Amyloid-β, p-tau and reactive microglia are pathological correlates of MRI cortical atrophy in Alzheimer's disease.
Alzheimer's disease is characterized by cortical atrophy on MRI and abnormal depositions of amyloid-beta, phosphorylated-tau and inflammation pathologically. However, the relative contribution of these pathological hallmarks to cortical atrophy, a widely used MRI biomarker in Alzheimer's disease, is yet to be defined. Therefore, the aim of this study was to identify the histopathological correlates of MRI cortical atrophy in Alzheimer's disease donors, and its typical amnestic and atypical non-amnestic phenotypes. Nineteen Alzheimer's disease (of which 10 typical and 9 atypical) and 10 non-neurological control brain donors underwent post-mortem in situ 3T 3D-T1, from which cortical thickness was calculated with Freesurfer. Upon subsequent autopsy, 12 cortical brain regions from the right hemisphere and 9 from the left hemisphere were dissected and immunostained for amyloid-beta, phosphorylated-tau and reactive microglia, and percentage area load was calculated for each marker using ImageJ. In addition, post-mortem MRI was compared to ante-mortem MRI of the same Alzheimer's disease donors when available. MRI-pathology associations were assessed using linear mixed models. Higher amyloid-beta load weakly correlated with higher cortical thickness globally (r = 0.22, P = 0.022). Phosphorylated-tau strongly correlated with cortical atrophy in temporal and frontal regions (-0.76 < r < -1.00, all P < 0.05). Reactive microglia load strongly correlated with cortical atrophy in the parietal region (r = -0.94, P < 0.001). Moreover, post-mortem MRI scans showed high concordance with ante-mortem scans acquired <1 year before death. In conclusion, distinct histopathological markers differently correlated with cortical atrophy, highlighting their different roles in the neurodegenerative process, and therefore contributing to the understanding of the pathological underpinnings of MRI atrophic patterns in Alzheimer's disease. In our cohort, no or only subtle differences were found in MRI-pathology associations in Alzheimer's disease phenotypes, indicating that the histopathological correlates of cortical atrophy in typical and atypical phenotypes might be similar. Moreover, we show that post-mortem in situ MRI can be used as proxy for ante-mortem in vivo MRI.


Biology of Robertsiella kaporensis snails and Malaysian Schistosoma.
Studies on the bionomics and host-parasite relationship of Robertsiella kaporensis and Malaysian Schistosoma were investigated. The study was divided into 4 parts: cultivation of snails, R. kaporensis, and maintenance of Malaysian Schistosoma life cycle, daily cercarial shedding cycle in R. kaporensis, miracidial load and cercarial shedding pattern and the infectivity of Malaysian Schistosoma cercariae. R. kaporensis were cultured in the laboratory with the use of plastic container provided with fine sand. The snails were fed with diatoms and Saraca leaves. The development period for the snail eggs was about 20-30 days, the young grew to maturity in 14-15 weeks, and the average growth rate of snails was 0.23 mm per week. The daily cercarial shedding cycle of snails had shown that the peak emergence of cercariae of Malaysian Schistosoma occurred at night, between 6-10 pm. The miracidial load which yielded the best results in terms of percentage infection rates of snails and cercarial output was the miracidial concentration of 8 miracidia per snail. The study on infectivity of Malaysian Schistosoma cercariae has shown that there was a decrease in infectivity of the cercariae to mammalian hosts as the cercariae increased in age. The percentage infection rate of mice and numbers of worms recovered were highest in mice infected with cercariae of 0-1/2 hr. old. Infection of cercariae fell rapidly after the cercariae were 16 hr. old.


California serogroup viruses from mosquitoes collected in the USSR.
Four California serogroup viruses isolated from mosquitoes in the USSR were tested for antigenic analogy with prototype viruses of the California serogroup. The topotype isolates are biologically similar to, but antigenically different from each other. One is a subtype of snowshoe hare virus, two are different subtypes of Tahyna, Lumbo, and snowshoe hare viruses, and one is identical to Inkoo virus, previously isolated only in Finland. The results indicate that molecular studies of these viruses are necessary to comprehend their evolution.


Comments on "Constraints on belief functions imposed by fuzzy random variables": some technical remarks on Romer/Kandel.
First, we would like to thank V. Kratschmer for his validation of our results in the paper regarding the belief measure by using a topological approach. Though assertions (1) and (3) are presented in a weakened fashion, our results still remain valid, as he claims. It is true that assertion (2) has been proved by us only for Borel sets B, which have at most countable components. We were not able to prove the same result for Borel sets with uncountable components (such as the irrational numbers, for example) using our line of reasoning. We therefore applaud the proof presented by V. Kratschmer for the more general Borel sets using an interesting use of some topological properties induced by the Hansdorff metric defined on the space of closed intervals of the real numbers. This certainly makes our original approach to fuzzy data analysis combining fuzzy sets theory and Dempster-Shafer even more useful.


On the optimality of neural-network approximation using incremental algorithms.
The problem of approximating functions by neural networks using incremental algorithms is studied. For functions belonging to a rather general class, characterized by certain smoothness properties with respect to the L2 norm, we compute upper bounds on the approximation error where error is measured by the Lq norm, 1< or =q< or =infinity. These results extend previous work, applicable in the case q=2, and provide an explicit algorithm to achieve the derived approximation error rate. In the range q< or =2 near-optimal rates of convergence are demonstrated. A gap remains, however, with respect to a recently established lower bound in the case q>2, although the rates achieved are provably better than those obtained by optimal linear approximation. Extensions of the results from the L2 norm to Lp are also discussed. A further interesting conclusion from our results is that no loss of generality is suffered using networks with positive hidden-to-output weights. Moreover, explicit bounds on the size of the hidden-to-output weights are established, which are sufficient to guarantee the established convergence rates.


Genetic Scores of eNOS, ACE and VEGFA Genes Are Predictive of Endothelial Dysfunction Associated Osteoporosis in Postmenopausal Women.
The present study aimed to examine the participation and contribution of endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE) and vascular endothelial growth factor (VEGFA) genes for the risk of endothelial dysfunction (ED)-associated osteoporosis risk in postmenopausal women of Punjab, India. Women with ED were categorized into women with osteoporosis (n = 346) and women without osteoporosis (n = 330). They were examined for selected SNPs within eNOS, ACE and VEGFA genes. Linear regression analysis revealed a positive association of ED with bone mineral densities (BMDs) at femoral neck (r2 = 0.78, p < 0.001) and lumbar spine (r2 = 0.24, p = 0.001) after Bonferroni correction. Three susceptibility haplotypes were exposed within eNOS (CTAAAT), ACE (ACDG) and VEGFA (GATA) genes. Bearers of CTAAAT (OR 2.43, p = 0.007), ACDG (OR 2.50, p = 0.002) and GATA (OR 2.10, p = 0.009) had substantial impact for osteoporosis after correcting the effects with traditional risk factors (TRD).With uncertainty measure (R2h) and Akaike information criterion (AIC), best fit models showed that CTAAAT manifested in multiplicative mode (β ± SE: 2.19 ± 0.86, p < 0.001), whereas ACDG (β ± SE: 1.73 ± 0.54, p = 0.001) and GATA (β ± SE: 3.07 ± 0.81, p < 0.001) expressed in dominant modes. Area under receiver operating characteristic curve using weighted risk scores (effect estimates) showed substantial strength for model comprising TRD + GATA (AUC = 0.8, p < 0.001) whereas, model comprising TRD + GATA + CTAAAT exhibited excellent ability to predict osteoporosis (AUC = 0.824, p < 0.001).


Combined modality therapy including intraoperative electron irradiation for locally recurrent colorectal cancer.
To evaluate survival, relapse patterns, and prognostic factors in patients with colorectal cancer relapse treated with curative-intent therapy, including intraoperative electron radiation therapy (IOERT). From April 1981 through January 2008, 607 patients with recurrent colorectal cancer received IOERT as a component of treatment. IOERT was preceded or followed by external radiation (median dose, 45.5 Gy) in 583 patients (96%). Resection was classified as R0 in 227 (37%), R1 in 224 (37%), and R2 in 156 (26%). The median IOERT dose was 15 Gy (range, 7.5-30 Gy). Median overall survival was 36 months. Five- and 10-year survival rates were 30% and 16%, respectively. Survival estimates at 5 years were 46%, 27%, and 16% for R0, R1, and R2 resection, respectively. Multivariate analysis revealed that R0 resection, no prior chemotherapy, and more recent treatment (in the second half of the series) were associated with improved survival. The 3-year cumulative incidence of central, local, and distant relapse was 12%, 23%, and 49%, respectively. Central and local relapse were more common in previously irradiated patients and in those with subtotal resection. Toxicity Grade 3 or higher partially attributable to IOERT was observed in 66 patients (11%). Neuropathy was observed in 94 patients (15%) and was more common with IOERT doses exceeding 12.5 Gy. Long-term survival and disease control was achievable in patients with locally recurrent colorectal cancer. Continued evaluation of curative-intent, combined-modality therapy that includes IOERT is warranted in this high-risk population.


Human immunodeficiency virus proviral DNA from peripheral blood and lymph nodes demonstrates concordant resistance mutations to zidovudine (codon 215) and didanosine (codon 74). Division of AIDS Treatment Research Initiative 003 Study Group.
Genotypes that confer drug resistance were evaluated in human immunodeficiency virus (HIV) proviral DNA obtained from peripheral blood mononuclear cells (PBMC) and lymphoid tissue at baseline and after 8 weeks of therapy with zidovudine alone or in combination with didanosine from 22 patients (8 zidovudine-naive and 14 zidovudine-experienced). There was evidence of zidovudine resistance at codon 215 in 27.3% (6/22) of patients. All 20 patients evaluable for codon 74 (site of didanosine resistance) had virus that remained wild type during the 8-week study period. When HIV proviral DNA from PBMC was compared with that from lymphoid tissue, 94.7% (18/19) of evaluable samples were concordant at codon 215 at baseline, while 85.7% (12/14) were concordant at week 8. Resistance in PBMC (but not in lymphoid tissue) developed in 1 of 8 zidovudine-naive patients; an increased proportion of resistant strains in PBMC (but not in lymphoid tissue) was observed in 2 of 14 zidovudine-experienced patients. These results suggest high concordance for drug resistance mutations in HIV proviral DNA from blood and lymph node tissue.


The measurement properties of the Swedish version of the Assessment of Communication and Interaction Skills.
The purpose of this study was to validate the Swedish translation of the Assessment of Communication and Interaction Skills (ACIS-S) and its applicability in Sweden. The ACIS is an observational rating scale designed to capture, in detail, a person's social interactional ability, while he/she is participating in meaningful occupations. Eighteen occupational therapists trained in administering the ACIS-S, completed 157 ACIS-S assessments of 67 subjects with psychosocial and learning disabilities. Many-faceted Rasch analysis was used to analyse the data. The results supported internal, construct and person response validity of the ACIS-S, and rater validity and reliability. The scale effectively categorized subjects according to the levels of communication and interaction ability.


Substituted benzyl-pyrimidines targeting thymidine monophosphate kinase of Mycobacterium tuberculosis: synthesis and in vitro anti-mycobacterial activity.
A series of N(1)-(4-substituted-benzyl)-pyrimidines were synthesized as potential inhibitors of thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt). Key SAR parameters included the chain length substitution in para position of the benzyl ring, the functional group terminating the alkyl chain, and the substituent on the C-5 pyrimidine ring. Synthesized molecules were assayed against both recombinant enzyme and mycobacteria cultures. The most potent compounds have K(i) values in the micromolar range and an MIC(50) of 50microg/mL against Mycobacterium bovis. These results will guide the design of a new generation of lead compounds.


[Genetic mapping of the rice telomeric regions through PCR].
By using RAPD primer mediated asymmetric PCR (RM-PCR) method, a new type of molecular marker based on the telomeric repeats sequence was developed. PCR-based genetic mapping of telomeric repeat associated sequences (TASs) was conducted with a rice doubled haploid (DH) population derived from the inter-subspecific cross between indica variety (Zhaiyeqing8) and japonica variety (Jingxil7). Twenty-three loci were mapped onto the genetic map. Of these loci, 12 loci were mapped to the most distal position of eight chromosome arms and some of which may be located in subtelomeric region, five loci were mapped to the approximate positions of centromeric regions and six loci were mapped to other interstitial chromosomal regions.


Detection of class 1 integrons in Salmonella Weltevreden and silent antibiotic resistance genes in some seafood-associated nontyphoidal isolates of Salmonella in south-west coast of India.
To study the antibiogram of 40 seafood isolates of Salmonella and use of PCR to detect the presence of integrons and genes coding for antibiotic resistance. In this study, 40 isolates of Salmonella were used for antibiogram analysis. The multidrug-resistant isolates were analyzed for the presence of integron using integron-specific primers. Twenty-five percentage of the isolates were multidrug resistant while 67·50% were resistant to at least two antibiotics. Antibiotic resistance genes catA1 and tetA were present in 57·52 and 60%, respectively. Although widespread presence of genes was observed, only 26·08% of the catA1-carrying isolates exhibited phenotypic resistance against the respective antibiotic. Integrons present in representative isolates of Salmonella Weltevreden and Salmonella Newport were sequenced. The former contained class 1 integron with a single gene dfrA7 in the integron cassette and an adjacent dihydropteroate synthetase gene along with the usual quaternary ammonium compound resistance gene, while the later contained class 1 integron with dhfrA1, OrfC, in the integron cassette and an adjacent dihydropteroate synthetase gene along with the usual quaternary ammonium compound resistance gene. This study demonstrates the presence of silent antibiotic resistance genes and class I integrons in seafood-associated Salmonella strains. The study also demonstrates the first report of class I integron in Salm. Weltevreden. Detection of catA1 genes in phenotypically sensitive bacteria suggests that these could be reservoirs in the environment. The manuscript provides novel results describing the existence of a high rate of antibiotic resistance in the Salmonella populations prevailing in environmental sources as well as an absence of correspondence between the presence of antibiotic resistance genes, and the exhibition of a the corresponding phenotypic trait of resistance against the respective antibiotic compound was observed. In addition, the manuscript reports the presence of the class I integron in Salm. Weltevreden.


HIV surveillance systems in the Asia Pacific region.
In 2011, the United Nations Joint Programme on HIV/AIDS (UNAIDS) Regional Support Team for Asia-Pacific conducted a stock-taking process of available strategic information in the Asia Pacific region. This paper summarizes the progress of HIV surveillance for 20 countries in the region, covering population size estimates of key populations at higher risk, HIV case reporting, HIV sentinel surveillance and probability surveys of behavioural and biological markers. Information on surveillance activities was obtained from publically available surveillance reports and protocols, supplemented by personal communication with the UNAIDS monitoring and evaluation advisers and surveillance experts in country. Key findings include substantial efforts in broadening the number and types of HIV surveillance components included in national HIV surveillance systems and adopting approaches to make surveillance more cost-efficient, such as integrating routine programme monitoring data and passive surveillance case reporting systems. More investment in regularly analysing and applying surveillance data to programme strengthening at the subnational level is needed but will require additional capacity-building and resources. The ability to triangulate multiple sources of surveillance data into a more comprehensive view of the HIV epidemic will be enhanced if more investment is made in better documentation and dissemination of surveillance activities and findings.


BRIGHT Coaching: A Randomized Controlled Trial on the Effectiveness of a Developmental Coach System to Empower Families of Children With Emerging Developmental Delay.
Background: In preschool-aged children with, or at elevated risk for, developmental disabilities, challenges and needs arise from vulnerabilities linked to critical and newly emerging cognitive, speech, motor, behavioral, and social skills. For families, this can be a stressful period as they witness the gradual unfolding of their child's differences and await to receive care. Nationally and internationally, service delivery models during this critical period are not standardized nor are they nimble or sufficient enough, leading to long wait times, service gaps and duplications. Given these struggles, there is a need to examine whether "health coaching", a structured educational program that is deliverable by different and more accessible means, can be effective in empowering families, by delivering information, providing social supports, and decreasing the demands on the overwhelmed health and developmental services. The primary objective is to evaluate the feasibility and the effectiveness of a coaching intervention (in comparison to usual and locally available care), for parents of children with emerging developmental delays. Method/Design: A multi-centered pragmatic randomized controlled trial design will be used. Families will be recruited from a representative sample of those awaiting publicly-funded regional child health services for children with developmental delays in four Canadian provinces. The target sample size is 392 families with children aged 1.5 to 4.5 years at recruitment date. Families will be randomly assigned to receive either the BRIGHT Coaching intervention (coach supported, hardcopy and online self-managed educational resources: 14 sessions, 2 sessions every 4 weeks for 6-9 months) or usual care that is locally available. In addition to the feasibility and acceptability measures, outcomes related to family empowerment, parental satisfaction and efficacy with caregiver competency will be evaluated at baseline, post-treatment (8 months), and follow-up (12 months). Discussion: This manuscript presents the background information, design, description of the interventions and of the protocol for the randomized controlled trial on the effectiveness of BRIGHT Coaching intervention for families of children with emerging developmental delays. Trial Registration: ClinicalTrials.gov, U.S. National Library of Medicine, National Institutes of Health #NCT03880383, 03/15/2019. Retrospectively registered.


Wide Variation and Excessive Dosage of Opioid Prescriptions for Common General Surgical Procedures.
To examine opioid prescribing patterns after general surgery procedures and to estimate an ideal number of pills to prescribe. Diversion of prescription opioids is a major contributor to the rising mortality from opioid overdoses. Data to inform surgeons on the optimal dose of opioids to prescribe after common general surgical procedures is lacking. We evaluated 642 patients undergoing 5 outpatient procedures: partial mastectomy (PM), partial mastectomy with sentinel lymph node biopsy (PM SLNB), laparoscopic cholecystectomy (LC), laparoscopic inguinal hernia repair (LIH), and open inguinal hernia repair (IH). Postoperative opioid prescriptions and refill data were tabulated. A phone survey was conducted to determine the number of opioid pills taken. There was a wide variation in the number of opioid pills prescribed to patients undergoing the same operation. The median number (and range) prescribed were: PM 20 (0-50), PM SLNB 20 (0-60), LC 30 (0-100), LIH 30 (15-70), and IH 30 (15-120). Only 28% of the prescribed pills were taken. This percentage varied by operation: PM 15%, PM SLNB 25%, LC 33%, LIH 15%, and IH 31%. Less than 2% of patients obtained refills.We identified the number of pills that would fully supply the opioid needs of 80% of patients undergoing each operation: PM 5, PM SLNB 10, LC 15, LIH 15, and IH 15. If this number were prescribed, the number of opioid initially prescribed would be 43% of the actual number prescribed. There is wide variability in opioid prescriptions for common general surgery procedures. In many cases excess pills are prescribed. Using our ideal number, surgeons can adequately treat postoperative pain and markedly decrease the number of opioids prescribed.


[Acute pancreatitis (a Coxsackie B2?) and associated anomalies].
Authors report one case of acute pancreatitis in an obese twelve-year-old girl. The clinical picture appeared, without antecedent causes, as acute abdomen which required operation. Reduced echodensity of the pancreas was not found. The patient improved and recovered completely, her course being uneventful two years later. Scoliosis due to hemivertebra, and renal hypoplasia were present. No pancreatic malformation according to hypothesis of commun pathogenic mechanism was identified. Antibody titer to coxsackie B2 suggesting etiologic role was obtained. Amylase creatinine clearance ratio was calculated and suitability of establishing diagnostic values for pediatric ages is emphasized.


[Reducing the need in donor blood in reconstructive surgery of the aorta: using a Cell Saver apparatus].
The possibility of using a Cell Saver "Sequestra 1000" apparatus (Medtronics) for reducing the need for donor blood in reconstructive surgery for aortic aneurism was evaluated within the case study. Thirty-seven patients, who were made different reconstructive procedures on the ascending and abdominal aorta, were examined. Twelve patients with aneurism in the ascending aorta section (AAS) and with insufficiency of the aortal valve were made prosthesis of AAS and aortal valve under extracorporeal circulation (AEC). Twenty-five patients, who were operated on the abdominal aorta section, were resected aneurysm with linear prosthesis (9), aorto-hip bifurcational alloprosthesis (15) and branching of arterio-venous fistula (1). Five patients with aneurysm in the abdominal aorta, including 3 cases of aneurysm rupture, were operated on the emergency basis. The use of a Sequestra 1000 (Medtronics) apparatus based on the Cell Saver technology aorta reconstructions cut essentially the need in donor packed red blood cells at the intraoperative (3.6 times) and postoperative (2.8 times) stages.


Scalp metastasis from esophageal adenocarcinoma.
There are few reported cases of cutaneous metastases of esophageal carcinoma, especially of esophageal adenocarcinoma, but reports may become more common as the incidence of esophageal cancer increases. We present a case of a 67-year-old man with metastatic esophageal cancer in the scalp. Clinical and histologic findings are discussed, and recommendations for clinicians are suggested.


Inhibition by plant phenols of benzo[a]pyrene-induced nuclear aberrations in mammalian intestinal cells: a rapid in vivo assessment method.
The polycyclic aromatic hydrocarbon, benzo[a]pyrene, induced dose-related nuclear damage (micronuclei, pyknotic nuclei and karyorrhectic bodies) in colonic epithelial cells of C57BL/6J mice within 24 hr when administered intrarectally in single doses of 0-200 mg/kg body weight. This damage was reduced when mice ingested the plant phenols, caffeic, ferulic and ellagic acids, and quercetin at levels of 4% or BHA at 2% (w/w) in the diet for 1 wk prior to the benzo[a]pyrene challenge (100 mg/kg body weight). Benzo[a]pyrene-induced nuclear damage was not significantly inhibited by 4% curcumin under similar conditions. The inhibition of nuclear damage is consistent with reported antimutagenic effects for these agents in vitro and in longer term animal studies. The procedure described here may provide a rapid in vivo method for assessing the potential of natural products to inhibit the carcinogenic process.


Induction of a VLA-2 (CD49b)-expressing effector T cell population by a cell-based neuroblastoma vaccine expressing CD137L.
In malignancies where no universally expressed dominant Ag exists, the use of tumor cell-based vaccines has been proposed. We have modified a mouse neuroblastoma cell line to express either CD80 (B7.1), CD137L (4-1BBL), or both receptors on the tumor cell surface. Vaccines expressing both induce a strong T cell response that is unique in that among responding CD8 T cells, a T effector memory cell (T(EM)) response arises in which a large number of the T(EM) express the alpha-chain of VLA-2, CD49b. We demonstrate using both in vitro and in vivo assays that the CD49b(+) CD8 T cell population is a far more potent antitumor effector cell population than nonfractionated CD8 or CD49b(-) CD8 T cells and that CD49b on vaccine-induced CD8 T cells mediates invasion of a collagen matrix. In in vivo rechallenge studies, CD49b(+) T cells no longer expanded, indicating that CD49b T(EM) expansion is restricted to the initial response to vaccine. To demonstrate a mechanistic link between the expression of costimulatory molecules on the vaccine and CD49b on responding T cells, we stimulated naive T cells in vitro with artificial APC expressing different combinations of anti-CD3, anti-CD28, and CD137L. Although some mRNA encoding CD49b was induced by combining anti-CD3 with anti-CD28 or CD137L, the highest level was induced when all three signals were present. This indicates that CD49b expression results from additive costimulation and that the level of CD49b message serves as an indicator of the effectiveness of T cell activation by a cell-based vaccine.


Transcriptome Analysis of mRNA and lncRNA Related to Muscle Growth and Development in Gannan Yak and Jeryak.
The production performance of Jeryak, resulting from the F1 generation of the cross between Gannan yak and Jersey cattle, exhibits a significantly superior outcome compared with that of Gannan yak. Therefore, we used an RNA-seq approach to identify differentially expressed mRNAs (DEMs) and differentially expressed lncRNAs (DELs) influencing muscle growth and development in Gannan yaks and Jeryaks. A total of 304 differentially expressed lncRNAs and 1819 differentially expressed mRNAs were identified based on the screening criteria of |log 2 FC| > 1 and FDR < 0.05. Among these, 132 lncRNAs and 1081 mRNAs were found to be down-regulated, while 172 lncRNAs and 738 mRNAs were up-regulated. GO and KEGG analyses showed that the identified DELs and DEMs were enriched in the entries of pathways associated with muscle growth and development. On this basis, we constructed an lncRNA-mRNA interaction network. Interestingly, two candidate DELs (MSTRG.16260.9 and MSTRG.22127.1) had targeting relationships with 16 (MYC, IGFBP5, IGFBP2, MYH4, FGF6, etc.) genes related to muscle growth and development. These results could provide a basis for further studies on the roles of lncRNAs and mRNAs in muscle growth in Gannan yaks and Jeryak breeds.


Chiral Transmission to Cationic Polycobaltocenes over Multiple Length Scales Using Anionic Surfactants.
Chiral polymers are ubiquitous in nature, and the self-assembly of chiral materials is a field of widespread interest. In this paper, we describe the formation of chiral metallopolymers based on poly(cobaltoceniumethylene) ([PCE] n+), which have been prepared through oxidation of poly(cobaltocenylethylene) (PCE) in the presence of enantiopure N-acyl-amino-acid-derived anionic surfactants, such as N-palmitoyl-l-alanine (C16-l-Ala) and N-palmitoyl-d-alanine (C16-d-Ala). It is postulated that the resulting metallopolymer complexes [PCE][C16-l/d-Ala] n contain close ionic contacts, and exhibit chirality through the axially chiral ethylenic CH2-CH2 bridges, leading to interaction of the chromophoric [CoCp2]+ units through chiral space. The steric influence of the long palmitoyl (C16) surfactant tail is key for the transmission of chirality to the polymer, and results in a brushlike amphiphilic macromolecular structure that also affords solubility in polar organic solvents (e.g., EtOH, THF). Upon dialysis of these solutions into water, the hydrophobic palmitoyl surfactant substituents aggregate and the complex assembles into superhelical ribbons with identifiable "handedness", indicating the transmission of chirality from the molecular surfactant to the micrometer length scale, via the macromolecular complex.


Non-aortic aneurysms - natural history and recommendations for referral and treatment.
Non-aortic aneurysms constitute a collection of conditions where the same pathology presents in multiple anatomic locations. They are often detected incidentally and the aetiology, natural history, clinical presentation and treatment of non-aortic aneurysms may differ completely, depending on their site. This article summarises current knowledge about non-aortic aneurysms in a structured manner, highlighting the natural history and recommendations for referral and treatment. Non-aortic aneurysms have an underestimated morbidity and mortality risk, and elective treatment has been demonstrated to prevent complications such as rupture or embolisation. Although endovascular repair has become increasingly popular, conventional open surgical repair has continued to play a substantial role in the treatment of non-aortic aneurysms. Treatment must be tailored to the patient and anatomic location, and early counselling and assessment by a vascular specialist is recommended.


The effects of sling exercise using vibration on trunk muscle activities of healthy adults.
[Purpose] This study compared the effects of sling exercises with and without vibration on the muscular activity of the internal oblique (IO), rectus abdominis (RA), multifidus (MF), and erector spinae (ES) muscles of healthy adults. [Methods] Eleven healthy university students (11 men) with a mean age of 22.8 years were enrolled in this study. Subjects performed supine and prone bridge exercises with the knees flexed using a sling suspension system with and without vibration. The amplitudes of the EMG activities of selected trunk muscles (internal oblique, rectus abdominis, erector spinae, multifidus) were recorded. Two types of exercise conditions were executed in a random sequence for 5 seconds each. The signals detected from the middle 3 seconds (after discarding the signals of the first and the last one seconds) were used in the analysis. A 3-minute break was given after each exercise to minimize muscle fatigue. [Results] During the supine bridge exercise with vibration, the activities of the IO, RA, MF, and ES muscles were significantly higher than those of the supine bridge exercise without vibration. Additionally, during the prone bridge exercise with vibration, the activities of the IO, RA, MF, and ES were significantly higher than those of the prone bridge exercise without vibration. [Conclusion] Sling exercises with vibration improved the trunk muscle activities of healthy adults compared to the sling exercises without vibration. The information presented here is important for clinicians who use lumbar stabilization exercises as an evaluation tool or a rehabilitation exercise.


Review article: ventilator-associated pneumonia in major burns.
Major burns victims are particularly susceptible to pneumonia, especially ventilator-associated pneumonia (VAP). VAP remains a prominent cause of morbidity and mortality, despite improvements in intensive care and burns surgery in recent times. Length of ventilation, type and size of burn (especially inhalational burns) are related to the incidence of VAP. Other risk factors (number of re-intubations, theatre visits) are also important. Effective preventative strategies should be adhered to, and protocols should be implemented to aid in the diagnosis and treatment of VAP. Clinical criteria, radiology, and broncho-alveolar lavage should be used to determine the causative organism, and there should be a low threshold for the early initiation of empiric therapy, based on the prevailing resistance patterns in the unit. Major burns should be managed in centres where there is ready access to multidisciplinary resources and expertise.


Long-term efficacy and tolerability of pentosan polysulphate sodium in the treatment of bladder pain syndrome.
The primary objective of this study is to report on the long-term efficacy and tolerability of pentosan polysulphate sodium (PPS) in patients with bladder pain syndrome (BPS). The secondary objective is to find the predictors of the long-term outcome. This is a single institution, retrospective study. The study period was from 1994 to 2008. All patients fulfilled the clinical criteria of BPS, as suggested by European Society for the Study of Interstitial Cystitis. We included only patients with de novo BPS diagnosis and no previous PPS or other treatment. The efficacy of PPS was measured with the global response assessment scale (GRA). Patients were stratified into 2 groups based on the duration of the treatment. Group 1 took the drug for less than 12 months. Group 2 took the drug for more than 12 months. There were 271 patients eligible for the study. Most of the patients were female (90%), with the mean age at presentation of 45.5 years. The average duration of symptoms was 28.5 months. The mean follow-up was 22 months (range 3-130). Out of all the patients, 147 patients (54.2%) reported over 50% improvement using the GRA. The reported efficacy was higher in Group 2 (60%). Ninety-three patients (34.3%) decided to stop taking the medication for various reasons. The most common reasons to stop the medication were poor outcome (16.6% of patients) and side effects (11.1% of patients). Poor outcome was associated with nocturia, smoking and detrusor overactivity. Good outcome was associated with longer PPS intake (>12 months) and severe cystoscopic findings of glomerulation. Pentosan polysulphate sodium is an effective oral therapy to control the symptoms of BPS with good long-term efficacy and tolerability.


A deep unrolled neural network for real-time MRI-guided brain intervention.
Accurate navigation and targeting are critical for neurological interventions including biopsy and deep brain stimulation. Real-time image guidance further improves surgical planning and MRI is ideally suited for both pre- and intra-operative imaging. However, balancing spatial and temporal resolution is a major challenge for real-time interventional MRI (i-MRI). Here, we proposed a deep unrolled neural network, dubbed as LSFP-Net, for real-time i-MRI reconstruction. By integrating LSFP-Net and a custom-designed, MR-compatible interventional device into a 3 T MRI scanner, a real-time MRI-guided brain intervention system is proposed. The performance of the system was evaluated using phantom and cadaver studies. 2D/3D real-time i-MRI was achieved with temporal resolutions of 80/732.8 ms, latencies of 0.4/3.66 s including data communication, processing and reconstruction time, and in-plane spatial resolution of 1 × 1 mm2. The results demonstrated that the proposed method enables real-time monitoring of the remote-controlled brain intervention, and showed the potential to be readily integrated into diagnostic scanners for image-guided neurosurgery.


Hydrogen potassium adenosine triphosphatase activity inhibition and downregulation of its expression by bioactive fraction DLBS2411 from Cinnamomum burmannii in gastric parietal cells.
This study assessed the gastric acid antisecretory effect of DLBS2411 fractionated from Cinnamomum burmannii. Hydrogen potassium adenosine triphosphatase (H(+)/K(+) ATPase) activity and its gene expression were observed, and the antioxidant activity of DLBS2411 was also investigated. Treatment of DLBS2411 decreased the level of H(+)/K(+) ATPase messenger RNA expression on human embryonic kidney 293 cells and rat gastric parietal cells in a dose-dependent manner, in vitro and ex vivo. DLBS2411 also acted as a competitive inhibitor by showing inhibition in gastric H(+)/K(+) ATPase activity at various pHs. In gastric ulcer animal models induced with indomethacin and ethanol, DLBS2411showed a reduction in the number of petechiae, suggesting that the fraction also confers gastroprotective activity. Moreover, DLBS2411 was also found to have potent antioxidant activity. Taken together, DLBS2411 is a promising novel agent for the management of dyspepsia, a condition of hyperacidity and diseases in the stomach requiring gastroprotection.


Migraine headaches: diagnosis and management.
In spite of the fact that migraines are one of the major problems seen by primary care providers, almost half of people with migraines do not obtain appropriate diagnosis and/or treatment. Migraine occurs in about 18% of women, and is often aggravated by hormonal shifts occurring around women's menses, during pregnancy, and during perimenopause. Quality of life with migraines is often greatly diminished, and many women miss work days and/or are less productive with migraines. Women's health care providers are very likely to see women with poorly managed migraines, but are often not comfortable diagnosing and treating their patients with headaches. A variety of self-care treatments, acute care prescription and non-prescription headache medications, and preventive medications are available and if used by a knowledgeable provider can provide relief for many women who might not otherwise receive appropriate care.


Language proficiency and nursing registration.
This discussion paper focuses on English proficiency standards for nursing registration in Australia, how Australia has dealt with the issue of language proficiency, and the factors which have led to the establishment of the current language standards. Also, this paper will provide a comparison of the two language tests that are currently accepted in Australia (OET and IELTS), including the appropriateness of these tests and the minimum standards used. The paper will also examine the use of educational background as an indicator of language proficiency. Finally, communication-based complaints in the post-registration environment will be explored, and some discussion will be provided about why pre-registration measures might have failed to prevent such problematic situations from occurring.


Prolonged macrophage activation and persistent anaemia in children with complicated malaria.
To determine if prolonged immune activation may be associated with the persistence of anaemia after treatment for severe malaria, we measured serum concentrations of neopterin and interleukin-4 during one week of antimalarial therapy and determined haemoglobin levels one month later. Neopterin is a clinically valuable marker for monitoring activation of macrophages by gamma-interferon and thus reflects the TH-1 immune response. Interleukin-4 is a major cytokine that tends to be inhibited by TH-1 activity. The study population consisted of 26 Zambian children < 6 years of age who presented with cerebral malaria to a rural hospital in 1994 and who were treated with quinine for seven days. Six children (23%) were anaemic (haemoglobin < 11 g/dl) one month after completing antimalarial therapy. On admission, concentrations of neopterin were markedly elevated in all patients. During the seven days of anti-malarial therapy, neopterin levels remained elevated in the 6 children who proved to have persistent anaemia one month after finishing treatment but declined significantly (P = 0.008) in the 20 children who corrected their haemoglobin levels by that time. Conversely, interleukin-4 levels declined in the children with persistent anaemia (P = 0.043) but not in the other children. Persistence of the TH-1 mediated immune response and associated activation of macrophages may be involved in the pathogenesis of lingering anaemia after treatment of malaria.


Multicellular tumor spheroids of human uveal melanoma induce genes associated with anoikis resistance, lipogenesis, and SSXs.
Uveal melanoma (UM) has a high propensity for metastatic spread, and approximately 40-50% of patients die of metastatic disease. Metastases can be found at the time of diagnosis but also several years after the tumor has been removed. The survival of disseminated cancer cells is known to be linked to anchorage independence, anoikis resistance, and an adaptive cellular metabolism. The cultivation of cancer cells as multicellular tumor spheroids (MCTS) by anchorage-independent growth enriches for a more aggressive phenotype. The present study examines the differential gene expression of adherent cell cultures, non-adherent MCTS cultures, and uncultured tumor biopsies from three patients with UM. We elucidate the biochemical differences between the culture conditions to find whether the culture of UM as non-adherent MCTS could be linked to an anchorage-independent and more aggressive phenotype, thus unravelling potential targets for treatment of UM dissemination. The various culture conditions were evaluated with microarray analysis, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), RNAscope, immunohistochemistry (IHC), and transmission electron microscopy (TEM) followed by gene expression bioinformatics. The MCTS cultures displayed traits associated with anoikis resistance demonstrated by ANGPTL4 upregulation, and a shift toward a lipogenic profile by upregulation of ACOT1 (lipid metabolism), FADS1 (biosynthesis of unsaturated fatty acids), SC4MOL, DHCR7, LSS (cholesterol biosynthesis), OSBPL9 (intracellular lipid receptor), and PLIN2 (lipid storage). Additionally, the present study shows marked upregulation of synovial sarcoma X breakpoint proteins (SSXs), transcriptional repressors related to the Polycomb group (PcG) proteins that modulate epigenetic silencing of genes. The MCTS cultures displayed traits associated with anoikis resistance, a metabolic shift toward a lipogenic profile, and upregulation of SSXs, related to the PcG proteins.


Optimized DFT-spread OFDM based visible light communications with multiple lighting sources.
Discrete Fourier transform spread orthogonal frequency-division multiplexing (DFT-S-OFDM) has demonstrated its capability in reducing peak to average ratio (PAPR), while maintaining reliable transmissions. This paper investigates the application of DFT-S-OFDM technology in visible light communications (VLC), and reveals the mechanism on how a multiple lighting distributed layout affects its performance. In addition, an optimization approach of lighting layout is proposed through making a trade-off between the strong interfered areas and the maximum delay spread inside. Eventually, a Gbit/s DFT-S-OFDM based multiple lighting VLC downlink prototype is achieved for the first time in the form of real-time baseband modem and compact size components.


Dynamics of molecular and polymeric interfaces probed with atomic beam scattering and scanning probe imaging.
The scattering of atomic and molecular beams from well-characterized surfaces is a useful method for studying the dynamics of gas-surface interactions, providing precise information on the energy and momentum exchange which occur in such encounters. We apply this technique to new systems including disordered films of macromolecules, complex interfaces of macromolecular systems, and hybrid organic-semiconductor interfaces. Time-lapse atomic force microscopy studies of diblock copolymer structural evolution and fluctuations complement the scattering data to give a more complete understanding of dynamical processes in these complex disordered films. Our new scattering findings quantitatively characterize changes in interfacial dynamics including confinement in thin films of poly(methyl methacrylate) and changes in the physical properties of poly(ethylene terephthalate) films as they transform from the glassy to their semicrystalline phase. Further measurements on a hybrid organic-semiconductor interface, methyl-terminated silicon (111), reveal that the surface thermal motion and gas-surface energy accommodation are dominated by local molecular vibrations while the interfacial lattice dynamics remain accessible through helium scattering. High temperature atomic force microscopy allows direct, real-time visualization of structural reorganization and defect migration in poly(styrene)-block-poly(methyl methacrylate) films, revealing details of film reorganization and thermal annealing. Moreover, we employed lithographically created channels to guide the alignment of polymer microdomains. This, in turn, allows direct observation of the mechanisms for diffusion and annihilation of dislocation and disclination defects. In summary, this paper elaborates on the power of combining atom scattering and scanning probe microscopy to interrogate the vibrational dynamics, energy accommodation, energy flow, and structural reorganization in complex interfaces.


Cdc42: An essential Rho-type GTPase controlling eukaryotic cell polarity.
Cdc42p is an essential GTPase that belongs to the Rho/Rac subfamily of Ras-like GTPases. These proteins act as molecular switches by responding to exogenous and/or endogenous signals and relaying those signals to activate downstream components of a biological pathway. The 11 current members of the Cdc42p family display between 75 and 100% amino acid identity and are functional as well as structural homologs. Cdc42p transduces signals to the actin cytoskeleton to initiate and maintain polarized gorwth and to mitogen-activated protein morphogenesis. In the budding yeast Saccharomyces cerevisiae, Cdc42p plays an important role in multiple actin-dependent morphogenetic events such as bud emergence, mating-projection formation, and pseudohyphal growth. In mammalian cells, Cdc42p regulates a variety of actin-dependent events and induces the JNK/SAPK protein kinase cascade, which leads to the activation of transcription factors within the nucleus. Cdc42p mediates these processes through interactions with a myriad of downstream effectors, whose number and regulation we are just starting to understand. In addition, Cdc42p has been implicated in a number of human diseases through interactions with its regulators and downstream effectors. While much is known about Cdc42p structure and functional interactions, little is known about the mechanism(s) by which it transduces signals within the cell. Future research should focus on this question as well as on the detailed analysis of the interactions of Cdc42p with its regulators and downstream effectors.


Intimal proliferation in an organ culture of human saphenous vein.
This study investigated whether intimal proliferation, the characteristic feature of the response of human saphenous vein to arterial implantation, also occurs in organ culture. Vein segments were maintained for 14 days in medium supplemented with 30% fetal bovine serum. Tissue viability (measured by adenosine triphosphate [ATP] concentration) decreased only 20% from 280 +/- 20 to 220 +/- 20 nmol/g wet weight. In veins prepared for culturing, endothelial loss (approximately 20%) was confined to near the cut edges. Cultured veins retained an endothelial layer in the initially undamaged areas, while the initially injured areas became covered by a mixture of endothelial and vascular smooth muscle cells. Autoradiography in conjunction with scanning electron microscopy showed the presence of proliferating cells on the intimal surface. Transverse sections of cultured veins showed the development of a new intima containing vascular smooth muscle cells identified by immunocytochemistry with anti-alpha-actin. There were also endothelial cells identified with Ulex europaeus lectin arranged in capillarylike structures. Pulse or continuous labeling of cultures with [3H]thymidine showed that proliferating cells were confined to the new intima and suggested that the smooth muscle cells in this layer arose from both immigration and proliferation. The results demonstrate that intimal proliferation occurs in organ culture of human saphenous veins.


Update on Antithrombotic Therapy after Percutaneous Coronary Intervention.
Percutaneous coronary intervention (PCI) has become a standard-of-care procedure in the setting of angina or acute coronary syndrome. Antithrombotic therapy is the cornerstone of pharmacological treatment aimed at preventing ischemic events following PCI. Dual antiplatelet therapy as the combination of aspirin and P2Y12 inhibitor has been proven to decrease stent-related thrombotic risks. However, the optimal duration of dual antiplatelet therapy, an appropriate P2Y12 inhibitor, and the choice of aspirin versus P2Y12 inhibitor as single antiplatelet therapy remain controversial. Furthermore, the combined use of oral anticoagulation in addition to antiplatelet therapy is a complex issue in clinical practice, such as in patients with atrial fibrillation. The key challenge concerning the optimal antithrombotic regimen is ensuring a balance between protection against thrombotic events and against excessive increases in bleeding risk. In this review article, we summarize the current evidence concerning antithrombotic therapy in patients with coronary artery disease undergoing PCI.


Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles.
Cisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics. Here, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6±9.6nm and 140.5±10.9nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH ∼ 5.6 (cervical cancer pH) and pH ∼ 7.4. In addition, a significant (P<0.05) decrease in IC50 value (8.3μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1μM) and cisplatin solution (40.2μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54±7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P<0.05) greater than 51.68±9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs. Therefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.


Completion of the entire hepatitis C virus life cycle in genetically humanized mice.
More than 130 million people worldwide chronically infected with hepatitis C virus (HCV) are at risk of developing severe liver disease. Antiviral treatments are only partially effective against HCV infection, and a vaccine is not available. Development of more efficient therapies has been hampered by the lack of a small animal model. Building on the observation that CD81 and occludin (OCLN) comprise the minimal set of human factors required to render mouse cells permissive to HCV entry, we previously showed that transient expression of these two human genes is sufficient to allow viral uptake into fully immunocompetent inbred mice. Here we demonstrate that transgenic mice stably expressing human CD81 and OCLN also support HCV entry, but innate and adaptive immune responses restrict HCV infection in vivo. Blunting antiviral immunity in genetically humanized mice infected with HCV results in measurable viraemia over several weeks. In mice lacking the essential cellular co-factor cyclophilin A (CypA), HCV RNA replication is markedly diminished, providing genetic evidence that this process is faithfully recapitulated. Using a cell-based fluorescent reporter activated by the NS3-4A protease we visualize HCV infection in single hepatocytes in vivo. Persistently infected mice produce de novo infectious particles, which can be inhibited with directly acting antiviral drug treatment, thereby providing evidence for the completion of the entire HCV life cycle in inbred mice. This genetically humanized mouse model opens new opportunities to dissect genetically HCV infection in vivo and provides an important preclinical platform for testing and prioritizing drug candidates and may also have utility for evaluating vaccine efficacy.


IGF-II and IGF binding protein (IGFBP-1, IGFBP-3) gene expression in fetal rhesus monkey tissues during the second and third trimesters.
The IGF system is a key modulator of somatic fetal growth. Studies with human fetal tissues have shown a specific spatial and temporal pattern of expression of IGF and IGF binding protein (IGFBP) mRNAs, but have been limited to defined periods during gestation (i.e. 8-20 wk gestation) because of tissue availability. To fully assess the role of these peptides in the primate growth process, a longitudinal study was conducted that focused on the expression of IGF-II and IGFBP-1 and IGFBP-3 genes in the rhesus monkey (Macaca mulatta). Liver, kidney, brain, and lung were collected from rhesus monkey fetuses approximately every 2 wk from 65 (early second trimester) through 150 d gestation (term 165 +/- 10 d) (n = 50), then processed for in situ hybridization using radiolabeled human cDNAs. IGF-II mRNA was abundantly expressed in fetal kidney (maturing glomerulus, supporting mesenchyme, cells of the developing nephrons), liver (hepatocytes), cerebral cortex (choroid plexus, capillaries), and lung (blood vessels, connective tissues, lamina propria, cartilage framework). IGFBP-1 was expressed only in the hepatocytes and IGFBP-3 mRNA was modestly expressed within the kidney (developing nephrons, collecting system mesenchyme), and liver (hepatocytes). These studies have shown that (1) IGF-II, IGFBP-1, and IGFBP-3 are expressed in specific cell types of the fetal monkey indicating a paracrine/autocrine role during development; (2) changes in IGF-II and IGFBP mRNA expression occur with advancing gestation; and (3) fetal monkey tissues express IGF-II and IGFBPs in a similar manner when compared with the human fetus.


Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276).
Chromophobe renal cell carcinoma (ChRCC) represents 5% of all RCC cases and frequently demonstrates multiple chromosomal losses and an indolent pattern of local growth, but can demonstrate aggressive features and resistance to treatment in a metastatic setting. Cell line models are an important tool for the investigation of tumor biology and therapeutic drug efficacy. Currently, there are few ChRCC-derived cell lines and none is well characterized. This study characterizes a novel ChRCC-derived cell line model, UOK276. A large ChRCC tumor with regions of sarcomatoid differentiation was used to establish a spontaneously immortal cell line, UOK276. UOK276 was evaluated for chromosomal, mutational, and metabolic aberrations. The UOK276 cell line is hyperdiploid with a modal number of 49 chromosomes per cell, and evidence of copy-neutral loss of heterozygosity, as opposed to the classic pattern of ChRCC chromosomal losses. UOK276 demonstrated a TP53 missense mutation, expressed mutant TP53 protein, and responded to treatment with a small-molecule therapeutic agent, NSC319726, designed to reactivate mutated TP53. Xenograft tumors grew in nude mice and provide an in vivo animal model for the investigation of potential therapeutic regimes. The xenograft pathology and genetic analysis suggested that UOK276 was derived from the sarcomatoid region of the original tumor. In summary, UOK276 represents a novel in vitro and in vivo cell line model for aggressive, sarcomatoid-differentiated, TP53 mutant ChRCC. This preclinical model system could be used to investigate the novel biology of aggressive, sarcomatoid ChRCC and evaluate the new therapeutic regimes.


Graphene oxide-based aerogel stimulates growth, mercury accumulation, photosynthesis-related gene expression, antioxidant efficiency and redox status in wheat under mercury exposure.
Mercury (Hg) pollution is a global concern in cropland systems. Hg contamination causes a disruption in the growth, energy metabolism, redox balance, and photosynthetic activity of plants. In the removal of Hg toxicity, a recent critical strategy is the use of aerogels with biodegradability and biocompatibility. However, it is unknown how graphene oxide-based aerogels stimulate the defense systems in wheat plants exposed to Hg toxicity. Therefore, in this study, the photosynthetic, genetic, and biochemical effects of reduced graphene oxide aerogel treatments (gA; 50-100-250 mg L-1) were examined in wheat (Triticum aestivum) under Hg stress (50 μM HgCl2). The relative growth rate (RGR) significantly decreased (84%) in response to Hg stress. However, the reduced RGR and water relations (RWC) of wheat were improved by gA treatments. The impaired gas exchange levels (stomatal conductance, carbon assimilation rate, intercellular CO2 concentrations, and transpiration rate) caused by stress were reversed under Hg plus gAs. Additionally, stress hampered chlorophyll fluorescence (Fv/Fo, Fv/Fm), and under Hg toxicity the expression of psaA genes was reduced (>0.4-fold), but psaB gene was significantly up-regulated (>3-fold) which are the genes involved in PSI. By increasing expression patterns of both genes relating to PSI, gAs reversed the adverse consequences on Fv/Fo and Fv/Fm in the presence of excessive Hg concentration. The activities of glutathione S-transferase (GST), glutathione reductase (GR), catalase (CAT), ascorbate peroxidase (APX) and dehydroascorbate reductase (DHAR) decreased under Hg toxicity. On the other hand, the activities of superoxide dismutase (SOD), APX, GST, and glutathione peroxidase (GPX) increased following gA treatments against stress, leading to the successful elimination of toxic levels of H2O2 and lipid peroxidation (TBARS content) by decreasing the levels by about 30%, and 40%. By modulating enzyme/non-enzyme activity/contents including the AsA-GSH cycle, gAs contributed to the protection of the cellular redox state. Most important of all, gA applications were able to reduce Hg intake by approximately 66%. Therefore, these results showed that gAs were effective in highly inhibiting Hg uptake and could significantly increase wheat tolerance to toxicity by eliminating Hg-induced oxidative damage and inhibiting metabolic processes involved in photosynthesis. The findings obtained from the study provide a new perspective on the alleviation roles of reduced graphene oxide aerogels as an effective adsorbent for decreasing damages of mercury toxicity in wheat plants.


Small nerve fiber pathology in critical illness.
Degeneration of intraepidermal nerve fibers (IENF) is a hallmark of small fiber neuropathy of different etiology, whose clinical picture is dominated by neuropathic pain. It is unknown if critical illness can affect IENF. We enrolled 14 adult neurocritical care patients with prolonged intensive care unit (ICU) stay and artificial ventilation (≥ 3 days), and no previous history or risk factors for neuromuscular disease. All patients underwent neurological examination including evaluation of consciousness, sensory functions, muscle strength, nerve conduction study and needle electromyography, autonomic dysfunction using the finger wrinkling test, and skin biopsy for quantification of IENF and sweat gland innervation density during ICU stay and at follow-up visit. Development of infection, sepsis and multiple organ failure was recorded throughout the ICU stay. Of the 14 patients recruited, 13 (93%) had infections, sepsis or multiple organ failure. All had severe and non-length dependent loss of IENF. Sweat gland innervation was reduced in all except one patient. Of the 7 patients available for follow-up visit, three complained of diffuse sensory loss and burning pain, and another three showed clinical dysautonomia. Small fiber pathology can develop in the acute phase of critical illness and may explain chronic sensory impairment and pain in neurocritical care survivors. Its impact on long term disability warrants further studies involving also non-neurologic critical care patients.


Barbiturate effects on hippocampal excitatory synaptic responses are selective and pathway specific.
Barbiturate actions on excitatory synaptic responses in CA 1 and dentate regions of hippocampal slices were studied to determine whether different effects occur on anatomically distinct synaptic pathways. Pentobarbital facilitated transmission between stratum radiatum inputs and CA 1 neurons at low concentrations (0.02-0.08 mM) and produced postsynaptic depression at higher concentrations. Only depression was observed for stratum oriens inputs to CA 1 and perforant path inputs to dentate granulae neurons. The (+) isomer of pentobarbital was approximately four times more potent than the (-) isomer of racemic mixture. Phenobarbital (0.04-0.12 mM) produced only depression of synaptic responses in CA 1 and dentate pathways. Comparison of effect on field excitatory postsynaptic potentials and population spike responses indicated that the barbiturates act at selective and pathway-specific sites. The results provide further evidence for specific cellular and membrane recognition sites for barbiturate action.


[Necrotizing soft tissue infection].
The dramatic course of necrotizing soft tissue infection represents a medical emergency, since it is limb- and life-threatening. Most necrotizing soft tissue infections are caused by mixed aerobic and anaerobic Gram-negative and Gram-positive organisms. Most case have been reported in immuno-compromised hosts after penetrating trauma or surgery. We describe a unique series of cases of necrotizing soft tissue infection. The mainstay of treatment is early and daily debridement of devitalized tissue and broad-spectrum antibiotics. Hyperbaric oxygen therapy should be considered.


A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial.
Standard treatment of critically ill patients undergoing mechanical ventilation is continuous sedation. Daily interruption of sedation has a beneficial effect, and in the general intesive care unit of Odense University Hospital, Denmark, standard practice is a protocol of no sedation. We aimed to establish whether duration of mechanical ventilation could be reduced with a protocol of no sedation versus daily interruption of sedation. Of 428 patients assessed for eligibility, we enrolled 140 critically ill adult patients who were undergoing mechanical ventilation and were expected to need ventilation for more than 24 h. Patients were randomly assigned in a 1:1 ratio (unblinded) to receive: no sedation (n=70 patients); or sedation (20 mg/mL propofol for 48 h, 1 mg/mL midazolam thereafter) with daily interruption until awake (n=70, control group). Both groups were treated with bolus doses of morphine (2.5 or 5 mg). The primary outcome was the number of days without mechanical ventilation in a 28-day period, and we also recorded the length of stay in the intensive care unit (from admission to 28 days) and in hospital (from admission to 90 days). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00466492. 27 patients died or were successfully extubated within 48 h, and, as per our study design, were excluded from the study and statistical analysis. Patients receiving no sedation had significantly more days without ventilation (n=55; mean 13.8 days, SD 11.0) than did those receiving interrupted sedation (n=58; mean 9.6 days, SD 10.0; mean difference 4.2 days, 95% CI 0.3-8.1; p=0.0191). No sedation was also associated with a shorter stay in the intensive care unit (HR 1.86, 95% CI 1.05-3.23; p=0.0316), and, for the first 30 days studied, in hospital (3.57, 1.52-9.09; p=0.0039), than was interrupted sedation. No difference was recorded in the occurrences of accidental extubations, the need for CT or MRI brain scans, or ventilator-associated pneumonia. Agitated delirium was more frequent in the intervention group than in the control group (n=11, 20%vs n=4, 7%; p=0.0400). No sedation of critically ill patients receiving mechanical ventilation is associated with an increase in days without ventilation. A multicentre study is needed to establish whether this effect can be reproduced in other facilities. Danish Society of Anesthesiology and Intensive Care Medicine, the Fund of Danielsen, the Fund of Kirsten Jensa la Cour, and the Fund of Holger og Ruth Hess.


Can energy landscape roughness of proteins and RNA be measured by using mechanical unfolding experiments?
By considering temperature effects on the mechanical unfolding rates of proteins and RNA, whose energy landscape is rugged, the question posed in the title is answered in the affirmative. Adopting a theory by Zwanzig [Zwanzig, R. (1988) Proc. Natl. Acad. Sci. USA 85, 2029-2030], we show that, because of roughness characterized by an energy scale epsilon, the unfolding rate at constant force is retarded. Similarly, in nonequilibrium experiments done at constant loading rates, the most probable unfolding force increases because of energy landscape roughness. The effects are dramatic at low temperatures. Our analysis suggests that, by using temperature as a variable in mechanical unfolding experiments of proteins and RNA, the ruggedness energy scale epsilon, can be directly measured.


Dynamics of turtle horizontal cell response.
The small- and large-field (cone) horizontal cells produce similar dynamic responses to a stimulus whose mean luminance is modulated by a white-noise signal. Nonlinear components increase with an increase in the mean luminance and may produce a mean square error (MSE) of up to 15%. Increases in the mean luminance of the field stimulus bring about three major changes: the incremental sensitivity defined by the amplitude of the kernels decreases in a Weber-Fechner fashion; the waveforms of the kernels are transformed from monophasic (integrating) to biphasic (differentiating); the peak response time of the kernels becomes shorter and the cells respond to much higher-frequency inputs. The dynamics of the horizontal cell response also depend on the area of the retina stimulated. Smaller spots of light produce monophasic kernels of a longer peak response time. The presence of a steady background produces three major changes in the spot kernels: the kernel's amplitude becomes larger (incremental sensitivity increases); the peak response times become shorter; the waveform of the kernels changes in a fashion similar to that observed with an increase in the mean luminance of the field stimulus. A similar enhancement in the incremental sensitivity by a steady background has also been observed in catfish, which shows that this phenomenon is a common feature of the horizontal cells in the lower vertebrate retina.


Comorbid persistent lower respiratory symptoms and posttraumatic stress disorder 5-6 years post-9/11 in responders enrolled in the World Trade Center Health Registry.
Co-occurrence of lower respiratory symptoms (LRS) and posttraumatic stress disorder (PTSD) has been increasingly recognized among responders and survivors of the World Trade Center (WTC) disaster. Information is limited on the degree which comorbidity intensifies symptoms and compromises quality of life across exposed groups. Among responders who completed the first and second Registry surveys, measures of respiratory illness, psychological distress, and diminished quality of life were compared between responders comorbid for LRS and PTSD and responders with only LRS or PTSD. Of 14,388 responders, 40% of those with LRS and 57% of those with PTSD were comorbid. When demographic and WTC exposure-related factors were controlled, comorbid responders compared to those with LRS alone were twice as likely to have frequent dyspnea and to have sought care for dyspnea. Compared to responders with PTSD alone, comorbid responders were 2.1 times more likely to report intense re-experiencing of the disaster, 2.5 times more likely to express feelings of significant non-specific psychological distress, and 1.4 times more likely to have received mental health care. Comorbid responders were approximately three times more likely to report only fair or poor general health and more than twice as likely to report being unable to perform usual activities for ≥14 of 30 days before interview. Outcomes in comorbid responders were similar to or more severe than in comorbid survivors. Health care and disaster relief providers must suspect comorbid illness when evaluating responders' respiratory or mental illnesses and consider treatment for both.


Melatonin protects against endometriosis via regulation of matrix metalloproteinase-3 and an apoptotic pathway.
The role of matrix metalloproteinases (MMPs) in endometriosis, a gynecological disease of women, is unclear. The study investigated the activity of MMP-3 and its interplay with MMP-9 during the onset of endometriosis. Additionally, the importance of MMP-3 on the apoptotic pathway in endometriosis and effect of melatonin thereon were investigated. A Significant increase in the activity of MMP-3 with the severity of endometriosis in human was observed which was found similar in mice also. During the early phase of endometriosis, MMP-3 but not MMP-9 was increased and associated with the expression of transcription factor, c-Fos. Moreover, urokinase plasminogen activator and tissue inhibitor of metalloproteinase (TIMP)-3 were involved in MMP-3 regulation during endometriosis. Furthermore, MMP-3 activity that was parallel to c-Fos expression in endometriosis was reduced by melatonin pretreatment as characterized by diminished activator protein (AP)-1 DNA-binding activity. Because decreased apoptosis is an explanation for the perpetuation of endometriosis, we tested the role of melatonin on apoptotic pathway in preventing endometriosis. Significant regression of glandular epithelium was observed in melatonin-treated when compared to untreated mice. Melatonin treatment increased apoptotic cells in endometriotic zones. This was related to reduced Bcl-2 expression along with increased Bax expression and caspase-9 activation. In summary, early induction of MMP-3 was distinct from MMP-9 during endometriosis, which was regulated by c-Fos and TIMP-3. Melatonin suppressed MMP-3 activity and amplified apoptosis while regressing endometriosis through a caspase-3 mediated pathway. Thus, melatonin may be a therapeutic agent for resolving endometriosis.


Differences in pO2 peaks of a murine fibrosarcoma between carbon-ion and X-ray irradiation.
We measured and compared the oxygen partial pressure (pO(2)) profiles in experimental tumors after irradiation with carbon ions and with X-rays. The NFSa fibrosarcomas grown in the hind legs of C3H male mice received isoeffect single doses of carbon ions or X-rays. Coaxial oxygen microelectrodes of high spatial resolution were inserted into the tumor with 20 microm steps by a computerized micromanipulator. The number of pO(2) peaks that reached 15 mmHg were at least 0.45 per 3,000 microm in unirradiated tumors and significantly increased to 1.55 per 3,000 microm as early as day 1 of carbon-ion irradiation (p < 0.001). The tumors that received X-ray irradiation also significantly increased pO(2) peaks, but as late as day 3. The time course of pO(2) peak appearance in the present study coincides with a previous report where reoxygenation was measured by paired growth delay assay. The pO(2) peaks appeared selectively in peripheral regions of X-ray irradiated tumors, but they appeared rather homogeneously in the tumor after carbon-ion irradiation. It is concluded that carbon-ion irradiation reoxygenated the NFSa fibrosarcomas earlier in time and deeper in space than the X-ray irradiation did.


Vincristine Disposition and Neurotoxicity are Unchanged in Humanized CYP3A5 Mice.
Previous studies have suggested that the incidence of vincristine-induced peripheral neuropathy (VIPN) is potentially linked with CYP3A5, a polymorphic enzyme that metabolizes vincristine in vitro, and with concurrent use of azole antifungals such as ketoconazole. The assumed mechanism for these interactions is through modulation of CYP3A-mediated metabolism, leading to decreased vincristine clearance and increased susceptibility to VIPN. Given the controversy surrounding the contribution of these mechanisms, we directly tested these hypotheses in genetically-engineered mouse models with a deficiency of the entire murine Cyp3a locus [Cyp3a(-/-) mice] and in humanized transgenic animals with hepatic expression of functional and non-functional human CYP3A5 variants. Compared to wild-type mice, the systemic exposure to vincristine was increased by only 1.15-fold (95% CI: 0.84-1.58) in Cyp3a(-/-) mice, suggesting that the clearance of vincristine in mice is largely independent of hepatic Cyp3a function. In line with these observations, we found that Cyp3a-deficiency or pretreatment with the CYP3A inhibitors ketoconazole or nilotinib did not influence the severity and time course of VIPN, and that exposure to vincristine was not substantially altered in humanized CYP3A5*3 mice or humanized CYP3A5*1 mice compared to Cyp3a(-/-) mice. Our study suggests that the contribution of CYP3A5-mediated metabolism to vincristine elimination and the associated drug-drug interaction potential is limited, and that plasma levels of vincristine are unlikely to be strongly predictive of VIPN. Significance Statement The current study suggests that CYP3A5 genotype status does not substantially influence vincristine disposition and neurotoxicity in translationally relevant murine models. These findings raise concerns about the causality of previously reported relationships between variant CYP3A5 genotypes or concomitant azole use with the incidence of vincristine neurotoxicity.


PET Reconstruction of the Posterior Image Probability, Including Multimodal Images.
In PET image reconstruction, it would be useful to obtain the entire posterior probability distribution of the image, because it allows for both estimating image intensity and assessing the uncertainty of the estimation, thus leading to more reliable interpretation. We propose a new entirely probabilistic model: the prior is a distribution over possible smooth regions (distance-driven Chinese restaurant process), and the posterior distribution is estimated using a Gibbs Markov chain Monte Carlo sampler. Data from other modalities (here one or several MR images) are introduced into the model as additional observed data, providing side information about likely smooth regions in the image. The reconstructed image is the posterior mean, and the uncertainty is presented as an image of the size of 95% posterior intervals. The reconstruction was compared with the maximum-likelihood expectation-maximization and OSEM algorithms, with and without post-smoothing, and with a penalized ML or MAP method that also uses additional images from other modalities. Qualitative and quantitative tests were performed on realistic simulated data with statistical replicates and on several clinical examinations presenting pathologies. The proposed method presents appealing properties in terms of obtained bias, variance, spatial regularization, and use of multimodal data, and produces, in addition, potentially valuable uncertainty information.


Polygenic Risk Scores for Psychiatric Disorders Reveal Novel Clues About the Genetics of Disordered Gambling.
Disordered gambling (DG) is a rare but serious condition that results in considerable financial and interpersonal harms. Twin studies indicate that DG is heritable but are silent with respect to specific genes or pathways involved. Existing genomewide association studies (GWAS) of DG have been substantially underpowered. Larger GWAS of other psychiatric disorders now permit calculation of polygenic risk scores (PRSs) that reflect the aggregated effects of common genetic variants contributing risk for the target condition. The current study investigated whether gambling and DG are associated with PRSs for four psychiatric conditions found to be comorbid with DG in epidemiologic surveys: major depressive disorder (MDD), attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD) and schizophrenia (SCZ). Genotype data and survey responses were analyzed from the Wave IV assessment (conducted in 2008) of the National Longitudinal Study of Adolescent to Adult Health, a representative sample of adolescents recruited in 1994-1995 and followed into adulthood. Among participants classified as having European ancestry based on genetic analysis (N = 5215), 78.4% reported ever having gambled, and 1.3% reported lifetime DG. Polygenic risk for BD was associated with decreased odds of lifetime gambling, OR = 0.93 [0.87, 0.99], p = .045, pseudo-R2(%) = .12. The SCZ PRS was associated with increased odds of DG, OR = 1.54 [1.07, 2.21], p = .02, pseudo-R2(%) = .85. Polygenic risk scores for MDD and ADHD were not related to either gambling outcome. Investigating features common to both SCZ and DG might generate valuable clues about the genetically influenced liabilities to DG.


Reasons for misuse of prescription medication among physicians undergoing monitoring by a physician health program.
Substance-related impairment of physicians is a small but serious problem, with significant consequences for patient safety and public health. The purpose of this study was to identify reasons for prescription drug misuse among physicians referred to a physician health program for monitoring because of substance-related impairment, to develop better mechanisms for prevention and intervention. A total of 55 physicians (94.5% male) who were being monitored by their State physician health program because of substance-related impairment participated in guided focus group discussions. Participation was anonymous. Discussions were transcribed from 9 separate focus groups, lasting 60 to 90 minutes each. Qualitative analyses were conducted to examine themes. All participants were diagnosed with substance dependence, and 69.1% of them endorsed a history of misusing prescription drugs. Participants documented the following 5 primary reasons for prescription drug misuse: (1) to manage physical pain, (2) to manage emotional/psychiatric distress, (3) to manage stressful situations, (4) to serve recreational purposes, and (5) to avoid withdrawal symptoms. Our results emphasize the importance of self-medication as a leading reason for misusing prescription medications, although recreational use was also an important factor. Prevention efforts targeting prescription drug misuse among physicians should be initiated during medical training, with continuing education requirements throughout the physicians' careers.


An autopsy case of Mycobacterium abscessus pulmonary infection complicated with rheumatoid arthritis.
We present the case of a 70-year-old man diagnosed with Mycobacterium abscessus pulmonary infection complicated with rheumatoid arthritis who was treated with corticosteroids. He died despite treatment according to the recommended regimen of imipenem, clarithromycin, and amikacin. Autopsy revealed granulomatous lesions throughout the bilateral lungs. We conclude that M. abscessus infection may have a fatal outcome because of the drug resistance of the pathogen. This case suggests that rheumatoid arthritis might be a risk factor for M. abscessus pulmonary infection, but further studies are necessary for clarification.


Effects of melanotropic peptides on fetal adrenal gland.
Adrenal glands from early, mid, and late fetuses of rabbit, guinea pig, and rat, and from newborn animals of each species, were incubated for 1-4 h with and without 0.1 nM-1 microM ACTH, alpha- or beta-melanocyte-stimulating hormone (alpha MSH or beta MSH). The effects of the peptides were measured on production of glucocorticoids, and on incorporation of labeled thymidine or leucine into DNA or protein, respectively. The findings were similar in all three species. ACTH stimulated synthesis of glucocorticoids throughout fetal life. Potency increased progressively, as reflected by declining minimal effective dose and rising maximal response. In early and mid fetus alpha MSH and beta MSH caused a modest glucocorticoid steroidogenic effect. ACTH and alpha MSH stimulated DNA and protein synthesis in the early and mid fetal gland. alpha MSH was more potent than ACTH in these respects, minimal effective dose being generally 10 times less and maximal response 25-200% greater. The effects diminished or disappeared in the late fetal and newborn gland. These data indicate that alpha- and beta MSH possess steroidogenic or growth-promoting properties, or both, for the fetal adrenal gland.


Reliability and robustness of oscillations in some slow-fast chaotic systems.
A variety of nonlinear models of biological systems generate complex chaotic behaviors that contrast with biological homeostasis, the observation that many biological systems prove remarkably robust in the face of changing external or internal conditions. Motivated by the subtle dynamics of cell activity in a crustacean central pattern generator (CPG), this paper proposes a refinement of the notion of chaos that reconciles homeostasis and chaos in systems with multiple timescales. We show that systems displaying relaxation cycles while going through chaotic attractors generate chaotic dynamics that are regular at macroscopic timescales and are, thus, consistent with physiological function. We further show that this relative regularity may break down through global bifurcations of chaotic attractors such as crises, beyond which the system may also generate erratic activity at slow timescales. We analyze these phenomena in detail in the chaotic Rulkov map, a classical neuron model known to exhibit a variety of chaotic spike patterns. This leads us to propose that the passage of slow relaxation cycles through a chaotic attractor crisis is a robust, general mechanism for the transition between such dynamics. We validate this numerically in three other models: a simple model of the crustacean CPG neural network, a discrete cubic map, and a continuous flow.


Predicting the Severity of Symptoms of the COVID Stress Syndrome From Personality Traits: A Prospective Network Analysis.
Psychological stress reactions to the COVID-19 pandemic are complex and multifaceted. Research provides evidence of a COVID Stress Syndrome (CSS), consisting of (1) worry about the dangerousness of getting infected with SARSCoV2 and coming into contact with infected surfaces, (2) worry concerning the personal socioeconomic consequences of COVID-19, (3) xenophobic fears that SARSCOV2 is being spread by foreigners, (4) COVID-19-related traumatic stress symptoms (e.g., nightmares), and (5) compulsive checking and reassurance-seeking about COVID-19. Little is known about how these symptoms are related to vulnerability and protective personality factors. Based on data from 1,976 US and Canadian adults, we conducted a prospective network analysis in which personality factors were initially assessed at Time 1 and then symptoms of the CSS were assessed at Time 2, 2.5 months later. Results indicated that trait optimism and trait resilience were negatively associated with negative emotionality, suggesting a modulatory (inhibitory) influence. Negative emotionality was positively linked to the narrower traits of intolerance of uncertainty and health anxiety proneness. These narrower traits, in turn, were prospectively linked to symptoms of the CSS. Results suggest that the effects of broad personality traits (e.g., negative emotionality, trait resilience) on symptoms of the CSS were mediated by narrower traits such as the intolerance of uncertainty. Treatment implications are discussed.


One stage, full-mouth, ultrasonic debridement in the treatment of severe chronic periodontitis in smokers: a preliminary, blind and randomized clinical trial.
The aim of this clinical trial was to assess the performance of a full-mouth ultrasonic debridement protocol in the treatment of severe chronic periodontitis in comparison with scaling and root planing in a quadrant-wise procedure in smokers. The trial consisted of 30 participants presenting with periodontitis divided into 3 groups: Group FMUD - full-mouth ultrasonic debridement, i.e., one session of 45 minutes of ultrasonic instrumentation for smokers (n = 10), Group SRP- scaling and root planing performed in a quadrant-wise manner for smokers (n = 10), and Group Control - SRP for nonsmokers (n = 10), treated following the same protocol as the SRP group. The parameters evaluated were: plaque/bleeding on probing indices, probing pocket depth, relative recession, and relative probing attachment level at baseline, 45, 90 and 180 days after therapy. Full-mouth ultrasonic debridement and scaling and root planing resulted in comparable gain of attachment 6 months after therapy. Both groups exhibited probing pocket depth reduction at all experimental periods as compared to baseline. Smokers, however, had less probing pocket depth reduction and relative probing attachment level gain compared to non-smokers, despite the mechanical protocol used (p < 0.05). Moreover, at 180 days, nonsmokers presented with fewer sites requiring re-treatment (probing pocket depth > 5 mm and bleeding on probing) than smokers (p < 0.05). Full-mouth ultrasonic debridement and scaling and root planing result in comparable clinical outcomes for the treatment of smokers with severe chronic periodontitis. Despite the non-surgical technique used, smokers had a less favorable clinical response than non-smokers.


Plastein reaction augments the metal chelating capabilities of silver carp (Hypophthalmichthys molitrix) hydrolysates: Unlocking the chemical modification mechanism.
Plastein reaction mechanisms and the alteration of its product properties have been studied for decades. This study investigated the plastein-mediated modifications in silver carp protein hydrolysate (SCPH) from both mechanistic and functional perspectives. Unlike prior research, this investigation uncovered that hydrogen bonding supplemented the dominant hydrophobic interactions in plastein's mechanism for the first time, as supported by peptide concentrations, molecular weight, amino acids, chemical forces, and peptide sequence by LC-MS/MS. This innovative reaction mechanism cascaded into the enhancement of SCPH functional attributes. Plastein induced increased COOH in SCPH's side-chain groups significantly enhanced Fe2+ (from 4.49 to 14.12 %) and Zn2+ (from 53.53 to 64.47 %) chelation. Moreover, the elevated DPPH (17.56 %-23.97 %) and hydroxyl radical (68.49 %-79.32 %) scavenging power indicated a broader improvement in SCPH with plastein. In SCPH, plastein elucidated reaction intricacies and enhanced its utility, propelling SCPH into a realm of extended potential.


Percutaneous transpedicular management of discitis.
To present the technique of percutaneous transpedicular biopsy and debridement of discs in diagnosis and management of discitis. Fifteen patients underwent disc biopsy through a transpedicular approach with local anesthesia and fluoroscopic guidance. An attempt was made to debride the disc as much as possible. A surgical vacuum drain was deployed through the transpedicular tract when there was persistent drainage. Fifteen patients underwent percutaneous transpedicular disc biopsy and debridement of disc for suspected discitis. Three patients underwent biopsy only and 12 underwent percutaneous discectomy. Six patients had at least one positive culture. Eight patients who underwent discectomy had immediate improvement of pain or neurologic symptoms, obviating emergency surgical debridement of the disc. Four patients did not improve and underwent surgical debridement and fusion. Transpedicular biopsy of the disc is an effective technique for adequate tissue retrieval and diagnosis of discitis. Adequate debridement in selected patients with antibiotic therapy may be definitive. Epidural extension of discitis and massive vertebral destruction precludes percutaneous treatment.


Age-related Impairment of Vascular Structure and Functions.
Among age-related diseases, cardiovascular and cerebrovascular diseases are major causes of death. Vascular dysfunction is a key characteristic of these diseases wherein age is an independent and essential risk factor. The present work will review morphological alterations of aging vessels in-depth, which includes the discussion of age-related microvessel loss and changes to vasculature involving the capillary basement membrane, intima, media, and adventitia as well as the accompanying vascular dysfunctions arising from these alterations.


Development of acute cholecystitis following laparoscopic partial cholecystectomy.
In cases where the dissection of Calot's triangle is difficult during laparoscopic cholecystectomy, laparoscopic partial cholecystectomy is an alternative to total cholecystectomy to prevent bile duct damage. However, recurrent symptoms and bile duct problems associated with the remaining gallbladder tissue may develop in patients over time. The case of a 45-year-old male who underwent laparoscopic partial cholecystectomy one year previously is presented here. In the postoperative period, as a result of tests for the continuing symptoms of cholecystitis, stones and surrounding abscess were detected in the remaining gallbladder tissue, so open completion cholecystectomy was applied. In acute cholecystitis, as severe inflammation of the hilar structures does not allow safe dissection, partial cholecystectomy can be applied. However, in these patients, there is a risk of recurrence of cholecystitis symptoms and the development of biliary pancreatitis and choledocolithiasis because of the remaining tissue. Therefore, it should not be forgotten that endoscopic and/or surgical intervention may be necessary at least in some patients.


Congenital central hypoventilation syndrome and Hirschsprung's disease.
Five cases of the Hirschsprung's disease-congenital central hypoventilation syndrome (CCHS) association are presented and 41 other published cases reviewed. These children have a distinct pattern of associated features, an equal sex incidence, and a characteristic spectrum of disease severity which suggests that the condition is genetically distinct from other cases of Hirschsprung's disease. While approximately 1.5% of Hirschsprung's disease patients, and 10% of those with total colonic aganglionosis, will have CCHS, up to 50% of CCHS patients will have Hirschsprung's disease. Approximately 20% of CCHS/Hirschsprung patients will also have neuroblastoma or ganglioneuroma, usually multiple. Abnormalities of the eye and autonomic nervous system are also common. The ventilatory abnormality is usually evident on the first day of life. The aganglionosis is also severe, with more than half (59%) of the patients having aganglionosis extending into the small bowel.


Relationship between genotoxicity biomarkers in somatic and germ cells: findings from a biomonitoring study.
A biomonitoring study to evaluate chromosome and DNA damage respectively in somatic and germ cells of a group of male workers exposed to styrene by using biomarkers of genotoxicity was carried out. Styrene-exposed workers from three different areas of Tuscany and healthy subjects, of comparable mean age, sex and lifestyle characteristics, as a control group not exposed to chemicals, have been enrolled. In addition to previous reports [L. Migliore, A. Naccarati, A. Zanello, R. Scarpato, L. Bramanti and M. Mariani (2002) Hum. Reprod., 17, 2912-2918; L. Migliore, A. Naccarati, F. Coppedè et al. (2006) Pharmacogenet. Genomics, 16, 87-99] we present now data on a cross-sectional investigation involving a homogeneous group of subjects for which data on both somatic and germ cells have been obtained from individuals (42 exposed and 25 controls). Somatic cell genotoxicity was assessed by analysing the frequency of micronucleated binucleated cells (MNBN) in blood lymphocytes. The micronucleus assay was coupled with centromeric fluorescence in situ hybridization (FISH) analysis. Primary DNA damage in germ cells was evaluated by alkaline single-cell gel electrophoresis (Comet assay) and the percentage of the tail DNA (%TD) was used as parameter of Comet evaluation. Moreover, to investigate the frequencies of aneuploidy and diploidy in sperm, we performed multicolour FISH, using DNA probes specific for the centromeric regions of sex chromosomes and chromosome 2, in decondensed sperm nuclei of samples with normal semen parameters in a subgroup of individuals. Mandelic and phenylglyoxylic acids (MAPGA) in end of shift samples were determined as biomarkers of internal dose. MAPGA excretion was consistent with an exposure to styrene above the threshold limit value-time weighted average concentration of 20 p.p.m. Styrene workers showed significantly higher frequency of MNBN as compared to controls (13.8 +/- 5.2 versus 6.2 +/- 5.1; P < 0.001), due to higher proportions of both micronuclei (MN) arising from chromosomal breakage (C-MN) and harbouring whole chromosomes (C+MN). DNA damage in sperm cells was also higher among styrene-exposed, the %TD being 11.02 +/- 2.99 versus 7.42 +/- 2.30 in controls (P < 0.001). The incidence of aneuploidy and diploidy for the tested chromosomes in sperm did not show a statistically significant difference between workers and controls. However, a positive correlation was found between genotoxic damage detected in somatic and in germ cells, even after removing the effect of age (r = 0.475; P < 0.001). Although cytogenetic biomarkers detected both in somatic and germ cells were interrelated, no relationships were apparent with exposure parameters. Styrene exposure may increase the likelihood of both chromosome and DNA damage in somatic and germ cells, thus supporting the hypothesis of an interference on reproductive capacity among exposed workers. This is the first time that a field study shows a correlation between two biomarkers of genotoxicity evaluated at the same time in somatic and germ cells.


Flowers as islands: spatial distribution of nectar-inhabiting microfungi among plants of Mimulus aurantiacus, a hummingbird-pollinated shrub.
Microfungi that inhabit floral nectar offer unique opportunities for the study of microbial distribution and the role that dispersal limitation may play in generating distribution patterns. Flowers are well-replicated habitat islands, among which the microbes disperse via pollinators. This metapopulation system allows for investigation of microbial distribution at multiple spatial scales. We examined the distribution of the yeast, Metschnikowia reukaufii, and other fungal species found in the floral nectar of the sticky monkey flower, Mimulus aurantiacus, a hummingbird-pollinated shrub, at a California site. We found that the frequency of nectar-inhabiting microfungi on a given host plant was not significantly correlated with light availability, nectar volume, or the percent cover of M. aurantiacus around the plant, but was significantly correlated with the location of the host plant and loosely correlated with the density of flowers on the plant. These results suggest that dispersal limitation caused by spatially nonrandom foraging by pollinators may be a primary factor driving the observed distribution pattern.