Pharmacotherapy for Neonatal Seizures: Current Knowledge and Future Perspectives.
Seizures are the most common neurological emergencies in the neonatal period and are associated with poor neurodevelopmental outcomes. Seizures affect up to five per 1000 term births and population-based studies suggest that they occur even more frequently in premature infants. Seizures are a sign of an underlying cerebral pathology, the most common of which is hypoxic-ischaemic encephalopathy in term infants. Due to a growing body of evidence that seizures exacerbate cerebral injury, effective diagnosis and treatment of neonatal seizures is of paramount importance to reduce long-term adverse outcomes. Electroencephalography is essential for the diagnosis of seizures in neonates due to their subtle clinical expression, non-specific neurological presentation and a high frequency of electro-clinical uncoupling in the neonatal period. Hypoxic-ischaemic encephalopathy may require neuroprotective therapeutic hypothermia, accompanying sedation with opioids, anticonvulsant drugs or a combination of all of these. The efficacy, safety, tolerability and pharmacokinetics of seven anticonvulsant drugs (phenobarbital, phenytoin, levetiracetam, lidocaine, midazolam, topiramate and bumetanide) are reviewed. This review is focused only on studies reporting electrographically confirmed seizures and highlights the knowledge gaps that exist in optimal treatment regimens for neonatal seizures. Randomised controlled trials are needed to establish a safe and effective treatment protocol for neonatal seizures.


Distribution of alpha-1 adrenoceptor subtypes in RNA and protein in rabbit eyes.
We investigated subtypes of alpha-1 adrenoceptor (AR) in rabbit ocular tissues using reverse transcription-polymerase chain reaction (RT - PCR), in situ hybridization (ISH) and binding studies. Competitive RT - PCR assays specific for the subtypes of alpha-1 AR revealed that the mRNA expression of alpha-1a AR was dominant, and that of each alpha-1b and alpha-1d was less than 10% and 0.5% of total alpha-1 ARs mRNA, respectively, in the iris, ciliary body, choroid and retina. In alpha-1a AR splice isoform-specific RT - PCR assays, we found a distinct proportion of each isoform mRNA in the iris, ciliary body and choroid. The results of the ISH assays for alpha-1a AR subtype showed that hybridization signals were clearly observed in the iris dilator muscle and in the epithelium of the ciliary processes. In binding studies, alpha-1A AR was a dominant subtype in the iris, choroid and retina in contrast to the ciliary body that had more alpha-1B than alpha-1A AR subtype at protein level.


Motor imagery ability in patients with traumatic brain injury.
To assess motor imagery (MI) ability in patients with moderate to severe traumatic brain injury (TBI). Prospective, cohort study. University hospital rehabilitation unit. Patients with traumatic brain injury (mean coma duration, 18d) undergoing rehabilitation (n=20) and healthy controls (n=17) matched for age and education level. Not applicable. The vividness of MI was assessed using a revised version of the Movement Imagery Questionnaire-Revised second version (MIQ-RS); the temporal features were assessed using the time-dependent motor imagery (TDMI) screening test, the temporal congruence test, and a walking trajectory imagery test; and the accuracy of MI was assessed using a mental rotation test. The MIQ-RS revealed a decrease of MI vividness in the TBI group. An increasing number of stepping movements was observed with increasing time periods in both groups during the TDMI screening test. The TBI group performed a significantly smaller number of imagery movements in the same movement time. The temporal congruence test revealed a significant correlation between imagery and actual stepping time in both groups. The walking trajectory test revealed an increase of the imagery and actual walking time with increasing path length in both groups, but the ratio of imaginary walking over actual walking time was significantly greater than 1 in the TBI group. Results of the hand mental rotation test indicated significant effects of rotation angles on imagery movement times in both groups, but rotation time was significantly slower in the TBI group. Our patients with TBI demonstrated a relatively preserved MI ability indicating that MI could be used to aid rehabilitation and subsequent functional recovery.


Molecular basis of dimethylglycine dehydrogenase deficiency associated with pathogenic variant H109R.
Dimethylglycine dehydrogenase (DMGDH) is a mitochondrial matrix flavoprotein that catalyses the demethylation of dimethylglycine to form sarcosine, accompanied by the reduction of the covalently bound FAD cofactor. Electron-transfer flavoprotein reoxidizes the reduced flavin and transfers reducing equivalents to the main mitochondrial respiratory chain through the enzyme ETF-ubiquinone oxidoreductase. DMGDH plays a prominent role in choline and 1-carbon metabolism. We have expressed the mature form of human DMGDH and the H109R variant identified in a DMGDH-deficient patient as N-terminally His(6)-tagged proteins in E. coli. The enzymes were purified to homogeneity by nickel affinity and anion exchange chromatography. The presence of FAD in the wild-type enzyme was confirmed by spectrophotometric analysis. The H109R variant, however, had only 47% of the wild-type level of bound flavin as expressed in E. coli, indicating its reduced affinity for FAD As previously described for rat enzyme studies, the wild-type human enzyme exhibited two K (m) values for N,N-dimethylglycine (K (m1) = 0.039 +/- 0.010 mmol/L and K(m2) = 15.4 +/- 1.2 mmol/L). The addition of 4 micromol/L tetrahydrofolate resulted in a slight decrease in specific activity and a substantial decrease in K (m2) (1.10 +/- 0.55 mmol/L). The flavinated H109R variant protein exhibited a 27-fold decrease in specific activity and a 65-fold increase in K (m), explaining its pathogenicity. Additionally, the current expression system represents a significant improvement over a previously described rat DMGDH expression system and will enhance our ability to further study this important metabolic enzyme.


Probe sialidase substrate specificity using chemoenzymatically synthesized sialosides containing C9-modified sialic acid.
A library of α2-3- and α2-6-linked sialyl galactosides containing C9-modified sialic acids was synthesized from C6-modified mannose derivatives using an efficient one-pot three-enzyme system. These sialosides were used in a high-throughput sialidase substrate specificity assay to elucidate the importance of C9-OH in sialidase recognition.


A multifunctional metal-organic framework nanosystem disrupts redox homeostasis for synergistic therapy.
Synergistic therapies of photodynamic therapy (PDT) and chemodynamic therapy (CDT) via metal-organic frameworks (MOF) for cancer treatment have recently attracted a lot of attentions because of the limitations of insufficient reactive oxygen species (ROS) in single-modality approaches. However, few studies explored on the use of increased ROS synergized with chemotherapy (CT) to address the issue of inadequate anti-tumor efficacy in single-modality regimens. Here, the desired cascade nanoplatforms (noted as MOF(Cu)@Dox-PL NPs) were fabricated by a solvothermal method using tetrakis (4-carboxyphenyl) porphyrin (TCPP) and zirconyl(di)chloride octahydrate (ZrOCl2·8H2O) as raw material, followed by Cu2+ introduced into the porphyrin ring and doxorubicin (DOX) loaded into the nanoframework. In addition, the nanoparticles (NPs) were electrostatically and hydrophobically coated with phospholipid (PL) to improve the biocompatibility of the nanosystems. Singlet oxygen (1O2) was created by the MOF(Cu)@Dox-PL NPs to disturb intracellular redox equilibrium. The acidic microenvironment in cancer cells may cause the prior release of DOX, which encourages the production of hydrogen peroxide (H2O2). And the doped Cu2+ could deplete overexpressed reduced glutathione (GSH) to produce hydroxyl radicals (·OH) by catalyzing H2O2, further causing redox dyshomeostasis. In vivo experiments revealed that MOF(Cu)@Dox-PL nanosystem possessed good biosafety and a compelling therapeutic effect in 4T1 tumor-bearing mice. As a novel nanosystem, MOF(Cu)@Dox-PL NPs showed great potential in synergistic therapy based on redox dyshomeostasis for improving anti-tumor efficacy with high specificity.


Withanolide A offers neuroprotection, ameliorates stress resistance and prolongs the life expectancy of Caenorhabditis elegans.
Withanolide A (steroidal lactone) forms the major constituent of the most popular herbal drug in Ayurvedic medicine, Ashwagandha. It has been used since ancient times as an alternative medicine for the treatment of a variety of age related disorders. Here we provide multiple lines of evidence indicating that Withanolide A improves healthspan, delays age-associated physiological changes and also extends the lifespan of Caenorhabditis elegans. We also report several neuroprotective benefits of this natural product, including its anti-amyloidogenic effects, alleviation of α-synuclein aggregation and neuroprotection through modulation of neural mediators like acetylcholine. We observed that Withanolide A mediates lifespan extension and promotes stress resistance via insulin/insulin-like growth factor signaling pathway. Such findings could be helpful to develop a therapeutic medicine from this natural product for the prevention or reversal of age-related ailments and to improve the survival of patients suffering from Alzheimer's or Parkinson's disease.


Patient perception of long-term burn-specific health and congruence with the Burn Specific Health Scale-Brief.
This qualitative study aims to explore former burn patients' perception of burn-specific health and investigate how these experiences correspond to the subscales in the Burn Specific Health Scale-Brief (BSHS-B). Respondents were former burn patients, admitted to the Uppsala Burn Centre between 2000 and 2007. A total of 20 respondents with a Total Body Surface Area (TBSA) of 20% or larger, were approached at 10-17years after burn and interviewed using a semi-structured guide. Data was analyzed using thematic analysis. Despite extensive burn injuries, respondents said they led a close-to-normal life. Their descriptions validated the significance of the existing themes of BSHS-B. Additional themes of importance for health after burn were skin related problems, morphine de-escalation, the importance of work, stress and avoidance, mentality and the healthcare system. The BSHS-B alone may not be sufficient in providing a comprehensive picture of former burn patients' self-perceived health in the long-term perspective. Investigating supplementary areas reflecting former patients' sociocultural and attitudinal environment, as well as personal factors, may be of great importance.


Development and validation a model for predicting overall survival of bladder cancer with lung metastasis: a population-based study.
Although the number of patients with bladder cancer and lung metastasis is increasing there is no accurate model for predicting survival in these patients. Patients enrolled in the Surveillance, Epidemiology, and End Results database between 2010 and 2015 were selected for the study. Univariate and multivariate Cox regression were used to determine independent prognostic factors, followed by development of a nomogram based on the multivariate Cox regression models. The consistency index, receiver operating characteristic curve, and calibration curve were used to validate the prognostic nomogram. 506 eligible bladder cancer patients with lung metastasis were enrolled in the study and then divided randomly into training and validation sets (n = 356 vs. n = 150). Multivariate Cox regression analysis indicated that age at diagnosis, primary site, histological type, surgery of the primary site, chemotherapy, bone metastasis, and liver metastasis were prognostic factors for overall survival (OS) in patients with lung metastasis in the training set. The C-index of the nomogram OS was 0.699 and 0.747 in the training and validation sets, respectively. ROC curve estimation of the nomogram in the training and validation sets showed acceptable accuracy for classifying 1-year survival, with an area under the curve (AUC) of 0.766 and 0.717, respectively. More importantly, the calibration plot showed the nomogram had favorable predictive accuracy in both the training and validation sets. The prognostic nomogram created in our study provides an individualized diagnosis, remedy, and risk evaluation for survival in patients with bladder cancer and lung metastasis. The nomogram would therefore enable clinicians to make more precise treatment decisions for patients with bladder cancer and lung metastasis.


Botulinum toxin to improve facial expression in a patient with Urofacial (Ochoa) Syndrome.
The Urofacial or Ochoa Syndrome is a very rare congenital disorder that includes vesical bladder dysfunction and a peculiar inverse facial expression, which brings patients to express a sad-crying face while they intend to laugh. Up-to-date treatments have addressed only the urological side of this disease. However, also the impaired facial mimicry has a strong impact on patients' quality of life. We treated a young patient with Botulinum toxin to address this impairment and obtained pleasing results, including a harmonic smile and a very satisfied patient. To the best of our knowledge, this is the first time that the use of Botulinum toxin is reported in literature to address the facial expression component of this disease.


Advances in assessing the volume of odontogenic cysts and tumors in the mandible: a retrospective clinical trial.
To compare two methods of creating three-dimensional representations of mandibular cysts and tumors on the basis of computed tomography (CT) and cone beam computed tomography (CBCT) data. A total of 71 patients with acquired jaw cysts took part in this retrospective clinical study. CT and CBCT scans were obtained from all patients and saved in the Digital Imaging and Communications in Medicine (DICOM) format. Data were analyzed twice with iPlan software. Analysis was performed manually and using an interpolarization algorithm. The accuracy of the two methods in assessing cyst volume was compared. Manual delineation did not provide more accurate results than the interpolarization algorithm. There are no major differences between manual analysis and analysis using the interpolarization algorithm. The use of the algorithm, however, has the advantage of rapidity.


Chemically induced DNA damage in isolated rabbit lung cells.
By use of an isolation procedure including centrifugal elutriation and density gradient centrifugation, relatively pure fractions of Clara cells and type II cells were obtained from rabbit lungs. These cells and alveolar macrophages isolated by lavage were exposed to methyl methanesulfonate (MMS), 1,2-dibromo-3-chloropropane (DBCP), 1-nitropyrene (1-NP), 2-nitrofluorene (2-NF), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N'-nitrosonornicotine (NNN), N-nitrosoheptamethyleneimine (NHMI) or phorbol 12-myristate 13-acetate (TPA). DNA damage measured as alkali-labile sites and/or single-strand breaks was then determined in the different lung cells by an automated alkaline elution system. The direct-acting compound MMS showed similar DNA-damaging effect in Clara cells, type II cells and alveolar macrophages. The nematocide DBCP, activated by both P450- and glutathione S-transferase(s)-dependent pathways, caused considerably less DNA damage in macrophages than in Clara or type II cells. Similar differences between the lung cells in induction of DNA damage as observed with DBCP were demonstrated after exposure to the activation-dependent nitrosamines NNK and NHMI and the tumor promoter TPA. The other test substances (1-NP, 2-NF, NNN) did not cause any marked DNA damage measured by the alkaline elution technique. These findings are in agreement with the known metabolic capacity of these cell types, indicating that Clara and type II cells are possible primary targets for lung toxic/carcinogenic compounds.


Evaluation of a midwifery network to guarantee outpatient postpartum care: a mixed methods study.
The necessity of outpatient postpartum care has increased due to shorter hospital stays. In a health care system, where postpartum care after hospital discharge must be arranged by families themselves, this can be challenging for those experiencing psychosocial disadvantages. Therefore, we compared characteristics of users of a midwifery network which referred women to outpatient postpartum care providers with those of women organising care themselves. Additionally, we investigated benefits of the network for women and health professionals. Evaluation of the services of a midwifery network in Switzerland. We combined quantitative secondary analysis of routine data of independent midwives with qualitative telephone interviews with users and a focus group with midwives and nurses. Descriptive statistics and logistic regression modelling were done using Stata 13. Content analysis was applied for qualitative data. Users of the network were more likely to be: primiparas (OR 1.52, 95% CI [1.31-1.75, p < 0.001]); of foreign nationality (OR 2.36, 95% CI [2.04-2.73], p < 0.001); without professional education (OR 1.89, 95% CI [1.56-2.29] p < 0.001); unemployed (OR 1.28, 95% CI [1.09-1.51], p = 0.002) and have given birth by caesarean section (OR 1.38, 95% CI [1.20-1.59], p < 0.001) compared to women organising care themselves. Furthermore, users had cumulative risk factors for vulnerable transition into parenthood more often (≥ three risk factors: 4.2% vs. 1.5%, p < 0.001). Women appreciate the services provided. The collaboration within the network facilitated work scheduling and the better use of resources for health professionals. The network enabled midwives and nurses to reach families who might have struggled to organise postpartum care themselves. It also facilitated the work organisation of health professionals. Networks therefore provide benefits for families and health professionals.


Correction to: Assessment of burnout in veterinary medical students using the Maslach Burnout Inventory-Educational Survey: a survey during two semesters.
An amendment to this paper has been published and can be accessed via the original article.


CD8 T cell quiescence revisited.
Naïve T cells are typically considered to be in a default state of quiescence, whereas memory T cells undergo basal proliferation and quickly exhibit effector responses when stimulated. Over the past few years, however, a more complex picture has emerged, with evidence that naïve T cell quiescence is actively enforced, and that heterogeneity among naïve T cells influences their capacity to escape quiescence in response to homeostatic cues. Furthermore, the active state of memory T cells may also be instructed, requiring contact with dendritic cells to avoid reversion to quiescence. Here, we discuss these new findings and propose that there is much more flexibility in the quiescent state of naïve and memory T cells than previously thought.


Optimal combination of discriminators for differentiating ventricular from supraventricular tachycardia by dual-chamber defibrillators.
Discriminators for ventricular/supraventricular tachycardia. Dual-chamber implantable cardioverter defibrillators (ICDs) use discriminators to differentiate between supraventricular tachycardias (SVTs) and ventricular tachycardias (VT), the accuracy of which may depend on the type and method used. ICDs can combine rate branching of tachyarrhythmias according to their A:V relationship with two SVT-VT discriminators in each rate branch, using ANY (either) or ALL (both) logic. Our goal was to determine the optimal discriminator combination. Stored electrogram data from 596 spontaneous tachyarrhythmias from 203 patients with Photon DR ICDs were analyzed. Arrhythmias are first classified by the relationship of atrial and ventricular rates (rate branches V<A, V=A, and V>A) followed by additional discriminators: morphology and/or sudden onset if V=A; morphology and/or interval stability if V<A. Data were analyzed for all combinations of ANY and ALL logic. Sensitivity and specificity were calculated for all spontaneous episodes in each analysis. V=A branch: ALL logic produced unacceptably low sensitivity, whereas morphology provided only similar sensitivity but better specificity than ANY logic. A>V branch: ANY logic provided adequate sensitivity. The combination of morphology only in V=A with interval stability or morphology (ANY logic) in V<A, provided the optimal result with sensitivity, specificity, positive, and negative predictive values of 99%, 79%, 87%, and 98%, respectively. SVT-VT combined discriminators strongly influence dual-chamber SVT-VT discrimination performance. In our study, optimal programming is morphology only in the V=A branch and morphology or interval stability (ANY) in the V<A branch. ALL logic should be used with caution due to loss of sensitivity.


Evaluation of three scoring systems for predicting renal prognosis in antineutrophil cytoplasmic antibody-associated glomerulonephritis.
Antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) is characterized by rapidly progressive glomerulonephritis, and timely initiation of treatment and evaluation is critical to prevent the progression of renal disease to end-stage renal disease (ESRD). The aim of this study was to evaluate predictive value of the renal risk score (RRS), Birmingham vasculitis activity score (BVAS), and renal vascular lesions (RVLs) score for renal prognosis in AAGN. A retrospective analysis of ninety-four patients diagnosed with AAGN after renal biopsy was performed. The RRS, BVAS, and RVLs score were evaluated in relation to clinicopathologic features and renal prognosis. A receiver operating characteristic curve (ROC) was used to evaluate their renal prognostic value. The median follow-up time was 36 months. Thirty-eight patients progressed to ESRD. Survival analysis showed that renal prognosis worsened in the RRS group in order of low, medium, and high RRS (P < 0.05). Within the RVLs group, the renal prognosis of the groups with severe and moderate RVLs was worse than that of the group without RVLs (P = 0.012, P < 0.001), and the group with mild RVLs was close to that of the group without RVLs. ROC analysis showed that the AUC of RRS, BVAS, RVLs score, RVLs score combined with RRS (RVLs score & RRS, RR), RVLs score, and RRS combined with BVAS (RVLs score & RRS & BVAS, RRB) were 0.865, 0.624, 0.763, 0.910, and 0.942, respectively. The predictive power of RRB and RR was comparable and significantly better than the RRS, BVAS, and RVLs score. Based on simplicity and validity, RR was selected as the best predictor, and the relationship between RRS, RVLs score, and RR was calculated using a linear fit, resulting in the linear equation RR = -0.4766 + 0.1231 × RVLs score + 0.395 × RRS (P < 0.001). In AAGN, the predictive power of RR for renal prognosis was superior to that of RRS, BVAS, and RVLs score. RR may serve as a new predictor of renal prognosis in AAGN.


BhGLM: Bayesian hierarchical GLMs and survival models, with applications to genomics and epidemiology.
BhGLM is a freely available R package that implements Bayesian hierarchical modeling for high-dimensional clinical and genomic data. It consists of functions for setting up various Bayesian hierarchical models, including generalized linear models (GLMs) and Cox survival models, with four types of prior distributions for coefficients, i.e. double-exponential, Student-t, mixture double-exponential and mixture Student-t. These functions adapt fast and stable algorithms to estimate parameters. BhGLM also provides functions for summarizing results numerically and graphically and for evaluating predictive values. The package is particularly useful for analyzing large-scale molecular data, i.e. detecting disease-associated variables and predicting disease outcomes. We here describe the models, algorithms and associated features implemented in BhGLM. The package is freely available from the public GitHub repository, https://github.com/nyiuab/BhGLM.


Abnormalities of erythrocyte membranes in biliary atresia: ultrastructure and lipid composition.
Biochemical and ultrastructural studies of red blood cell membranes from seven patients with congenital biliary atresia have been performed. Scanning electron microscopic observations revealed that more than half of these cells were of abnormal shapes, such as target, spur and cup-formed cells. By freeze-fracture electron microscopy, membrane particle-free smooth areas were noted in the fracture faces. In addition, the number of membrane-associated particles was 20% less than those in control subjects. The lipid analysis of red blood cells showed a significant increase in phospholipid and a marked increase in cholesterol content. The increase of phospholipid content was primarily caused by the increase of lecithin. The acyl chain analysis of erythrocyte lecithin demonstrated an increase in palmitic, palmitoleic and oleic acid, and a decrease in stearic and linoleic acid. These observations are similar to those of acquired biliary obstruction. The fluidity of erythrocyte membrane lipid, studied by a fluorescence technique using fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH), was found to be less in an individual with congenital biliary atresia than in the control subject.


Met kinetic signature derived from the response to HGF/SF in a cellular model predicts breast cancer patient survival.
To determine the signaling pathways leading from Met activation to metastasis and poor prognosis, we measured the kinetic gene alterations in breast cancer cell lines in response to HGF/SF. Using a network inference tool we analyzed the putative protein-protein interaction pathways leading from Met to these genes and studied their specificity to Met and prognostic potential. We identified a Met kinetic signature consisting of 131 genes. The signature correlates with Met activation and with response to anti-Met therapy (p<0.005) in in-vitro models. It also identifies breast cancer patients who are at high risk to develop an aggressive disease in six large published breast cancer patient cohorts (p<0.01, N>1000). Moreover, we have identified novel putative Met pathways, which correlate with Met activity and patient prognosis. This signature may facilitate personalized therapy by identifying patients who will respond to anti-Met therapy. Moreover, this novel approach may be applied for other tyrosine kinases and other malignancies.


Onset of frequent dust storms in northern China at ~AD 1100.
Dust storms in northern China strongly affect the living and health of people there and the dusts could travel a full circle of the globe in a short time. Historically, more frequent dust storms occurred during cool periods, particularly the Little Ice Age (LIA), generally attributed to the strengthened Siberian High. However, limited by chronological uncertainties in proxy records, this mechanism may not fully reveal the causes of dust storm frequency changes. Here we present a late Holocene dust record from the Qaidam Basin, where hydrological changes were previously reconstructed, and examine dust records from northern China, including the ones from historical documents. The records, being broadly consistent, indicate the onset of frequent dust storms at ~AD 1100. Further, peaked dust storm events occurred at episodes of high total solar irradiance or warm-dry conditions in source regions, superimposed on the high background of frequent dust storms within the cool LIA period. We thus suggest that besides strong wind activities, the centennial-scale dust storm events over the last 1000 years appear to be linked to the increased availability of dust source. With the anticipated global warming and deteriorating vegetation coverage, frequent occurrence of dust storms in northern China would be expected to persist.


High-Dimensional Phenotyping of Human Myeloid-Derived Suppressor Cells/Tumor-Associated Macrophages in Tissue by Mass Cytometry.
Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are heterogeneous cells that share myeloid markers and are not easily distinguishable in human tumors due to their lack of specific markers. These cells are a major player in the tumor microenvironment and are involved in the prognosis and physiopathology of various tumors. Here is presented a scheme to decipher these cells by mass cytometry.


Resident-performed neodymium:YAG laser posterior capsulotomy.
To investigate the outcomes of resident-performed Nd:YAG laser posterior capsulotomy. Combined retrospective and prospective study. Patients (N = 301) who underwent Nd:YAG capsulotomy by ophthalmology residents at Rassoul Akram Hospital, Tehran, Iran. Assessment of visual outcomes and complications and the results of second- and third-year residents. In the retrospective arm, 131 eyes of 129 patients were enrolled. Mean best-corrected visual acuity (BCVA) improved significantly from 1.15 ± 0.26 to 0.54 ± 0.39 logMAR (p < 0.001). Mean intraocular pressure (IOP) before capsulotomy and at the final visit was 13.1 ± 2.34 mm Hg and 13.6 ± 2.17 mm Hg, respectively (P = 0.30). Retinal detachment occurred in 2 eyes (1.5%). No case of intraocular lens decentration or endophthalmitis was detected. In the prospective arm on 173 eyes of 172 patients, mean pre-YAG BCVA was 1.14 ± 0.25 logMAR and increased to 0.51 ± 0.37 logMAR after surgery (p < 0.001). There was no significant difference between pre-laser IOP measurements compared with the 1-month IOP measurements (P = 0.32). The postoperative changes in mean BCVA and IOP between the second- and third-year residents were not significant; however, the applied laser power, the number of laser spots, rate of incomplete capsulotomies, and the amount of total and central laser-induced IOL pits were significantly higher among the second-year residents. Resident-performed capsulotomy appears to be effective with a low complication profile. Despite the lower levels of surgical skills, second-year residents could achieve good visual outcomes. The laser parameters and IOL-related complications improved with increasing surgical experience.


Management of the frostbitten hand.
Twenty cases of moderate and severe frostbite of the hands were analysed to establish trends in surgical treatment. Excision of large blisters and early mobilization in flamazine bags were found to be beneficial. In those patients whose initial skin changes did not extend to the base of the fingers only minor amputations were necessary. The small amounts of necrotic tissue did not interfere with hand movement and operation was therefore delayed until six or seven weeks, so that maximal digital length could be preserved. In contrast, those patients whose initial skin changes involved the whole length of the fingers or extended on to the hands, more proximal amputations were necessary and these amputations were performed at three to four weeks in order to remove the larger amounts of necrotic tissue and facilitate early mobilisation.


Prospective evaluation of inappropriate unable-to-assess CAM-ICU documentations of critically ill adult patients.
Delirium occurs in the intensive care unit and identification is often performed using a validated assessment tool such as the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) patients. The CAM-ICU has three ratings: positive, negative, and unable to assess (UTA). Patients may often be assigned UTA when it is inappropriate given the level of sedation or medical condition. The purpose of this study is to evaluate the rate of inappropriate UTA CAM-ICU documentations. A single-center prospective observational analysis was performed evaluating CAM-ICU documentations from October 27, 2014, to December 26, 2014. Patients admitted to the medical and surgical ICU were included and excluded if admitted to the ICU for less than 24 h. CAM-ICU assessments were performed per institutional guidelines using CAM-ICU scoring as validated in literature. CAM-ICU patient documentations were recorded as positive, negative, UTA, or not assessed. Patients with an appropriate UTA documentation were deeply sedated, non-English speaking, or not medically able to participate in the assessment. The major endpoint assessed rates of inappropriate UTA CAM-ICU documentations. Minor endpoints evaluated adherence to CAM-ICU documentations and use of pharmacologic agents for symptoms of delirium. Sixty-one patients were identified with 45 (74 %) medical, 16 (26 %) surgical, of which 27 (44.3 %) were mechanically ventilated. There were 116 UTA documentations with 35 (30.2 %) identified as inappropriate. Of the 906 identified CAM-ICU documentation opportunities, adherence was 439 (48.5 %). Overall, 18 (29.5 %) of the 61 patients were administered pharmacologic agents for delirium management and 5 (27.7 %) had a positive CAM-ICU documented within 24 h. Rates of inappropriate UTA CAM-ICU documentations may be significantly higher than reported in literature. Additional research is needed to identify an acceptable rate of inappropriate UTA CAM-ICU assessments and its clinical impact on delirium management.


Oviposition behaviour of two tephritid fruit flies, Dacus tryoni and Dacus jarvisi, as influenced by the presence of larvae in the host fruit.
When offered a choice, females of the fruit flies Dacus tryoni (Frogg.) and D. jarvisi (Tryon) strongly preferred to lay in fruits without larvae rather than fruits which already contained larvae. Fruits which contained even low densities of larvae, including newly hatched ones, received many fewer eggs than control fruits. This preference was not influenced by the species of larvae present in the fruits nor by the distance to uninfested fruits. Discrimination occurred when fruits with and without larvae were close together (10 cm apart) and also when they were separated by distances of about one metre. Laboratory assays suggested that the flies detect chemical changes in the fruit associated with the decomposition which accompanies larval feeding, but they do not seem to detect the larvae Perse. This behaviour may be significant when these two species utilise the same host since the species which is able to infest fruits first will reduce the availability of hosts for the other species. In contrast to many other Tephritids (e.g. Rhagoletis, Anastrepha and Ceratitis) female Dacus don't discriminate against fruits which contain eggs nor do they deposit a pheromone to deter oviposition by females that subsequently visit the fruit. An hypothesis is proposed to explain the absence of oviposition-deterring pheromones in Dacus, and their presence in many other species of Tephritidae, on the basis of differences in life history and population structure.


Videofluoroscopic evidence of aspiration predicts pneumonia and death but not dehydration following stroke.
In order to assess the risk of pneumonia, dehydration, and death associated with videofluoroscopic evidence of aspiration following stroke, the clinical records of 26 patients with aspiration and 33 randomly selected, case-matched, dysphagic controls without videofluoroscopic evidence of aspiration were reviewed. The videofluoroscopic modified barium swallow technique included 5 ml-thin and thick liquid barium, 5 ml barium pudding, and 1/4 cookie coated with barium, plus additional 20 and 30 ml of thin liquid barium. Patients were assessed a mean of 2 +/- 1 SD months poststroke and were followed for a mean of 16 +/- 8 SD months poststroke. The odds ratio for developing pneumonia was 7.6 times greater for those who aspirated any amount of barium irrespective of its consistency (p = 0.05). The odds ratio for developing pneumonia was 5.6 times greater for those who aspirated thickened liquids or more solid consistencies compared with those who did not aspirate, or who aspirated thin liquids only (p = 0.06). Dehydration was unrelated to the presence or absence of aspiration. The odds ratio for death was 9.2 times greater for those aspirating thickened liquids or more solid consistencies compared with those who did not aspirate or who aspirated thin liquids only (p = 0.01). Aspiration documented by modified videofluoroscopic barium swallow technique is associated with a significant increase in risk of pneumonia and death but not dehydration following stroke.


Dynamics of thermodynamically stable, kinetically trapped, and inhibitor-bound states of pepsin.
The pepsin folding mechanism involves a prosegment (PS) domain that catalyzes folding, which is then removed, resulting in a kinetically trapped native state. Although native pepsin (Np) is kinetically stable, it is irreversibly denatured due to a large folding barrier, and in the absence of the PS it folds to a more thermodynamically stable denatured state, termed refolded pepsin (Rp). This system serves as a model to understand the nature of kinetic barriers and folding transitions between compact states. Quasielastic neutron scattering (QENS) was used to characterize and compare the flexibility of Np, as a kinetically trapped state, with that of Rp, as a thermodynamically stable fold. Additionally, the dynamics of Np were compared with those of a partially unfolded form and a thermally stabilized, inhibitor-bound form. QENS revealed length-scale-dependent differences between Np and Rp on a picosecond timescale and indicated greater flexibility in Np, leading to the conclusion that kinetic stabilization likely does not correspond to reduced internal dynamics. Furthermore, large differences were observed upon inhibition, indicating that QENS of proteins in solution may prove useful for examining the role of conformational entropy changes in ligand binding.


Piperine inhibits PMA-induced cyclooxygenase-2 expression through downregulating NF-κB, C/EBP and AP-1 signaling pathways in murine macrophages.
Piperine is a major component of black (Piper nigrum Linn) and long (Piper longum Linn) peppers, and is widely used as a traditional food and medicine. It also exhibits a variety of biological activities, which include antioxidant, anti-tumor and anti-pyretic properties. In the present study, we investigated the inhibitory effects of piperine on phorbol 12-myristate 13-acetate (PMA)-induced cyclooxygenase-2 (COX-2) gene expression and analyzed the molecular mechanism of its activity in murine RAW 264.7 macrophages. Piperine dose-dependently decreased PMA-induced COX-2 expression and PGE(2) production, as well as COX-2 promoter-driven luciferase activity. Transient transfections utilizing COX-2 promoter deletion constructs and COX-2 promoter constructs, in which specific enhancer elements were mutagenized, revealed that the nuclear factor-κB (NF-κB), CCAAT/enhancer binding protein (C/EBP) and activator protein-1 (AP-1), were the predominant contributors to the effects of piperine. In addition, piperine inhibited PMA-induced NF-κB, C/EBP and c-Jun nuclear translocation. Furthermore, piperine significantly inhibited PMA-induced activation of the Akt and ERK. These findings demonstrate that piperine effectively attenuates COX-2 production, and provide further insight into the signal transduction pathways involved in the anti-inflammatory effects of piperine.


Influence of isoproterenol on the incorporation in vitro of [3H]-leucine and n-acetyl-[14C]-mannosamine into proteins and glycoproteins of the parotid glands of the mouse.
The in-vitro incorporation of [3H]-Leu in murine parotid glands started rapidly and continued during the whole incubation period of 10 h and was not stimulated significantly by isoproterenol, except during the first half hour. Secretion of [3H]-Leu incorporated was already observed after 30 min and continued up to 10 h. Isoproterenol stimulated the secretion of 3H-labelled protein during the whole period, but maximally after 4 h. Incorporation of [14C]-ManNAc proceeded at a much slower rate than that of [3H]-Leu. It was at least 1 h before incorporated [14C]-ManNAc appeared in the incubation medium. The secretion of [14C]-ManNAc incorporated was increased by isoproterenol between 2 and 6 h. A major part of [3H]-Leu was incorporated in amylase. The electrophoretically slowest moving isoenzyme of amylase incorporated substantial amounts of [14C]-ManNAc, in agreement with the presence of sialic acid in the isoenzyme. The onset of the [14C]-ManNAc uptake in amylase was slow compared to [3H]-Leu uptake. The [14C]-label could be detected in the secreted amylase after at least 4 h of incubation. It is suggested that isoproterenol decreased the incorporation of [14C]-ManNAc relative to that of [3H]-Leu into the secreted amylase.


Adjuvant Palbociclib May be Associated with Delayed Recurrence in Completely Resected Retroperitoneal Liposarcoma: Results of a Single-Institution Retrospective Cohort Study.
Retroperitoneal liposarcomas are locally aggressive and frequently recur following complete surgical resection. Palbociclib, a cyclin-dependent kinase (CDK) 4/CDK6 inhibitor, is effective in the treatment of metastatic or unresectable liposarcoma. The purpose of this study was to describe our initial experience using adjuvant palbociclib to delay recurrence. Patients with resected RPS were identified from a prospectively maintained institutional database. In 2017, we began offering adjuvant palbociclib to patients following complete gross resection. Treatment interval, defined as the time between surgical resection and re-resection or change in systemic therapy, was compared between patients selected for adjuvant palbociclib or observation. Between 2017 and 2020, 12 patients underwent a total of 14 operations (14 patient cases) and were selected for adjuvant palbociclib for recurrence prevention. These patients were compared with 14 patients who, since 2010, underwent a total of 20 operations (20 patient cases) and were selected for observation. Histology was primarily dedifferentiated liposarcoma for both groups (observation: 70% [14/20]; adjuvant palbociclib: 64% [9/14]). All patients underwent complete gross resection. Neither age, number of previous surgeries, histologic grade, or Eastern Cooperative Oncology Group (ECOG) performance status differed between groups (p > 0.05 for all). Patients selected for adjuvant palbociclib experienced a longer treatment interval than those selected for observation, although it did not reach statistical significance (20.5 months vs. 13.1 months, p = 0.08, log rank). Adjuvant palbociclib may be associated with a prolonged interval between liposarcoma resection and the need for re-resection or other systemic therapy. Palbociclib may be effective in delaying liposarcoma recurrence, and its use for this indication warrants prospective study.


An in vitro assessment of wound dressing conformability.
An in vitro assessment technique has been developed to determine the conformability of wound dressings. The technique employed is based on an inflation technique which provides a measurement of the minimum radius of curvature which a specific dressing will adopt under pressure. A pressure of 40 mmHg was chosen as this had been shown to be the maximum tolerable pressure before the occurrence of tissue breakdown. This radius is then matched to the natural radii of the body surfaces and an assessment of conformability can be made. A series of commercially available dressings have been assessed with respect to their conformability, and to the enhancement of their conformability due to viscoelastic creep behaviour.


Usefulness of echocardiography and Doppler in the detection of segmental myocardial ischemia.
Echocardiography and Doppler was performed in 20 patients during percutaneous transluminal coronary angioplasty of a right coronary artery to evaluate the usefulness of echocardiography and Doppler in the detection of segmental myocardial ischemia. Wall motion analysis was also compared to the occurrence of chest pain in relation to electrocardiographic and hemodynamic changes. Even in the case of small segmental myocardial ischemia, the two-dimensional echocardiographic evaluation of wall motion is superior to all other measured parameters. Contrary to this, the Doppler examination of transmitral flow is not sensitive enough in the detection of such small segmental myocardial ischemia, induced by right coronary artery occlusion.


Environmental controls on the speciation and distribution of mercury in surface sediments of a tropical estuary, India.
Distribution and speciation of mercury (Hg) in the sediments from a tropical estuary (Godavari estuary) was influenced by the changing physico-chemical parameters of the overlying water column. The sediments from the upstream and downstream of the estuary were uncontaminated but the sediments from the middle of the estuary were contaminated by Hg. The concentrations of Hg became considerably less during the monsoon and post monsoon period. Total Hg concentrations and its speciation (at the middle of the estuary) were dependent on the salinity of the overlying water column. However, salinity had little or no effect on Hg association with organic phases in the sediments at downstream. Increasing pH of the overlying water column corresponded with an increase in the total Hg content in the sediments. Total organic carbon in the sediments played an important role in controlling Hg partitioning in the system. Uncomplexed Hg binding ligands were available in the sediments.


Half analytical method with application to the high order Laue zone effects in monoclinic and triclinic crystals.
The simulation of the high order Laue zone (HOLZ) diffractions of monoclinic and triclinic crystals is a very complicated problem. The conventional multislice (MS) method suffers from the problem of infinity of the phase grating size. To avoid the difficulty of the infinity, Chen et al. arranged the phase grating plane along the ab plane of the crystal lattice. In this paper we introduce a new method which allows the incident and exit wavefunction planes perpendicular to the zone axis without the difficulty of infinity. We name the method half analytical method. The results calculated by half analytical method are in good agreement with those calculated by the conventional MS method.


Efficient lithium extraction using redox-active Prussian blue nanoparticles-anchored activated carbon intercalation electrodes via membrane capacitive deionization.
Global demand for lithium (Li) resources has dramatically increased due to the demand for clean energy, especially the large-scale usage of lithium-ion batteries in electric vehicles. Membrane capacitive deionization (MCDI) is an energy and cost-efficient electrochemical technology at the forefront of Li extraction from natural resources such as brine and seawater. In this study, we designed high-performance MCDI electrodes by compositing Li+ intercalation redox-active Prussian blue (PB) nanoparticles with highly conductive porous activated carbon (AC) matrix for the selective extraction of Li+. Herein, we prepared a series of PB-anchored AC composites (AC/PB) containing different percentages (20%, 40%, 60%, and 80%) of PB by weight (AC/PB-20%, AC/PB-40%, AC/PB-60%, and AC/PB-80%, respectively). The AC/PB-20% electrode with uniformly anchored PB nanoparticles over AC matrix enhanced the number of active sites for electrochemical reaction, promoted electron/ion transport paths, and facilitated abundant channels for the reversible insertion/de-insertion of Li+ by PB, which resulted in stronger current response, higher specific capacitance (159 F g-1), and reduced interfacial resistance for the transport of Li+ and electrons. An asymmetric MCDI cell assembled with AC/PB-20% as cathode and AC as anode (AC//AC-PB20%) displayed outstanding Li+ electrosorption capacity of 24.42 mg g-1 and a mean salt removal rate of 2.71 mg g min-1 in 5 mM LiCl aqueous solution at 1.4 V with high cyclic stability. After 50 electrosorption-desorption cycles, 95.11% of the initial electrosorption capacity was retained, reflecting its good electrochemical stability. The described strategy demonstrates the potential benefits of compositing intercalation pseudo capacitive redox material with Faradaic materials for the design of advanced MCDI electrodes for real-life Li+ extraction applications.


Synthetic peptides of the effector-binding domain of rab enhance secretion from digitonin-permeabilized chromaffin cells.
There is evidence that the rab class of low molecular weight GTP-binding proteins is involved in vesicular transfer from endoplasmic reticulum to Golgi and between Golgi cisternae. To determine whether similar proteins play a role in regulated exocytosis, the effects of synthetic peptides derived from low molecular weight GTP-binding proteins on catecholamine secretion from digitonin-permeabilized chromaffin cells were investigated. The synthetic peptides represent the putative effector-binding domains of the rab, ras and ral classes of low molecular weight GTP-binding proteins and correspond to ras(33-48). Two rab peptides but neither a ras nor a ral peptide enhanced Ca(2+)-dependent secretion by approximately 30%. Maximal secretion in response to Ca2+ was increased. The enhancement was not blocked by the pseudosubstrate inhibitor of protein kinase C, PKC(19-31), thus indicating that activation of protein kinase C was not responsible for the enhancement of secretion. Similarly a rab peptide but neither a ras nor a ral peptide enhanced GppNHp-induced secretion 30-70%. The peptides had little or no effect in the absence of Ca2+ or GppNHp. The data are consistent with a protein of the rab class playing a role in regulated exocytosis.


A scoping review of theories used to investigate clinician adherence to clinical practice guidelines.
Routine utilization of evidence-based clinical practice guidelines (CPGs) is an effective strategy to optimize patient care and reduce practice variation. Healthcare professionals' failure to adhere to CPGs introduces risks to both patients and the sustainability of healthcare systems. The integration of theory to investigate adherence provides greater insight into the often complex reasons for suboptimal behaviors. To determine the coverage of literature surrounding the use of theory in studies of CPG adherence, report the key findings and identify the knowledge gaps. In April 2021, three bibliographic databases were searched for studies published since January 2010, adopting theory to investigate health professionals' adherence to CPGs. Two reviewers independently screened the articles for eligibility and charted the data. A narrative approach to synthesis was employed. The review includes 12 articles. Studies were limited to primarily investigations of physicians, quantitative designs, single disease states and few countries. The use of behavioral theories facilitated pooling of data of barriers and facilitators of adherence. The domains and constructs of a number of the reported theories are captured within the Theoretical Domains Framework (TDF); the most common barriers aligned with the TDF domain of environmental context and resources, fewer studies reported facilitators. There is emerging use of behavioral theories investigating physicians' adherence to CPGs. Although limited in number, these studies present specific insight into common barriers and facilitators, thus providing valuable evidence for refining existing and future implementation strategies. Similar investigations of other health professionals are warranted.


Erosion of Transplantation Tolerance After Infection.
Recent clinical studies suggest that operational allograft tolerance can be persistent, but long-term surviving allografts can be rejected in a subset of patients, sometimes after episodes of infection. In this study, we examined the impact of Listeria monocytogenes (Lm) infection on the quality of tolerance in a mouse model of heart allograft transplantation. Lm infection induced full rejection in 40% of tolerant recipients, with the remaining experiencing a rejection crisis or no palpable change in their allografts. In the surviving allografts on day 8 postinfection, graft-infiltrating cell numbers increased and exhibited a loss in the tolerance gene signature. By day 30 postinfection, the tolerance signature was broadly restored, but with a discernible reduction in the expression of a subset of 234 genes that marked tolerance and was down-regulated at day 8 post-Lm infection. We further demonstrated that the tolerant state after Lm infection was functionally eroded, as rejection of the long-term surviving graft was induced with anti-PD-L1 whereas the same treatment had no effect in noninfected tolerant mice. Collectively, these observations demonstrate that tolerance, even if initially robust, exists as a continuum that can be eroded following bystander immune responses that accompany certain infections.


Metabolic derangements in deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier.
Citrin, encoded by SLC25A13, is a liver-type mitochondrial aspartate-glutamate carrier (AGC), of which deficiency, in autosomal recessive trait, causes neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). NICCD patients have jaundice, hypoproteinemia, hypoglycemia, galactosemia, growth retardation, fatty liver and multiple aminoacidemia including citrulline, methionine, threonine and tyrosine. Some of the neonates who have experienced NICCD suffer from severe CTLN2 more than 10 years or several decades later. In CTLN2, neuropsychotic symptoms such as disorientation, aberrant behavior, coma and death are observed. Laboratory findings reveal hyperammonemia, citrullinemia, fatty liver and liver-specific decrease in a urea cycle enzyme, argininosuccinate synthetase (ASS). In some cases, hyperlipidemia, pancreatitis and hepatoma are accompanied with CTLN2. Citrin as a liver-type AGC plays a role in supplying aspartate to the cytosol for urea, protein and nucleotide synthesis by exchanging mitochondrial aspartate for cytosolic glutamate and proton, and transporting cytosolic NADH reducing equivalent to mitochondria as a member of malate aspartate shuttle essential for aerobic glycolysis. AGC is also important for gluconeogenesis from lactate. Although it is difficult to explain pathogenesis of the symptoms such as cholestasis in NICCD and liver-specific decrease of ASS protein in CTLN2 from the functions of the AGC, some are understandable by the loss of citrin functions. Many CTLN2 patients have been treated with a low protein and high carbohydrate diet and glycerol at the hyperammonemic coma. We argue that those treatments may result in fatty liver, hyperlipidemia, hyperammonemia and even death due to loss of the citrin functions. Loss of citrin first cause deficiency of aspartate in the cytosol, which results in an increase in cytosolic NADH/NAD(+) ratio and then activation of fatty acid synthesis pathway to compensate the aberrant ratio. This follows inhibition of fatty acid oxidation. The peculiar fondness for food of CTLN2 patients who like protein and dislike carbohydrate and sweets may be related to their metabolic requirements.


Changes in inflammatory mediators as a result of intermittent hypoxia in obstructive sleep apnea syndrome.
Inflammation plays an important role in obstructive sleep apnea syndrome (OSAS). The objective of this study was to investigate the relationship of serum C-reactive protein (CRP), pentraxin-3 (PTX-3), procalcitonin (ProCT), interleukin-33 (IL-33) and its soluble receptor ST2 (sST2) with the syndrome severity and to show theirs importance as biomarkers. This study comprises a total of 84 identical (sex and age wise) cases. Full-night polysomnography was performed in each patient. OSAS diagnosis and severity index being based on the widely used criterion known as Apnea Hypopnea Index(AHI). Subgroups were as follows: 24(AHI < 5) controls, 28 mild-moderate OSAS(AHI 5-30) and 32 severe OSAS(AHI > 30). PTX-3, IL-33 and sST2 receptors were significantly higher in OSAS groups than the control group (P < .001). However, both CRP and ProCT levels were similar in all subjects. There was a positive correlation between PTX-3 and BMI (r = 0.446; P < .01), ODI (r = 0.555; P < .01), IL-33 (r = 0.348; P = .001) and sST2 (r = 326; P = .002), while there was a negative correlation with minimum SaO2 (r = -0.672; P < .01) in patient group. PTX-3 as a predictor of OSAS showed highest specificity (%91.7) and sensitivity (%91.7) (P < .001). PTX-3 can be a new indicator reflecting the inflammatory state in patients with OSAS. Since patients with OSAS could have more hypoxic state during sleep, we found higher PTX-3 level in those patients and a negative correlation between PTX-3 and minimum SaO2 , which could explain that PTX-3 levels can increase with the severity of disease. Our results suggest that PTX-3 as an inflammatory biomarker may play a crucial role as an indicator of syndrome severity in OSAS.


Synthesis, identification, chiral separation and crystal structure of (3R,4R,7S,8S)-3,4,7,8-tetrachlorodecane and its stereoisomers.
Chlorinated paraffins (CPs) are a notoriously known class of compounds that stand amongst the most wide-spread persistent organic pollutants. Therefore, their reliable, repeatable, and reproducible quantitative analysis using well-defined reference standards is of utmost importance. In view of the increasing demand for constitutionally and stereochemically defined CP standards, we have synthesized a stereoisomeric mixture of 3,4,7,8-tetrachlorodecane. One stereoisomer - (3R,4R,7S,8S)-3,4,7,8-tetrachlorodecane was separated from the mixture, and enriched fractions of residual stereoisomers were achieved through crystallisation of the residual mother liquors. The molecular structure of the single isolated stereoisomer was confirmed through single-crystal X-ray crystallographic data. One fraction of 3,4,7,8-tetrachlorodecane stereoisomers was successfully separated on a chiral stationary phase using supercritical fluid chromatography hyphenated to mass spectrometry (column: Chiral ART Amylose-C; mobile phase: CO2/MeOH (96/4 v/v) with 0.1% diethylamine). The reported separation of stereoisomers is unprecedented in CP analysis so far.


Prevention and treatment of elbow and shoulder injuries in the tennis player.
Tennis injuries are common in both the upper and lower extremities. The most common, and often most difficult, upper extremity injuries are shoulder tendinitis and tennis elbow (lateral and medial). Key considerations in the treatment of tendinitis include an understanding of the injury process and the resultant character and quantity of the pathologic spectrums. Tendon degeneration rather than tendon repair is the primary pathologic entity secondary to intrinsic muscle-tendon overload. For best treatment results, the protocols of treatment, both surgical and nonsurgical, must be individualized.


Body mass index and dental caries in children aged 5 to 8 years attending a dental paediatric referral practice in the Netherlands.
Obesity and dental caries are widely-recognised problems that affect general health. The prevention of both dental caries and obesity have proven very difficult: children and their parents may need professional support to achieve behaviour change. To find out whether both dental caries and overweight in childhood can be targeted using a common risk factor approach, it is necessary to establish whether the two diseases are indeed linked. The aim of the present study was therefore to use anthropometric data obtained professionally to investigate the association between Body Mass Index and dental caries experience in children aged 5-8 years receiving treatment in a referral centre for paediatric dental care in the Netherlands. Children's dmft and dmfs scores were calculated using dental records and sociodemographic data were also extracted from these records. Dentists were trained to measure standing height and weight in a standardised way. Body Mass Index was calculated by dividing kilograms by height squared (kg/m(2)). Extended International (International Obesity Task Force) body mass index cut-offs were used to define 'no overweight' and 'overweight' (with the latter category including obesity). No statistically significant differences were found between the mean dmft or dmfs scores of the two groups (overweight and non-overweight), even after correction for the effect of the potential confounders sex, socio-economic status and ethnicity. The percentage of caries-active children in the non-overweight group was almost the same as in the overweight group. No statistically significant differences were found. We hypothesised to find a positive association between body mass index and dental caries experience in children aged 5-8 years attending our practice. However, this study did not find a relationship of this kind. A common risk factor approach for the prevention of caries and overweight is therefore not supported by our study.


The ophthalmic registered nurse's responsibility to the adult patient with low vision.
A key goal in the care of adult patients with low vision is to help them focus on their visual abilities rather than their disabilities. This article presents information that every ophthalmic nurse can use to teach patients with low vision some practical ways to change their personal environment to enhance visibility and safety. There are also some myths and misunderstandings about low vision that the nurse can dispel. Before referring patients to low-vision specialty clinics or organizations, every ophthalmic nurse can begin the visual rehabilitation for patients with low vision.


Combined cataract phacoemulsification and aniridia endocapsular rings implantation in a patient with bilateral congenital aniridia and cataract: A case report.
The objective of this article was to determine the long-term outcome of surgical treatment in a patient with bilateral congenital aniridia and congenital cataracts. The patient was treated by cataract removal and implantation of a single piece IOL in both eyes. Two aniridia rings were also implanted in the capsular bag. The best-corrected visual acuity (BCVA), intraocular pressure (IOP), stability of the intraocular lens (IOL) and subjective glare reduction were measured for two years after the surgery. After 10 months, the IOP in the left eye had increased to 26 mmHg despite the fact that anti-glaucoma medication was added. Therefore, the patient was scheduled for an Ahmed valve implantation. These results suggest that good visual outcomes can be achieved in patients with bilateral congenital aniridia and cataracts. Nevertheless, the IOPs must be continuously monitored, and glaucoma screening performed to prevent further complications.


Sex differences in morphology of the brain stem and cerebellum with normal ageing.
The cerebral hemispheres become atrophic with age. The sex of the individual may affect this process. There are few studies of the effects of age and sex on the brain stem and cerebellum. We used MRI morphometry to study changes in these structures in 152 normal subjects over 40 years of age. In the linear measurements, men showed significant age-associated atrophy in the tegmentum and pretectum of the midbrain and the base of the pons. In women, only the pretectum of the midbrain showed significant ageing effects after the age of 50 years, and thereafter remained rather constant. Only men had significant age-associated reduction in area of the cerebellar vermis area after the age of 70 years. Both men and women showed supratentorial brain atrophy that progressed by decades. There were significant correlations between supratentorial brain atrophy and the diameter of the ventral midbrain, pretectum, and base of the pons in men, and between brain atrophy and the diameter of the fourth ventricle in women.


Myositis ossificans following total knee replacement. A report on two cases.
Two cases of myositis ossificans involving the quadriceps femoris muscle are described following total knee replacement arthroplasty. This condition appears to be a very rare complication of this operation. One case was helped by ultrasound therapy.


Reference genes for the study of herbicide stress responses in Leptochloa chinensis (L.) Nees and estimation of ACCase expression in cyhalofop-butyl resistant populations.
Cyhalofop-butyl resistance in Leptochloa chinensis (L.) Nees is a threat to rice production. Qualitative changes to the acetyl-CoA carboxylase gene (ACCase) have been reported to induce cyhalofop-butyl resistance in some weed species, but the role of ACCase in cyhalofop-butyl resistance through quantitative changes remains uncertain. The accurate assessment of transcriptional changes in the functional genes associated with herbicide resistance in L. chinensis is challenging owing to the lack of available reference genes for expression normalization. Here, we selected nine candidate reference genes in L. chinensis and assessed their transcription stability in populations susceptible and resistant to cyhalofop-butyl. Transcription stability was compared under conditions of herbicide stress and control conditions using BestKeeper, NormFinder, and geNorm. Elongation factor 1 alpha, eukaryotic initiation factor 4A, and cap-binding protein CBP20 were the most stable reference genes under cyhalofop-butyl treatment. Transcription levels of ACCase were evaluated in seven resistant populations, one of which showed higher transcription than the susceptible population after 24 h cyhalofop-butyl treatment. However, the slight up-regulation of ACCase (approximately 2.0-fold) is unlikely to be responsible for the high resistance levels in these populations of L. chinensis.


Misdirection of dosage compensation underlies bidirectional sex-specific death in Wolbachia-infected Ostrinia scapulalis.
Endosymbiotic bacteria of the genus Wolbachia often manipulate the reproductive system of their hosts to propagate themselves in host populations. Ostrinia scapulalis moths infected with Wolbachia (wSca) produce female-only progeny (sex chromosomes: ZW), whereas females cured of the infection by antibiotic treatment produce male-only progeny (ZZ). The occurrence of female- and male-only progeny has been attributed to the specific death of the opposite sex during embryonic and larval development. In this bidirectional sex-specific lethality, embryos destined to die express a phenotypic sex opposite to their genotypic sex. On the basis of these findings, we suggested that wSca carries a genetic factor that feminizes the male host, the W chromosome of the host has lost its feminizing function, and discordance between the genotypic and phenotypic sexes underlies this sex-specific death. In the present study, we examined whether the failure of dosage compensation was responsible for this sex-specific mortality. Quantitative PCRs showed that Z-linked gene expression levels in embryos destined to die were not properly dosage compensated; they were approximately two-fold higher in the male progeny of wSca-infected females and approximately two-fold lower in the female progeny of infected-and-cured females. These results support our hypothesis that misdirection of dosage compensation underlies the sex-specific death.


Discrimination of three varieties of Codonopsis Radix based on fingerprint profiles of oligosaccharides by high performance liquid chromatography- evaporative light scattering detector combined with multivariate analysis.
Codonopsis Radix (CR) is a plant that is important in the practice of traditional Chinese medicine (TCM). The Chinese Pharmacopoeia 2020 records dried roots prepared from three varieties of Campanulaceae plants under the designation CR ("Dang-shen" in Chinese), including Codonopsis pilosula (Franch.) Nannf (C. pilosula), Codonopsis pilosula Nannf.var.modesta (Nannf.) L81. T. Shen (C. pilosula var. modesta) and Codonopsis tangshen Oliv (C. tangshen). As major constituents of CR, oligosaccharides might contribute to its clinical efficacy except for other known active compounds, yet the differences in the oligosaccharide profiles of these three varieties of CR remain incompletely understood. In the present study, 135 samples from these different CR varieties were harvested, and oligosaccharide fingerprints for these samples were characterized via HPLC-ELSD, with 19 common peaks being matched. Oligosaccharides were further identified through the combination of electrospray ionization MS/MS (ESI-MS/MS) with nuclear magnetic resonance (NMR). Principal component analysis and linear discriminant analysis (LDA) approaches were then used to compare the oligosaccharide profiles of these three CR varieties. These analyses ultimately revealed that CR was compared with principal component analysis (PCA) and linear discriminant (LDA) methods. The analyses ultimately revealed that these CR samples contained high levels of inulin- and levan-type fructooligosaccharides (FOS), with variations in the relative levels of these FOS compounds among the three analyzed CR varieties. Through the combined analysis of oligosaccharide fingerprints and LDA results, it was possible to differentiate among these CR varieties, with an accurate classification rate of 96.3% and a cross-validation rate of 95.6%. Together, these results highlight a valuable approach to the classification and identification of different CR varieties.


Olfactory Preferences of the Parasitic Nematode Howardula aoronymphium and its Insect Host Drosophila falleni.
Many parasitic nematodes have an environmental infective stage that searches for hosts. Olfaction plays an important role in this process, with nematodes navigating their environment using host-emitted and environmental olfactory cues. The interactions between parasitic nematodes and their hosts are also influenced by the olfactory behaviors of the host, since host olfactory preferences drive behaviors that may facilitate or impede parasitic infection. However, how olfaction shapes parasite-host interactions is poorly understood. Here we investigated this question using the insect-parasitic nematode Howardula aoronymphium and its host, the mushroom fly Drosophila falleni. We found that both H. aoronymphium and D. falleni are attracted to mushroom odor and a subset of mushroom-derived odorants, but they have divergent olfactory preferences that are tuned to different mushroom odorants despite their shared mushroom environment. H. aoronymphium and D. falleni respond more narrowly to odorants than Caenorhabditis elegans and Drosophila melanogaster, consistent with their more specialized niches. Infection of D. falleni with H. aoronymphium alters its olfactory preferences, rendering it more narrowly tuned to mushroom odor. Our results establish H. aoronymphium-D. falleni as a model system for studying olfaction in the context of parasite-host interactions.


Milk protein concentrates: opportunities and challenges.
Poor solubility of milk protein concentrates (MPCs) is a key deterrent factor in their wider applications in the food industry as compared to other protein-rich dried products such as casein, caseinates and whey protein concentrates and isolates. Apart from the processing factors, the protein content of a MPC also decides its solubility. Solubility is a pre-requisite property of MPCs on which its other functional properties are majorly depended. Further, there is a confusion about the term MPC itself in the literature. An attempt has been made to describe MPC and provide an understanding on the manufacture of MPCs. Further, mechanisms of insolubility, factors affecting solubility of MPCs and an insight into the recently evolved strategies for overcoming the challenges related to their poor heat stability and solubility have been reviewed. Potential applications of MPC to be utilized as a novel ingredient in food industry are also outlined.


Individual differences in experiencing intrusive memories: the role of the ability to resist proactive interference.
This study explored whether a relatively poor ability to resist or inhibit interference from irrelevant information in working memory is associated with experiencing undesirable intrusive memories. Non-selected participants (N=91) completed a self-report measure of intrusive memories, and carried out experimental tasks intended to measure two different types of inhibition: resistance to proactive interference and response inhibition (i.e., the ability to prevent automatically triggered responses). The results showed a significant relationship between inhibition at the cognitive level (i.e., resistance to proactive interference) and the frequency of intrusive memories (especially in the group of female participants) whereas no such relationship with measures of response inhibition emerged. These findings are consistent with the idea that deficient inhibitory control reflects a vulnerability factor for experiencing intrusive memories. Implications for research investigating risk factors for the development of posttraumatic stress disorder (PTSD) are discussed.


Control of mineral scale deposition in cooling systems using secondary-treated municipal wastewater.
Secondary-treated municipal wastewater (MWW) is a promising alternative to freshwater as power plant cooling system makeup water, especially in arid regions. A prominent challenge for the successful use of MWW for cooling is potentially severe mineral deposition (scaling) on pipe surfaces. In this study, theoretical, laboratory, and field work was conducted to evaluate the mineral deposition potential of MWW and its deposition control strategies under conditions relevant to power plant cooling systems. Polymaleic acid (PMA) was found to effectively reduce scale formation when the makeup water was concentrated four times in a recirculating cooling system. It was the most effective deposition inhibitor of those studied when applied at 10 mg/L dosing level in a synthetic MWW. However, the deposition inhibition by PMA was compromised by free chlorine added for biogrowth control. Ammonia present in the wastewater suppressed the reaction of the free chlorine with PMA through the formation of chloramines. Monochloramine, an alternative to free chlorine, was found to be less reactive with PMA than free chlorine. In pilot tests, scaling control was more challenging due to the occurrence of biofouling even with effective control of suspended bacteria. Phosphorous-based corrosion inhibitors are not appropriate due to their significant loss through precipitation reactions with calcium. Chemical equilibrium modeling helped with interpretation of mineral precipitation behavior but must be used with caution for recirculating cooling systems, especially with use of MWW, where kinetic limitations and complex water chemistries often prevail.


Determinants of placebo effects.
Determinants of placebo effects and placebo response can be considered from multiple intrinsic and extrinsic perspectives. Intrinsic factors may influence the patient and the clinician/researcher. Patient expectations and previous experiences are considered two of the major intrinsic determinants of placebo response. Other patient determinants include the neural systems under treatment/study, situational factors and reactions to the environment, and personality traits. Clinician/researcher determinants of placebo response include personality factors such as empathy, perceived expertise, the clinical relationship with the patient, and the clinician's belief in the efficacy of the treatment. Extrinsic determinants include the type of study design, influence of advertising or branding, and forces expressed by the cultural milieu. These determinants do not act in isolation, but rather form a complex interaction that ultimately impacts the promotion or deterrence of the placebo effect in clinical and research settings.


Use of an Arabin pessary to prevent preterm birth in pregnancy complicated by a short cervix after cervical conization for cervical adenocarcinoma with residual disease: A case report and literature review.
Surgical conization of the cervix for cervical cancer increases the risk of preterm birth in subsequent pregnancies. The ideal intervention to prevent preterm births in women with cervical insufficiency resulting from conization is not known. When histological margins of the cone biopsy are suspected to have residual malignancy, surveillance and oncological management during a concurrent pregnancy can be challenging. This case outlines the management of a pregnancy complicated by a short cervix secondary to conization for adenocarcinoma of cervix, with margins suspected to be not clear of disease. The patient had progressive shortening of the cervix despite vaginal progesterone, but maintained a cervical length of 16 mm following Arabin pessary insertion. She delivered a healthy neonate at 34 + 3 weeks of gestation (105 days following pessary insertion). The cervical pessary in combination with vaginal progesterone may be safe and effective in preventing preterm birth in a pregnancy with possible residual cervical cancer and a short cervix.


Design of artificial α-helical peptides targeting both gp41 deep pocket and subpocket as potent HIV-1 fusion inhibitors.
Both the deep pocket region and its neighboring subpocket site on the N-trimer of HIV-1 gp41 protein can serve as targets for the development of HIV-1 entry inhibitors. Pocket-binding domain (PBD)-containing peptides with the potential to inhibit HIV-1 fusion through targeting the deep pocket have been extensively exploited. However, using an artificial peptide strategy, we herein report the design of α-helical lipopeptides with non-native protein sequences as HIV-1 fusion inhibitors that can occupy both gp41 deep cavity and subpocket sites. The most active compound, PP24C, inhibited HIV-1 replication, including T20-resistant HIV-1 mutants, at low nanomolar level. Biophysical approaches revealed that both the artificial α-helical peptide P35A4 and its cholesterol-tagged peptide PP24C could bind to T21 peptide used as a target surrogate comprising both pockets. Our study offers a new template for the design of artificial anti-HIV-1 therapeutics and highlights the novel concept of peptide secondary structure-based virus fusion inhibitors.


Dopamine versus dobutamine after open-heart surgery.
The haemodynamic effects of dopamine and dobutamine were compared in a cross-over study of 12 patients in the early postoperative phase after open-heart surgery. The drug infusion rates (dopamine (microgram/kg/min) mean 6.5, range 2.8-12, dobutamine (microgram/kg/min) mean 7.9, range 4.3-12.3) were adjusted so that the cardiac output increased by 50%. With both drugs this was achieved through simultaneous increases in stroke volume (dopamine + 16%, dobutamine + 9%) and heart rate (dopamine + 31%, dobutamine + 38%). The systemic vascular resistance did not change with dopamine but decreased significantly (-18%) with dobutamine. Therefore, the systolic and diastolic arterial blood pressures rose significantly more with dopamine than with dobutamine. The left atrial pressure increased with dopamine but was unchanged with dobutamine. The urine output was significantly higher with dopamine than with dobutamine.


[Purification and properties of membrane-bound methane hydroxylase from Methylococcus capsulatus (strain M)].
Membrane fraction of Methylococcus capsulatus (strain M) were treated with [14C]acetylene, an affinity label binding to the active center of membrane-bound methane monooxygenase (MMO). High-purity particulate form of methane hydroxylase (pMH) was obtained by ion exchange and hydrophobic chromatography. According to SDS-PAGE data, the enzyme contained three polypeptides with molecular weights of 47 (alpha), 27 (beta), and 25 (gamma) kDa in the ratio 1:1:1. The radiolabel was contained in the beta-subunit of pMH. The protein contained 1 or 2 atoms of nonheme iron and 2-4 atoms of copper per a minimum molecular weight of 99 kDa. This protein did not oxidize methane or propylene in the presence of NADH but was able to oxidize low quantities of methane in the presence of duroquinol. It was established that methanol dehydrogenase (MD) and NADH oxidoreductase (NADH-OR) are peripheral membrane proteins. Possible causes of low activity of high-purity methane hydroxylase are discussed.


Education Standards for Pharmacists Providing Comprehensive Medication Management in Outpatient Nephrology Settings.
Chronic kidney disease is a public health problem that has generated renewed interest due to poor patient outcomes and high cost. The Advancing American Kidney Health initiative aimed to transform kidney care with goals of decreasing the incidence of kidney failure and increasing the number of patients receiving home dialysis or a kidney transplant. New value-based models of kidney care that specify inclusion of pharmacists as part of the kidney care team were developed to help achieve these goals. To support this Advancing American Kidney Health-catalyzed opportunity for pharmacist engagement, the pharmacy workforce must have a fundamental knowledge of the core principles needed to provide comprehensive medication management to address chronic kidney disease and the common comorbid conditions and secondary complications. The Advancing Kidney Health through Optimal Medication Management initiative was created by nephrology pharmacists with the vision that every person with kidney disease receives optimal medication management through team-based care that includes a pharmacist to ensure medications are safe, effective, and convenient. Here, we propose education standards for pharmacists providing care for individuals with kidney disease in the outpatient setting to complement proposed practice standards.


[Severe accidental hypothermia].
Two cases of severe accidental hypothermia (core temperature below 25 degrees C) are reported. Both occurred in an urban area during the same winter period. Both patients had the same age and similar clinical symptoms. In the first patient, the EEG, the echocardiography and the blood gases were in favour of a good tolerance of hypothermia, which led to choice a non aggressive rewarming method. The latter included the rewarming of inhaled gas mixture as well as i.v. fluids and gastro-intestinal lavage fluid. The outcome was uneventful. In the second patient, the visceral and biological consequences were more important (pH: 6.80, blood glucose concentration: 1.48 mmol.L-1, major coagulation disorders). Therefore a rapid rewarming via a cardiopulmonary bypass was preferred. The patient died from a prolonged shock with disseminated intravascular coagulation. The use of cardiopulmonary bypass which is essential in case of cardiac arrest rhythm, is controversial in case of severe hypothermia with a still beating heart.


A two-factor model of disordered eating.
General psychopathology (i.e., personality disturbance, mood/affect dysregulation) has been identified as common and perhaps etiologically important in eating disorder (ED) patients. In this context, we examined a two-factor model of disordered eating which implicated the independent and interactive contribution of (a) general psychopathology (personality) and (b) eating-related psychopathology (body esteem) in explaining deviant eating patterns. A sample of 266 female college/university students (M age=22.1) and 76 women with a clinically diagnosed ED (M age=28.09) completed paper and pencil questionnaires of deviant eating patterns, body esteem, and personality pathology. First, a K-means cluster procedure revealed a compelling three-cluster solution among the nonclinical women based on deviant eating variables: <<deviant eaters>>(n=61), <<restrainers>> (n=92), and <<nondeviant eaters>> (n=103). The ED women were classified as Cluster 4; <<clinical>> (n=76). Second, to evaluate our two-factor model, multinomial logistic regression (MLR) was used with cluster membership as the outcome variable and the following variables as predictors: body esteem, personality pathology, and all two-way interactions. In addition to several significant main effects, three interaction terms were marginally significant: Body esteem appearance x Narcissism (P=.047), Body esteem weight x Narcissism (P=.044), and Body esteem attribution x Stimulus seeking(P=.051). The overall extent of correct cluster classification was 63%. These results indicate that the presence of both low body esteem and maladaptive personality, and the interactive operation of these two factors, seems to contribute to the likelihood of having an eating disorder, beyond the independent contribution of either factor alone. Results are considered in the context of etiological models in which general psychopathology presents a vulnerability factor in ED development.


Characterizing multiple sclerosis disease progression using a combined structural and functional connectivity metric.
A combined resting state functional connectivity MRI (fcMRI) and diffusion tensor imaging (DTI) metric called structural and functional connectivity index (SFCI) was recently proposed for tracking disease status and progression in multiple sclerosis (MS). The metric combines fcMRI and transverse diffusivity (TD) along different functional pathways involved in principle symptomatic domains of MS. In a longitudinal study of patients with MS receiving the same MS therapy, initial worsening of transcallosal (TC) motor and frontoparietal (FP) cognitive networks, as measured by fcMRI and DTI over the first year was followed by stabilization in the second year of follow-up. In this study we have (i) probed relationships between individual and composite neurological measures of MS with SFCI and its individual components along TC motor and FP cognitive pathways and (ii) compared sensitivity of SFCI to treatment-induced longitudinal changes with each individual imaging measure. Twenty five patients with MS (15 female, age 42 ± 8 y) participated in this study and were scanned at 3 T whole body MRI scanner with diffusion tensor imaging (DTI) and resting-state functional connectivity MRI (fcMRI) scan protocol at baseline and 6, 12, 18 and 24 months after starting fingolimod. fcMRI and TD along TC and FP pathways were combined to form structural and functional connectivity index (SFCI) at each time point. Correlations between individual/combined neurological measures and individual imaging components/SFCI at baseline and were evaluated and compared. In addition, efficacies of individual and combined imaging metrics in tracking network integrity were compared. Individual TD along the TC pathway was significantly inversely correlated with all individual/composite neurological scores. There were moderate correlations of TC and FP components of SFCI with most of the neurological scores, and the pathway-combined SFCI was significantly correlated with all neurological scores. Trend-level increases of both TC and FP fcMRI were observed during the second year of follow-up, both TC and FP TD increased significantly in the first year and then stabilized during the second year. A trend toward a decrease in combined imaging metrics along TC and FP were observed during the first year, followed by a trend toward an increase in these metrics during the second year, while a significant decrease in SFCI during the first year followed by a significant increase during the second year was observed. SFCI was more effective in tracking network integrity/disease progression than individual pathway-specific components, which supports its use as an imaging marker for MS disease status and progression.


Spatial modeling via geostatistics of the bed in a compost barn system: thermal performance assessments.
For all the benefits of a compost barn system to be achieved, the management, especially with the bedding, must be done correctly. One should consider the requirements regarding the revolving of the material, use of good quality organic matter, suitable ventilation, and an ideal animal stocking rate, so that the composting occurs efficiently. Given this, this work aimed to evaluate the spatial variability of thermal characteristics of rice straw bedding, using values of temperature (surface and internal) and humidity. The temperature and moisture values of the litter were recorded at intervals during the morning shift, from 6:00 am to 7:00 am and from 8:00 am to 9:00 am, and during the afternoon shift, from 3:00 pm to 4:00 pm and from 5:00 pm to 6:00 pm, considering the management of the turn-over, that is, before and after the movement of the litter. Litter variables were collected at points distributed on a 39-point grid. There were no differences between litter surface temperatures before and after turning over in the morning shift, but in the afternoon shift, the surface temperature was lower (P < 0.05) before, when compared to after turning. The internal temperature and litter moisture were higher (P < 0.05) before revolving in both shifts. Spatial dependence was verified (IDE) for the variables studied. Based on the geostatistical analysis, it is concluded that the IDE was rated as strong for surface and internal temperatures, which demonstrates heterogeneity among the points evaluated and a large spatial variability regarding bed temperatures. In the case of litter moisture, the greatest variability occurred in the morning period. The litter surface temperature values did not exceed the ambient air temperature values.


Advances in the Genetics and Genomics of Heart Failure.
The purpose of this review is to provide an update on the recent advances in the genetics and genomics of dilated cardiomyopathy and heart failure. Over the last decade, the approach to the discovery of the genetic contribution to heart failure has evolved from investigation of rare variants implicated in Mendelian cardiomyopathies through linkage studies and candidate gene studies to the exploration of the contribution of common variants through large-scale genome-wide association and genome-first studies. The combination and integration of multiple of case-control heart failure cohorts, refinement of the heart failure phenotype, and utilization of large biobanks linked to electronic health records have advanced the understanding of the heritability of heart failure.


Stability analysis of the bacteriophage phiKMV lysin gp36C and its putative role during infection.
The kinetic, thermodynamic and structural stability of gp36C, the virion-associated peptidoglycan hydrolase domain of bacteriophage phiKMV, is analyzed. Recombinant gp36C is highly thermoresistant (k = 0.595 h(-1) at 95 degrees C), but not thermostable (T(m) = 50.2 degrees C, DeltaH(cal) = 6.86 x 10(4) cal mol(-1)). However, aggregation influences kinetic stability in an unusual manner since aggregation is more pronounced at 55 degrees C than at higher temperatures. Furthermore, gp36C reversibly unfolds in a two-state endothermic transition, and circular dichroism analysis shows that gp36C almost completely refolds after a 3-h heat treatment at 85 degrees C. These properties are in agreement with gp36C being part of the extensible tail which is ejected in an unfolded state during phage infection.


p53 expression and its relationship to DNA alterations in bone and soft tissue sarcomas.
The p53 gene is one of the best studied tumour suppressor genes. Recently we performed mutation analysis on the p53 gene in a large number of bone and soft tissue sarcomas, and found that approximately one-third of the sarcomas have some type of DNA alteration at the p53 locus (Toguchida et al., 1992). However, the expression of the p53 protein resulting from these alterations still remains to be clarified. In this study, p53 expression in the sarcoma tissues was analysed immunohistochemically using antibody PAb421 (Oncogene Science) and its relationship to DNA alterations was examined. Of 113 tumours, 29 (25.7%) showed positive staining for the p53 protein. These included 19 of 67 osteosarcomas, five of 20 chondrosarcomas, four of 11 malignant fibrous histiocytomas (MFHs) and one Ewing's sarcoma. In chondrosarcomas, most of the p53-positive tumours belonged to highly malignant and atypical tumour types (dedifferentiated or mesenchymal type), suggesting a role for p53 mutation in the progression of cartilaginous tumours. All the cases with a missense mutation showed strongly positive staining, while no immunoreactivity was observed in the remaining three-quarters with DNA alterations including gross rearrangement, frame-shift mutation, nonsense mutation or mutation at splicing site except in one case. These results demonstrated the dominance of the p53 mutations with null protein expression in bone and soft tissue sarcomas, showing a unique characteristic of these types of tumours compared with other malignancies such as colon carcinomas.


Focused suggestion with somatic anchoring technique: rapid self-hypnosis for pain management.
This article details a self-hypnosis technique designed to teach patients how to manage acute or chronic pain through directed focus. The focused suggestion with somatic anchoring technique has been used with various types of pain, including somatic pain (arthritis, post-injury pain from bone breaks, or muscle tears), visceral pain (related to irritable bowel disease), and neuropathic pain (related to multiple sclerosis). This technique combines cognitive restructuring and mindfulness meditation with indirect and direct suggestions during hypnosis. The case examples demonstrate how the focused suggestion with somatic anchoring technique is used with both acute and chronic pain conditions when use of long-term medication has been relatively ineffective.


Mesoscopic simulation studies on the formation mechanism of drug loaded polymeric micelles.
In this work, the formation of polymeric micelles as drug delivery vehicles in an aqueous environment is investigated by dissipative particle dynamics (DPD) simulations. Doxorubicin (DOX) is selected as the model drug, whereas docosahexaenoic acid (DHA) conjugated His10Lys10 (DHA-His10Lys10) as the drug carrier. It is shown from DPD simulation that drug molecules and DHA-His10Lys10 molecules could aggregate and form micelles under a defined composition recipe; drug molecules are homogeneously distributed inside the carrier matrix, on whose surface the stabilizer lysine segments are absorbed. Under different compositions of drug and water, aggregate morphologies of polymeric micelles are observed as spherical, columnar, and lamellar structures. We finally proposed the formation mechanism of drug loaded polymeric micelles and apply it in practice by analyzing the simulated phenomena. All the results can effectively guide the experimental preparation of drug delivery system with desired properties or explore a novel polymeric micelle with high performance.


Periodic density functional theory calculations of bulk and the (010) surface of goethite.
Goethite is a common and reactive mineral in the environment. The transport of contaminants and anaerobic respiration of microbes are significantly affected by adsorption and reduction reactions involving goethite. An understanding of the mineral-water interface of goethite is critical for determining the molecular-scale mechanisms of adsorption and reduction reactions. In this study, periodic density functional theory (DFT) calculations were performed on the mineral goethite and its (010) surface, using the Vienna Ab Initio Simulation Package (VASP). Calculations of the bulk mineral structure accurately reproduced the observed crystal structure and vibrational frequencies, suggesting that this computational methodology was suitable for modeling the goethite-water interface. Energy-minimized structures of bare, hydrated (one H2O layer) and solvated (three H2O layers) (010) surfaces were calculated for 1 x 1 and 3 x 3 unit cell slabs. A good correlation between the calculated and observed vibrational frequencies was found for the 1 x 1 solvated surface. However, differences between the 1 x 1 and 3 x 3 slab calculations indicated that larger models may be necessary to simulate the relaxation of water at the interface. Comparison of two hydrated surfaces with molecularly and dissociatively adsorbed H2O showed a significantly lower potential energy for the former. Surface Fe-O and (Fe)O-H bond lengths are reported that may be useful in surface complexation models (SCM) of the goethite (010) surface. These bond lengths were found to change significantly as a function of solvation (i.e., addition of two extra H2O layers above the surface), indicating that this parameter should be carefully considered in future SCM studies of metal oxide-water interfaces.


A case of fatal West Nile virus meningoencephalitis associated with receipt of blood transfusions after open heart surgery.
First identified in the United States in 1999, West Nile virus caused approximately 3,500 infections in the late summer and fall of 2002. The virus is predominantly transmitted by mosquitoes, and the risk of infection through blood product transfusion is believed to be low. We present a case of West Nile virus encephalitis transmitted by red blood cell transfusion at the time of coronary artery bypass grafting that resulted in the patient's death. Individuals undergoing procedures with high blood product transfusion requirements, such as cardiac surgery or organ transplantation, may be at higher risk of this nosocomial infection during epidemics.