A dynamic model of hypothermia as an adaptive response by small birds to winter conditions.
We present a dynamic programming model which is used to investigate hypothermia as an adaptive response by small passerine birds in winter. The model predicts that there is a threshold function of reserves during the night, below which it is optimal to enter hypothermia, and above which it is optimal to rest. This threshold function decreases during the night, with a particularly sharp drop at the end of the night, representing the time and energy costs associated with returning to normal body temperature. The results of the model emphasise the trade-off between energy and predation, not just between foraging options, but also between foraging during the day and entering hypothermia at night. The value of being able to use hypothermia represents not just energy savings, but also reduced predation risk due to changes in the optimal foraging strategy. Conditions which give a high value of hypothermia are short photoperiod, variable food supply, low temperatures, poor and scarce food supplies.


Blue rubber bleb nevus syndrome: a rare multisystem affliction.
About 200 cases of blue rubber bleb nevus syndrome (BRBNS) have been reported in the literature. The disorder affects both sexes equally and the occurrence is mostly sporadic except for a few reports of cases with autosomal dominant inheritance pattern. Herein we report an 11-year-old girl with progressive BRBNS and onset at 5 years of age.


Inhibition or initiation of a radical polymerization reaction by an ultraviolet-induced enzymatic process.
alpha-Chymotrypsin was modified to a light-controllable enzyme derivative by acylating active serine 195 residue with a cinnamoyl group or analogue. Upon UV irradiation the acylgroup could be isomerized, leading to release of the inhibiting group. Enzymatic activity could thus be regulated by means of UV light. A full 100% inhibition of the enzymatic activity could not be reached by the cinnamoyl derivative. Only posttreatment with diisopropylfluorophosphate yields a fully inactive enzyme derivative. The shelf-life of the inhibited enzyme was rather poor. Only freeze-dried samples could be used for several months without significant recovery of activity. Adapting the sensitivity of the system to visible light seems limited to the size of an enzyme's active site. Combination of the enzymatic system producing an inhibitor or an initiator with a polymerization reaction can result in a photographic process with a higher amplification factor.


2',3'-Didehydro-2',3'-dideoxy-5-hydroxymethyluridine.
The furanose ring in C10H12N2O5 adopts the O(4')-endo envelope conformation (0E) and the glycosidic torsion angle C(2)--N(1)--C(1')--O(4'), chi, is 245.2 (3) degrees. The pseudo-rotational parameters are P = 102.7 degrees and tau m = 5.2 degrees. The CH2OH group on C(5') has the t conformation [gamma = 179.2 (2) degrees].


Synthesis of 4-hydroperoxy derivatives of ifosfamide and trofosfamide by direct ozonation and preliminary antitumor evaluation in vivo.
A one-step synthesis of 4-hydroperoxyifosfamide and 4-hydroperoxytrofosfamide is described. The method involves direct ozonation of ifosfamide and trofosfamide and offers improved yields in comparison with Fenton oxidation and greater convenience in comparison with ozonation of the appropriate 3-butenyl phosphorodiamidate. Evaluation of the 4-hydroperoxy derivatives of cyclophosphamide, ifosfamide, and trofosfamide against leukemia L1210 in vivo suggests a superior effect for the ifosfamide derivatie.


Cellular Heterogeneity and Molecular Reprogramming of the Host Response during Influenza Acute Lung Injury.
An exuberant host response contributes to influenza A virus (IAV) (or influenza)-mediated lung injury. However, despite significant information on the host response to IAV, the cellular framework and molecular interactions that dictate the development of acute injury in IAV-infected lungs remain incompletely understood. We performed an unbiased single-cell RNA sequencing (scRNAseq) analysis to examine the cellular heterogeneity and regulation of host responses in the IAV model of acute lung injury. At the cellular level, IAV infection promoted the overwhelming recruitment of monocytes that exhibited the cell differentiation trajectory to monocyte-derived macrophages. Together, monocytes and monocyte-derived myeloid cells constituted over 50% of the total immune cells in IAV-infected lungs. In contrast, IAV infection resulted in a significant loss of nonhematopoietic cells. Molecularly, our data show the multidimensional cell-cell communication dynamics of interferon and chemokine signaling between immune and nonimmune cells and the cell-specific molecular pathways regulating the host responses during IAV-induced lung injury. Our data provide a foundation for further exploring the mechanistic association of the IAV host response with acute lung injury. IMPORTANCE A dysregulated host response develops acute lung injury during IAV infection. However, the pathological immune mechanism(s) associated with acute lung injury during IAV infection is yet to be elucidated. In this study, we performed scRNAseq to examine the dynamics of host responses during the peak of IAV-mediated lung injury. At the cellular level, our data reveal significant myelopoiesis predominated by monocytes and macrophages and the simultaneous disruption of the nonhematopoietic cell framework, crucial for regulating inflammation and barrier integrity in IAV-infected lungs. Molecularly, we observed a complex cellular network involving cell-cell communications and a number of unique regulons dictating the outcome of interferon and chemokine responses during peak lung injury. Our data present a unique atlas of cellular changes and the regulation of global and cell-specific host responses during IAV infection. We expect that this information will open new avenues to identify targets for therapeutic intervention against IAV lung injury.


Pressure natriuresis and control of arterial pressure during chronic norepinephrine infusion.
The goal of this study was to quantitate changes in mean arterial pressure (MAP) and renal function during chronic increases in plasma levels of norepinephrine, and to determine the role of the renal pressure natriuresis mechanism in controlling sodium balance in norepinephrine hypertension. In six conscious dogs in which renal artery pressure (RAP) was allowed to increase during 7 days of norepinephrine infusion (0.2 micrograms/kg per min), sodium excretion (UNaV) rose from 66 +/- 3 to 112 +/- 15 mmol/day and MAP increased from 100 +/- 3 to 109 +/- 3 mmHg on the first day. On days 2-7, UNaV returned toward the control level while MAP averaged 108 +/- 2 mmHg. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) did not change significantly, averaging 85.9 +/- 4.0 and 235 +/- 17 ml/min, respectively, during 7 days of norepinephrine, compared to controls of 84.1 +/- 3.9 and 252 +/- 20 ml/min. When RAP was servo-controlled for 7 days during norepinephrine infusion, the natriuresis was abolished; UNaV averaged 76 +/- 8 during control, 77 +/- 13 during the first day of norepinephrine and 65 +/- 4 mmol/day during 7 days of norepinephrine. GFR and ERPF did not change significantly during norepinephrine infusion with RAP held constant. MAP did not reach a plateau but continued to rise from 102 +/- 3 to 137 +/- 3 mmHg after 7 days of norepinephrine and servo-control of RAP.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum antibodies to human fetal antigens in patients with systemic lupus erythematosus (SLE).
Serum antibodies to human fetal antigens were measured by a radiolabeled anti-immunoglobulin binding assay by using human fetal fibroblasts (Flow cell line No. 1000) as target cells. High titers of IgG antibody to the fetal cells were found in sera of patients with systemic lupus erythematosus (SLE). The antibody reacted with surface membrane antigens shared by various fetal tissues of human and murine origin but not by adult tissues. The reaction of the SLE antibody to the fetal cells was inhibited by heterologous antiserum to the Flow 1000 cells and antiserum to murine embryonic fibroblasts, but not by antiserum to human alpha-fetoprotein or human fibronectin. Absorption of SLE serum with isolated nuclei did not abolish the reaction indicating that these were not anti-nuclear antibodies. The antibody activity was found to reside in the F(ab')2 fragment. The serum titer of the anti-fetal antibody was higher in SLE patients with active disease than those in clinical remission.


Development and Validation of a New Stability-Indicating RP-UPLC Method for the Quantitative Determination of Bromfenac Sodium and Its Impurities in an Ophthalmic Dosage Form.
A new rapid stability-indicating reversed-phase UPLC method was developed and validated for the determination of Bromfenac sodium and its impurities in Bromfenac ophthalmic solution. During literature search, only a few publications were found about Bromfenac sodium. There is no official monograph in the pharmacopoeias about Bromfenac sodium. Chromatographic separation has been achieved on a polar-embedded Waters Acquity BEH Shield RP18 (100 mm × 2.1 mm, 1.7 μm) column under gradient elution by using a binary mixture of potassium dihydrogen phosphate (0.01 M, pH 3.3) and acetonitrile (ACN) at a flow rate of 0.5 mL/min. Chromatogram was monitored at 265 nm using a photodiode array detector (PDA). The drug and its related impurities are eluted within 13 min. Resolution of Bromfenac sodium and all eight potential impurities have been achieved greater than 4.0 for all pairs of compounds. To prove the stability-indicating power of the method, the drug was subjected to hydrolytic (acid, alkaline and water), oxidative, photolytic and thermal stress, and the major degradation products were identified based on LC-MS analysis. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, precision, accuracy and robustness.


Defining the ligand specificity of the deleted in colorectal cancer (DCC) receptor.
The growth and guidance of many axons in the developing nervous system require Netrin-mediated activation of Deleted in Colorectal Cancer (DCC) and other still unknown signaling cues. Commissural axon guidance defects are more severe in DCC mutant mice than Netrin-1 mutant mice, suggesting additional DCC activating signals besides Netrin-1 are involved in proper axon growth. Here we report that interaction screens on extracellular protein microarrays representing over 1,000 proteins uniquely identified Cerebellin 4 (CBLN4), a member of the C1q-tumor necrosis factor (TNF) family, and Netrin-1 as extracellular DCC-binding partners. Immunofluorescence and radio-ligand binding studies demonstrate that Netrin-1 competes with CBLN4 binding at an overlapping site within the membrane-proximal fibronectin domains (FN) 4-6 of DCC and binds with ∼5-fold higher affinity. CBLN4 also binds to the DCC homolog, Neogenin-1 (NEO1), but with a lower affinity compared to DCC. CBLN4-null mice did not show a defect in commissural axons of the developing spinal cord but did display a transient increase in the number of wandering axons in the brachial plexus, consistent with a role in axon guidance. Overall, the data solidifies CBLN4 as a bona fide DCC ligand and strengthens its implication in axon guidance.


Attention capture in birds performing an auditory streaming task.
Numerous animal models have been used to investigate the neural mechanisms of auditory processing in complex acoustic environments, but it is unclear whether an animal's auditory attention is functionally similar to a human's in processing competing auditory scenes. Here we investigated the effects of attention capture in birds performing an objective auditory streaming paradigm. The classical ABAB… patterned pure tone sequences were modified and used for the task. We trained the birds to selectively attend to a target stream and only respond to the deviant appearing in the target stream, even though their attention may be captured by a deviant in the background stream. When no deviant appeared in the background stream, the birds experience the buildup of streaming process in a qualitatively similar way as they did in a subjective paradigm. Although the birds were trained to selectively attend to the target stream, they failed to avoid the involuntary attention switch caused by the background deviant, especially when the background deviant was sequentially unpredictable. Their global performance deteriorated more with increasingly salient background deviants, where the buildup process was reset by the background distractor. Moreover, sequential predictability of the background deviant facilitated the recovery of the buildup process after attention capture. This is the first study that addresses the perceptual consequences of the joint effects of top-down and bottom-up attention in behaving animals.


Intrathecal rituximab in immunoglobulin G4-hypertrophic pachymeningitis.
We describe the case of a 69-year-old man who presented with symptoms of headache and severe vision loss due to G4 immunoglobulin (IgG4) hypertrophic pachymeningitis (HP). The patient was initially responsive to corticotherapy, but vision loss progressed when steroid therapy was first tapered. No improvement was noticed with intravenous rituximab. The patient showed clinical and radiological improvement after intrathecal rituximab, which can be an efficacious alternative treatment option.


Psychosocial factors, lifestyle, and fetal growth: the added value of both pre- and post-natal assessments.
Psychosocial resources as well as lifestyle habits during pregnancy have been shown to effect the risk of having a small-for-gestational-age (SGA) child. Most previous studies are based on a single assessment of these exposures, which does not take into account the possibility of different effects during early and late stages of pregnancy. The impact of psychosocial and lifestyle factors on the risk of giving birth to an SGA child (as measured by ultrasound) was examined among 747 nulliparous Swedish women who completed both a prenatal baseline, and a post-partum assessment. Those registering low social participation on both assessments showed increased risk of giving birth to an SGA infant (OR = 2.44 and 95% CI: 1.06-5.66), while at one assessment (OR = 1.70 and 95% CI: 0.74-3.91). Maternal smoking confirmed by both or one assessments yielded an OR = 2.72 and 95% CI: 1.37-5.39 and OR = 1.60 and 95% CI: 0.58-4.46, respectively. During early pregnancy, poor instrumental support, maternal smoking, or passive smoking yielded increased risks of SGA, adjusted for confounding (OR = 2.39 and 95% CI: 1.11-5.17; OR = 2.38 and 95% CI: 1.27-4.49; OR = 2.92 and 95% CI: 1.17-7.32, respectively). In late pregnancy, only maternal smoking yielded a significant association (OR = 2.34 and 95% CI: 1.24-4.41). Scheduling repeated assessments of psychosocial resources and lifestyle factors during pregnancy yielded additional information. The findings suggest that there can be differential effects of such exposures depending on gestational stage. This information is of importance when designing appropriate intervention strategies for maternal health services as well as for public health relevant policy formulation (e.g. regarding exposure to environmental tobacco during pregnancy).


Dilatation of ureteral orifice for ureterorenoscopy.
The history of endoscopic ureteral dilatation began before the turn of the century, and many of those older methods are still in use with the aid of updated instruments. The recent development of controlled hydraulic dilatation promises to make ureteroscopy a one-step procedure.


[Comparative study of multifocal LASIK for the correction of pre-presbyopic myopia].
To evaluate the feasibility of multifocal LASIK for the correction of pre-presbyopic myopia In this prospective,comparative case series, thirty-two patients were recruited into the study,mean age was (38.5 +/- 2.7) years, standard LASIK using Planoscan was performed on the patient's dominant eye, while multifocal LASIK was performed on the nondominant eye. Routine examinations included distance and near vision, refraction, corneal topography, intraocular pressure, ultrasonic corneal pachymetry, contrast sensitivity function, amplitude of accommodation ,depth of defocus, wavefront aberration. The mean follow-up duration was 6.67 +/- 2.75 (range, 6 to 11 months). In the nondominant eyes,the near visual acuity was statistically significant difference, better in the postoperative visual acuity, however, there was no statistically significant difference between preoperation and postoperation in dominant eyes. The Q value of 6 mm diameter in the nondominant eyes was 0.081 +/- 0.274 (range, -0.53 to +0.53) and 0.464 +/- 0.266 (range, - 0.02 to +0.99) in the dominant eyes, significant difference were noted between two groups. Topography revealed high degree refractive power zone of (5.64 +/- 3.05) mm2 at central cornea in nondominant eyes. The wavefront analysis showed that after the multifocal procedure, a positive spherical aberration was induced ,which is opposite to that normally seen following a standard LASIK treatment for myopia. At 6 months, the nondominant eyes attained pseudoaccommodation of (0.84 +/- 0.61) diopters (range, 0 to 2.25 D), the amplitude of pseudoaccommodation are related to corneal multifocal index, spherical aberration. However, amplitude of accommodation was decreased (0. 10 +/- 0.67) diopters in dominant eyes at 6 months visit. The results of this study show that multifocal LASIK is safe and effective in preserving near vision for pre-presbyopic myopia patients . Multifocal LASIK are reasonably to induce pseudoaccommodation by decreasing negative spheric aberration.


Trait Emotional Intelligence in Surgeons.
Trait emotional intelligence (trait EI or trait emotional self-efficacy) concerns people's perceptions of their emotional functioning. Two studies investigated this construct in surgeons and comparison occupations. We hypothesized that trait EI profiles would differ both within surgical specialties as well as between them and other professions. Study 1 (N = 122) compared the trait EI profiles of four different surgical specialties (General, Orthopedic, Head and Neck, and Miscellaneous surgical specialties). There were no significant differences amongst these specialties or between consultant surgeons and trainees in these specialties. Accordingly, the surgical data were combined into a single target sample (N = 462) that was compared against samples of engineers, executives and senior managers, lawyers, junior military managers, nurses, and salespeople. Surgeons scored significantly higher on global trait EI than junior military managers, but lower than executives and senior managers, salespeople, and nurses. There were no significant differences vis-à-vis engineers or lawyers. A MANOVA confirmed a similar pattern of differences in the four trait EI factors (Wellbeing, Self-control, Sociability, and Emotionality). Global trait EI scores correlated strongly with single-question measures of job satisfaction (r = 0.47) and job performance (r = 0.46) in the surgical sample. These findings suggest that interventions to optimize the trait EI profiles of surgeons can be helpful in relation to job satisfaction, job performance, and overall psychological wellbeing.


Activation of the small GTPase Ral in platelets.
Ral is a ubiquitously expressed Ras-like small GTPase which is abundantly present in human platelets. The biological function of Ral and the signaling pathway in which Ral is involved are largely unknown. Here we describe a novel method to measure Ral activation utilizing the Ral binding domain of the putative Ral effector RLIP76 as an activation-specific probe. With this assay we investigated the signaling pathway that leads to Ral activation in human platelets. We found that Ral is rapidly activated after stimulation with various platelet agonists, including alpha-thrombin. In contrast, the platelet antagonist prostaglandin I2 inhibited alpha-thrombin-induced Ral activation. Activation of Ral by alpha-thrombin could be inhibited by depletion of intracellular Ca2+, whereas the induction of intracellular Ca2+ resulted in the activation of Ral. Our results show that Ral can be activated by extracellular stimuli. Furthermore, we show that increased levels of intracellular Ca2+ are sufficient for Ral activation in platelets. This activation mechanism correlates with the activation mechanism of the small GTPase Rap1, a putative upstream regulator of Ral guanine nucleotide exchange factors.


Skeletal abnormalities are common features in Aymé-Gripp syndrome.
Aymé-Gripp syndrome (AYGRPS) is a recognizable condition caused by a restricted spectrum of dominantly acting missense mutations affecting the transcription factor MAF. Major clinical features of AYGRPS include congenital cataracts, sensorineural hearing loss, intellectual disability, and a distinctive flat facial appearance. Skeletal abnormalities have also been observed in affected individuals, even though these features have not been assessed systematically. Expanding the series with four additional patients, here we provide a more accurate delineation of the molecular aspects and clinical phenotype, particularly focusing on the skeletal features characterizing this disorder. Apart from previously reported malar flattening and joint limitations, we document that carpal/tarsal and long bone defects, and hip dysplasia occur in affected subjects more frequently than formerly appreciated.


Identification of circulating microRNAs as potential biomarkers for detecting acute myeloid leukemia.
Acute myeloid leukemia (AML) is the most common acute leukemia in adults. The disease is characterized by various cytogenetic and molecular abnormalities with distinct prognoses and gene expression profiles. Emerging evidence has suggested that circulating microRNAs (miRNAs) could serve as noninvasive biomarkers for cancer detection; however, little is known about circulating miRNA profiles in AML patients. In this study, a genome-wide serum miRNA expression analysis was performed using Solexa sequencing for initial screen, followed by validation with real-time PCR assays. The analysis was conducted on training and verification sets of serum samples from 140 newly diagnosed AML patients and 135 normal adult donors. After a two-phase selection and validation process, 6 miRNAs, miR-10a-5p, miR-93-5p, miR-129-5p, miR-155-5p, miR-181b-5p and miR-320d, were found to have significantly different expression levels in AML compared with control serum samples. Furthermore, unsupervised clustering analysis revealed the remarkable ability of the 6-miRNA profile to differentiate between AML patients and normal controls. The areas under the ROC curve for the selected miRNAs ranged from 0.8129 to 0.9531. More importantly, miR-181b-5p levels in serum were significantly associated with overall survival. These data demonstrated that the expression patterns of circulating miRNAs were systematically altered in AML and miR-181b-5p may serve as a predictor for overall survival in AML patients.


Progress in hypertension research: 1900-2000.
The author reviews the various factors (sodium, aldosterone, renin-angiotensin system, and norepinephrine; each of these factors being influenced by others) involved in the mechanism of human hypertension. A coherent picture is emerging, with the final pathway of these mechanisms converging on the renin-angiotensin system in the presence of a positive sodium balance and responsible for arteriolar resistance and responsiveness to pressor agents. This would correspond to the labile phase of hypertension, which leads with time to arteriolar restructuring and the increased media/lumen ratio, as demonstrated by Schiffrin and coworkers, and which can revert to normal structure with the administration of antihypertensive drugs such as converting-enzyme inhibitors, calcium-blocking drugs, and antagonists of the angiotensin II type 1 receptor. The author also presents the experience obtained in the Hypertension Clinic of the Clinical Research Institute of Montréal, which has been in existence since 1953; this experience is based on the observation of senior observers (clinical scientists, clinicians, and nurses) that the blood pressure of hypertensive patients can be controlled to normal levels in almost all cases for years and decades with a proper combination of the present antihypertensive drugs.


[The role of stress-induced chronic subclinical inflammation in the pathogenesis of the chronic pelvic pain syndrome IIIB in men].
This literature review of recent clinical and experimental studies describes the role of oxidative stress in the multifactorial and interdisciplinary pathogenesis of non-inflammatory chronic pelvic pain syndrome IIIB (CPPS-IIIB) in men. The authors outline general biological nature of oxidative stress and its mechanisms. More detailed information is presented on cytokine-mediated chronic subclinical inflammation, one of the key mechanisms of oxidative stress, which is currently being actively studied. It is shown that the imbalance between pro- and anti-inflammatory cytokines observed in patients with CPPS-IIIB can explain some features of the clinical course (in particular, the characteristics of the pain syndrome) and the progression of this disease. In this regard, cytokine profiling of prostatic secretion can provide valuable diagnostic, prognostic and monitoring information in the management of this category of patients. Recently published evidence has demonstrated the essential role of the cytokine-mediated chronic inflammatory response as a mechanism of oxidative stress in the pathogenesis of CPPS-IIIB. Further studies in this area are warranted and in the long term may become a basis for the development of new effective pathogenetic pharmacotherapy of CPPS-IIIB.


[Serum bile acids in dyslipidemic patients].
The sensitivity of total serum bile acid concentration as an index of hepatic damage has long been recognised. In addition serum bile acid measurement is significantly more specific than conventional hepatic function tests. However the concentration might be affected by factors other than hepatic dysfunction. Several authors have reported variations in the synthesis of serum bile acids in dyslipidaemic patients. This might potentially reduce the value of concentration measurement in the diagnosis of hepatic diseases especially considering the relative prevalence of hyperlipidaemia. The present article reports on radioimmunological serum bile acid measurement before and after meals in 10 patients with dyslipidaemia and in 22 controls. No difference was revealed between the two groups. Therefore dyslipidaemia appears not to affect the specificity of the test nor does it invalidate the use of radioimmunological measurement of total serum bile acids in the study of hepatic function.


Significant Structural Alterations and Functional Connectivity Alterations of Cerebellar Gray Matter in Patients With Somatic Symptom Disorder.
Recent studies have revealed a strong association between the cerebellum and psychiatric disorders. However, the structural changes in the cerebellar regions and functional connectivity (FC) patterns in patients with somatic symptom disorder (SSD) have not been elucidated. Thirty-seven patients with SSD (29 drug-naive and 8 medicated patients) and 37 sex- and age-matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging scans. The spatially unbiased infratentorial (SUIT) cerebellar atlas-based voxel-based morphometry was used to investigate the changes in cerebellar regional gray matter (GM). Seed-based FC was further computed to explore the pattern of abnormal FC across the whole brain. Correlations were calculated to investigate the relationship between cerebellar structural (and FC) changes and clinical characteristics. After controlling for age, sex, total intracranial volume, medication, and mean FD covariates, all patients with SSD had increased mean GM volume (GMV) in the posterior lobules of the cerebellum bilaterally when compared with HCs, specifically, in the bilateral cerebellar crura I and II. Patients with SSD showed significantly stronger FC between the right crura I and II and bilateral precuneus inferior parietal region, and postcentral gyrus, extending to the superior parietal lobe, cingulate gyrus, and the white matter subgyral. In addition to the two clusters, right lingual gyrus was also a surviving cluster with significantly higher FC. Partial correlation analysis revealed that the degree of regional GMV increases in the two significant clusters and the Hamilton Depression Scale (HAMD) score was negatively correlated. Moreover, the FC of right crura I and II with the left parietal lobe and right lingual gyrus were also negatively associated with the HAMD score. SSD exhibited significant microstructural changes and changes in FC pattern in the posterior cerebellar lobe. These results shed new light on the psychological and neural substrates of SSD and may serve as a potential treatment target for SSD based on the cerebellar area.


Influence of aerobic fitness and body fatness on tolerance to uncompensable heat stress.
This study examined the independent and combined importance of aerobic fitness and body fatness on physiological tolerance and exercise time during weight-bearing exercise while wearing a semipermeable protective ensemble. Twenty-four men and women were matched for aerobic fitness and body fatness in one of four groups (4 men and 2 women in each group). Aerobic fitness was expressed per kilogram of lean body mass (LBM) to eliminate the influence of body fatness on the expression of fitness. Subjects were defined as trained (T; regularly active with a peak aerobic power of 65 ml x kg LBM(-1) x min(-1)) or untrained (UT; sedentary with a peak aerobic power of 53 ml x kg LBM(-1) x min(-1)) with high (High; 20%) or low (Low; 11%) body fatness. Subjects exercised until exhaustion or until rectal temperature reached 39.5 degrees C or heart rate reached 95% of maximum. Exercise times were significantly greater in T(Low) (116 +/- 6.5 min) compared with their matched sedentary (UT(Low); 70 +/- 3.6 min) or fatness (T(High); 82 +/- 3.9 min) counterparts, indicating an advantage for both a high aerobic fitness and low body fatness. However, similar effects were not evident between T(High) and UT(High) (74 +/- 4.1 min) or between the UT groups (UT(Low) and UT(High)). The major advantage attributed to a higher aerobic fitness was the ability to tolerate a higher core temperature at exhaustion (the difference being as great as 0.9 degrees C), whereas both body fatness and rate of heat storage affected the exercise time as independent factors.


Controllably interfacing with metal: a strategy for enhancing CO oxidation on oxide catalysts by surface polarization.
Heterogeneous catalysis often involves charge transfer from catalyst surface to adsorbed molecules, whose activity thus depends on the surface charge density of catalysts. Here, we demonstrate a unique solution-phase approach to achieve controllable interfacial lengths in oxide-metal hybrid structures. Resulting from their different work functions, surface polarization is induced by the Ag-CuO interface and acts to tailor the surface charge state of CuO. As a result, the designed hybrid catalysts exhibit enhanced intrinsic activities in catalyzing CO oxidation in terms of apparent activation energy, as compared with their counterparts. Moreover, the CO conversion rate can be enhanced by maximizing the Ag-CuO interfacial length and thus the number of active sites on the CuO. This work provides a new strategy for tuning catalytic performance by controlling interface in hybrid catalysts.


Targeting interleukin-1 signaling in chronic inflammation: focus on P2X(7) receptor and Pannexin-1.
Innate immunity is the most ancient system to protect multicellular hosts from infections. In vertebrates it is regulated by an extensive and complex network of cytokines that orchestrate inflammation, a response of the body to invasion by infectious agents or to tissue damage. One of the key cytokines that initiates inflammation is interleukin (IL)-1 and aberrant production of IL-1, due to a failure in any of its regulatory steps, leads to chronic inflammatory diseases. The discovery of new proteins regulating IL-1 processing and release opens an exciting field for the design of novel antiinflammatory drugs. Among those are the purinergic ATP-gated P2X(7) receptor (P2X(7)R) and its downstream signaling molecule Pannexin-1 (Panx-1), both involved in the control of the activation and the release of mature IL-1alpha, IL-1beta and IL-18. This review will focus on the potential targets for each step in the IL-1 signaling process, from gene expression through activation of IL-1 receptor by released cytokines, with particular attention paid to the involvement of P2X(7)R and Panx-1.


Delivery room intervention: improving the outcome.
The authors have conducted video review of neonatal resuscitations since 1999. Over this 10-year period 3 phases of our experience have been recognized. Our early reviews helped us recognize what we were doing in the delivery room, an area that had been ignored in improved intervention. It was noted that on many occasions multiple people were trying to accomplish the same task, that bag and mask ventilation was almost exclusively the purview of the respiratory therapists and was not performed well by others, and that infants with low birth weight were often hypothermic on admission. After determining what was being done and how well it was being done, we moved on to how to do it better. This period included making environmental changes by warming the room, the use of occlusive wrap, determining the effectiveness of bag and mask ventilation with colorimetric CO(2) detectors, and the introduction of crew resource management to develop consistent and effective communication. The third and current phase of our experience is to determine how these interventions affect delivery room and potentially later outcomes. Well-designed clinical trials are still needed to further establish the most optimal resuscitation interventions.


The clinicopathological characteristics of gastric polyps and the relationship between fundic gland polyps, Helicobacter pylori infection, and proton pump inhibitors.
To explore the clinical characteristics of different types of gastric polyps and the relationship between fundic gland polyps, Helicobacter pylori (HP) infection, and proton pump inhibitor (PPI) use. The clinical data of 186 patients diagnosed with gastric polyps under endoscopy were selected for retrospective analysis, and the clinical data, gastroscopy, polyp histopathology, HP infection, and PPI usage of all subjects were analyzed. Among the 186 patients with gastric polyps, there were significantly more women (131 cases) than men (55 cases), with a ratio of 2.38:1. PPIs were used in 78% of cases for more than 5 years. The pathological types of patients with gastric polyps in this study were fundic gland polyps, hyperplastic polyps, inflammatory fibrous polyps, and adenomatous polyps. Fundic gland polyps were mainly located in the fundus and gastric body, while hyperplastic polyps were mostly located in the gastric body (P<0.05). The positive rate of HP infection in patients with fundic gland polyps was significantly lower than that in patients with other types of polyps (P<0.05). In patients with long-term use of PPIs, the incidence of fundic gland polyps increased significantly (P<0.05). There were significant differences among the different types of gastric polyps in terms of polyp position, shape, and size. The positive rate of HP infection in patients with fundic gland polyps was low. Long-term use of PPIs (>5 years) increased the incidence of fundic gland polyps to some extent. The mechanisms underlying the relationship between gastric polyps, HP infection, and the use of PPIs remain to be further studied.


Behavioral assessments of BTBR T+Itpr3tf/J mice by tests of object attention and elevated open platform: Implications for an animal model of psychiatric comorbidity in autism.
Autism spectrum disorders (ASD) are diagnosed based on the behavioral criteria of impaired social interaction, defective communication and repetitive behaviors. Psychiatric comorbidities, such as anxiety and intellectual disability, are commonly present in ASD. The BTBR T+ Itpr3tf/J (BTBR) mice display a range of autistic phenotypes, yet whether this mouse model is appropriate to study psychiatric comorbidity in ASD remains unclear. We addressed this issue by subjecting the BTBR animals to three-chambered apparatus, open field, object attention test and elevated open platform. Compared to C57BL/6J control mice, the BTBR mice displayed hyperactivity in most of the tests. In the three-chamber assessment, they exhibited deficits in sociability. In the open field, more grooming and thigmotaxis and less rearing behaviors were observed. They also showed impaired object-based attention. On the elevated open platform, the BTBR animals stayed more to the edges than in the center of the platform. To further examine the properties of this test, naïve C57BL/6J mice were randomly administrated with saline or an anxiogenic substance, caffeine. The caffeine group demonstrated a similar behavioral pattern as the BTBR mice. When the saline group was re-exposed to the same platform, the time they stayed in the center substantially increased, likely due to reduced anxiety by habituation. These results indicate that the BTBR were more anxious than control mice on the open platform. Taken together, the BTBR strain exhibit emotional and cognitive impairments in addition to autistic behaviors, suggesting that they can be a valid model for ASD with psychiatric comorbidity.


Spatiotemporal model for depth perception in electric sensing.
Electric sensing involves measuring the voltage changes in an actively generated electric field, enabling an environment to be characterized by its electrical properties. It has been applied in a variety of contexts, from geophysics to biomedical imaging. Some species of fish also use an active electric sense to explore their environment in the dark. One of the primary challenges in such electric sensing involves mapping an environment in three-dimensions using voltage measurements that are limited to a two-dimensional sensor array (i.e. a two-dimensional electric image). In some special cases, the distance of simple objects from the sensor array can be estimated by combining properties of the electric image. Here, we describe a novel algorithm for distance estimation based on a single property of the electric image. Our algorithm can be implemented in two simple ways, involving either different electric field strengths or different sensor thresholds, and is robust to changes in object properties and noise.


Amino Acid Metabolism and Transport Mechanisms as Potential Antifungal Targets.
Discovering new drugs for treatment of invasive fungal infections is an enduring challenge. There are only three major classes of antifungal agents, and no new class has been introduced into clinical practice in more than a decade. However, recent advances in our understanding of the fungal life cycle, functional genomics, proteomics, and gene mapping have enabled the identification of new drug targets to treat these potentially deadly infections. In this paper, we examine amino acid transport mechanisms and metabolism as potential drug targets to treat invasive fungal infections, including pathogenic yeasts, such as species of Candida and Cryptococcus, as well as molds, such as Aspergillus fumigatus. We also explore the mechanisms by which amino acids may be exploited to identify novel drug targets and review potential hurdles to bringing this approach into clinical practice.


[Vertebral Body Height after Balloon Kyphoplasty vs. Radiofrequency Kyphoplasty].
Kyphoplasty is used to alleviate pain and to restore the initial height of osteoporotic vertebral fractures (OVF). One of the most recent procedures is radiofrequency-targeted vertebral augmentation (RFTVA). We investigated whether restoration with this method is similar and as adequate as with the established procedure of balloon kyphoplasty (BKP), as assessed by the anatomical height of the vertebral body. The aim of our study was to compare the intravertebral angles (base-endplate) post- and preoperatively with these two procedures. The base and endplate angles were measured on 142 vertebral bodies treated by kyphoplasty (67 BKP and 75 RFTVA), on the basis of pre- and postoperative X-rays in the upright position in 87 volunteers (46 BKP and 41 RFTVA). The main object was to detect the degree of correction (Δpost-preop) with BKP compared to RFTVA. Furthermore, the sagittal alignment of the adjacent heathy levels were measured. Significant correction was detected with both BKP (BKPpre: 11.5 ± 6.0°, BKPpost: 6.2 ± 4.6°, p < 0.001) and RFTVA (RFTVApre: 9.9 ± 6.2°, RFTVApost: 6.3 ± 4.4°, p < 0.001). Potential correction was greater with BKP than with RFTVA (Δpost-pre BKP: - 5.3 ± 4.4°, Δpost-pre RFK: - 3.6 ± 4.4°, p = 0.03). Neither procedures gave a significant change in the sagittal angle in the adjacent segment (segment BKPpre: 13.8 ± 8.0°, Segment BKPpost: 12.5 ± 9,2°, p = 0.638; Segment RFTVApre: 18,8 ± 14,3°, Segment RFTVApost: 15.0 ± 13.2°, p = 0.330). BKP gave significantly better correction, even though both methods were able to restore significant improvement in the kyphotic angle. In the adjacent levels, correction of the sagittal angle was not significant, although the influence of the intervention on alignment tended to be less.


Rational Design of Wide Spectral-Responsive Heterostructures of Au Nanorod Coupled Ag3PO4 with Enhanced Photocatalytic Performance.
Noble metallic nanomaterials with surface plasmon resonance (SPR) effects and hot electron cell effects open new opportunities for designing efficient visible-light-driven hybrid photocatalysts. In this work, we reported a broadband visible-light responsive photocatalyst by incorporating Au nanorods (AuNRs) into Ag3PO4 nanostructures. The longitudinal plasma of AuNRs enabled AuNRs/Ag3PO4 heterostructures to harvest light energy up to 800 nm. The obtained AuNRs/Ag3PO4 hybrid exhibited enhanced photocatalytic efficiency toward the degradation of rhodamine B (RhB) under solar irradiation. Ag3PO4, RhB, and AuNRs played different roles according to the distinct optical properties of each individual component. The dominant photocatalytic process in the different light regions were divided as follows: direct excitation of Ag3PO4 for λ ≥ 420 nm, RhB sensitization for λ ≥ 550 nm, and SPR effect for λ ≥ 600 nm. The relationship between the pathway of charge transfer and the photocatalytic activity of the AuNRs/Ag3PO4 heterostructures was investigated systematically, revealing the specific role of AuNRs in regulating the photocatalytic activity. This work presents an innovative strategy for determining the comprehensive function of the SPR effect in relevant semiconductor-based photocatalysis and functional nanodevices with a broadband light responses.


[EFFECTIVENESS OF LIMITED INTERNAL FIXATION COMBINED WITH HINGED SUPER-ARTICULAR EXTERNAL FIXATOR FOR TYPE C3 FRACTURE OF DISTAL HUMERUS IN ADULT].
To investigate the effectiveness of limited internal fixation combined with hinged super-articular external fixator to treat type C3 fracture of the distal humerus. Between September 2007 and November 2012, 37 cases of type C3 fracture of the distal humerus were treated. There were 22 males and 15 females with an average age of 43.6 years (range, 22-66 years). The causes were accident injury in 24 cases, falling injury in 5 cases, falling from height in 4 cases, heavy crush injury in 2 cases, machine injury in 1 case, and other injury in 1 case. There were 22 cases of open injury and 15 cases of closed injury. The time from injury to operation was 3-46 hours (mean, 18 hours). Needle tract reaction and incision infection occurred in 3 cases and 1 case respectively, healing of incision by first intension was obtained in the other cases. Thirty-six patients were followed up 9-48 months (mean, 25.4 months). Heterotopic ossification occurred in 3 cases after operation and no recurrence was found by release after fracture healing. Fractures healed in the other patients after 6-14 months (mean, 9 months) of operation except 1 patient who suffered chronic osteomyelitis. One patient had delayed ulnar neuritis at 12 months after operation, and the nerve function returned to normal after the ulnar nerve transposition. There was no bone ischemic necrosis, elbow joint instability, or loosening of internal fixation. At last follow-up, the average range of motion of injured elbow was 105.0° in flexion, -25.0° in extension, 69.2° in pronation, and 75.6° in supination. According to Mayo elbow joint function score (MEPS) and disability of arm shoulder and hand (DASH) score, the results were excellent in 22 cases, good in 8 cases, fair in 4 cases, and poor in 2 cases with an excellent and good rate of 83.3%; and according to Cassebaum elbow joint function score, the results were excellent in 21 cases, good in 7 cases, fair in 5 cases, and poor in 3 cases with an excellent and good rate of 77.8%. A combination of limited internal fixation and hinged super-articular external fixator has satisfactory clinical curative effect for type C3 fractures of the distal humerus, relatively few complications.


Tetracyclines inhibit Porphyromonas gingivalis-induced alveolar bone loss in rats by a non-antimicrobial mechanism.
Tetracyclines have been widely used as adjuncts in periodontal therapy due to the antimicrobial efficacy of these drugs. Recently, their ability to inhibit host-derived matrix metalloproteinases (collagenase and gelatinase) and bone resorption in organ culture has also been invoked as a therapeutic rationale. The current study was undertaken to determine whether tetracyclines can inhibit alveolar bone loss in vivo due to a non-antimicrobial action of these drugs. Experimental periodontitis was induced by inoculating adult, male Sprague-Dawley rats with P. gingivalis (strain 381) following kanamycin/ampicillin pretreatment. Doxycycline, non-antimicrobial chemically-modified tetracycline (CMT-1) and vehicle alone were administered daily to 3 infected groups of rats (n = 6 rats per group; each group housed in a sterilized inflatable isolator) beginning 10 days after P. gingivalis inoculation. The control group (n = 6; non-infected rats) received only vehicle. After 5 weeks of daily drug administration by gastric intubation, the experiment was terminated and blood samples were taken from each animal to determine antibody levels against P. gingivalis. Plaque samples were collected from each group of animals before and after P. gingivalis inoculation and at the end of the experiment for microbiological examination. The jaws were removed from each rat, defleshed and then analyzed morphometrically and radiographically to assess bone loss. Serum antibody levels against P. gingivalis were significantly elevated in the 3 infected groups compared to the non-infected controls. This, together with the microbiologic findings, indicated that these groups of rats were infected with P. gingivalis.(ABSTRACT TRUNCATED AT 250 WORDS)


Neural Language Processing in Adolescent First-Language Learners: Longitudinal Case Studies in American Sign Language.
One key question in neurolinguistics is the extent to which the neural processing system for language requires linguistic experience during early life to develop fully. We conducted a longitudinal anatomically constrained magnetoencephalography (aMEG) analysis of lexico-semantic processing in 2 deaf adolescents who had no sustained language input until 14 years of age, when they became fully immersed in American Sign Language. After 2 to 3 years of language, the adolescents' neural responses to signed words were highly atypical, localizing mainly to right dorsal frontoparietal regions and often responding more strongly to semantically primed words (Ferjan Ramirez N, Leonard MK, Torres C, Hatrak M, Halgren E, Mayberry RI. 2014. Neural language processing in adolescent first-language learners. Cereb Cortex. 24 (10): 2772-2783). Here, we show that after an additional 15 months of language experience, the adolescents' neural responses remained atypical in terms of polarity. While their responses to less familiar signed words still showed atypical localization patterns, the localization of responses to highly familiar signed words became more concentrated in the left perisylvian language network. Our findings suggest that the timing of language experience affects the organization of neural language processing; however, even in adolescence, language representation in the human brain continues to evolve with experience.


Optimizing the Targeting of Mouse Parvovirus 1 to Murine Melanoma Selects for Recombinant Genomes and Novel Mutations in the Viral Capsid Gene.
Combining virus-enhanced immunogenicity with direct delivery of immunomodulatory molecules would represent a novel treatment modality for melanoma, and would require development of new viral vectors capable of targeting melanoma cells preferentially. Here we explore the use of rodent protoparvoviruses targeting cells of the murine melanoma model B16F10. An uncloned stock of mouse parvovirus 1 (MPV1) showed some efficacy, which was substantially enhanced following serial passage in the target cell. Molecular cloning of the genes of both starter and selected virus pools revealed considerable sequence diversity. Chimera analysis mapped the majority of the improved infectivity to the product of the major coat protein gene, VP2, in which linked blocks of amino acid changes and one or other of two apparently spontaneous mutations were selected. Intragenic chimeras showed that these represented separable components, both contributing to enhanced infection. Comparison of biochemical parameters of infection by clonal viruses indicated that the enhancement due to changes in VP2 operates after the virus has bound to the cell surface and penetrated into the cell. Construction of an in silico homology model for MPV1 allowed placement of these changes within the capsid shell, and revealed aspects of the capsid involved in infection initiation that had not been previously recognized.


Cellulose acetate butyrate and polycaprolactone for ketoprofen spray-dried microsphere preparation.
Ketoprofen-loaded microspheres made with a polymeric blend were prepared by a spray-drying technique. Organic solutions of two polymers, cellulose acetate butyrate (CAB) and poly(epsilon-caprolactone) (PCL), in different weight ratios, and of ketoprofen (Ket) were prepared and sprayed, in different experimental conditions, achieving drug-loaded microspheres. The obtained spray-dried microspheres were characterized in terms of yield of production, shape, size, surface properties and drug content, and their in vitro drug release behaviours were determined at different pH values.


Tight junction protein MAGI-1 is up-regulated by transfection with connexin 32 in an immortalized mouse hepatic cell line: cDNA microarray analysis.
Gap junctions are considered to play a crucial role in differentiation of epithelial cells, including hepatocytes. Recently, we found that Cx32 but not Cx26 was closely related to tight junctional proteins in primary cultured rat hepatocytes (Kojima et al., Exp Cell Res 263:193-201, 2001) and that Cx32 formation and/or Cx32-mediated intercellular communication could induce expression and function of tight junctions in a mouse hepatic cell line (Kojima et al., Exp Cell Res 276:40-51, 2002). In this study, to investigate the mechanisms of induction of tight junctions by transfection with Cx32, we performed cDNA microarray analysis of Cx32 transfectants, compared with parental cells derived from Cx32-deficient hepatocytes. In cDNA microarray analysis, a 2.5-fold increase in expression of membrane-associated guanylate kinase with inverted orientation-1 (MAGI-1), which is known to be localized at adherens and tight junction regions, was observed. High expression of MAGI-1 in Cx32 transfectants was confirmed by Western blotting and RT-PCR. MAGI-1 was colocalized with occludin, claudin-2, ZO-1, and F-actin, but not with E-cadherin in the apical-most regions at cell borders of Cx32 transfectants, similar to junctional adhesion molecule-1 (JAM-1), which may play a crucial role in formation and assembly of tight junctions. Treatment with the gap junction blocker 18beta-glycyrrhetinic acid did not affect expression of MAGI-1 and JAM-1 in Cx32 transfectants. These results suggest that Cx32 expression is in part related to induction of tight junctions through modulation of MAGI-1 expression in an immortalized mouse hepatic cell line.


Determination of sinus pericranii resectability by external compression during angiography: technical note.
Sinus pericranii is an uncommon congenital cranial venous malformation that may become symptomatic in the pediatric population. Both dominant and accessory sinus pericranii, as determined by the intracranial venous drainage pattern, have been described. The dominant variety drain a significant proportion of the intracranial venous outflow while the accessory variety have minimal or no role in this. Classic teachings hold that dominant sinus pericranii should never be treated while accessory sinus pericranii may be safely obliterated. This determination of dominance is solely based on a qualitative assessment of standard venous phase catheter cerebral angiography, leaving some doubt regarding the actual safety of obliteration. In this paper the authors describe a simple and unique method for determining whether intracranial venous outflow may be compromised by sinus pericranii treatment. This involves performing catheter angiography while the lesion is temporarily obliterated by external compression. Analysis of intracranial venous outflow in this setting allows visualization of angiographic changes that will occur once the sinus pericranii is permanently obliterated. Thus, the safety of surgical intervention can be more fully appraised using this technique.


Identification of novel lncRNAs involved in the pathogenesis of childhood acute lymphoblastic leukemia.
This study aimed to explore novel long non-coding RNAs (lncRNAs) and the underlying mechanisms involved in childhood acute lymphoblastic leukemia (cALL). The GSE67684 dataset was downloaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) and lncRNAs (DELs) between Days 0, 8, 15 and 33 were isolated using random variance model corrective analysis of variance. Overlapping DEGs and DELs were clustered using Cluster 3.0. Bio-functional enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Interactions between lncRNAs and mRNAs were calculated using dynamic simulations, and interactions among mRNAs were predicted using the STRING database. lncRNA-mRNA and protein-protein interaction (PPI) networks were visualized using Cytoscape. Subsequently, the expression levels of lncRNAs in biological samples from children with or without cALL were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 593 overlapping DEGs and 21 DELs were identified. After clustering, Profile 26 exhibited a continuously increasing temporal trend, whereas Profile 1 exhibited a continuous decreasing trend. Upregulated DEGs were significantly enriched in 1,825 GO terms and 166 KEGG pathways, whereas downregulated DEGs were significantly enriched in 196 GO terms and 90 KEGG pathways. The lncRNAs NONHSAT027612.2 and NONHSAT134556.2 were the top two regulators in the lncRNA-mRNA network. Toll-like receptor 4, cathepsin G, nucleotide-binding oligomerization domain containing 2 and cathepsin S may be considered the hub genes of the PPI network. RT-qPCR results indicated that the expression levels of the lncRNAs NONHSAT027612.2 and NONHSAT134556.2 were significantly elevated in the blood and bone marrow of patients with cALL compared with the controls. In conclusion, the lncRNAs NONHSAT027612.2 and NONHSAT134556.2 may serve important roles in the pathogenesis of cALL via regulating immune response-associated pathways.


[Immobilization of lipase labeled with fluorescent probe and its stability].
The lipase labeled with the fluorescein isothiocyanat (FITC) was immobilized on the derivatives of the polyethylene glycol. The article discussed the effect of factors on the characters of lipase and analyzed the relationships among the activity of lipase, conformation, and fluorescence spectrum while the activity and the fluorescence spectrum of immobilized lipase were determined. The results demonstrated that polyethylene glycol 400-diacrylate could form appropriate network to improve the activity of enzyme. Adding ligand induced the lipase's catalytic conformation to increase the activity twice more than before. The active centre of lipase could be released by the extraction of ligand thus increasing the activity. After immobilization, the stability of labeled lipase improved greatly: immobilized lipases retained more than 70% and 60% of initial activity under conditions of 90 degrees C and strong acid or alkali, respectively. After immersing immobilized lipases into guanidine hydrochloride or urea for 15 days, the lipases retained upwards of 70% activity. The fluorescence spectrum could obviously reflect the changes of the activity and conformation of lipase. The fluorescence intensity was the minimum in the optimal pH and temperature. In the denaturing agent it declined as time passed. These results indicated that the unfolded processes of immobilized lipases are different under different conditions.


Amlodipine-induced gingival overgrowth.
Gingival overgrowth represents an over-exuberant response to a variety of local and systemic conditions. Certain anticonvulsants, immuno-suppressive drugs and a number of calcium channel blockers have been shown to produce similar gingival overgrowths in certain susceptible patients. Amlodipine is a comparatively new calcium channel blocker and has been used with increasing frequency in the management of hypertension and angina. Although amlodipine is considered as a safe drug, very rarely it may induce gingival overgrowth also. A rare case of amlodipine-induced gingival overgrowth has been reported herein in a 50-year-old female patient. The treatment aspect included Phase-1 therapy, substitution of the drug, the surgical excision and the maintenance and supportive therapy resulting in excellent clinical outcome.


Considering video production? Lessons learned from the production of a blood pressure measurement video.
It is important that innovative tools that are created to enhance student learning are efficient and effective. Satisfying both criteria presents many challenges to contemporary nurse educators who wish to embark on creating alternative media to augment student nurse education. This paper is based on the author's own experience of producing a teaching video with the assistance of two multimedia students. This project was made possible by a university teaching and learning grant. Some recommendations are made arising from the 'lessons learned' from this project are highlighted. These are broadly categorised into pre-production, production and post-production considerations. In general, a good working relationship within the production team was beneficial in clarifying discrepancies between multimedia perspectives and nurse educator perspectives. It is hoped that this paper will be helpful to prospective nurse educators intending to produce similar video material.


Controlling anisotropic nanoparticle growth through plasmon excitation.
Inorganic nanoparticles exhibit size-dependent properties that are of interest for applications ranging from biosensing and catalysis to optics and data storage. They are readily available in a wide variety of discrete compositions and sizes. Shape-selective synthesis strategies now also yield shapes other than nanospheres, such as anisotropic metal nanostructures with interesting optical properties. Here we demonstrate that the previously described photoinduced method for converting silver nanospheres into triangular silver nanocrystals--so-called nanoprisms--can be extended to synthesize relatively monodisperse nanoprisms with desired edge lengths in the 30-120 nm range. The particle growth process is controlled using dual-beam illumination of the nanoparticles, and appears to be driven by surface plasmon excitations. We find that, depending on the illumination wavelengths chosen, the plasmon excitations lead either to fusion of nanoprisms in an edge-selective manner or to the growth of the nanoprisms until they reach their light-controlled final size.


Copper-Alkyne Complexation Responsible for the Nucleolar Localization of Quadruplex Nucleic Acid Drugs Labeled by Click Reactions.
G-Quadruplex(es) (G4) are noncanonical nucleic-acid structures found in guanine-rich sequences. They can be targeted with small molecules (G4 ligands) acting as reporters, for tracking both in vitro and in cells. We explored the cellular localization of PhenDC3 , one of the most powerful G4 ligands, by synthesizing two clickable azide and alkyne derivatives (PhenDC3 -alk, PhenDC3 -az) and labeling them in situ with the corresponding Cy5 click partners. A careful comparison of the results obtained for the copper-based CuAAC and copper-free SPAAC methodologies in fixed cells implicated CuI /alkyne intermediates in the nonspecific localization of ligands (and fluorophores) to the nucleoli. By contrast, SPAAC yielded similar nucleoplasmic labeling patterns in fixed and live cells. Our findings demonstrate the need for great care when using CuAAC to localize drugs in cells, and show that SPAAC gives results that are more consistent between fixed and live cells.


Pexophagy: Molecular Mechanisms and Implications for Health and Diseases.
Autophagy is an intracellular degradation pathway for large protein aggregates and damaged organelles. Recent studies have indicated that autophagy targets cargoes through a selective degradation pathway called selective autophagy. Peroxisomes are dynamic organelles that are crucial for health and development. Pexophagy is selective autophagy that targets peroxisomes and is essential for the maintenance of homeostasis of peroxisomes, which is necessary in the prevention of various peroxisome-related disorders. However, the mechanisms by which pexophagy is regulated and the key players that induce and modulate pexophagy are largely unknown. In this review, we focus on our current understanding of how pexophagy is induced and regulated, and the selective adaptors involved in mediating pexophagy. Furthermore, we discuss current findings on the roles of pexophagy in physiological and pathological responses, which provide insight into the clinical relevance of pexophagy regulation. Understanding how pexophagy interacts with various biological functions will provide fundamental insights into the function of pexophagy and facilitate the development of novel therapeutics against peroxisomal dysfunction-related diseases.


First use of hypertonic saline dextran in children: a study in safety and effectiveness for atrial septal defect surgery.
Hypertonic saline dextran (7.5% NaCl + 6% Dextran-70) has been used in adults in several studies and shown beneficial effects in hypovolemic shock, trauma, cardiogenic shock, and cardiac surgery. There have never been studies of this solution in children. This work studies its effect in children undergoing surgery for the correction of atrial septal defects. Twenty-five children underwent correction of atrial septal defect using cardiopulmonary bypass with bloodless priming. Children were divided in five groups and each received an incremental hypertonic saline dextran dose of 0.1, 0.5, 1.0, 2.0, and 4.0 mL/kg, 5 min before the beginning of cardiopulmonary bypass. Collected data were fluid balance, amount of bleeding, blood/derivative transfusion occurrence, plasma sodium, and hematocrit. Patients were divided into low-dose (0-1 mL/kg) and high-dose (2-4 mL/kg) groups. Analysis of variance was used to determine differences in blood loss between groups. The fluid balance and blood/derivative requirements were compared through Student's t test and Fisher's exact test (2-tail), respectively. All patients were discharged from hospital with corrected atrial septal defect. No hypertonic saline dextran-related complications occurred. There were no differences in the amount of bleeding. The high-dose group exhibited a significant decrease in fluid balance and in blood/derivative requirements in comparison with the low-dose group. In this study, the use of hypertonic saline dextran in the pediatric population submitted to cardiopulmonary bypass is safe and does not raise the amount of bleeding. Its effective doses produce negative fluid balance and reduce blood/derivative requirements.


Relative Rates of Dementia By Multiple Case Definitions, Over Two Prevalence Periods, In Three Sociocultural Groups.
The North Manhattan Aging Project registry, using both Reporting and Survey Components, identifies dementia cases among Latino, African-American, and non-Latino white sociocultural groups (9,349 persons 65 years of age or older) in contiguous census tracts. During a 2-year prevalence period of the reporting component, 1,592 persons were reported to the Registry and screened with five widely used brief cognitive measures; 844 were evaluated in a "clinical core," and 452 met research criteria for dementia, covering all subtypes, according to DSM-III-R criteria. Thirteen different case definitions for dementia were applied to the sociocultural groups at three levels of educational achievement, examining for associations with rates of dementia cases and controlling for age. The following findings were robust across case definitions: sociocultural membership was not associated, but lower education was associated, with increased rates of recorded dementia; however, the patterns of the association with education varied across sociocultural groups.


Association of adiponectin gene variants with idiopathic recurrent miscarriage according to obesity status: a case-control study.
This study addresses whether the association of adiponectin gene (ADIPOQ) variants with idiopathic recurrent pregnancy loss (RPL) is influenced by obesity. Retrospective case-control study performed in outpatient obstetrics/gynecology clinics. Study subjects comprised 308 women with RPL, defined as ≥ 3 consecutive miscarriages of unknown etiology, and 310 control women. ADIPOQ genotyping was done by allele exclusion method on real-time PCR. Of the 14 ADIPOQ variants tested, the minor allele frequency (MAF) of rs4632532, rs17300539, rs266729, rs182052, rs16861209, and rs7649121 were significantly higher, while rs2241767, and rs1063539 MAF were lower in RPL cases, hence assigning RPL-susceptibility and protection to these variants, respectively. Higher frequencies of heterozygous rs17300539 and rs16861209, and homozygous rs4632532, rs266729, and rs182052 genotypes, and reduced frequencies of heterozygous rs1063539 and rs2241767, homozygous rs2241766 genotypes were seen in RPL cases. ADIPOQ rs4632532, and rs2241766 were associated with RPL in obese, while rs1063539 and rs16861209 were associated with RPL in non-obese women; rs182052 and rs7649121 associated with RPL independently of BMI changes. Based on LD pattern, two haplotype blocks were identified. Within Block 1 containing rs4632532, rs16861194, rs17300539, rs266729, rs182052, rs16861209, rs822396, and rs7649121, increased frequency of CAGGACAT and TAACGAAA, and reduced frequency of TAGCGCAA haplotypes were seen in RPL cases when compared to controls, thereby assigning RPL susceptibility and protection, respectively. This is the first study to document contribution of ADIPOQ variants and haplotypes with RPL, and also to underscore the contribution of obesity to genetic association studies.


Endogenous opioid inhibition and facilitation of gonadotropin-releasing hormone release from the median eminence in vitro: potential role of catecholamines.
The intrahypothalamic site(s) of endogenous opioid regulation of GnRH secretion remains to be resolved. Accordingly, we used an in vitro acute incubation system to evaluate GnRH, dopamine (DA), and norepinephrine (NE) release from adult male rat median eminences (MEs) in response to the opiate receptor agonist morphine (MOR) and the opiate receptor antagonist naloxone (NAL). MOR (2 mM) stimulated basal and K+-induced GnRH release from isolated MEs, but 0.25, 5, or 100 microM MOR was without significant effect. NAL (1 mg/ml; 2.8 mM) increased basal GnRH release, but 0.01 mg NAL/ml suppressed basal GnRH release, and neither 0.001 nor 0.1 mg NAL/ml had an appreciable effect. NAL did not significantly alter K+-induced GnRH release. In a separate experiment, 1 mg NAL/ml stimulated but 0.01 mg NAL/ml inhibited basal release of DA and NE from the ME. NAL (1 ng/ml) also decreased K+-induced DA and NE release. The rates of basal and K+-induced DA and NE release were highly correlated with GnRH release during corresponding 0, 0.01, and 1.0 mg/ml NAL treatments in the preceding experiment (r = 0.98 and 0.93, respectively). Thus, 2 mM MOR stimulated but different NAL dosages either stimulated or inhibited GnRH release from isolated MEs, suggesting complex opioid regulation at the level of the GnRH neurosecretory terminals. The precise correlation between GnRH and DA/NE release suggests that the catecholamine terminals close to both GnRH- and endorphin-containing terminals in the ME may mediate this opioid regulation.


[Therapeutic study of intractable vasculitis].
Vasculitis is a clinicopathological entity characterized by primary inflammation and necrosis of blood vessels. Vasculitis virtually involves any size or type of blood vessels in any organ systems. Within a category of vasculitis, there are several of the more serious vasculitides, such as polyarteritis nodosa, Wegener's granulomatosis and the systemic necrotizing vasculitides of the polyarteritis nodosa group are known to be extremely poor prognosis. However, early diagnosis and early treatment with steroid and/or immunosuppressant has been shown to prolong extraordinarily their survival. In this sense, appropriate agents where efficacy has been proven, such as corticosteroid in allergic granulomatous angiitis; cyclophosphamide in Wegener's granulomatosis should be chosen for the proper treatment, which in turn prolong survival of patients with serious vasculitis.


Melatonin in patients with cancer receiving chemotherapy: a randomized, double-blind, placebo-controlled trial.
The MIRCIT trial was a randomized, double-blind, placebo-controlled study of advanced Non-small cell lung cancer (NSCLC). Patients were randomized to receive 10 mg or 20 mg of melatonin or placebo. Assessment of health-related quality of life (HRQoL) was completed at baseline, and at 2, 3 and 7 months. Survival and adverse events were collected. DNA damage marker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) was measured during the first three months of chemotherapy. Patients in the melatonin-treated group had better adjusted HRQoL scores, with a slightly significantly better score (2.69 points, 95% confidence interval (CI)=0.01-5.38, p=0.049) being found in social well-being. Median survival was 7.3 months (95% CI=3.42-11.14) without significant difference. A great amont of DNA damage marker was observed in the placebo-treated group, and this was associated with lower survival (r(2)=-0.656, p=0.02), implying the protective effect of melatonin in healthy cells. Melatonin in combination with chemotherapy did not affect survival and adverse events of advanced patients with NSCLC, but there was a trend for better HRQoL.


Unusual high blood glucose in ketoacidosis as first presentation of type 1 diabetes mellitus
Diabetic ketoacidosis is a life-threatening complication of diabetes mellitus. It usually occurs in patients with type 1 diabetes where it is typically associated with only moderately increased blood glucose. Here, we report the case of a 52-year-old female patient who was admitted to the emergency unit with severely altered mental status but stable vital signs. Laboratory results on admission revealed very high blood glucose (1687 mg/dL/93.6 mmol/L) and severe acidosis (pH <7) with proof of ketone bodies in serum and urine. Past history revealed a paranoid schizophrenia diagnosed 10 years ago and for which the patient was treated with risperidone for many years. Acute treatment with intravenous fluids, intravenous insulin infusion and sodium bicarbonate improved the symptoms. Further laboratory investigations confirmed diagnosis of autoimmune type 1 diabetes. After normalization of blood glucose levels, the patient could soon be discharged with a subcutaneous insulin therapy. Learning points: •• Diabetic ketoacidosis as first manifestation of type 1 diabetes can occur with markedly elevated blood glucose concentrations in elder patients. •• Atypical antipsychotics are associated with hyperglycemia and an increased risk of new-onset diabetes. •• First report of risperidone-associated diabetic ketoacidosis in new-onset type 1 diabetes. •• Patients treated with atypical antipsychotics require special care and regular laboratory examinations to detect hyperglycemia and diabetic ketoacidosis. •• In cases when the diagnosis is in doubt, blood gas analysis as well as determination of C-peptide and islet autoantibodies can help to establish the definite diabetes type.


Controlled Human Malaria Infection Leads to Long-Lasting Changes in Innate and Innate-like Lymphocyte Populations.
Animal model studies highlight the role of innate-like lymphocyte populations in the early inflammatory response and subsequent parasite control following Plasmodium infection. IFN-γ production by these lymphocytes likely plays a key role in the early control of the parasite and disease severity. Analyzing human innate-like T cell and NK cell responses following infection with Plasmodium has been challenging because the early stages of infection are clinically silent. To overcome this limitation, we examined blood samples from a controlled human malaria infection (CHMI) study in a Tanzanian cohort, in which volunteers underwent CHMI with a low or high dose of Plasmodium falciparum sporozoites. The CHMI differentially affected NK, NKT (invariant NKT), and mucosal-associated invariant T cell populations in a dose-dependent manner, resulting in an altered composition of this innate-like lymphocyte compartment. Although these innate-like responses are typically thought of as short-lived, we found that changes persisted for months after the infection was cleared, leading to significantly increased frequencies of mucosal-associated invariant T cells 6 mo postinfection. We used single-cell RNA sequencing and TCR αβ-chain usage analysis to define potential mechanisms for this expansion. These single-cell data suggest that this increase was mediated by homeostatic expansion-like mechanisms. Together, these data demonstrate that CHMI leads to previously unappreciated long-lasting alterations in the human innate-like lymphocyte compartment. We discuss the consequences of these changes for recurrent parasite infection and infection-associated pathologies and highlight the importance of considering host immunity and infection history for vaccine design.


Periodontal Treatment Reduces Circulating Pro-Inflammatory Cytokine and Chemokine Levels in African American HIV+ Individuals with Virological Suppression.
Periodontal Disease (PD), a chronic inflammatory disease, is highly prevalent among Persons Living With HIV (PLWH) and is characterized by microbial symbiosis and oxidative stress. Our hypothesis stipulates that periodontal therapy attenuates systemic inflammatory and bacterial burden while improving periodontal status in PLWH. Sixteen African Americans (AA) with suppressed HIV viremia on long-term Antiretroviral Therapy (ART) were recruited to this study. Participants were placed into two groups, based on their dental care status: group 1 (In-Care, IC) and group 2 (Out of Care, OC). Periodontal health was investigated at baseline, 3 months, 6 months, and 12 months. Cytokine/chemokines, microbial phyla, and Asymmetric Dimethylarginine (ADMA, a marker for endothelial cell dysfunction) levels were assessed in the serum. Statistical comparisons between groups and at different visits were performed using multiple comparison tests. Across longitudinal visits, periodontal treatment significantly reduced the levels of several cytokines and chemokines. At baseline, the out of care group had significantly higher blood levels of ADMA and actinobacteria than the IC group. Periodontal treatment significantly altered the abundance of circulating genomic bacterial DNA for various phyla in out of care group. Periodontal treatment interventions effectively attenuated circulating pro-inflammatory cytokines and altered microbial translocation, both critical drivers of systemic inflammation in PLWH.


Computation and modeling of the stone-growth related urinary depletion effect using "depletion V1.0".
During metabolic evaluation stone patients often present with calculi in the urinary tract or are suffering from high frequent formation of small microliths passing routinely the urinary tract. These concrements are presumably in a state of continuous growth. Consequently, the concentrations of the lithogenic components in the voided urine must decrease. Thus, treatment schemes inevitably fail to focus on the true pathogenic urinary composition. Instead, they focus on underestimated concentrations. This can attain high clinical relevance. In recent publications, we introduced a complex physical approach and provided mathematical equations which can be solved analytically. However, to date, solving the equations with a pocket calculator remains cumbersome. Depletion V1.0 was developed to integrate the calculation of the depletion effect into the daily treatment of stone patients. Minimum requirement for Depletion V1.0 is the Java 1.2 platform runtime environment, which is supported on nearly all operation systems including Linux, MacOS X, and Windows. The program can be used directly within a Java-compliant web browser (e.g. Firefox, Mozilla, Internet Explorer) or from the program's storage location. The implemented data base provides stone type relevant parameters. Data input is performed via an easy-to-handle graphical user interface. Results are given as values and interactive plots; computation and update of plots are performed in real time. Result sheets can be exported to platform-independent EPS-format or printed out directly. Depletion V1.0 enables the medical practitioner to obtain an improved interpretation of the stone patient's health status. As input, only one set of easy-to-achieve clinical standard parameters is required. The program will be available from the authors as freeware.


Magnetic resonance of the brain: the optimal screening technique.
Seventy consecutive patients were examined with magnetic resonance (MR) and computed tomography (CT) of the brain. Each study was independently reviewed. Focal abnormalities were detected by one or both modalities in 51 patients. Neoplastic, infectious, vascular, demyelinating, metabolic, and congenital disorders of the brain were included. The MR pulse sequence that best detected these abnormalities was a spin-echo multisection technique that used a long interval between RF excitations (TR = 1500 or 2000 msec). Forty-eight of 51 patients showed focal lesions with this technique. A supplementary MR pulse sequence with a short TR (500 msec) was useful in helping to characterize certain lesions with a long T1 relaxation component, but in 10 of 26 positive cases in which this sequence was added it would have missed the abnormality had it been the sole sequence used. MR missed focal lesions in 3 of 51 patients. These were lesions that required thin-section (1.5 mm) CT techniques. Two were intrasellar, and one was an intracanalicular neurinoma. In 17 of 48 patients, CT missed the focal lesion seen with MR. Based on this experience, it is concluded that the long TR multisection spin-echo sequence is the optimal MR screening technique for detection of most brain abnormalities, and is more sensitive than CT. Currently, CT remains the screening modality of choice when high-resolution, thin-section studies in the pituitary, inner ear, and orbital regions are indicated.


The influence of sera, follicular fluids and seminal plasma on human sperm-zona pellucida binding.
The purpose of this study was to assess the influence of male, female and fetal cord sera, follicular fluid, and seminal plasma on human sperm-zona pellucida binding, using the hemizona assay. Steroids, gonadotrophins, growth hormone and prolactin concentrations in follicular fluid and sera were also analysed. The influence of follicular fluid (10 or 50%, v/v) and sera (10%) on sperm-zona pellucida binding was investigated by supplementing the sperm processing medium as well as the sperm-hemizona incubation medium. Different seminal plasma concentrations (1 or 10%) were added to the sperm-hemizona incubation medium. Supplementation with 10% day 3 donor serum was used as a control throughout experimentation. Although supplementation with male sera and fetal cord serum exerted a stimulatory effect (36 and 90% respectively; P < 0.029) on sperm-zona pellucida binding, hemizona indices obtained with addition of male sera, fetal cord serum and sera obtained from sub-fertile in-vitro fertilization (IVF) patients on day 12 of their menstrual cycle did not differ significantly (P > 0.05). Final progesterone concentrations in sperm-zona pellucida incubation media (10% follicular fluid supplementation), which ranged from 0.788 to 3.85 microg/ml, enhanced sperm binding to the zonae by >100% (P < 0.02). The utilization of follicular fluid (10%) as a natural physiological stimulus to enhance sperm-zona pellucida binding in an IVF setting is recommended. The presence of seminal plasma in the spermzona pellucida incubation media showed no beneficial effect on the binding ability of sperm, and can be viewed as an unfavourable substance in the proximity of the oocyte.


A tractometry principal component analysis of white matter tract network structure and relationships with cognitive function in relapsing-remitting multiple sclerosis.
Understanding the brain changes underlying cognitive dysfunction is a key priority in multiple sclerosis (MS) to improve monitoring and treatment of this debilitating symptom. Functional connectivity network changes are associated with cognitive dysfunction, but it is less well understood how changes in normal appearing white matter relate to cognitive symptoms. If white matter tracts have network structure it would be expected that tracts within a network share susceptibility to MS pathology. In the present study, we used a tractometry approach to explore patterns of variance in white matter metrics across white matter (WM) tracts, and assessed how such patterns relate to neuropsychological test performance across cognitive domains. A sample of 102 relapsing-remitting MS patients and 27 healthy controls underwent MRI and neuropsychological testing. Tractography was performed on diffusion MRI data to extract 40 WM tracts and microstructural measures were extracted from each tract. Principal component analysis (PCA) was used to decompose metrics from all tracts to assess the presence of any co-variance structure among the tracts. Similarly, PCA was applied to cognitive test scores to identify the main cognitive domains. Finally, we assessed the ability of tract co-variance patterns to predict test performance across cognitive domains. We found that a single co-variance pattern which captured microstructure across all tracts explained the most variance (65% variance explained) and that there was little evidence for separate, smaller network patterns of pathology. Variance in this pattern was explained by effects related to lesions, but one main co-variance pattern persisted after this effect was regressed out. This main WM tract co-variance pattern contributed to explaining a modest degree of variance in one of our four cognitive domains in MS. These findings highlight the need to investigate the relationship between the normal appearing white matter and cognitive impairment further and on a more granular level, to improve the understanding of the network structure of the brain in MS.


ESHAP chemotherapy is efficient in refractory/relapsed primary central nervous system lymphoma: report of four cases.
Primary central nervous system non-Hodgkin's lymphoma is a rare presentation, almost always of diffuse large B-cell type. Although there is no consensus regarding therapy for this condition, induction regimens are based on high-dose methotrexate and consolidation whole-brain radiotherapy, or, more preferred recently, blood-brain barrier penetrating drugs such as etoposide, cytarabine, and alkylating agents like temozolomide, ifosfamide, and lomustine. We present here four cases of relapsed/refractory primary central nervous system lymphoma treated with ESHAP (etoposide, solumedrol, high-dose cytarabine, and platinum) chemotherapy to complete remission, with the eligible patients proceeding to autologous transplantation. We want to draw attention to this interesting, relatively well tolerated, underused therapeutic option, in a setting where treatment options are scarce and evidence-based recommendations are lacking.


High rate of advanced colorectal polyps in a 10-year-long retrospective study in Qazvin, Iran.
Polyps are common lesions in the gastrointestinal (GI) tract. Colon cancer is mostly a result of progression from polyps. The present study aimed to evaluate demographic, clinical, and histological characteristics of colorectal polyps in Iran, particularly neoplastic and advanced types. Over a period of 10 years, specimens of all colorectal polyps obtained from colonoscopy were studied. The variables subjected to statistical analysis were age, sex, and the chief clinical complaint of the patients who underwent colonoscopy, their motivation, and the site, size, and histological types of detected polyps. The level of significance was set at p value<0.05. Data were obtained from a total of 352 patients. No difference was seen between male and female patients regarding histological types. Only in nine patients was screening the reason for colonoscopy. Almost two-thirds (66.2%) of the polyps were neoplastic. Familial polyposis syndrome and inflammatory bowel disease were seen in 4.3% and 3.0% of the patients with neoplastic polyps, respectively. Sites of polyps were the sigmoid, rectum, and descending colon in 40.1%, 34.5%, and 17% of the cases, respectively. The advanced type made up 58.8% of neoplastic polyps. Only 3.6% of the patients undergoing colonoscopy in the study period had biopsied polyps. No difference was observed between male and female patients in terms of overall incidence of polyps, histological and anatomical profiles, and mean age distribution. Anatomical and histological profiles agreed with the studies performed in areas with a low risk of colon cancer. The findings show that colonoscopy was not performed when it was necessary. A meaningful increase in the number polyp biopsy cases and a corresponding decrease in polyp size in the last few years of the study can be associated with the presence of more GI specialist clinicians in hospital centers, and this holds out much hope for the further improvement of the situation in the future.


Photoemission, resonant photoemission, and x-ray absorption of a Ru(II) complex adsorbed on rutile TiO2(110) prepared by in situ electrospray deposition.
An experimental study of the bonding geometry and electronic coupling of cis-bis(isothiocyanato)bis(2,2(')-bipyridyl-4,4(')-dicarboxylato)-ruthenium(II) (N3) adsorbed on rutile TiO(2)(110) is presented, along with supporting theoretical calculations of the bonding geometry. Samples were prepared in situ using ultrahigh vacuum electrospray deposition. Core-level photoemission spectroscopy was used to characterize the system and to deduce the nature of the molecule-surface bonding. Valence band photoemission and N 1s x-ray absorption spectra were aligned in a common binding energy scale to enable a quantitative analysis of the bandgap region. A consideration of the energetics in relation to optical absorption is used to identify the photoexcitation channel between the highest occupied and lowest unoccupied molecular orbitals in this system, and also to quantify the relative binding energies of core and valence excitons. The core-hole clock implementation of resonant photoemission spectroscopy is used to reveal that electron delocalization from N3 occurs within 16 fs.


In situ starch and crude protein degradation in the rumen and in vitro gas production kinetics of wheat genotypes.
The objective of this study was to determine the variation of in situ ruminal degradation characteristics of dry matter (DM), crude protein (CP) and starch (ST), and to determine the effective degradation (ED) of wheat genotypes. Further, multivariate associations of these in situ values with their corresponding in vitro gas production (GP) kinetics and laboratory measurements were evaluated using correlation and multiple linear regression analyses. Grains of 20 genotypes of wheat were characterized by proximate constituents, amino acid (AA) composition and physical characteristics. Ruminal degradation kinetics were determined by in situ degradation of DM, CP and ST, and subsequent evaluation of in vitro GP relative to time courses. In situ and GP measurements were fitted to an exponential equation, and ED was calculated using passage rates in the rumen of 5%/h (ED5) and 8%/h (ED8). To predict ED8 of CP (EDCP8) and ST (EDST8), correlations were evaluated and stepwise multiple linear regression analyses were applied. Estimated degradation parameters varied considerably between wheat genotypes irrespective of the nutrient tested. Variance in a, b and c was not reflected in the variation of the ED, due to high degradation rates (c). The assumed passage rate also impacted estimation of the ED minimally. Estimated GP parameters varied only slightly among wheat genotypes. Nevertheless, regression models explained up to 80 and 99% of the variance in EDCP8 and EDST8, respectively, and associations between EDST8 and EDCP8 and chemical and physical characteristics of grains were detected. As ST is the primary nutrient in wheat grains and can comprise substantial portions of dairy rations, the total amount of ST as well as its ED in the rumen should be taken into account when wheat is incorporated into dairy rations. Conversely, variance in wheat grain CP degradation was very low and can largely be neglected in practical ration formulation for ruminants.


[Duodenal Linphoma asociated to Strongyloides stercoralis infection. Two types of HTLV-1 infection].
Infection by the Human T- Lymphotropic virus I (HTLV-1) causes Adult T cell Leukemia-lymphoma (ATLL), being the duodenal involvement rare. Commonly, patients co-infected with HTLV-1 and Strongyloides stercoralis are seen due to the lack of TH2 response found on these patients. We describe a 48-year- old woman, from the jungle of Peru, with a family history of HTLV-1 infection, who presented with a History of chronic diarrhea and weight loss. HTLV-1 infection with ATLL and strongyloidiasis were diagnosed. Ivermectin treatment and chemotherapy were initiated, being stabilized, and discharged. We report this case because of the unusual coexistence in the duodenum of ATLL and strongyloidiasis.


Field variable associations with scratch orientation dependence of UHMWPE wear: a finite element analysis.
Scratches on the metal bearing surface of metal-on-polyethylene total joint replacements have been found to appreciably accelerate abrasive/adhesive wear of polyethylene, and constitute a source of the considerable variability of wear rate seen within clinical cohorts. Scratch orientation with respect to the local direction of relative surface sliding is presumably a factor affecting instantaneous debris liberation during articulation. A three-dimensional local finite element model was developed, of orientation-specific polyethylene articulation with a scratched metal counterface, to explore continuum-level stress/strain parameters potentially correlating with the orientation dependence of scratch wear in a corresponding physical experiment. Computed maximum stress values exceeded the yield strength of ultra-high molecular weight polyethylene (UHMWPE) for all scratch orientations but did not vary appreciably among scratch orientations. Two continuum-level parameters judged most consistent overall with the direction dependence of experimental wear were (1) cumulative compressive total normal strain in the direction of loading, and (2) maximum instantaneous compressive total normal strain transverse to the sliding direction. Such stress/strain metrics could be useful in global computational models of wear acceleration, as surrogates to incorporate anisotropy of local metal surface roughening.


Three p-xylene-solvated pseudopolymorphs of bis[1,3-bis(pentafluorophenyl)propane-1,3-dionato]copper(II).
The Cu(2+) ions in the title compounds, namely bis[1,3-bis(pentafluorophenyl)propane-1,3-dionato-κ(2)O,O']copper(II) p-xylene n-solvate, [Cu(C15HF10O2)2]·nC8H10, with n = 1, (I), n = 2, (II), and n = 4, (III), are coordinated by two 1,3-bis(pentafluorophenyl)propane-1,3-dionate ligands. The coordination complexes of (I) and (II) have crystallographic inversion symmetry at the Cu atom and the p-xylene molecule in (I) also lies across an inversion centre. The p-xylene molecules in (I) and (II) interact with the pentafluorophenyl groups of the complex via arene-perfluoroarene interactions. In the crystal of (III), two of the p-xylene molecules interact with the pentafluorophenyl groups via arene-perfluoroarene interactions. The other two p-xylene molecules are located on the CuO4 coordination plane, forming a uniform cavity produced by metal···π interactions.


Cognitive-psychomotor functions with regard to fitness for driving of psychiatric patients treated with neuroleptics and antidepressants.
In contrast to the usual type of drug studies it is not our intention to single out specific drug effects, but we are interested in cognitive-psychomotor functioning of psychiatric patients across various periods of therapy, whether due to drug treatment or to underlying mental-affective disorders. 3 groups of psychiatric male patients (7 anxious/inhibited depressives, 7 schizophrenics, 6 patients with psychotic episodes) matched for age (mean = 30 years) and education (no academic training) with a group of healthy controls (n = 7) were examined three times during the first 6-8 weeks of their ordinary clinical therapy. The major criterion for the inclusion of a patient next to these diagnostic categories was an initial favorable response to the specified drugs (amitriptyline for the depressives, haloperidol for the schizophrenics, and thioridazine for the patients with psychotic episodes). Each subject was tested in an experimental laboratory with respect to cognitive-psychomotor performance (vigilance, divided attention, choice reaction time), mood, subjective fitness for driving, depression, and paranoia. All groups of patients improved significantly between the acute and the chronic phase. However, healthy controls showed a sharper increase of achievement. While the depressives and the patients with psychotic episodes function on a level of questionable fitness for driving, schizophrenics vary greatly intra- and interindividually, generally on a lower level.


Precision Medicine in Non Communicable Diseases.
Non-communicable diseases (NCDs) are the leading cause of death and disease burden globally, cardiovascular diseases (CVDs) account for the major part of death related to NCDs followed by different types of cancer, chronic obstructive pulmonary disease (COPD), and diabetes. As the World Health Organization (WHO) and the United Nations have announced a 25% reduction in mortality of NCDs by 2025, different communities need to adopt preventive strategies for achieving this goal. Personalized medicine approach as a predictive and preventive strategy aims for a better therapeutic goal to the patients to maximize benefits and reduce harms. The clinical benefits of this approach are already realized in cancer targeted therapy, and its impact on other conditions needs more studies in different societies. In this review, we essentially describe the concept of personalized (or precision) medicine in association with NCDs and the future of precision medicine in prediction, prevention, and personalized treatment.


Improving outcomes for posterolateral knee injuries.
Until recently, the posterolateral corner of the knee was noted both for its complex anatomy and diagnostic challenges. To improve the understanding of the posterolateral knee, we completed a comprehensive and stepwise research program with a focus on five primary areas: (1) surgical approach and relevant anatomy; (2) diagnosis; (3) clinically relevant biomechanics; (4) natural history; and (5) surgical treatment. Based on this comprehensive research program, the diagnosis and outcomes following treatment of posterolateral knee injuries have been significantly improved comparing the preoperative state to the state of the knee at a minimum 2 year follow-up in the cases series presented here. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:485-491, 2014.