disease.
With better understanding of the molecular mechanisms underpinning chronic kidney disease, the roles of inflammation and fibrosis are becoming increasingly inseparable. The progression of renal disease is characterized by pathomorphological changes that consist of early inflammatory responses followed by tubulointerstitial fibrosis, tubular atrophy, and glomerular and vascular sclerosis. Currently available therapies that reduce hypertension, proteinuria, hyperglycemia, and interruption of the renin-angiotensin-aldosterone system are at best only partially effective. Hence, there remains a need to explore agents targeting nonrenin-angiotensin-aldosterone system pathways. In this review, we discuss mechanistic aspects in the physiological and pathological role of semicarbazide-sensitive amine oxidase, a protein enzyme involved in cellular trafficking and inflammation, with respect to the kidney. We explore the evidence for the use of semicarbazide-sensitive amine oxidase inhibitors as potential agents in renal fibrosis to delay the onset and progression of chronic kidney disease.


Characteristics of socially successful elementary school-aged children with autism.
The extant literature demonstrates that children with autism spectrum disorder (ASD) often have difficulty interacting and socially connecting with typically developing classmates. However, some children with ASD have social outcomes that are consistent with their typically developing counterparts. Little is known about this subgroup of children with ASD. This study examined the stable (unlikely to change) and malleable (changeable) characteristics of socially successful children with ASD. This study used baseline data from three intervention studies performed in public schools in the Southwestern United States. A total of 148 elementary-aged children with ASD in 130 classrooms in 47 public schools participated. Measures of playground peer engagement and social network salience (inclusion in informal peer groups) were obtained. The results demonstrated that a number of malleable factors significantly predicted playground peer engagement (class size, autism symptom severity, peer connections) and social network salience (autism symptom severity, peer connections, received friendships). In addition, age was the only stable factor that significantly predicted social network salience. Interestingly, two malleable (i.e., peer connections and received friendships) and no stable factors (i.e., age, IQ, sex) predicted overall social success (e.g., high playground peer engagement and social network salience) in children with ASD. School-based interventions should address malleable factors such as the number of peer connections and received friendships that predict the best social outcomes for children with ASD.


The Plastidic Sugar Transporter pSuT Influences Flowering and Affects Cold Responses.
Sucrose (Suc) is one of the most important types of sugars in plants, serving inter alia as a long-distance transport molecule, a carbon and energy storage compound, an osmotically active solute, and fuel for many anabolic reactions. Suc biosynthesis and degradation pathways are well known; however, the regulation of Suc intracellular distribution is poorly understood. In particular, the cellular function of chloroplast Suc reserves and the transporters involved in accumulating these substantial Suc levels remain uncharacterized. Here, we characterize the plastidic sugar transporter (pSuT) in Arabidopsis (Arabidopsis thaliana), which belongs to a subfamily of the monosaccharide transporter-like family. Transport analyses with yeast cells expressing a truncated, vacuole-targeted version of pSuT indicate that both glucose and Suc act as substrates, and nonaqueous fractionation supports a role for pSuT in Suc export from the chloroplast. The latter process is required for a correct transition from vegetative to reproductive growth and influences inflorescence architecture. Moreover, pSuT activity affects freezing-induced electrolyte release. These data further underline the central function of the chloroplast for plant development and the modulation of stress tolerance.


Moisturization and skin barrier function.
Over the past decade, great progress has been made toward elucidating the structure and function of the stratum corneum (SC), the outermost layer of the epidermis. SC cells (corneocytes) protect against desiccation and environmental challenge by regulating water flux and retention. Maintenance of an optimal level of hydration by the SC is largely dependent on several factors. First, intercellular lamellar lipids, organized predominantly in an orthorhombic gel phase, provide an effective barrier to the passage of water through the tissue. Secondly, the diffusion path length also retards water loss, since water must traverse the tortuous path created by the SC layers and corneocyte envelopes. Thirdly, and equally important, is natural moisturizing factor (NMF), a complex mixture of low-molecular-weight, water-soluble compounds first formed within the corneocytes by degradation of the histidine-rich protein known as filaggrin. Each maturation step leading to the formation of an effective moisture barrier--including corneocyte strengthening, lipid processing, and NMF generation--is influenced by the level of SC hydration. These processes, as well as the final step of corneodesmolysis that mediates exfoliation, are often disturbed upon environmental challenge, resulting in dry, flaky skin conditions. The present paper reviews our current understanding of the biology of the SC, particularly its homeostatic mechanisms of hydration.


Safe and rapid palliation of dysphagia for carcinoma of the esophagus.
Patients with carcinoma of the esophagus continue to present late when their tumors are inoperable. This makes palliation of their dysphagia the main therapeutic aim. The Nd-YAG laser has been used in our department to treat dysphagia resulting from cancer of the esophagus since 1986. Our rapid, one-stage cannulation technique using the Nd-YAG laser in both contact and noncontact modes was applied to 35 cases of carcinoma of the esophagus with the aim of achieving rapid and safe palliation of dysphagia. During the treatment we aimed not to coagulate the tumor and await sloughing, but to vaporize the tumor and ablate as much as possible in a single session. In this way there was less need for repeat sessions to create an adequate lumen. In a small number of patients (9) who had tight strictures with no visible lumen, a pre-laser dilation was required to allow visualization of the lumen and tumor vaporization. For nondilated patients (26) we achieved a 15-mm lumen in an average of 1.6 sessions, and in the dilated patients (9) this was achieved in one session in all patients. Functional improvement occurred in 28 patients (80%). There were four minor complications and no mortality associated with the procedure.


Genetic analysis of recently identified osteoporosis susceptibility genes in southern Chinese.
Fifty-six genomic loci recently were identified as associated with bone mineral density (BMD) in a large meta-analysis study of mainly European-descent subjects. Circulating factors related to calcium and phosphate metabolism, eg, serum levels of calcium, phosphate, vitamin D metabolites, PTH, and alkaline phosphatase (ALP), may affect bone turnover and metabolism. We aimed to investigate the effects of these reported variants, as well as their interactions with 5 studied circulating factors, on BMD in a southern Chinese prospective cohort (n = 2670). The identified interactions were further replicated in an independent cohort of 800 Chinese females. Approximately half (n = 27) of the reported variants were successfully replicated in our sample of southern Chinese individuals. We further demonstrated a significant interaction between MARK3 and serum ALP levels (Pmeta = 9.89 ×10(-6)); the effect of MARK3 rs11623869 on BMD was stronger in the presence of high serum levels of ALP. In addition, several interactions between other genes and circulating factors were suggested. Our study has provided an independent replication of associations between several reported loci and BMD in a large sample of southern Chinese individuals. These replicated loci may represent osteoporosis susceptibility genes in both Chinese and European-descent populations. Furthermore, we have shown that serum ALP levels modified the association of MARK3 with BMD. Understanding the mechanisms of the interactions between BMD-related loci and circulating factors may help to determine the pathogenesis of susceptibility to osteoporosis and could have implications for clinical care.


Two new acylgluconic acids from the nearly ripe fruits of Evodia rutaecarpa.
Two new acylgluconic acids, trans-feruloylgluconic acid (1) and trans-caffeoylgluconic acid (2), together with three known compounds, myo-inositol (3), phthalic acid dibutyl ester (4), and wuzhuyuamide-I (5), were isolated from the water soluble part of the dried nearly ripe fruits of Evodia rutaecarpa (Juss.) Benth. Their structures were determined by spectroscopic methods, including IR, UV, ESITOFMS, HRSIMS, 1D and 2D NMR spectral analyses.


Bisphosphonates inhibit the growth of mesothelioma cells in vitro and in vivo.
Bisphosphonates (such as risedronate and zoledronate) are widely used inhibitors of bone resorption. Despite their in vitro antiproliferative effects in various cancer cells, bisphosphonates have not exhibited significant antitumor efficacy in animal models of visceral cancer, which may be due to their poor bioavailability. The diagnostic use of radioactive bisphosphonates has revealed the accumulation of bisphosphonates in mesothelioma, which prompted us to test the antitumor efficacy of bisphosphonates in this disease. Treatment with either risedronate or zoledronate (2 x 10(-4) to 2 x 10(-6) mol/L) inhibited the growth of AB12 and AC29 mouse mesothelioma cells and induced the accumulation of unprenylated Rap1A in these cells. Both these in vitro effects were reversed by geranygeraniol, an end product of the mevalonate pathway that these bisphosphonates inhibit. Both bisphosphonates also induced the phosphorylation of the p38 mitogen-activated protein kinase in AB12 and AC29 cells. The inhibition of p38 augmented bisphosphonate-induced growth inhibition in these cells. Bisphosphonate-induced p38 phosphorylation was not reversible by geranylgeraniol. Risedronate (15 mg/kg) and zoledronate (0.5 mg/kg) inhibited the growth of s.c. tumors and increased the median survival of mice with i.p. mesothelioma tumors in vivo. In conclusion, risedronate and zoledronate inhibit the mevalonate pathway and induce p38 activation in mesothelioma cells in vitro. The effects on the mevalonate pathway dominate because the net result is growth inhibition. Both bisphosphonates also inhibit mesothelioma tumor growth in vivo and prolong the survival of mesothelioma-bearing mice. These results support further study of bisphosphonates in the management of mesothelioma.


Microarray analysis of the hyperthermophilic archaeon Pyrococcus furiosus exposed to gamma irradiation.
The remarkable survival of the hyperthermophilic archaeon Pyrococcus furiosus to ionizing radiation was previously demonstrated. Using a time course study and whole-genome microarray analyses of mRNA transcript levels, the genes and regulatory pathways involved in the repair of lesions produced by ionizing irradiation (oxidative damage and DNA strand breaks) in P. furiosus were investigated. Data analyses showed that radA, encoding the archaeal homolog of the RecA/Rad51 recombinase, was moderately up regulated by irradiation and that a putative DNA-repair gene cluster was specifically induced by exposure to ionizing radiation. This novel repair system appears to be unique to thermophilic archaea and bacteria and is suspected to be involved in translesion synthesis. Genes that encode for a putative Dps-like iron-chelating protein and two membrane-bound oxidoreductases were differentially expressed following gamma irradiation, potentially in response to oxidative stress. Surprisingly, the many systems involved in oxygen detoxification and redox homeostasis appeared to be constitutively expressed. Finally, we identified several transcriptional regulators and protein kinases highly regulated in response to gamma irradiation.


Identification of Lys116 as the target of N-ethylmaleimide inactivation of ferredoxin:NADP+ oxidoreductase.
Oxidized ferredoxin:NADP+ oxidoreductase (FNR) was slowly and irreversibly inactivated by N-ethylmaleimide. Complete protection against inactivation was afforded by saturating concentrations of NADP+. In the presence of NADPH, a rapid inhibition of the enzyme ensued; however, this inhibition was found to be reversible. In the tryptic map of the flavoprotein, modified with N-ethyl[2,3-14C]maleimide in oxidizing conditions, a unique radioactive peptide was found. Its sequence comprised residues 110-117 of the enzyme: Lys116 was shown to be the residue alkylated by N-ethylmaleimide. It is noteworthy that the same residue of FNR was found to be modified by 5-dimethylaminoaphthalene-1-sulfonyl(dansyl) chloride at the putative NADP(H)-binding site [Cidaria, D., Biondi, P. A., Zanetti, G. & Ronchi, S. (1985) Eur. J. Biochem. 146, 295-299]. Furthermore, the data reported here demonstrate that the sulfhydryl groups of FNR are not involved in enzyme inactivation by N-ethylmaleimide.


Familial parkinsonism, dementia, and Lewy body disease: study of family G.
Genetic influences are thought by many to play an important role in the cause of Parkinson's disease. We studied two closely intermarried families (Family G) whose ancestors immigrated to the United States from Russia. We investigated this family clinically, genealogically, and pathologically. Our pedigree contained 102 members spanning six generations, with 10 affected individuals and 1 affected spouse. Detailed telephone interviews were conducted with affected individuals, with their spouses, and with their at-risk siblings. Medical records of deceased and living affected patients were collected. Physical examinations were performed on 7 at-risk and 5 affected persons. Typical levodopa-responsive parkinsonism with bradykinesia, rigidity, resting tremor, and impaired postural reflexes was seen in 4 members, dementia was present in 3, and 3 had both dementia and parkinsonism. An autopsy completed on 1 individual, our index case, demonstrated Lewy bodies in the brainstem and neocortex and ubiquitin-positive neuritic degeneration in the CA2-3 region of the hippocampus, consistent with the limbic (transitional) form of Lewy body disease. This family is distinct both clinically and pathologically from several previously reported parkinsonian kindreds.


The rationale and use of three-dimensional radiation treatment planning for lung cancer.
Treatment of lung cancer with conventional radiation therapy is associated with suboptimal local tumor control and poor long-term survival. Poor local tumor control may result from inaccurate tumor targeting, failure to satisfactorily conform to dose distribution with the target volume, and/or inadequate radiation doses. Three-dimensional treatment planning is a radiotherapy technique that provides more accurate dose targeting via the direct transfer of three-dimensional anatomic information from diagnostic scans into the planning process. This technology can assist treatment planning by providing dose-volume histograms, an estimation of normal tissue complication probabilities, and facilitate dose escalation. Preliminary clinical studies suggest that this is a feasible approach worthy of additional study. The three-dimensional tools provide new opportunities to better understand radiation-induced changes in pulmonary function.


Diagnostic prediction model development using data from dried blood spot proteomics and a digital mental health assessment to identify major depressive disorder among individuals presenting with low mood.
With less than half of patients with major depressive disorder (MDD) correctly diagnosed within the primary care setting, there is a clinical need to develop an objective and readily accessible test to enable earlier and more accurate diagnosis. The aim of this study was to develop diagnostic prediction models to identify MDD patients among individuals presenting with subclinical low mood, based on data from dried blood spot (DBS) proteomics (194 peptides representing 115 proteins) and a novel digital mental health assessment (102 sociodemographic, clinical and personality characteristics). To this end, we investigated 130 low mood controls, 53 currently depressed individuals with an existing MDD diagnosis (established current MDD), 40 currently depressed individuals with a new MDD diagnosis (new current MDD), and 72 currently not depressed individuals with an existing MDD diagnosis (established non-current MDD). A repeated nested cross-validation approach was used to evaluate variation in model selection and ensure model reproducibility. Prediction models that were trained to differentiate between established current MDD patients and low mood controls (AUC = 0.94 ± 0.01) demonstrated a good predictive performance when extrapolated to differentiate between new current MDD patients and low mood controls (AUC = 0.80 ± 0.01), as well as between established non-current MDD patients and low mood controls (AUC = 0.79 ± 0.01). Importantly, we identified DBS proteins A1AG1, A2GL, AL1A1, APOE and CFAH as important predictors of MDD, indicative of immune system dysregulation; as well as poor self-rated mental health, BMI, reduced daily experiences of positive emotions, and tender-mindedness. Despite the need for further validation, our preliminary findings demonstrate the potential of such prediction models to be used as a diagnostic aid for detecting MDD in clinical practice.


Impact of Microfluidization on the Emulsifying Properties of Zein-Based Emulsions: Influence of Diutan Gum Concentration.
Microfluidization is a preparation method that can be used to obtain emulsions with submicron droplet sizes. The first objective of this study was to evaluate the influence of homogenization pressure and cycles on droplet sizes using response surface methodology. Secondly, the influence of the diutan gum concentration incorporated in the optimized emulsion on rheological properties, microstructure, and physical stability was investigated. Taking the response surface analysis into account, the emulsion processed at 20,000 psi after four cycles seemed to show the smallest Sauter diameter values. Hence, this emulsion was the starting point to incorporate diutan gum. Interestingly, the formation of a 3D network in the emulsion, observed by FESEM, was provoked by diutan gum. The emulsion formulated with 0.4 wt.% of diutan gum presented rheological gel properties and enhanced physical stability. This work highlights the importance of selecting optimized processing variables using the microfluidization technique and extends the knowledge of using diutan gum in combination with zein.


Comparison of childhood burns associated with use of microwave ovens and conventional stoves.
To identify the incidence, type, and severity of burns associated with microwave oven (MW) use and to compare MW-associated burns with those associated with use of conventional stoves, we conducted a review of a national data base. Data were obtained from the US Consumer Product Safety Commission Injury Information Clearinghouse for 1986 through 1990 concerning burn injuries to children (0 to 19 years). There were an estimated 5160 burns associated with MW use. The mean age was 7.6 years (median, 6 years); 25% of burns were to children younger than 36 months old. Fifty-eight percent involved females. Most MW burns were scalds (95%); 16% of these scalds were from exploding eggs or other food. No MW burn involved a body surface area greater than 25% and no patient required hospital admission. Microwave oven burns were compared with stove burns. There were an estimated 41198 stove-associated burns to children. The mean age was 5.8 years; the median was 3 years. Forty-five percent of burns were to children younger than 36 months old; 55% were to males. Most stove burns (74%) were thermal; 7% involved a body surface area greater than 25%. Five percent of children with stove burns required hospital admission. We conclude that (1) burns to children associated with MW use are less frequent and less severe than stove burns; (2) MW burns predominantly affect females; and (3) burn prevention efforts should emphasize the hazards of stoves, which vastly exceed those of MWs.


Racial variation in the distribution of Ha-ras-1 alleles.
Restriction fragment length polymorphism analyses of the Ha-ras-1 proto-oncogene were undertaken in white and black populations residing in the Baltimore-Washington metropolitan area to address whether specific rare alleles of the Ha-ras-1 proto-oncogene locus vary in their distribution among different racial groups. High-molecular-weight genomic DNA samples from the lungs of 80 lung cancer patients and 92 accident victims were digested with appropriate restriction enzymes and subjected to Southern analysis using the 6.6-kb BamHI human Ha-ras-1 recombinant fragment from the plasmid pEC. Thirty allelomorphs of different sizes were detected among the 172 study subjects. An association was observed between race and specific alleles. Rare alleles were more frequent in black cancer patients and trauma victims than in whites. Within each racial category, lung cancer patients had an excess of rare alleles. These data indicate the importance of controlling for racial variation when designing studies to determine human cancer risk factors.


Characterization of a novel model of global forebrain ischaemia-reperfusion injury in mice and comparison with focal ischaemic and haemorrhagic stroke.
Stroke is caused by obstructed blood flow (ischaemia) or unrestricted bleeding in the brain (haemorrhage). Global brain ischaemia occurs after restricted cerebral blood flow e.g. during cardiac arrest. Following ischaemic injury, restoration of blood flow causes ischaemia-reperfusion (I/R) injury which worsens outcome. Secondary injury mechanisms after any stroke are similar, and encompass inflammation, endothelial dysfunction, blood-brain barrier (BBB) damage and apoptosis. We developed a new model of transient global forebrain I/R injury (dual carotid artery ligation; DCAL) and compared the manifestations of this injury with those in a conventional I/R injury model (middle-cerebral artery occlusion; MCAo) and with intracerebral haemorrhage (ICH; collagenase model). MRI revealed that DCAL produced smaller bilateral lesions predominantly localised to the striatum, whereas MCAo produced larger focal corticostriatal lesions. After global forebrain ischaemia mice had worse overall neurological scores, although quantitative locomotor assessment showed MCAo and ICH had significantly worsened mobility. BBB breakdown was highest in the DCAL model while apoptotic activity was highest after ICH. VCAM-1 upregulation was specific to ischaemic models only. Differential transcriptional upregulation of pro-inflammatory chemokines and cytokines and TLRs was seen in the three models. Our findings offer a unique insight into the similarities and differences in how biological processes are regulated after different types of stroke. They also establish a platform for analysis of therapies such as endothelial protective and anti-inflammatory agents that can be applied to all types of stroke.


Childhood pancreatitis.
Acute pancreatitis is a rare finding in childhood but probably more common than is generally realized. This condition should be considered in the evaluation of children with vomiting and abdominal pain, because it can cause significant morbidity and mortality. Clinical suspicion is required to make the diagnosis, especially when the serum amylase concentration is normal. Recurrent pancreatitis may be familial as a result of inherited biochemical or anatomic abnormalities. Patients with hereditary pancreatitis are at high risk for pancreatic cancer.


Repeat operations in pediatric patients with recurrent craniopharyngiomas.
Controversy continues over the optimal management of recurrent craniopharyngiomas. Our strategy for approaching repeatedly recurrent craniopharyngiomas in pediatric patients has been to decompress vital structures and relieve the symptoms as early as possible. The purpose of this study was to present our experiences of repeatedly recurrent craniopharyngiomas and the pattern of failure associated with treatment. A retrospective review was conducted on 7 pediatric patients who underwent resection >2 times in a single institution between 1990 and 2004. Resections were performed 3-8 times for each patient. Variables including tumor size, consistency and location, extent of resection, adjuvant therapy and morbidity were evaluated. Thirty-two operations were performed in 7 pediatric patients. Total resection was not achieved by the third surgery and thereafter, and the interval between each surgery became shorter. Appetite disorders, neurocognitive disorders and behavioral disorders occurred following repeat surgeries. Repeat operations are associated with a high failure rate of tumor control, even though they can help relieve neurologic symptoms. It is suggested that the number of repeat operations should be limited.


The use of Lactobacillus rhamnosus in the therapy of bacterial vaginosis. Evaluation of clinical efficacy in a population of 40 women treated for 24 months.
Bacterial vaginosis (BV) is the most prevalent vaginal disorder in adult women worldwide. A number of clinical studies indicate that re-establishment of the physiological ecosystem by re-colonization of vaginal mucosa by lactobacilli may be an effective therapy for BV both after initial antimicrobial therapy or when given alone. A vaginal pH <4.5 is considered physiological and its measurement has been reported as an objective parameter, very sensitive to alterations of vaginal microflora and correlated with clinically relevant BV. The aims of this work were to assess the effectiveness of a long-term (24 months) intravaginal treatment with Lactobacillus rhamnosus (NORMOGIN) on the vaginal pH and on the clinical symptoms in a group of 40 women affected by BV diagnosed by the Amsel criteria. A prospective open clinical trial was performed in 40 consecutive cases evaluated for B.V. by the Amsel criteria. Vaginal pH was above the physiological value of 4.5 in 36 out of 40 patients at the first visit. It returned under 4.5 value in 24/40 and 32/40 women after 12 and 24 months of treatment, respectively. pH values were significantly decreased at 12 month treatment (P < 0.001) and further reduction in pH values was found at 24 months of treatment (P < 0.02 vs. 12 months). The gradual return to a vaginal physiological pH was associated with a reduction of the intensity of symptoms as shown by the decrease in the symptoms score. The present study supports the use of pH measurement for sensitive, objective, and simple therapy follow-up in women with BV and shows that long-term administration of vaginal tablets containing Lactobacillus rhamnosus represents an effective and safe treatment for restoring the physiological vaginal pH and controlling BV symptoms.


Isospin Symmetry at High Spin Studied via Nucleon Knockout from Isomeric States.
One-neutron knockout reactions have been performed on a beam of radioactive ^{53}Co in a high-spin isomeric state. The analysis is shown to yield a highly selective population of high-spin states in an exotic nucleus with a significant cross section, and hence represents a technique that is applicable to the planned new generation of fragmentation-based radioactive beam facilities. Additionally, the relative cross sections among the excited states can be predicted to a high level of accuracy when reliable shell-model input is available. The work has resulted in a new level scheme, up to the 11^{+} band-termination state, of the proton-rich nucleus ^{52}Co (Z=27, N=25). This has in turn enabled a study of mirror energy differences in the A=52 odd-odd mirror nuclei, interpreted in terms of isospin-nonconserving (INC) forces in nuclei. The analysis demonstrates the importance of using a full set of J-dependent INC terms to explain the experimental observations.


Saliva sample pooling for the detection of SARS-CoV-2.
As the battle against coronavirus disease 2019 pandemic continues, an increase in workload and medical expenses have been a concern to the health care system worldwide. Developing a measure that helps to conserve the health care resource is, therefore, highly desirable, and the pooling of the specimens for testing is one of the attractive strategies. Recently, we showed that saliva could be a potential alternative specimen for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time polymerase chain reaction (RT-PCR). In the present study, we performed the pooling of saliva specimens for testing by SARS-CoV-2 RT-PCR. We showed that the saliva pool of either 5 or 10 samples, by allowing the detection of either gene in the pool at an increased cycle threshold cutoff value, further performing individual sample testing in the positive pools did not compromise the detection of SARS-CoV-2.


Effect of fixed orthodontic treatment on oral microbiota and salivary proteins.
The aim of the present prospective comparative cohort study was to analyze changes in Streptococcus (S.) mutans and Lactobacillus in the saliva of patients with fixed orthodontics. Salivary parameters, including secretory immunoglobulin A (sIgA), myeloperoxidase (MPO) and lactate dehydrogenase (LDH), were investigated during orthodontic treatment, as well as immune response and inflammatory processes. A total of 15 patients were included and treated with fixed appliances. Whole saliva was obtained at four time-points: Prior to bonding (T1), 3 months after bonding (T2), 6 months after bonding (T3) and 18 months after bonding (T4). Quantitative polymerase chain reaction was performed to evaluate changes in total bacteria, S. mutans and Lactobacillus DNA in saliva. ELISA was applied to measure sIgA, MPO and LDH levels. The level of total bacteria remained stable during the 18-month treatment period, and the quantity of Lactobacillus exhibited a slight but non-significant increase. S. mutans remained stable over the first 6 months and significantly increased at T4 (P<0.05), and there was a significant difference in S. mutans levels between two types of braces. A higher level of S. mutans was found in patients with conventional braces, as compared to those with self-ligating braces (P<0.05) who exhibited an unchanged level of S. mutans during this period. The amount of sIgA, MPO and LDH remained constant during the orthodontic treatment period. No correlation was detected between sIgA and bacterial quantity. In conclusion, S. mutans in patients with conventional braces increased significantly in the late period of treatment, which indicated that white spot lesions may occur after long-term orthodontic treatment. As the type of braces may be considered a latent influencing factor, self-ligating braces should be preferred. However, the effect of fixed orthodontic treatment on Lactobacillus and sIgA, MPO and LDH in the oral microenvironment was insignificant (Chinese Clinical Trial Registry no. ChiCTR-RCH-13003295).


[Lung problems in acute to subacute exposure to medium altitudes].
The hypobaric hypoxia of moderate altitude elicits various mechanisms of acute to subacute physiologic adaptations of the healthy lung: First of all it causes a hyperventilation, which increases the diminished arterial pO2. Because of hypoxemia-induced vasoconstriction, pulmonary arterial hypertension develops. The adrenergic stimulation of the cardiac output also increases the pulmonary perfusion. Most likely because of the diminished density of ambient air there is a measurable increase of exspiratory bronchial flow or, respectively, a diminution of the peripheral airway resistance. In higher altitudes, limitation of oxygen-diffusion under physical exertion is observed. The consequences of acute hypobaric hypoxia for diseased lungs depend on preexisting ventilation/perfusion mismatch or diffusion impairment. Arterial hypoxemia and hence also pulmonary arterial hypertension are increased. In the presence of normal chemoreceptor sensitivity (type pink puffer), a hyperventilation, which is often perceived as dyspnea by the patient, is induced. Mostly patients with chronic obstructive pulmonary disease adapt, however, surprisingly well to moderate altitude. Bronchial asthma improves frequently because allergen concentrations are low and air density is diminished. On the other hand, physical exertion in dry and cold ambient air may also elicit acute asthmatic exacerbations. The assessment of moderate altitude tolerance by patients with chronic lung diseases and prophylactic precautions before the ascent are discussed. The only altitude-specific disease of the healthy lung is the so-called high-altitude pulmonary edema. The major pathogenetic factor for its development is an inadequate or overshooting response to hypobaric hypoxia (nonuniform pulmonary arterial vasoconstriction, diminished hypoxic ventilatory drive, retention of fluid, centralization of blood volume and capillary leak). Prophylactic and therapeutic implications are discussed.


Roxithromycin: a pharmacokinetic review of a macrolide.
In humans, roxithromycin is rapidly absorbed from the gastrointestinal tract producing peak levels (Cmax) within 2 h. The drug is eliminated with a half-life (T1/2) of about 10 h. Roxithromycin is not extensively metabolized. Approximately 53% is excreted in the faeces and about 10% of the dose is eliminated in urine. Although dose-dependency (with doses from 150 to 450 mg) was observed for certain pharmacokinetic parameters, dose-proportionality could only be demonstrated with urine data. During multiple dosing, steady state is usually reached by day four and is dose-dependent. There is a slight but clinically unimportant increase in the T1/2 of the drug with repeated administration. While the rate of absorption is not affected by age, the rate of elimination and renal clearance are decreased in the elderly subjects. No significant differences were observed for Cmax and Tmax between normal and renally impaired subjects. AUCs and elimination T1/2 were greater, and significantly less drug was excreted in renally impaired patients. In patients with liver cirrhosis Cmax, Tmax, and AUCs are not affected. The bioavailability of the drug is not affected to a clinically important extent when it is given either with milk or food. Less than 0.05% of a single 300 mg dose is excreted in the breast milk of lactating women. After oral dosing a very high concentration of roxithromycin is achieved in pulmonary, prostatic, and tonsillar tissues. However, roxithromycin was not detected in the cerebrospinal fluid of subjects with non-inflamed meninges. It is concluded that 150 mg roxithromycin twice daily or 300 mg once a day should provide plasma levels above the minimum inhibitory concentrations required for antibacterial activity.


Resilience, trauma, context, and culture.
This article reviews the relationship between factors associated with resilience, and aspects of the individual's social ecology (environment) that promote and protect against the negative impact of exposure to traumatic events. It is shown that the Environment × Individual interactions related to resilience can be understood using three principles: (1) Resilience is not as much an individual construct as it is a quality of the environment and its capacity to facilitate growth (nurture trumps nature); (2) resilience looks both the same and different within and between populations, with the mechanisms that predict positive growth sensitive to individual, contextual, and cultural variation (differential impact); and (3) the impact that any single factor has on resilience differs by the amount of risk exposure, with the mechanisms that protect against the impact of trauma showing contextual and cultural specificity for particular individuals (cultural variation). A definition of resilience is provided that highlights the need for environments to facilitate the navigations and negotiations of individuals for the resources they need to cope with adversity. The relative nature of resilience is discussed, emphasizing that resilience can manifest as either prosocial behaviors or pathological adaptation depending on the quality of the environment.


Primary Malignant Melanoma of the Oral Cavity Around Dental Implants: Report of an Unusual Case.
Primary oral melanoma is an uncommon malignant tumor that originates from the proliferation of melanocytes. A 78-year-old man presented with a pigmented lesion around the maxillary anterior implant prosthesis. The lesion was excised and diagnosed as a melanoma. Biopsy showed a malignant pigmented neoplasm that included proliferation of dysplastic melanocytes into the superficial layers of the submucosa. Initial testing, including a positron emission tomography scan, showed no metastasis; however, after 7 months, the patient developed a cervical lymphadenopathy. A neck dissection was performed and indicated that there was metastasis of the primary melanoma. After surgery, the patient received chemotherapy. Histologic examination of the excised lesion revealed the presence of a malignant melanoma in association with a junctional nevus of the oral mucosa. The patient was referred to the oral and maxillofacial department for further evaluation.


Lung protection by thiol-containing antioxidants.
It is becoming increasingly clear that certain types of pulmonary injury may be closely related to oxidant-antioxidant imbalance in the lung, resulting from the production of reactive oxygen species within the lung during endogenous metabolism and xenobiotic insult. We have investigated the role of glutathione in pneumoprotection from such reactive species and, in particular, methods of manipulating the resident antioxidant capacity of lung glutathione. One such approach has been the use of the thiol-containing drug N-acetylcysteine. We have shown that N-acetylcysteine is able to both support intracellular glutathione biosynthesis and act as a 'scavenger' of reactive electrophilic species through the chemical reactivity of its thiol group. N-acetylcysteine reduces hydrogen peroxide to water, with the commensurate formation of N-acetylcysteine disulphide both when the peroxide was supplied directly or generated enzymatically. This basal reduction of hydrogen peroxide by N-acetylcysteine was greatly enhanced by the inclusion of catalytic amounts of the selenium-containing heterocycle, Ebselen, in the incubations. Thus, Ebselen mimics the activity of glutathione peroxidase but, unlike the enzyme, is able to use N-acetylcysteine as a co-substrate. Thus, the combination of N-acetylcysteine and Ebselen may provide a useful therapeutic tool in conditions of pulmonary toxicity associated with oxidant insult.