Fourier transform (FT)-artifacts and power-function resolution filter in Fourier transform mass spectrometry.
Peak picking algorithms in mass spectrometry face the challenge of picking the correct signals from a mass spectrum. In some cases signal wiggles (side lobes) are also chosen in the produced mass list as if they were real signals. Constraints which are defined in such algorithms do not always guarantee wiggle-free accurate mass list generation out of raw mass spectra. This problem intensifies with acquisitions, which are accompanied by longer transients. Thus, the problem represents a contemporary issue, which propagates with modern high-memory digitizers and exists in both MS and MS/MS spectra. A solariX FTMS mass spectrometer with an Infinity ICR cell (Bruker Daltonics, Bremen, Germany) coupled to a 12 Tesla magnet (Magnex, UK) was used for the experimental study. Time-domain transients of several different data point lengths 512k, 1M, 2M, 4M, 8M were obtained and were Fourier-transformed to obtain frequency spectra which show the effect of the transient truncation on sinc wiggle developments in FT-ICR-MS. MATLAB simulations were also performed to investigate the origin of the Fourier transform (FT)-artifacts. A new filter has been developed to identify and remove FT-artifacts (sinc side lobes) from both frequency and mass spectra. The newly developed filter is based on distinguishing between the FWHM of the correct frequency/mass signals and the FWHM of their corresponding wiggles. The filter draws a reliable confidence limit of resolution range, within which a correct frequency/mass signal is identified. The filter is applicable over a wide mass range of metabolic interest (100-1200 amu). The origin of FT-artifacts due to time-domain transient truncations was thoroughly investigated both experimentally and by simulations in this study. A new solution for this problem with automatic recognition and elimination of these FT-artifacts (side lobes/wiggles) is provided, which is independent of any intensity thresholds, magnetic field strengths and time-domain transient lengths.


Solvent-free MALDI investigation of the cationization of linear polyethers with alkali metals.
The MALDI technique with solvent-free sample preparation has been applied to evaluate relative gas-phase affinities of polyether chain polymers with alkali metal cations. The study is performed on poly(ethylene glycol) and poly(propylene glycol) polymers of different lengths (PEG600, PEG1000, PPG425, PPG750) and the alkali metal cations Li(+), Na(+), K(+), and Cs(+). The experiments show that the lattice energy of the alkali metal salts employed as cation precursors can have a strong influence on the outcome of conventional MALDI measurements. With the solvent-free method, these crystal binding effects can be made negligible by combining in the same sample alkali metal salts with different counterions. The recorded MALDI spectra show that the polyether-cation aggregation efficiencies decrease systematically with growing cation size. This cation size selectivity is considerably enhanced for the polymers with the shorter chains, which can be attributed to the reduced ability of the polymer to build a coordination shell around the larger cations. The steric effects introduced by the side CH3 group of propylene glycol with respect to ethylene glycol also enhance the preference for cationization of the polymer by the smaller cations. These observations correct some qualitative trends derived from previous studies, which did not account for lattice energy effects of the cation precursors.


The Temporal Order of Changes in Physical Activity and Subjective Sleep in Depressed Versus Nondepressed Individuals: Findings From the MOOVD Study.
Epidemiological studies have shown an association between physical activity and sleep, but it is unclear what the temporal order of this association is and whether it differs for depressed patients and healthy controls. Using a multiple repeated observations design, 27 depressed and 27 pair-matched nondepressed participants completed daily measurements of subjective sleep quality and duration during 30 consecutive days while an accelerometer continuously registered their physical activity. Changes in sleep duration, not quality, predicted next-day changes in physical activity (B = -0.21, p < .001), but not the other way around. Significant heterogeneity between individuals was observed, but the effect was not different for depressed and nondepressed participants. The findings underline the strength of a multiple repeated observations design in observational sleep research.


Correlation of Model for End Stage Liver Disease (MELD), MELD-Sodium (MELD-Na), and Child-Turcotte-Pugh (CTP) Score With Frailty in Patients With Hepatitis C Virus (HCV) Related Cirrhosis.
The model for end stage liver disease (MELD), model for end stage liver disease-sodium (MELD Na), and Child-Turcotte-Pugh (CTP) score are independent predictors of mortality in cirrhotic patients. Approximately 43% of cirrhotic patients with advanced disease are frail and can have detrimental effects on the disease prognosis and survival including delisting from the transplant list and increased risk of post-transplant complications. Therefore, our aim was to determine the correlation of MELD, MELD-Na, and CTP score with frailty in patients with hepatitis C virus (HCV) related cirrhosis. This cross-sectional study was conducted at the Department of Hepato-gastroenterology, Sindh Institute of Urology and Transplantation from 1st January 2022 to 30th June 2022. All the patients of either gender aged between 18 and 70 years with serological evidence of HCV and features of cirrhosis on ultrasound abdomen were included in the study. Patients with conditions over estimating frailty were excluded from the study. Liver Frailty Index (LFI) was calculated using grip strength measured in kilograms, timed chair stands, and balance testing. CTP and MELD-Na scores for each patient were also recorded. All the data were analyzed using SPSS version 22.0 (IBM Corp., Armonk, NY). The correlation of MELD, MELD-Na, and CTP with LFI was analyzed using the Pearson correlation coefficient and a p-value < 0.05 was considered statistically significant. A total of 274 patients were included in the study. Out of them, 185 (67.5%) were males. The mean CTP score was 8.1 + 2.1, MELD score of 13.6 + 7.1, MELD-Na score of 15 + 6.6, and LFI of 4.1 + 0.83. LFI was found to be weakly correlated with MELD (r = 0.278) (p < 0.001), MELD-Na score (r = 0.41) (p < 0.001), and CTP score (r = 0.325) (p < 0.001). Weak correlation was noted between LFI, CTP, MELD, and MELD-Na scores in HCV-associated chronic liver disease. Therefore, frailty along with MELD, MELD-Na, and CTP must be assessed before considering the patients for liver transplantation.


Agreement and discordance of parents' and teachers' reports of behavioural problems among Pacific children living in New Zealand.
Research suggests that ratings of child psychopathology by parents and teachers are generally not highly correlated. We examined the agreement and discordance between the child behaviour ratings of parents and teachers of a cohort of 6-year-old Pacific children living in New Zealand, based on scores from the Child Behaviour Checklist and the Teacher Report Form. Mother's reports were obtained for 1019 children, of whom, 602 also had father's reports and 559 had teacher's reports. Rater agreement was low between all pairs of informants. Fathers and teachers had higher agreement than mothers and fathers, the latter in turn had higher agreement than mothers and teachers, and agreement was generally higher for Externalizing problems than Internalizing problems. In terms of discordance, mothers reported more aggressive behaviour than fathers, while fathers reported more Internalizing and Total problems than mothers. Mothers and fathers generally reported more behaviour problems than teachers. The higher agreement found between informants from different settings (fathers and teachers) than between informants from similar settings (mothers and fathers) is in contrast with some of the literature. Further research is needed to investigate how child, informant, and setting characteristics affect ratings of children's behaviour.


Histone H3K36M mutation and trimethylation patterns in chondroblastoma.
Histones are essential components of chromatin, and mutations in histones lead to alterations in methylation and acetylation, which play an important role in tumorigenesis. Most of the chondroblastomas harbour the H3K36M mutation. With the availability of a mutation-specific antibody, we sought to assess the sensitivity of this antibody and the alterations of histone methylation in a series of chondroblastoma cases. Immunohistochemical staining with antibodies against H3K36M, trimethylated histones (H3K27me3 and H3K36me3) and an osteoblastic marker (SATB2) was performed on 27 chondroblastomas from 27 patients. The clinical and radiological characteristics of each patient were reviewed. All 27 tumours showed typical radiological and histological features of chondroblastoma, with a subset of cases showing secondary aneurysmal bone cyst changes (11/27), giant-cell-rich foci (4/27), and matrix-rich areas mimicking chondromyxoid fibroma (1/27). All except one case (26/27, 96%) showed positive H3K36M immunostaining (nuclear). In the majority of cases, there was a diffuse staining pattern. Immunohistochemical staining for H3K27me3 and H3K36me3 showed a heterogeneous staining pattern in all cases, regardless of mutation status. None of the cases showed loss of positivity or diffuse positivity. Focal or diffuse SATB2 expression was seen in 21 of 26 tumours (81%). Our results demonstrate that the vast majority of chondroblastomas are positive for H3K36M by immunohistochemical analysis, confirming its diagnostic value. H3K27me3 expression and H3K36me3 expression are heterogeneous in these tumours.


Human disturbance amplifies Amazonian El Niño-Southern Oscillation signal.
The long-term interaction between human activity and climate is subject to increasing scrutiny. Humans homogenize landscapes through deforestation, agriculture, and burning and thereby might reduce the capacity of landscapes to provide archives of climate change. Alternatively, land-use change might overwhelm natural buffering and amplify latent climate signals, rendering them detectable. Here we examine a sub-annually resolved sedimentary record from Lake Sauce in the western Amazonian lowlands that spans 6900 years. Finely-laminated sediments were deposited from ca. 5000 years ago until the present, and human activity in the watershed was revealed through the presence of charcoal and maize agriculture. The laminations, analyzed for color content and bandwidth, showed distinctive changes that were coupled to more frequent occurrence of fossil maize pollen. As agricultural activity intensified ca. 2200 cal. BP, the 2- to 8-year periodicity characteristic of El Niño-Southern Oscillation became evident in the record. These agricultural activities appeared to have amplified an existing, but subtle climatic signal that was previously absorbed by natural vegetation. When agricultural activity slowed, or land use around Lake Sauce changed at ca. 800 cal. BP, the signal of El Niño-Southern Oscillation (ENSO) activity became erratic.


[DNase II activation in rat liver in the course of acute diethylnitrosamine-induced damage (author's transl)].
Single oral treatment of rats with acutely toxic doses of diethylnitrosamine (DENA) caused a temporary increase of liver-deoxyribonuclease II (DNase II) in homogenate, parenchymal cell, and diverse cell compartments. Highest stimulation resulted in nuclear fraction and cytosol. Due to largely congruent in vitro features, it was suggested that the normal as well as the DENA-activated DNase II were identical. Non-ionic detergents enhanced the enzyme activity only in control samples to a relatively small extent. Suitable conditions of reaction provided, the activation was suppressed by cycloheximide. The results indicated different mechanisms of DNase II activation in the course of an acute DENA-intoxication: 1. release of structurally bound DNase II fractions into cytosol; 2. induction of the enzyme and/or of an effector; 3. enhancement of the nucleus bound enzyme activity by translocation of activated DNase II from cytosolic to nuclear area.


Bridges to sustainable tropical health.
Ensuring sustainable health in the tropics will require bridge building between communities that currently have a limited track record of interaction. It will also require new organizational innovation if much of the negative health consequences of large-scale economic development projects are to be equitably mitigated, if not prevented. We focus attention on three specific contexts: (i) forging linkages between the engineering and health communities to implement clean water and sanitation on a broad scale to prevent reworming, after the current deworming-only programs, of people by diverse intestinal parasites; (ii) building integrated human and animal disease surveillance infrastructure and technical capacity in tropical countries on the reporting and scientific evidence requirements of the sanitary and phytosanitary agreement under the World Trade Organization; and (iii) developing an independent and equitable organizational structure for health impact assessments as well as monitoring and mitigation of health consequences of economic development projects. Effective global disease surveillance and timely early warning of new outbreaks will require a far closer integration of veterinary and human medicine than heretofore. Many of the necessary surveillance components exist within separate animal- and human-oriented organizations. The challenge is to build the necessary bridges between them.


Hemodynamic effects of N-acetylprocainamide in heart disease.
In six normal subjects and 6 patients with primary cardiomyopathy, left ventricular performance was evaluated at rest and during isometric handgrip exercise after 4 days of oral N-acetylprocainamide (NAPA) at each of the three dosage levels (3, 4, 5, and 6 gm/day). Changes in heart rate, blood pressure, and echocardiographic performance indices were noted during isometric exercise, but no effect of NAPA could be demonstrated. In five additional patients with ventricular dysrhythmias due to cardiac diseases, NAPA was given by vein until dysrhythmias were controlled and then a maintenance infusion was continued for 48 hr. Continuous ECG recordings showed excellent dysrhythmia control in four of the five patients, but no effect of NAPA on heart rate, blood pressure, mean pulmonary artery pressure, mean pulmonary artery wedge pressure, or cardiac output was demonstrated, either at the peak of initial infusion (serm NAPA 27 +/- 6.7 microgramsm/ml) or at steady state during the maintenance infusion (16 +/- 4.5 microgramm/ml). We conclude that NAPA by vein and mouth in clinically appropriate doses should be safe in patients with the reduced left ventricular performance due to cardiac disease.


Drug Discovery of DKK1 Inhibitors.
Dickkopf-1 (DKK1) is a well-characterized Wnt inhibitor and component of the Wnt/β-catenin signaling pathway, whose dysregulation is associated with multiple abnormal pathologies including osteoporosis, Alzheimer's disease, diabetes, and various cancers. The Wnt signaling pathway has fundamental roles in cell fate determination, cell proliferation, and survival; thus, its mis-regulation can lead to disease. Although DKK1 is involved in other signaling pathways, including the β-catenin-independent Wnt pathway and the DKK1/CKAP4 pathway, the inhibition of DKK1 to propagate Wnt/β-catenin signals has been validated as an effective way to treat related diseases. In fact, strategies for developing DKK1 inhibitors have produced encouraging clinical results in different pathological models, and many publications provide detailed information about these inhibitors, which include small molecules, antibodies, and nucleic acids, and may function at the protein or mRNA level. However, no systematic review has yet provided an overview of the various aspects of their development and prospects. Therefore, we review the DKK1 inhibitors currently available or under study and provide an outlook on future studies involving DKK1 and drug discovery.


Systemic infections affecting the liver. Some cause jaundice, some do not.
The patient who has clinical jaundice, abnormal results on liver function tests, or both presents a difficult diagnostic challenge. Many infectious diseases affect the liver, and the extent of involvement determines the degree of clinically apparent jaundice. Some diseases that affect the liver minimally cause no jaundice at all. An important clue to the cause of the disorder is the pattern of abnormal results on liver function tests. Increased alkaline phosphatase predominates with Q fever, secondary or tertiary syphilis, clonorchiasis, and hepatic candidiasis, while elevated levels of serum transaminases characterize viral hepatitis, leptospirosis, mononucleosis syndromes, legionnaires' disease, typhoid fever, toxic shock syndrome, and yellow fever. Increases in serum bilirubin are typical with jaundice caused by clostridial myelonecrosis, severe bacterial sepsis, and relapsing fever (borreliosis). These findings together with the patient's history, physical findings, and basic laboratory tests provide a presumptive diagnosis in most cases.


Heterologous over-expression of ACC SYNTHASE8 (ACS8) in Populus tremula x P. alba clone 717-1B4 results in elevated levels of ethylene and induces stem dwarfism and reduced leaf size through separate genetic pathways.
Plant height is an important agronomic and horticultural trait that impacts plant productivity, durability and esthetic appeal. A number of the plant hormones such as gibberellic acid (GA), auxin and ethylene have been linked to control of plant architecture and size. Reduction in GA synthesis and auxin transport result in dwarfism while ethylene may have a permissive or repressive effect on tissue growth depending upon the age of plant tissues or the environmental conditions considered. We describe here an activation-tagged mutant of Populus tremula x P. alba clone 717-1B4 identified from 2000 independent transgenic lines due to its significantly reduced growth rate and smaller leaf size. Named dwarfy, the phenotype is due to increased expression of PtaACC SYNTHASE8, which codes for an enzyme in the first committed step in the biosynthesis of ethylene. Stems of dwarfy contain fiber and vessel elements that are reduced in length while leaves contain fewer cells. These morphological differences are linked to PtaACS8 inducing different transcriptomic programs in the stem and leaf, with genes related to auxin diffusion and sensing being repressed in the stem and genes related to cell division found to be repressed in the leaves. Altogether, our study gives mechanistic insight into the genetics underpinning ethylene-induced dwarfism in a perennial model organism.


Volume and enthalpy changes of proton transfers in the bacteriorhodopsin photocycle studied by millisecond time-resolved photopressure measurements.
The volume and enthalpy changes associated with proton translocation steps during the bacteriorhodopsin (BR) photocycle were determined by time-resolved photopressure measurements. The data at 25 degrees C show a prompt increase in volume followed by two further increases and one decrease to the original state to complete the cycle. These volume changes are decomposed into enthalpy and inherent volume changes. The positive enthalpy changes support the argument for inherent entropy-driven late steps in the BR photocycle [Ort, D. R., and Parson, W. M. (1979) Enthalpy changes during the photochemical cycle of bacteriorhodopsin. Biophys. J. 25, 355-364]. The volume change data can be interpreted by the electrostriction effect as charges are canceled and formed during the proton transfers. A simple glutamic acid-glutamate ion model or a diglutamate-arginine-protonated water charge-delocalized model for the proton-release complex (PRC) fit the data. A conformational change with a large positive volume change is required in the slower rise (M --> N of the optical cycle) step and is reversed in the decay (N --> O --> BR) steps. The large variation in the published values for both the volume and enthalpy changes is greatly ameliorated if the values are presented per absorbed photon instead of per mole of BR. Thus, it is the highly differing assumptions about the quantum or reaction yields that cause the variations in the published results.


Dynamics of defects in Ce³⁺ doped silica affecting its performance as protective filter in ultraviolet high-power lasers.
We investigate defects forming in Ce³⁺-doped fused silica samples following exposure to nanosecond ultraviolet laser pulses and their relaxation as a function of time and exposure to low intensity light at different wavelengths. A subset of these defects are responsible for inducing absorption in the visible and near infrared spectral range, which is of critical importance for the use of this material as ultraviolet light absorbing filter in high power laser systems. The dependence of the induced absorption as a function of laser fluence and methods to most efficiently mitigate this effect are presented. Experiments simulating the operation of the material as a UV protection filter for high power laser systems were performed in order to determine limitations and practical operational conditions.


Long-Term Stability of Root Coverage by Coronally Advanced Flap Procedures.
This study compared 6-month and 3-year outcomes for root coverage (RC) by coronally advanced flap (CAF) procedures in localized gingival recessions. Two centers, that had participated in a 6-month multinational multicenter randomized clinical trial (RCT), followed up 18 patients with 36 Miller Class I and II defects that had been treated in a split-mouth design with CAF procedures or CAF + xenogeneic collagen matrix (CMX). Percentage of RC, complete root coverage (CRC), width, and thickness of keratinized tissue were assessed by the same masked examiners as after the 6-month RCT. There was a high correlation between 6-month and 3-year RC outcomes for both CAF procedures. Mean RC after CAF + CMX amounted to 89.9% after 6 months and 91.7% after 3 years (Pearson's correlation: 0.91). Corresponding values for CAF were 83.7% versus 82.8% (Pearson's correlation: 0.94). Likewise, CRC was stable with 61%/61% for CAF + CMX and 39%/39% for CAF after 6 months/3 years, respectively. In this 3-year follow-up of a subgroup of patients from a previous 6-month RCT, there was a high correlation between the results for RC after 6 months and 3 years, indicating their stability. These data suggest that 6-month outcomes may be useful to predict long-term outcomes in CAF procedures with or without additional use of CMX.


Full-scale increased iron dosage to stimulate the formation of vivianite and its recovery from digested sewage sludge.
The recovery of phosphorus from secondary sources like sewage sludge is essential in a world suffering from resources depletion. Recent studies have demonstrated that phosphorus can be magnetically recovered as vivianite (Fe(II)3(PO4)2∗8H2O) from the digested sludge (DS) of Waste Water Treatment Plants (WWTP) dosing iron. To study the production of vivianite in digested sludge, the quantity of Fe dosed at the WWTP of Nieuwveer (The Netherlands) was increased (from 0.83 to 1.53 kg Fe/kg P in the influent), and the possible benefits for the functioning of the WWTP were evaluated. Higher Fe dosing is not only relevant for P-recovery, but also for maximal recovery of organics from influent for e.g. biogas production. The share of phosphorus present as vivianite in the DS increased from 20% to 50% after the increase in Fe dosing, making more phosphorus available for future magnetic recovery. This increase was directly proportional to the increase of Fe in DS, suggesting that vivianite could be favored not only thermodynamically, but also kinetically. Interestingly, analyses suggest that several types of vivianite are formed in the WWTP, and could differ in their purity, oxidation state or crystallinity. These differences could have an impact on the subsequent magnetic separation. Following the Fe dosing increase, P in the effluent and H2S in the biogas both decreased: 1.28 to 0.42 ppm for P and 26 to 8 ppm for H2S. No negative impact on the nitrogen removal, biogas production, COD removal or dewaterability was observed. Since quantification of vivianite in DS is complicated, previous studies were reviewed and we proposed a more accurate Mössbauer spectroscopy analysis and fitting for sludge samples. This study is important from a P recovery point of view, but also because iron addition can play a crucial role in future resource recovery wastewater facilities.


Medicare-certified home health services: national and regional supply in the 1980s.
The number of Medicare-certified home health agencies nearly doubled from 1980 to 1990. Using Health Care Financing Administration data, this study documented national and regional patterns of entry and exist by Medicare home health providers from 1980 to 1990. Nationally, agency origination rates accelerated during the early 1980s and then dropped abruptly in the second half of the decade. The proprietary sector, accounting for approximately 42% of agencies in existence during the period of the study, exhibited the greatest volatility. Regional differences are also evident. Both expansion and contraction in Medicare home health services appear to be a response to the incentives of legislation implemented during this period.


Pancoast-Tobias Syndrome: A Unique Presentation of Lung Cancer.
A 65-year-old man with 50 pack-year smoking history presented to the emergency department for evaluation of upper back and right shoulder pain secondary to a fall. Physical examination was notable for anisocoria with a constricted left pupil (miosis), mild ptosis of the left eyelid, and bilateral shoulder pain, right more than left, with both passive and active movements. Chest computed tomography identified a soft tissue mass at the left lung apex with extension into the pleural surface, associated with destructive osseous changes of the right scapula, adjacent ribs, and thoracic vertebral bodies. Imaging of the brain revealed multiple masses suspicious of metastatic brain lesions. Biopsy of the right supraclavicular lymph node revealed lung tissue adenocarcinoma and negative Kirsten rat sarcoma viral oncogene homolog (K-Ras), epidermal growth factor receptor (EGFR), B-raf proto-oncogene (BRAF), C-ros oncogene 1 (ROS1), and anaplastic lymphoma kinase (ALK) rearrangement. Recognizing Pancoast syndrome in patients with significant smoking history, anisocoria, and shoulder pain is crucial for identifying the underlying etiology and expediting the treatment.


Detection of gene deletions by PCR analysis in a Malaysian patient with Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD), the commonest X-linked disorder, is a progressive, eventually fatal disease. With the advent of molecular genetics, the Duchenne gene and its protein product, dystrophin, have been characterised. Molecular diagnosis of DMD, identification of carriers and antenatal diagnosis are now possible. We describe here the use, in a Malaysian boy with DMD, of a recent innovation, multiplex polymerase chain reaction (PCR), to obtain molecular diagnosis by detection of dystrophin gene deletions.


Truth, healing, and systems change: the Maine Wabanaki-state child welfare truth and reconciliation commission process.
Maine state child welfare staff understand the Indian Child Welfare Act requirements, yet their knowledge of Wabanaki history is limited because it has excluded the voices of the Wabanaki people. A group of Native people and state representatives are creating a truth and reconciliation commission process in Maine, designed to reckon with this history as a way of improving the child welfare system and promoting healing for Wabanaki children and families.


Intramolecular alpha-helix-beta-structure-random coil transition in polypeptides. II. Dynamic case.
The conformational changes of polypeptides which are capable of forming the alpha-helix. beta-structure and random coil (or the unordered) conformations are discussed. The kinetics of this system are studied as the time evolution of the probabilities describing the conformational states of the system. The time behavior of the average numbers of the alpha-helix and the beta-structure reveals the existence of intermediate states which are not found and not stable at equilibrium. These intermediates make the kinetics of this system more complex. Such situations can occur in protein folding and unfolding processes in such a way that a conformation absent in the tertiary structure appears in the intermediate stages and disappears finally, and the time course of the reaction is described by the sum of two or more exponential terms, in other words, the protein folding and unfolding processes display multiphasic kinetics. These intermediates, which are formed by short-range interactions, may usually be destroyed but sometimes can be stabilized by medium- and long-range interactions and remain stable for a fairly long time in the process of renaturation in real proteins.


Pulsed-field gel electrophoresis and distribution of the genes zag and fnz in isolates of Streptococcus equi.
Streptococcus equi subsp. equi and subsp. zooepidemicus are important pathogens of the equine respiratory tract. Isolates of both subspecies were examined by pulsed-field gel electrophoresis (PFGE). With the exception of eight isolates, a unique band pattern was displayed for each of the 48 subsp. zooepidemicus isolates tested. A method to distinguish isolates of the genetically very homogeneous subsp. equi has hitherto not been available, although several methods have been tested. By the use of PFGE, 50 isolates of subsp. equi could be divided into eleven groups, each with a unique pulsotype. In addition, the recently characterised genes encoding the cell-wall proteins ZAG and FNZ of S. equi subsp. zooepidemicus strain ZV were shown by Southern blots to be present in all 98 tested isolates, including the type strains of the two subspecies. Binding assays showed that the expression of the two genes clearly differentiate between the two subspecies.


Self-reported traumatic brain injury and in vivo measure of AD-vulnerable cortical thickness and AD-related biomarkers in the ADNI cohort.
In this study, we aimed to investigate whether self-reported mild traumatic brain injury (mTBI) was associated with decreased AD-vulnerable cortical thickness, and to assess the relationship between AD-vulnerable cortical thickness and AD-related biomarker in the Alzheimer's Disease Neuroimaging Initiative subjects. We identified 45 self-reported mTBI subjects, who had structural MRI, 18F-AV45 PET, and cerebrospinal fluid (CSF) data. Of them, eight subjects were normal; ten were preclinical AD; seventeen were MCI due to AD; ten were AD. Additional demographics-controlled 45 subjects were included. Cortical thickness of eight AD-vulnerable regions, mean AD-vulnerable cortical thickness, 18F-AV45 PET mean amyloid SUVR, CSF Aβ42, CSF total tau (T-tau), and CSF phosphorylated tau (P-tau) were compared between mTBI and non-TBI groups. Correlational analysis was done to investigate the relationship between mean AD-vulnerable cortical thickness and mean amyloid SUVR, CSF Aβ42, CSF T-Tau, CSF P-Tau. Our study revealed that preclinical AD subjects with self-reported mTBI had smaller cortical thickness in mean and three AD-vulnerable cortical regions than non-TBI subjects (P<0.05). The mean AD-vulnerable cortical thickness was correlated with CSF T-tau (r=-0.81, P=0.001). There was no statistical difference in the comparison of normal, MCI due to AD, and AD groups. Our study indicated that among individuals with preclinical AD, but not normal, MCI due to AD and AD subjects, self-reported mTBI was associated with more decreased AD-vulnerable cortical thickness which was related to CSF tau pathology, suggesting the possible early involvement of tau pathology in the decreased AD-vulnerable cortical thickness of self-reported TBI subjects.


Hydroboration of CO2 catalyzed by bis(phosphinite) pincer ligated nickel thiolate complexes.
We report the hydroboration of CO2 with catecholborane catalyzed by a series of bis(phosphinite) pincer ligated nickel thiolate complexes. Turnover frequencies (TOFs) up to 2400 h-1 were achieved at room temperature under an atmospheric pressure of CO2. This represents the highest TOF value known to date for the reduction of CO2 to the methoxide level under mild conditions.


Walking the Line: Balancing Access to Research and Protecting Prisoners.
Prisoners are often excluded from participating in clinical research (ie clinical trials and clinical investigations related to medicinal products and medical devices) due to the historical precedent of their abuse and exploitation. The exclusion of prisoners from clinical research is often deemed necessary to guarantee their protection from such abuse and exploitation. However, in this article, we argue that the right to science, which encompasses the right to access the benefits of science and research participation, is an emerging human right that is applicable to prisoners and may only be limited when this is necessary and proportionate. Whether this is necessary depends in part on the validity of a prisoner's informed consent. We discuss the importance of prison conditions for voluntary consent and examine the relationship between prison overcrowding and sub-par prison conditions by analysing the jurisprudence of the European Court of Human Rights on Article 3 of the European Convention on Human Rights on the prohibition of torture and inhuman treatment. We contend that the special circumstances of being in prison warrant additional protective measures, concurring with the Belgian Advisory Committee on Bioethics that research without the explicit aim of improving the situation of the individual prisoner or the prison community should be excluded. Given the complexity of the question of whether prisoners can give valid informed consent, rigorous oversight by an ethics committee with expertise concerning the prison system is necessary to provide a proportional balance between offering prisoners access to research and protection from abuse and exploitation.


The Reaction of CO2 with a Borylnitrene: Formation of an 3-Oxaziridinone.
The reaction of a borylnitrene with carbon dioxide is studied under cryogenic matrix isolation conditions. Photogenerated CatBN (Cat=catecholato) reacts with CO2 under formation of the cycloaddition product CatBNCO2 , a 3-oxaziridinone derivative, after photoexcitation (>550 nm). The product shows Fermi resonances between the CO stretching and ring deformation modes that cause unusual 13 C and 18 O isotopic shifts. A computational analysis of the 3-oxaziridinone shows this cyclic carbamate to be less strained than an α-lactone or an α-lactame.


Coexistence of muscle atrophy and high subcutaneous adipose tissue radiodensity predicts poor prognosis in hepatocellular carcinoma.
We aimed to assess the prognostic implications of muscle atrophy and high subcutaneous adipose tissue (SAT) radiodensity in patients with hepatocellular carcinoma (HCC). In this retrospective study, muscle atrophy was assessed using the psoas muscle index (PMI) obtained from computed tomography. SAT radiodensity was evaluated based on radiodensity measurements. Survival and multivariate analyses were performed to identify factors associated with prognosis. The impact of muscle atrophy and high SAT radiodensity on prognosis was determined through survival analysis. A total of 201 patients (median age: 71 years; 76.6% male) with HCC were included. Liver cirrhosis was observed in 72.6% of patients, and the predominant Child-Pugh grade was A (77.1%). A total of 33.3% of patients exhibited muscle atrophy based on PMI values, whereas 12.9% had high SAT radiodensity. Kaplan-Meier survival analysis demonstrated that patients with muscle atrophy had significantly poorer prognosis than those without muscle atrophy. Patients with high SAT radiodensity had a significantly worse prognosis than those without it. Muscle atrophy, high SAT radiodensity, the Barcelona Clinic Liver Cancer class B, C, or D, and Child-Pugh score ≥ 6 were significantly associated with overall survival. Further classification of patients into four groups based on the presence or absence of muscle atrophy and high SAT radiodensity revealed that patients with both muscle atrophy and high SAT radiodensity had the poorest prognosis. Muscle atrophy and high SAT radiodensity are significantly associated with poor prognosis in patients with HCC. Identifying this high-risk subgroup may facilitate the implementation of targeted interventions, including nutritional therapy and exercise, to potentially improve clinical outcomes.


Outer membrane protein F (porin) preparation of Pseudomonas aeruginosa as a protective vaccine against heterologous immunotype strains in a burned mouse model.
Outer membrane (OM) protein F (porin) was purified by extraction from polyacrylamide gels of cell envelope proteins of the Pseudomonas aeruginosa PA01 strain. Mice were immunized intramuscularly with 10 micrograms of protein F preparation on days 1 and 14 and then subjected to burn and challenge on day 28. Protein F immunization afforded significant protection above that provided by PA01 lipopolysaccharide (LPS) immunization against subsequent challenge with six of six heterologous LPS immunotype strains of P. aeruginosa. By an ELISA, the murine immune response revealed an IgG titer of 5,120 to protein F by day 30. Immunoblot analysis of antisera from protein F-immunized mice revealed bands with both protein F and protein H of cell envelopes of all immunotypes tested. Active immunization with OM protein H did not, however, afford significant protection to mice in this burned mouse model. These data show the efficacy of OM protein F as a protective vaccine in a murine model representative of human infection.


Spinal fusion using adipose stem cells seeded on a radiolucent cage filler: a feasibility study of a single surgical procedure in goats.
To assess the feasibility of a one-step surgical concept, employing adipose stem cells (ASCs) and a novel degradable radiolucent cage filler (poly-L-lactide-co-caprolactone; PLCL), within polyetheretherketone cages in a stand-alone caprine spinal fusion model. A double-level fusion study was performed in 36 goats. Four cage filler groups were defined: (i) acellular PLCL, (ii) PLCL + SVF (freshly harvested stromal vascular fraction highly enriched in ASCs); (iii) PLCL + ASCs (cultured to homogeneity); and (iv) autologous iliac crest bone graft (ABG). Fusion was assessed after 3 and 6 months by radiography, micro-CT, biomechanics, and biochemical analysis of tissue formed inside the cage after 6 months. No adverse effects were observed in all groups. After 3 months, similar and low fusion rates were found. Segmental stability did not differ between groups in all tested directions. Micro-CT imaging revealed significantly higher amounts of mineralized tissue in the ABG group compared to all others. After 6 months, interbody fusion rates were: PLCL 53%, SVF 30%, ASC 43% and ABG 63%. A trend towards higher mineralized tissue content was found for the ABG group. Biochemical and biomechanical analyses revealed equal maturity of collagen cross-links and similar segmental stability between all groups. This study demonstrates the technical feasibility and safety of the one-step surgical procedure for spinal fusion for the first time. The radiolucent PLCL scaffold allowed in vivo monitoring of bone formation using plain radiography. Addition of stem cells to the PLCL scaffolds did not result in adverse effects, but did not enhance the rate and number of interbody fusions under the current conditions. A trend towards superior results with ABG was found. Further research is warranted to optimize the spinal fusion model for proper evaluation of both PLCL and stem cell therapy.


Methodologic basis for the radioimmunoassay of endogenous steroids in human prostatic tissue.
Methods are presented for the accurate radioimmunoassay of tissue dihydrotestosterone, testosterone, estradiol-17 beta, estrone, and progesterone that require significantly less time than other methods. Benign prostatic hyperplasia concentrated dihydrotestosterone, estradiol-17 beta, and estrone at levels significantly greater than those found in normal prostate or male plasma. These findings provide additional support for the importance of endocrine factors in the etiology of benign prostatic hyperplasia. A wide range of dihydrotestosterone and estrogen levels was found in prostatic adenocarcinoma samples and may reflect the proportion of endocrine-dependent cells in each tumor. Levels of endogenous steroids may provide a rational basis for the selection of endocrine therapy in the treatment of prostatic neoplasia.


Sensitivity enhanced nanothermal sensors for photoacoustic temperature mapping.
Photoacoustic imaging can be used to guide and validate the therapeutic outcome of nanoparticle-mediated photothermal therapy through its ability to visualize the delivery of nanoparticle contrast agents, image the temperature distribution inside living tissue, and confirm tissue coagulation. In this image-guided process, temperature mapping plays a critical role for thermal dosage control. Therefore, developing a sensitive and accurate photoacoustic technique to quantitatively measure the temperature distribution during thermal therapy is essential. In this study, we investigated and demonstrated that silica-coated gold nanorods, can provide a multi-fold improvement in sensitivity of the photoacoustic temperature mapping compared to gold nanorods without silica coating, and serve as a nanothermal sensor to accurately and quantitatively visualize temperature distributions during photothermal therapy.


Neuroinflammation in a Rat Model of Tourette Syndrome.
Tourette syndrome (TS) is a group of childhood-onset chronic neuropsychiatric disorders characterized by tics, i.e., repetitive, sudden, and involuntary movements or vocalizations, which is often associated with various psychopathological and/or behavioral comorbidities, including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and sleep disorders and have a worse prognosis. The mechanism of TS is still not clear. The relationship between immune activation, neuroinflammation, and neuropsychiatric disorders has attracted much attention in the past two decades. To explore the underlying mechanism in TS, the relationship between neuroinflammation and behavioral alterations in TS rats was investigated in this study. A total of 36 Sprague-Dawley male rats were divided into three groups randomly as follows: the TS, control (CON), and drug intervention groups. The TS rat group was treated with haloperidol (Hal) (the TS + Hal group). The TS rat model was established using 3,3-iminodipropionitrile (IDPN), which is a well-known animal model of TS. The behavioral syndromes, brain tissue cytokines, like interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α), and microglial activation of the three groups were assessed. The behavioral scores of rats in the TS group and the TS + Hal group were higher than those in the CON group (P < 0.05), but the scores of behavioral tests in the TS + Hal group were lower than those in the TS group (P < 0.05). The levels of IL-6 and TNF-α in the rat brain tissue were significantly higher in the TS group than in the CON group (P < 0.05), while no significant differences were found between the CON group and the TS + Hal group (P > 0.05). The microglia was significantly activated in the TS group and slightly activated in the TS + Hal group, which was considerably less than that in the TS group. The IDPN-induced TS rats had significant neuroinflammation in the brain, and the interaction between dopamine (DA) dysregulation and immune dysfunction may play a vital role in the pathogenic mechanisms of TS.


The Association of Metabolic Dysfunction and Mood Across Lifespan Interacts With the Default Mode Network Functional Connectivity.
Background: Numerous studies suggest a relationship between depression and metabolic syndrome, which is likely influenced by age. Interestingly, functional imaging analysis has shown an association between functional connectivity in the default mode network (DMN-FC) and components of metabolic syndrome, which is explored in this study. Methods: From a larger longitudinal cohort study on healthy aging, 943 individuals were extensively characterized for mood and cognition. Among these, 120 individuals who were selected for displaying extreme cognitive performance within the normal range (good and poor performers) were further studied. Here, in a cross-sectional design, using confirmatory factor analysis (CFA), the association between metabolic dysfunction and depressive mood as a function of age and its relationship with DMN-FC was studied. Results: Metabolic dysfunction was modeled as a second-order latent variable using CFA. First-order latent variables were obesity, glucose dysmetabolism, lipids imbalance, and blood pressure. Using multiple linear regression models, this study observed that metabolic dysfunction, glucose dysmetabolism, and lipids imbalance were linearly associated with depressive mood, and the association with obesity was U-shaped. The association of metabolic dysfunction, obesity, and glucose dysmetabolism with depressive mood is positive for the younger individuals in our sample and vanishes with aging. The FC of the right superior temporal gyrus with the DMN correlated with both obesity and depressive mood. In participants with higher obesity scores, FC increased with higher GDS scores, while in those with lower GDS scores, FC decreased. Age and blood pressure were associated with a more complex pattern of association between FC of the right supramarginal gyrus and GDS score. Conclusion: The association of metabolic dysfunction with depressive mood is influenced by age and relates with differential patterns of DMN-FC. The combination of the effects of age, mood, and metabolic dysfunction is likely to explain the heterogeneity of DMN-FC, which deserves further investigation with larger and longitudinal studies.


Clinical review of pulmonary manifestations of IgG4-related disease.
IgG4-related disease (IgG4-RD) is a recently recognized systemic disease characterized by tumefactive lesions in various organ systems. The list of organs that can be involved continues to expand, and recently computed tomography (CT) descriptions of the pulmonary lesions found in the disease have been described. The clinical symptoms are nonspecific and may include cough, dyspnea, chest pain, and fever. The appropriate clinical presentation along with elevated serum IgG4 concentrations and pathologic evidence of lymphoplasmacytic infiltrates with abundant IgG4-positive plasma cells and storiform fibrosis is consistent with the disease. Steroids are used to treat this disease in addition to immunosupressives such as cyclosporine or rituxumab for steroid refractory disease. The pulmonary manifestations and imaging features can often mimic malignancy, and as such knowledge of the diagnostic, clinicopathologic, and radiographic features of the disease is required in order to provide appropriate diagnostic workup and treatment.


Selective deletion of zinc transporter 3 in amacrine cells promotes retinal ganglion cell survival and optic nerve regeneration after injury.
Vision depends on accurate signal conduction from the retina to the brain through the optic nerve, an important part of the central nervous system that consists of bundles of axons originating from retinal ganglion cells. The mammalian optic nerve, an important part of the central nervous system, cannot regenerate once it is injured, leading to permanent vision loss. To date, there is no clinical treatment that can regenerate the optic nerve and restore vision. Our previous study found that the mobile zinc (Zn2+) level increased rapidly after optic nerve injury in the retina, specifically in the vesicles of the inner plexiform layer. Furthermore, chelating Zn2+ significantly promoted axonal regeneration with a long-term effect. In this study, we conditionally knocked out zinc transporter 3 (ZnT3) in amacrine cells or retinal ganglion cells to construct two transgenic mouse lines (VGATCreZnT3fl/fl and VGLUT2CreZnT3fl/fl, respectively). We obtained direct evidence that the rapidly increased mobile Zn2+ in response to injury was from amacrine cells. We also found that selective deletion of ZnT3 in amacrine cells promoted retinal ganglion cell survival and axonal regeneration after optic nerve crush injury, improved retinal ganglion cell function, and promoted vision recovery. Sequencing analysis of reginal ganglion cells revealed that inhibiting the release of presynaptic Zn2+ affected the transcription of key genes related to the survival of retinal ganglion cells in postsynaptic neurons, regulated the synaptic connection between amacrine cells and retinal ganglion cells, and affected the fate of retinal ganglion cells. These results suggest that amacrine cells release Zn2+ to trigger transcriptomic changes related to neuronal growth and survival in reginal ganglion cells, thereby influencing the synaptic plasticity of retinal networks. These results make the theory of zinc-dependent retinal ganglion cell death more accurate and complete and provide new insights into the complex interactions between retinal cell networks.


Mechanism of morusin on breast cancer via network pharmacology and in vitro experiments.
This study aimed to investigate the therapeutic effect of morusin on breast cancer and decode its underlying molecular mechanism using network pharmacology and in vitro techniques. Swiss Target Prediction and PharMmapper were applied to screen morusin targets. The targets of human breast cancer were obtained from the GeneCards database, and the overlapping targets were screened. A protein-protein interaction network was constructed based on the overlapping targets by String and Cytoscape. Performed Gene Ontology enrichment as well as Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the shared targets of the drug and disease using the David database. Additionally, performed molecular docking using PyMoL and AutoDock software. Finally, the impact of morusin on breast cancer was demonstrated by cell experiments and western blot. A total of 101 target genes were obtained through screening including ESR1, EGFR, ALB, CTNNB1, AKT1, and so on. Based on the annotation of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, the anticancer properties of morusin are linked to apoptosis, migration, and PI3K-AKT signaling pathways. Molecular docking showed an interaction between morusin and PIK3CA, AKT1. In vitro data demonstrated that morusin causes apoptosis and inhibits cell migration. Morusin also increased the expression of cleaved-PARP while decreasing the expression of p-PI3K and p-AKT. Through network pharmacology analysis and in vitro experiments, this study showed that morusin promotes apoptosis and inhibits migration by modulating the PI3K-AKT axis. Morusin plays a key role in the treatment of breast cancer.


Effect of the van der Waals interaction on the electron energy-loss near edge structure theoretical calculation.
The effect of the van der Waals (vdW) interaction on the simulation of the electron energy-loss near edge structure (ELNES) by a first-principles band-structure calculation is reported. The effect of the vdW interaction is considered by the Tkatchenko-Scheffler scheme, and the change of the spectrum profile and the energy shift are discussed. We perform calculations on systems in the solid, liquid and gaseous states. The transition energy shifts to lower energy by approximately 0.1eV in the condensed (solid and liquid) systems by introducing the vdW effect into the calculation, whereas the energy shift in the gaseous models is negligible owing to the long intermolecular distance. We reveal that the vdW interaction exhibits a larger effect on the excited state than the ground state owing to the presence of an excited electron in the unoccupied band. Moreover, the vdW effect is found to depend on the local electron density and the molecular coordination. In addition, this study suggests that the detection of the vdW interactions exhibited within materials is possible by a very stable and high resolution observation.


Epidemiology and natural history of benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) afflicts the majority of elderly men, and if current rates of surgery persist, the average 40-year-old man in the United States will have a 30 to 40 per cent chance of undergoing a prostatectomy if he survives to age 80. Age is by the far the most important determinant of BPH occurrence. Symptomatic BPH has a waxing and waning course, and a few men may have long-term remission. Surprisingly, the natural history of BPH is poorly defined, particularly with regard to the magnitude of the risks of its complications.


[Regulation of the NLRP3 inflammasome].
The innate immunity constitutes an efficient barrier by rapidly detecting pathogens and tissue damages through pattern recognition receptors including NLRP3. Moreover, inappropriate NLRP3 activation causes deleterious inflammation and contributes to various conditions including atherosclerosis, diabetes, gout and Alzheimer's diseases. NLRP3 assembles a multimeric inflammasome complex serving as an activation platform for caspase-1 that controls processing and release of cytosolic inflammatory factors and cytokines including IL-1β Inflammasome assembly is tightly controlled and requires coordinated NLRP3 priming, through cytokine or other pattern recognition receptors, followed by activation by cellular stress. Here, we describe recent advances in the understanding of the signalling pathways supporting the priming and activation of NLRP3, with a special focus on the key role of post-translational modifications of NLRP3, including phosphorylation and ubiquitination, in inflammasome regulation.


Competing Theories of Borderline Personality Disorder.
The authors review four theories that propose different conceptualizations of borderline personality disorder's (BPD) core psychopathology: excess aggression, emotional dysregulation, failed mentalization, and interpersonal hypersensitivity. The theories are compared in their ability to explain BPD's coaggregation of four usually distinct sectors of psychopathology, their high overlap with other disorders, their ability to distinguish BPD from other disorders, their integration of heritability, and their clinical applicability. The aims of this review are to increase awareness of these theories, to stimulate improved theories, and to f ster testable hypotheses so that research can advance our knowledge about BPD's core.


Defensive Perimeter in the Central Nervous System: Predominance of Astrocytes and Astrogliosis during Recovery from Varicella-Zoster Virus Encephalitis.
Varicella-zoster virus (VZV) is a highly neurotropic virus that can cause infections in both the peripheral nervous system and the central nervous system. Several studies of VZV reactivation in the peripheral nervous system (herpes zoster) have been published, while exceedingly few investigations have been carried out in a human brain. Notably, there is no animal model for VZV infection of the central nervous system. In this report, we characterized the cellular environment in the temporal lobe of a human subject who recovered from focal VZV encephalitis. The approach included not only VZV DNA/RNA analyses but also a delineation of infected cell types (neurons, microglia, oligodendrocytes, and astrocytes). The average VZV genome copy number per cell was 5. Several VZV regulatory and structural gene transcripts and products were detected. When colocalization studies were performed to determine which cell types harbored the viral proteins, the majority of infected cells were astrocytes, including aggregates of astrocytes. Evidence of syncytium formation within the aggregates included the continuity of cytoplasm positive for the VZV glycoprotein H (gH) fusion-complex protein within a cellular profile with as many as 80 distinct nuclei. As with other causes of brain injury, these results suggested that astrocytes likely formed a defensive perimeter around foci of VZV infection (astrogliosis). Because of the rarity of brain samples from living humans with VZV encephalitis, we compared our VZV results with those found in a rat encephalitis model following infection with the closely related pseudorabies virus and observed similar perimeters of gliosis. Investigations of VZV-infected human brain from living immunocompetent human subjects are exceedingly rare. Therefore, much of our knowledge of VZV neuropathogenesis is gained from studies of VZV-infected brains obtained at autopsy from immunocompromised patients. These are not optimal samples with which to investigate a response by a human host to VZV infection. In this report, we examined both flash-frozen and paraffin-embedded formalin-fixed brain tissue of an otherwise healthy young male with focal VZV encephalitis, most likely acquired from VZV reactivation in the trigeminal ganglion. Of note, the cellular response to VZV infection mimicked the response to other causes of trauma to the brain, namely, an ingress of astrocytes and astrogliosis around an infectious focus. Many of the astrocytes themselves were infected; astrocytes aggregated in clusters. We postulate that astrogliosis represents a successful defense mechanism by an immunocompetent human host to eliminate VZV reactivation within neurons.


Male circumcision for HIV prevention: Awareness, risk compensation, and risk perceptions among South African women.
Medical male circumcision (MMC) is a proven method of HIV risk reduction for men in southern Africa. MMC promotion campaigns and scale-up programmes are widely implemented throughout the Republic of South Africa. However, the impact of promoting MMC on women's awareness, beliefs, and behaviours has been understudied. We conducted a self-administered anonymous survey of 279 women receiving health services in an impoverished township located in Cape Town, South Africa. Results showed that two in three women were unaware that male circumcision partially protects men from contracting HIV. Women who were aware of MMC for HIV prevention also endorsed beliefs that male circumcision reduces the need for men to worry about HIV and reduces the need for men to use condoms. Male circumcision awareness was also related to reduced perceptions of HIV risk among women. Multivariable models showed that women's MMC awareness, circumcision risk compensation beliefs, and risk perceptions were associated with decreased condom use and higher HIV risk index scores defined as number of condomless vaginal intercourse X number of sex partners. These results suggest a need for MMC education efforts tailored for women living in communities with high-HIV prevalence where men are targeted for MMC.


[New hypnotics ramelteon for the treatment of insomniacs with circadian rhythm disturbance].
Ramelteon is a new class of sleep agent that selectively binds to the melatonin type 1 (MT1) and type 2 (MT2) receptors in the suprachiasmatic nucleus (SCN), instead of binding to GABA-A receptors such as with traditional hypnotics benzodiazepines. Ramelteon exhibits not only acute sleep-promoting effect but also circadian phase-shifting effect via MT1 and MT2 receptors respectively, and has been revealed to contribute to the treatment of acute and chronic insomnia in patients with circadian rhythm sleep disorders(sleep-wake rhythm disorders) or with inappropriate timing of sleep habits. Optimal administration plan for insomniac patients to induce these characteristic sleep-modulating effects by ramelteon was discussed.


Induction spectrometry using an ultrafast hollow-cored toroidal-coil (HTC) detector.
Ultrafast photoelectron and photoion spectroscopy (as well as their combination known as "coincidence spectroscopy") utilizes detectors based on different electron multipliers such as microchannel plates or single-channel electron multipliers. These detectors have a few important limitations such as fast-signal distortion (low pass operation), mutually exclusive positive or negative mode, dead time, and requirement of trigger. A high-pass induction detector, based on a hollow-cored toroidal coil, was developed that overcomes the above-mentioned limitations. The frequency-dispersive response and linearity of different configurations were analyzed. It is shown that the response is enhanced for ultrafast electron signals, dependent on construction parameters, thus offering response flexibility by design. Kinetic energy distributions of pseudospark-induced electron pulses are characterized in order to validate the capabilities in real applications.


Pediatrician Ambiguity in Understanding Palliative Sedation at the End of Life.
Palliative sedation is a means of relieving intractable symptoms at the end of life, however, guidelines about its use lack consistency. In addition, ethical concerns persist around the practice. There are reports of palliative sedation in the pediatric literature, which highlight various institutional perspectives. This survey of 4786 pediatric providers sought to describe their knowledge of and current practices around pediatric palliative sedation. Our survey was administered to pediatricians who care for children at the end of life. The survey assessed agreement with a definition of palliative sedation, as well as thoughts about its alignment with aggressive symptom management. Bivariate analyses using χ2 and analysis of variance were calculated to determine the relationship between responses to closed-ended questions. Open-ended responses were thematically coded by the investigators and reviewed for agreement. Nearly half (48.6%) of the respondents indicated that the stated definition of palliative sedation "completely" reflected their own views. Respondents were split when asked if they viewed any difference between palliative sedation and aggressive symptom management: Yes (46%) versus No (54%). Open-ended responses revealed specifics about the nature of variation in interpretation. Responses point to ambiguity surrounding the concept of palliative sedation. Pediatricians were concerned with a decreased level of consciousness as the goal of palliative sedation. Respondents were split on whether they view palliative sedation as a distinct entity or as one broad continuum of care, equivalent to aggressive symptom management. Institutional-based policies are essential to clarify acceptable practice, enable open communication, and promote further research.


Unilateral pedal lymphangiography with non-contrast computerized tomography is valuable in the location and treatment decision of idiopathic chylothorax.
To identify the value of unilateral pedal lymphangiography (LAG) with non-contrast CT in the location and treatment decision of idiopathic chylothorax after failure of thoracic duct ligation. Twenty four patients aged 9-84 year old (median 44 yr) who had idiopathic chylothorax were involved, and unilateral pedal LAG with non-contrast CT was performed in every patient. All patients failed to previous right supra-diaphragmatic thoracic duct ligation. The amount of iodized oil used was 6-14 ml with no related complications. LAG demonstrated 8 patients with thoracic duct leaks and 10 patients with leaks elsewhere, but no visible chylous leak in 6 patients. Ligation of thoracic duct was performed as the primary treatment in all 8 cases as having thoracic duct leakage and cured 7(87.5%) patients. For 8 patients not having thoracic duct lesion under LAG, the successful rate of thoracic duct ligation was 25% (2 out of 8 patients), which was significantly lower than patients due to thoracic duct lesions (P=0.02). Meanwhile, non-operative therapy had significantly higher successful rate (87.5% vs 25%, P=0.02). Unilateral pedal LAG with non-contrast CT could identify the causes and locate the leaks of idiopathic chylothorax in 75% of patients after failure of thoracic duct ligation. Two thirds of patients were found not to have thoracic duct leakage and would be better managed by non-operative treatment.


Effect of plasma component transfusion on conventional coagulation screening tests.
Conventional coagulation screening tests such as Prothrombin time, International normalized ratio (INR) and activated partial thromboplastin time are often used to predict bleeding in various clinical situations. We aimed to observe the effect of Fresh-frozen plasma (FFP) on these parameters. Patients' demographics, pre- and post-transfusion coagulation parameters were noted to assess the level of correction. The magnitude of improvement in INR was determined using the formula given by Holland and Brooks. Data was analyzed using IBM SPSS Statistics 20. Among 2082 episodes, 4991 units of FFP were transfused at an average of 5 units per patient. Median dose of FFP administered per episode was 10 mL/kg (5.8-13.4). The mean change in INR following transfusion was 8.9% of the pre-transfusion INR and thus considered to be statistically significant. FFP transfusions as a prophylactic measure especially in patients with mildly deranged conventional coagulation screening tests without any empirical evidence of clinical bleeding needs further scrutiny. Reduction in INR following FFP transfusions was better in cohort having higher pre-transfusion INR value (> 3.0).


How to unveil chronic respiratory diseases in clinical practice? A model of alliance between general practitioners and pulmonologists.
Asthma and COPD are under-diagnosed and undertreated in adult populations, mainly due to the discrepancy between guideline recommendations and clinicians' practices. One of the reasons of this discrepancy is the difficulty encountered in real life in sharing the management of chronic respiratory diseases between general practitioners (GPs) and respiratory physicians. An explorative, population-based investigation was performed to test whether, and to what extent, an active collaboration between GPs and pulmonologists increases the diagnosis and proper treatment of chronic obstructive airway diseases. The "COPD action" involved an in-house intervention by pulmonologists who trained GPs on how to diagnose the disease and interpret the spirometry, yielding a final agreed diagnosis. A total of 210 subjects (M/F: 156/54; age: 62.5 ± 13.8, mean ± SD) were consecutively invited by 20 GPs and classified in a) healthy, b) symptomatic with no airway obstruction, and 3) affected by chronic respiratory diseases. 11% of previously defined "healthy" subjects were diagnosed with COPD, and symptomatic subjects were diagnosed with asthma (20%) or COPD (23%). In addition, in those who already carried a diagnosis of chronic respiratory diseases as judged by GPs, the diagnosis of COPD decreased significantly after respiratory specialist intervention (p = 0.001), in favor of asthma and chronic bronchitis. Furthermore, following the clinical and lung function assessments performed by the respiratory physicians, changes in inhaled treatments were statistically significant for each therapeutic category (test-retest reliability: r = 0.42; p < 0.001). In conclusion, the collaboration between GPs and pulmonologists based on a pro-active approach to the individuals attending the primary care offices followed by an in-house intervention by specialists may largely improve the diagnosis and management of chronic respiratory diseases.


[Leigh syndrome due to mitochondrial respiratory chain complex II deficiency].
Mitochondrial respiratory chain complex II deficiency is a rare documented cause of mitochondrial diseases. This study reported a case of Leigh syndrome due to isolated complex II deficiency. A boy presented with progressive weakness, motor regression and dysphagia after fever from the age of 8 months and hospitalized at the age of 10 months. Elevated blood levels of lactate and pyruvate were observed. Brain magnetic resonance image showed symmetrical lesions in the basal ganglia. Mitochondrial respiratory chain complex I-V activities in peripheral leukocytes were measured using spectrophotometric assay. Mitochondrial gene screening of common point mutations was performed. The complex II activity in the peripheral leukocytes decreased to 21.9 nmol/min per mg mitochondrial protein (control: 47.3±5.3 nmol/min per mg mitochondrial protein). The ratio of complex II activity to citrate synthase activity (22.1%) also decreased (control: 50.9%±10.7 %). No point mutation was found in mitochondrial DNA. The boy was diagnosed as Leigh syndrome due to isolated complex II deficiency. Psychomotor improvements were observed after the treatment. The patient is 22 months old and in a stable condition.


[Contribution of ultrasonography to the diagnosis of non-hormonal acquired clitoromegalia: a case report].
We report the case of a 30-year-old woman, consulting for a painful clitoromegaly which developed progressively and rapidly. The gyneco-endocrinological assessment ruled out hyperandrogenism. Ultrasound examination of the clitoris revealed the presence of a clitoral cyst. Acquired clitoromegaly is a symptom which occurs in severe hyperandrogenism. Other organic etiologies include clitoral cysts of various nature and solid tumors. An ultrasonographic examination should be included in the diagnostic work-up for acquired clitoromegaly.


Proposal of a Decision-Making Model for the Provisional Restoration Alternatives in Single-Tooth Implant Treatment.
Background The decision-making of the most appropriate provisional restoration option in single-tooth implant practice is complex under multi-criteria conditions. The aim of our study is to conduct a case study on the determination of the appropriate provisional treatment option to be used in a single-tooth dental implant interim period after placement with the help of an entropy-based additive ratio assessment. Methodology Eight important criteria for fulfilling this purpose have been extracted from the literature search: "esthetic potential," "patient comfort," "treatment time," "laboratory cost," "occlusal clearance," "ease of removal," "durability," and "ease of modification." Provisional treatment alternatives are "removable partial denture," "vacuum-formed appliances," "bonded extracted tooth or denture," "metal or fiber-reinforced resin-bonded fixed partial denture," "wire-retained resin-bonded fixed partial denture," "acrylic resin provisional fixed partial denture," and "implant-supported fixed provisional restoration." It has been examined which of these alternatives is most appropriate in terms of both reported specifications and artificially generated dominance scenarios. The scenarios employed are S0 (criteria are equal-weighted), S1 (the criterion is tri-fold dominant), and S2 (the criterion is two-fold dominant). Results "Patient comfort" was the most important criterion (wj = 0.19). The remaining criteria were ranked as "modifications," "treatment time," "durability," "esthetic potential," "laboratory cost," "occlusal clearance," and "ease of removal." The "implant-supported fixed provisional restoration" treatment option had the maximum degree of utility in the S0 (Ki = 0.782) and S2 (Ki = 0.80) categories. If "treatment time" or "occlusal clearance" is the dominant variable, "vacuum-formed appliances" had the highest degree of utility (Ki = 0.69) in S1. Conclusions According to the rankings and scenarios created utilizing entropy-based additive ratio assessment methods, the "implant-supported fixed provisional restoration" is the appropriate provisional option for a single-tooth implant treatment. If "treatment time" or "occlusal clearance" is an absolute criterion, the "vacuum-formed provisional appliance" will replace the appropriate option.


Current nutrition management of infants with chronic lung disease.
Preterm infants with lung disease present nutrition challenges to health care providers. Malnutrition is common, develops shortly after birth, and may continue into early childhood. Although there are many studies identifying the nutrient deficiencies in infants with chronic lung disease, few randomized trials have explored the effects of nutrition support on the prevention and treatment of chronic lung disease. The purpose of this article is to review current practices and ongoing controversies in the nutrition management of infants with chronic lung disease.


Histological evaluation of repair of the rotator cuff in a primate model.
The establishment of a suitable animal model of repair of the rotator cuff is difficult since the presence of a true rotator cuff anatomically appears to be restricted almost exclusively to advanced primates. Our observational study describes the healing process after repair of the cuff in a primate model. Lesions were prepared and repaired in eight 'middle-aged' baboons. Two each were killed at four, eight, 12 and 15 weeks post-operatively. The bone-tendon repair zones were assessed macroscopically and histologically. Healing of the baboon supraspinatus involved a sequence of stages resulting in the reestablishment of the bone-tendon junction. It was not uniform and occurred more rapidly at the sites of suture fixation than between them. Four weeks after repair the bone-tendon healing was immature. Whereas macroscopically the repair appeared to be healed at eight weeks, the Sharpey fibres holding the repair together did not appear in any considerable number before 12 weeks. By 15 weeks, the bone-tendon junction was almost, but not quite mature. Our results support the use of a post-operative rehabilitation programme in man which protects the surgical repair for at least 12 to 15 weeks in order to allow maturation of tendon-to-bone healing.


Rhabdomyosarcoma in Adults: Case Series and Literature Review.
Rhabdomyosarcoma, a common soft tissue malignant tumor in children and adolescents, is exceedingly rare in adults. Nevertheless, The outcome in adults is very poor, especially when compared to outcomes in children in whom significant improvements in treatment has been achieved. The first case was of a 24-year-old pregnant Chinese woman with a rare primary site of rhabdomyosarcoma in the perineal body. She presented with a perineal mass and was diagnosed during the second trimester of pregnancy, which is a very rare occurrence. The second case was a 70-year-old Chinese woman who suffered from right lower abdominal pain for 1 month and was misdiagnosed with an epithelial ovarian carcinoma. Mesenteric pleomorphic rhabdomyosarcoma was later confirmed by postoperative pathology. Both cases had undergone preoperative examination with chest and abdominal computed tomography (CT) and pelvic magnetic resonance imaging (MRI) examinations, as well as examination of complete blood count, liver panel, renal panel, and serum tumor markers. Diagnosis was based on histopathology and immunohistochemistry. The patient in the first case received chemotherapy after which the mass decreased in size; however, the patient was lost to follow-up. The second case underwent tumor resection and received chemotherapy and radiotherapy.


Evaluation of the toric implantable collamer lens for simultaneous treatment of myopia and astigmatism.
Myopic astigmatism is a prevalent condition that can be treated with spectacles, contact lenses, or laser refractive surgery. However, these treatment options have functional limitations at higher levels of refractive error. The toric implantable collamer lens is designed to treat a broad range of refractive error, generally up to -18 diopters with +1 to +6 diopters of astigmatism. Approval for a more limited treatment range of up to 15 diopters of myopia with +1 to +4 diopters of astigmatism is being sought in the US, where this device has not yet received marketing approval. Surgical correction of high-myopic astigmatism can be life-altering and allow people to participate in activities that were not previously feasible because of visual limitations. The toric implantable collamer lens is implanted behind the iris and in front of the natural crystalline lens. With earlier lens designs, it was necessary to create an iridectomy or iridotomy to prevent pupillary block. The newest toric implantable collamer lens model has a small central hole that is not visually noticeable. This eliminates the need to create a hole in the iris, thereby enhancing the safety of the procedure.


Geometric H/D isotope effects and cooperativity of the hydrogen bonds in porphycene.
We investigate the primary, secondary, and vicinal hydrogen/deuterium (H/D) isotope effects on the geometry of the two intramolecular hydrogen bonds in porphycene. Multidimensional potential energy surfaces describing the anharmonic motion in the vicinity of the trans isomer are calculated for the different symmetric (HH/DD) and asymmetric (HD) isotopomers. From the solution of the nuclear Schrödinger equation the ground-state wavefunction is obtained, which is further used to determine the quantum corrections to the classical equilibrium geometries of the hydrogen bonds and thus the geometric isotope effects. In particular, it is found that the hydrogen bonds are cooperative, that is, both expand simultaneously even in the case of an asymmetric isotopic substitution. The theoretical predictions compare favorably with NMR chemical-shift data.


NGF controls axonal receptivity to myelination by Schwann cells or oligodendrocytes.
Axons dictate whether or not they will become myelinated in both the central and peripheral nervous systems by providing signals that direct the development of myelinating glia. Here we identify the neurotrophin nerve growth factor (NGF) as a potent regulator of the axonal signals that control myelination of TrkA-expressing dorsal root ganglion neurons (DRGs). Unexpectedly, these NGF-regulated axonal signals have opposite effects on peripheral and central myelination, promoting myelination by Schwann cells but reducing myelination by oligodendrocytes. These findings indicate a novel role for growth factors in regulating the receptivity of axons to myelination and reveal that different axonal signals control central and peripheral myelination.


TRIENNIAL GROWTH AND DEVELOPMENT SYMPOSIUM: Molecular mechanisms related to bovine intramuscular fat deposition in the longissimus muscle.
The intramuscular fat (IMF) content of the LM, also known as marbling, is particularly important in determining the price of beef in Korea, Japan, and the United States. Deposition of IMF is influenced by both genetic (e.g., breed, gender, and genotype) and nongenetic factors (e.g., castration, nutrition, stressors, animal weight, and age). Castration of bulls markedly increases deposition of IMF, resulting in improved beef quality. Here, we present a comparative gene expression approach between bulls and steers. Transcriptomic and proteomic studies have demonstrated that the combined effects of increases in lipogenesis, fatty acid uptake, and fatty acid esterification and decreased lipolysis are associated with increased IMF deposition in the LM. Several peripheral tissues (LM, adipose tissues, and the liver) are involved in lipid metabolism. Therefore, understanding the significance of the tissue network in lipid metabolism is important. Here, we demonstrate that lipid metabolism in LM tissues is crucial for IMF deposition, whereas lipid metabolism in the liver plays only a minor role. Metabolism of body fat and IMF deposition in bovine species has similarities with these processes in metabolic diseases, such as obesity in humans and rodents. Extensive studies on metabolic diseases using epigenome modification (DNA methylation, histone modification, and microRNA), microbial metagenomics, and metabolomics have been performed in humans and rodents, and new findings have been reported using these technologies. The importance of applying "omics" fields (epigenomics, metagenomics, and metabolomics) to the study of IMF deposition in cattle is described. New information on the molecular mechanisms of IMF deposition may be used to design nutritional or genetic methods to manipulate IMF deposition and to modify fatty acid composition in beef cattle. Applying nutrigenomics could maximize the expression of genetic potential of economically important traits (e.g., marbling) in animals.


Distribution, hosts, 16S rDNA sequences and phylogenetic position of the Neotropical tick Amblyomma parvum (Acari: Ixodidae).
The hosts, distribution, intraspecific genetic variation and phylogenetic position of Amblyomma parvum (Acari: Ixodidae) have recently been re-assessed. Data on this tick's hosts and distribution were obtained not only from existing literature but also from unpublished records. Sequences of the ticks' mitochondrial 16S ribosomal DNA (rDNA) were used to evaluate genetic variation among specimens of A. parvum from different localities in Argentina and Brazil, and to explore the phylogenetic relationships between this tick and other Amblyomma species. Although several species of domestic and wild mammal act as hosts for adult A. parvum, most collected adults of this species have come from cattle and goats. Caviid rodents of the subfamily Caviinae appear to be the hosts for the immature stages. So far, A. parvum has been detected in 12 Neotropical biogeographical provinces (Chaco, Cerrado, Eastern Central America, Venezuelan Coast, Pantanal, Parana Forest, Caatinga, Chiapas, Venezuelan Llanos, Monte, Western Panamanian Isthmus, and Roraima) but the Chaco province has provided significantly more specimens than any other (P<0.0001). The 16S rDNA sequences showed just 0.0%-1.1% divergence among the Argentinean A. parvum investigated and no more than 0.2% divergence among the Brazilian specimens. The observed divergence between the Argentinean and Brazilian specimens was, however, greater (3.0%-3.7%). Although there is now molecular and morphological evidence to indicate that A. parvum, A. pseudoparvum, A. auricularium and A. pseudoconcolor are members of a natural group, previous subgeneric classifications do not reflect this grouping. The subgeneric status of these tick species therefore needs to be re-evaluated. The 16S-rDNA-based evaluation of divergence indicates that the gene flow between Argentinean and Brazilian 'A. parvum' is very limited and that the Argentinean 'A. parvum' may be a different species to the Brazilian.


Investigations on possible resistance in Aedes vexans field populations after a 10-year application of Bacillus thuringiensis israelensis.
In the Upper Rhine Valley (Germany), Bacillus thuringiensis var. israelensis has been widely used against floodwater mosquitoes over an area of approximately 500 km2 for more than 10 years. The susceptibility of larvae of Aedes vexans field populations in 3 untreated (Lake Constance) and 3 treated areas (Upper Rhine Valley) was assessed by means of bioassays with B.t.i. (Bactimos WP, 6,000 AAU/mg), following WHO guidelines. Log-probit analyses and statistical evaluations of the data showed that the LC50 values as well as slopes of bioassays of the larvae deriving from the different areas showed no significant differences. Two populations in the treated area were even more susceptible than populations from the untreated areas. These results have been confirmed by resistance ratios, which were less than one in all tests carried out.


Maintaining Community-engaged Research with Young People in A Virtual setting.
Partnering with young people to conduct research is fundamental to community mobilization. Recent restrictions on in-person interactions and engagement presented limitations for continued partnership with young people. To present a practical strategy and lessons learned to facilitate community-engaged research with youth in a virtual setting. Based on youth engagement tenets, the TEAM (tailor the compensation package, ensure meetings are accessible, accommodate personal needs, and maintain the structure of in-person meetings) strategy was used to adapt the partnership to a virtual setting. Three lessons are discussed 1) the importance of maintaining social connectedness, 2) maximizing flexibility, and 3) focusing on creativity and competency building. The COVID pandemic forced researchers to rethink previous engagement practices that relied heavily on in-person interactions to be sustainable. The TEAM strategy is one way to successfully adapt practices and engage young people in virtual settings.


Incidence of thrombosis after gynecologic surgery evaluated by an improved 125I-fibrinogen uptake test.
Two hundred and seventy-six women over 50 years of age who had gynecologic surgery were followed postoperatively with the 125I-fibrinogen uptake test (125I-FUT) to detect deep venous thrombosis (DVT). By using a newly devised technique based on conventional 125I-FUT, the exact depth of thrombi could be determined. The correlation between the results with our new technique and those from phlebography was almost 100%. Forty-seven (17%) of the women developed DVT postoperatively, 60% of them occurring in the calf muscle veins. Patients subjected to abdominal hysterectomies for malignant diseases had the highest incidence of DVT (36%), whereas those operated on for benign diseases with the same technique had the lowest (11%). Patients operated on for uterine prolapse had an intermediate DVT frequency of 15% but advanced age and estrogens given preoperatively increased the frequency. Neither the type of anesthesia (epidural or general), nor the duration of the operation, significantly influence the incidence of DVT in this study.


Exercise and small intestinal transit.
The transit of 99Tcm-labelled particles through the small intestine has been monitored in nine healthy subjects undergoing three levels of exercise. The mean +/- 1S.D. small intestine transit times under conditions of minimal, moderate and strenuous activity were 4.5 +/- 1.7 h, 5.4 +/- 2.5 h and 4.1 +/- 1.8 h, respectively. These findings indicate that the bioavailability of drugs from controlled release preparations passing through the small intestine is unlikely to be affected by variations in normal daily activity.


Imaging diagnosis of lumbar foraminal stenosis in the fifth lumbar nerve root: reliability and reproducibility of T1-weighted three-dimensional lumbar MRI.
Various magnetic resonance imaging (MRI) techniques have been reported in detection of lumbar foraminal stenosis (LFS), especially for T2-weighted three-dimensional MRI (3D-MRI) describing the shape of nerve roots. The detection of LFS in the fifth lumbar nerve root (L5 root), however, is still less reliable compared to other lumbar nerve roots. Then we have been using T1-weighted 3D-MRI aiming to depict the shape of, and also pathology affecting the L5 root. The aim of this study is to evaluate our T1-weighted 3D-MRI in diagnosing LFS of the L5 root. This retrospective study included 24 patients with intracanal stenosis (ICS) at L4-5, and 30 patients with LFS at L5-S causing unilateral L5 root lesion. The pre-operative T1-weighted 3D-MRI aiming bilateral L5 nerve roots of each patient were blinded and reviewed twice by five spine surgeons, independently. The image evaluation was performed in two conditions: (I) the symptomatic side was judged in 30 patients of LFS patients, and (II) the symptomatic side or the absence of LFS was judged in images of all the 54 patients including LFS and ICS patients. The correct-answer-rate, sensitivity and specificity of the imaging study were calculated. Also, the intra- and interobserver agreement of the imaging study by five spine surgeons were evaluated by the kappa (κ) statistics. For conditions (I) and (II) above, the mean correct-answer-rate was 92.3% and 69.8%, respectively. The sensitivity and specificity of the imaging study was 72.6% and 66.3%, respectively. The average of intraobserver κ-value of five examiners was 0.874 and 0.708, and the average of interobserver κ-value was 0.837 and 0.578, respectively. As well as previously reported T2-weighted 3D-MRI, our T1-weighted 3D-MRI was found to be reliable in diagnosing LFS of the L5 root.


Tribal benefits counseling program: expanding health care opportunities for tribal members.
American Indian tribal clinics hired benefits counselors to increase the number of patients with public and private insurance coverage, expand the range of health care options available to tribal members, and increase third-party revenues for tribal clinics. Benefits counselors received intensive training, technical assistance, and evaluation over a 2-year period. Six tribal clinics participated in the full training program, including follow-up, process evaluation, and outcomes reporting. Participating tribal sites experienced a 78% increase in Medicaid enrollment among pregnant women and children, compared with a 26% enrollment increase statewide during the same period. Trained benefits counselors on-site at tribal clinics can substantially increase third-party insurance coverage among patients.


Determinants of serum ALT normalization after phlebotomy in patients with chronic hepatitis C infection.
Phlebotomy is performed to reduce excessive iron accumulation in hepatic tissue. We studied serum alanine aminotransferase (ALT) normalization rates and 50% reduction in initial serum ALT (ALT(50%) reduction rate) in patients with hepatitis C viral (HCV) infection and investigated the factors that influenced the response to phlebotomy therapy. We evaluated 23 consecutive patients with HCV infection who underwent phlebotomy. Phlebotomy was performed a few times per week, then a few times per month, and 200-400 ml of blood was removed at each session, depending on the clinical response. During the course of therapy, hemoglobin (Hb), serum ALT, and ferritin levels were assessed monthly. In patients with Hb of less than 11 g/dl, the ALT(50%) reduction rate was 87.5%. In patients with a serum ferritin level of less than 10 g/dl the ALT(50%) reduction rate was 83.3%. In patients with Hb of less than 11 g/dl, the ALT normalization rate was 50%, and in those with a serum ferritin level of less than 10 g/dl, the ALT normalization rate was 41.7%. Multivariate analysis identified ALT less than 100 IU/l at the start of phlebotomy as an independent factor associated with ALT normalization. Of the 7 patients who showed no response to phlebotomy, 85.7% were obese (body mass index > or =25 kg/m(2)), and 40% showed more than 30% steatosis on liver histology. The cumulative ALT normalization rate in relation to the total volume of blood loss was 43.9% with a blood less or more than 3 l, and thus was optimal above 3 l. Although the sample number was relatively small, the results of our study suggest that phlebotomy is effective therapy for HCV patients who are nonobese, show little or no steatosis on liver histology, and have a baseline serum ALT level of less than 100 IU/l.


Analytical-physical profile of the novel macrolide antibiotic flurithromycin ethylsuccinate.
Data are reported on the structural characterization of flurithromycin ethylsuccinate (FE, CAS 82730-23-2), a novel macrolide antibiotic. UV, IR, NMR and MS spectra confirmed the structure; in particular the presence of ketonic-hemiketalic equilibrium, already described for flurithromycin A, is supported by NMR and HPLC studies. Moreover physico-chemical properties and stability were studied; the product exhibits a good stability at solid state, whereas degradation products are present both in acidic and basic solution. Microbiological activity and principal pharmaceutical features were carried out.


Assessment of prognostic factors in breast fine-needle aspirates.
Because of the enhanced effects of new chemotherapeutic agents on the survival of patients with breast cancer, there has been increased interest in the use of prognostic factors. In the last several years, the literature has been saturated with new information about the prognostic/predictive value of traditional factors as well as the newly recognized biomarkers. Controversy, however, remains about the validity of each of the factors as independent prognostic indicators. The standard prognostic factors, recognized by the National Cancer Institute in 1990, include lymph node status, tumor size, nuclear grade, steroid receptor content, tumor type, and cellular proliferation rate. It is also recommended that for patients who undergo preoperative chemotherapy or radiotherapy, breast fine-needle aspirates can be used to provide prognostic information. This article is designed to discuss the traditional and also the newly recognized factors, such as DNA ploidy and proliferation rate, HER-2/neu oncogene, and tumor suppressor gene p53, in breast fine-needle aspirates and their clinical application in breast cancer management. An overview of the proposed guidelines developed by the National Cancer Institute is also presented.


The spectrum of Escherichia coli--Bacteroides fragilis pathogenic synergy in an intraabdominal infection model.
Pathogenic synergy between Escherichia coli and Bacteroides fragilis was investigated in an intraabdominal infection model. Defined inocula of E. coli and B. fragilis, alone or in combination, were enmeshed within a fibrin clot and surgically implanted into the peritoneal cavity of rats. A spectrum of bacterial synergy ranging from synergistic abscess formation to synergistic lethality was demonstrated using this model. The type of synergy exhibited was dependent upon the initial E. coli inoculum. When combined with B. fragilis, high inocula of E. coli (greater than 10(8) cfu/clot) produced synergistic lethality while low inocula (2 x 10(2) to 2 x 10(7) cfu/clot) resulted in synergistic abscess formation. With respect to abscess formation, there was reciprocal synergy between E. coli and B. fragilis. Abscesses resulting from mixed inocula were larger and had significantly higher numbers of E. coli and B. fragilis than abscesses initiated by monomicrobial inocula. These studies define a clinically relevant model of bacterial interactions in the setting of intraabdominal infection and suggest that conclusions drawn from experimental models of bacterial synergy should consider the type of model examined, the strains of bacteria studied, and the number of bacteria inoculated.


The bidirectional longitudinal association between depressive symptoms and HbA1c : A systematic review and meta-analysis.
To investigate whether there is a bidirectional longitudinal association of depression with HbA1c . We conducted a systematic literature search in PubMed, PsycINFO, CINAHL and EMBASE for observational, longitudinal studies published from January 2000 to September 2020, assessing the association between depression and HbA1c in adults. We assessed study quality with the Newcastle-Ottawa-Scale. Pooled effect estimates were reported as partial correlation coefficients (rp ) or odds ratios (OR). We retrieved 1642 studies; 26 studies were included in the systematic review and eleven in the meta-analysis. Most studies (16/26) focused on type 2 diabetes. Study quality was rated as good (n = 19), fair (n = 2) and poor (n = 5). Of the meta-analysed studies, six investigated the longitudinal association between self-reported depressive symptoms and HbA1c and five the reverse longitudinal association, with a combined sample size of n = 48,793 and a mean follow-up of 2 years. Higher levels of baseline depressive symptoms were associated with subsequent higher levels of HbA1c (partial r = 0.07; [95% CI 0.03, 0.12]; I2 38%). Higher baseline HbA1c values were also associated with 18% increased risk of (probable) depression (OR = 1.18; [95% CI 1.12,1.25]; I2 0.0%). Our findings support a bidirectional longitudinal association between depressive symptoms and HbA1c . However, the observed effect sizes were small and future research in large-scale longitudinal studies is needed to confirm this association. Future studies should investigate the role of type of diabetes and depression, diabetes distress and diabetes self-management behaviours. Our results may have clinical implications, as depressive symptoms and HbA1c levels could be targeted concurrently in the prevention and treatment of diabetes and depression. PROSPERO ID CRD42019147551.


Duplex Doppler ultrasound in the diagnosis of cavernous transformation of the portal vein.
Duplex Doppler ultrasound scans were performed in 10 patients with proven cavernous transformation of the portal vein. All cases exhibited absence of the normal portal vein lumen with replacement by numerous tortuous vessels. Doppler studies revealed a characteristic "flat" waveform with a reduction in the time averaged velocity to less than 8 cm/s which is well below the normal range. The combination of real-time and Doppler ultrasound enabled an accurate diagnosis to be made in all cases.