Patient dissatisfaction in a paediatric accident and emergency department.
This paper presents a review of the patient complaints and those who walked out prior to receiving care in the Accident and Emergency (A&E) Department of the Children's Hospital, Camperdown. The walkout rate was 1.7% (424/27,082) in 1992. Walkouts were greatest in winter when the department was busiest, peak period being between 2000 and 0200 hours. The waiting time was presented as the main reason for walking out. Most parents were prepared to wait the advertised waiting time before leaving. The presenting complaints of children who were not seen covered a spectrum of illnesses with the potential for significant morbidity. The majority, however, were triaged as non-urgent cases. Despite attempts to follow up on walkouts, the outcome for 53% of patients was unknown. Written complaints were fewer in number and tended to focus more on the quality of care (66.6%). There were few recorded compliments. With the increasing customer focus on health, greater attention needs to be given to system failures.


The 3D structure of the binding pocket of the human oxytocin receptor for benzoxazine antagonists, determined by molecular docking, scoring functions and 3D-QSAR methods.
Molecular docking and 3D-QSAR studies were performed to determine the binding mode for a series of benzoxazine oxytocin antagonists taken from the literature. Structural hypotheses were generated by docking the most active molecule to the rigid receptor by means of AutoDock 3.05. The cluster analysis yielded seven possible binding conformations. These structures were refined by using constrained simulated annealing, and the further ligands were aligned in the refined receptor by molecular docking. A good correlation was found between the estimated deltaG(bind) and the pKi values for complex F. The Connolly-surface analysis, CoMFA and CoMSIA models q2(CoMFA) = 0.653, q2(CoMSA) = 0.630 and r2(pred,CoMFA) = 0.852 , r2(pred,CoMSIA) = 0.815) confirmed the scoring function results. The structural features of the receptor-ligand complex and the CoMFA and CoMSIA fields are in closely connected. These results suggest that receptor-ligand complex F is the most likely binding hypothesis for the studied benzoxazine analogs.


Into the deep. Vandewater may buy Alabama not-for-profits.
After a few years of lying low since resigning from Columbia/HCA amid a massive federal fraud probe, former President and COO David Vandewater is back in the thick of things with a new company and a deal to purchase not-for-profit hospitals.


Abnormal elevation of resting pressure at the upper esophageal sphincter of Parkinson's disease patients.
We investigated the oral and pharyngeal swallowing function in seven Parkinson's disease (PD) patients, using videomanofluorometry, which is videofluorographic and manometric evaluation conducted simultaneously. Abnormal elevations of resting pressure were found at the upper esophageal sphincter (UES) in three of the seven cases, when they were asked to hold a bolus in the mouth and initiate swallowing. One of these three cases showed an abnormal elevation of resting pressure, intermingled with a normal pressure pattern. Since the UES showed complete relaxation in these three cases, it is inappropriate to suppose that irreversible pathophysiological changes at the level of peripheral nerves had occurred. Our results suggested that altered resting pressure resulted from dysfunction at a more central level, such as a lack of dopaminergic stimulation at the supramedullary level causing skeletal muscle rigidity. Since a tonic abnormality of the UES cannot be measured by only videofluorography, both videofluorographic and manometric evaluation will be necessary to assess the pharyngeal phase of swallowing in PD patients.


Mass spectrometric approaches for the identification and quantification of reactive carbonyl species protein adducts.
Our current knowledge of the occurrence of proteins covalently modified by reactive carbonyl species (RCS) generated by lipid peroxidation indicates their involvement as pathogenic factors associated with several chronic degenerative diseases. Proteomics and mass spectrometry (MS) in the last decade have played a fundamental role in this context, allowing the demonstration of the formation of RCS-protein adducts in vitro and in vivo under different experimental conditions. In conjunction with functional and computational studies, MS has been widely applied in vitro to study the stoichiometry of the protein-RCS adduct formation, and, by identifying the site(s) of modification, to elucidate the molecular mechanisms of protein carbonylation and the physiologic impact of such modification on protein function. This review will provide an update of the MS methods commonly used in detecting and characterizing protein modification by RCS generated by lipid peroxidation, among which 4-hydroxy-trans-2-nonenal and acrolein represent the most studied and cytotoxic compounds. Research in this field, employing state-of-the-art MS, is rapidly and continuously evolving, owing also to the development of suitable derivatization and enrichment procedures enabling the improve MS detectability of RCS-protein adducts in complex biological matrices. By considering the emerging role of RCS in several human diseases, unequivocal analytical approaches by MS are needed to provide levels of intermediate diagnostic biomarkers for human diseases. This review focuses also on the different MS-based approaches so far developed for RCS-protein adduct quantification. This article is part of a Special Issue entitled: Posttranslational Protein modifications in biology and Medicine.


A supramolecular five-component relay switch that exposes the mechanistic competition of dissociative versus associative binding to cucurbiturils by ratiometric fluorescence monitoring.
A putrescine derivative of aminomethyladamantane is established as a ditopic guest with two mutually exclusive binding sites for cucurbit[6]uril and cucurbit[7]uril. A mixture containing both hosts, the ditopic guest, and two fluorescent dyes affords a relay system with a ratiometric fluorescence response and enables a kinetic analysis of the switching mechanism.


[Language acquisition in cleft lip-palate (CLP) children. 2. Linguistic diagnosis and therapeutic approaches].
The major tests and methods used in language acquisition diagnosis in CLP children of 3 months to 6 years of age are described. Apart from methods for phonetic analysis, such as spectrography, emphasis is being placed on the assessment of listening by hearing and of semantic and meta-linguistic acquisition. Additional information is obtained on the motoric, cognitive and social development (for detecting any possible multiple handicaps in these areas). In this context the major problems covered in cleft palate parent groups are also pointed out. Finally, the speech therapy provided for preschool children with severe speech problems (as compared with the control group) is outlined.


Effectiveness of an intervention to reduce stigma towards people with a mental disorder diagnosis in university students of healthcare careers.
Students in healthcare careers present stigma towards people with psychiatric diagnoses, so the development of interventions to reduce it is essential. This study aimed to evaluate the effectiveness of an intervention to reduce stigma towards people diagnosed with mental disorders in healthcare students in Chile. A randomized clinical trial with a before and after measurement was carried out. The intervention was part of a compulsory course and combined educational and contact strategies. A total of 244 fourth-semester students of medicine, nursing, dentistry, obstetrics, psychology, and social work participated. The intervention was effective in reducing stigmatizing attitudes and the desire for social distance. For almost all variables, the magnitude of the stigma reduction depended on the initial level of stigma, not on the profession. The intervention had positive effects on all careers. In conclusion, incorporating a stigma reduction intervention into mandatory professional training, with the active participation of the teacher in charge and experts by experience, can be a valuable tool to promote humanized and non-stigmatizing treatment.


Mechanism of metolachlor action due to alterations in cell cycle progression.
Metolachlor, a commonly used herbicide in the Midwestern USA, functions by inhibiting chlorophyll and protein synthesis in target plants. Herbicide exposure has led to detrimental effects in several organisms, affecting their growth and behavior; however, its mechanism of action in nontarget organisms is not yet clear. The EPA does not currently have enforceable regulations for maximal limits allowed in drinking water. Previous growth studies from our lab have demonstrated that increasing metolachlor concentrations and increasing time of exposure results in decreased growth of liver cells. The objective of this study was to elucidate a mechanism for this decrease of HepG2 cell growth after herbicide exposure. Results show that metolachlor at environmentally relevant levels (50-100 ppb) that previously led to decreased cell number does not lead to cell death by either necrosis or apoptosis. However, it was demonstrated that the levels of the retinoblastoma protein including two of its hyperphosphorylated forms are decreased in metolachlor exposed cells possibly leading to cell cycle arrest. The levels of another protein involved in cell cycle progression, p53, a mediator in the DNA damage response of cells, was not significantly altered except at the highest level of metolachlor (1,000 ppb) and after a 72-h exposure. These results suggest that the decrease in cell number after low-level metolachlor exposure is most likely due to an alteration in the cell cycle and not due to cell death in human liver cells.


The Future of Biomarkers.
Numerous compounds have been tested as potential biomarkers for multiple possible applications within intensive care medicine but none is or will ever be sufficiently specific or sensitive for the heterogeneous syndromes of critical illness. New technology and access to huge patient databases are providing new biomarker options and the focus is shifting to combinations of several or multiple biomarkers rather than the single markers that research has concentrated on in the past. Biomarkers will increasingly be used as part of routine clinical practice in the future, complementing clinical examination and physician expertise to provide accurate disease diagnosis, prediction of complications, personalized treatment guidance, and prognosis.


Incidence and risk factors associated with human albumin administration following total joint arthroplasty: a multicenter retrospective study.
Enhanced recovery after surgery (ERAS) program advocates implementation of perioperative goal-directed fluid therapy and reduced application of colloidal fluids. It should be used reasonably selectively in high-risk patients despite the clear efficacy of human albumin (HA). Therefore, it is vital to identify the risk factors for the use of HA. This study aims to determine the incidence and risk factors of HA administration in patients undergoing total hip or knee arthroplasty (THA, TKA). We identified patients undergoing THA or TKA in multiple institutions from 2014 to 2016 and collected patient demographics and perioperative variables. The criterion of HA administration was defined as a postoperative albumin level < 32 g/L or 32 to 35 g/L for at-risk patients. We compared 14 variables between patients who received HA administration and those who did not after stratification by the preoperative albumin (pre-ALB) level. Multivariable regressions identified the independent risk factors associated with HA administration. In total, 958 (20.3%) of 4713 patients undergoing THA and 410 (9.7%) of 4248 patients undergoing TKA received HA administration. In addition to pre-ALB < 35 g/L, preoperative anemia (odds ratio [OR] 2.12, P = 0.001; OR 1.39, P < 0.001) and drain use (OR 3.33, P = 0.001; OR 4.25, P < 0.001) were also independent risk factors for HA administration after THA regardless pre-ALB < 35 g/L or not, and patients undergoing TKA diagnosed of rheumatoid arthritis or ankylosing spondylitis tended to receive HA administration regardless pre-ALB < 35 g/L or not (OR 3.67, P = 0.002; OR 2.06, P < 0.001). The incidence of HA administration was high in patients undergoing THA or TKA, and several variables were risk factors for HA administration. This finding may aid surgeons in preoperatively identifying patients requiring HA administration and optimizing perioperative managements.


Adjuvant Treatment with Oral Dydrogesterone in the Prevention of Preterm Labor: A Randomized, Double-Blinded, Placebo-Controlled Trial.
We conducted a double-blind, randomized, placebo-controlled clinical trial to evaluate the efficacy of oral dydrogesterone (DG) on maternal and neonatal consequences in the treatment of preterm labor. We included 100 nulliparous mothers (24-34 weeks) with normal pregnancy who had preterm labor pain. Participants who received magnesium sulfate were randomly assigned to the investigation group (DG 30 mg/day) or placebo group. Maternal and neonatal outcomes were compared between the two groups. Recurrent uterine contraction (UC) rates (92% vs. 88%, P = 0.862) and the incidence of preterm delivery (66% vs. 58%, P = 0.834) were not different in the DG and placebo groups. No significant differences were observed in terms of gestational age at delivery (33.5 ± 3.5 vs. 34.2 ± 3.2, P = 0.281), latency period (5.53 ± 2.29 days vs. 5.59 ± 2.57 days, P = 0.622), cervical dilation (1.82 ± 0.26 cm vs. 1.84 ± 0.29 cm, P = 0.281), and effacement (53 ± 4.47% vs. 57.21 ± 6.27%, P = 0.622) between the placebo and DG groups. The percentage of neonates with a 1-min Apgar score < 7 was higher in the placebo group compared with that of the DG group (12% vs. 0%, P = 0.0001). However, both groups were similar in the frequency of a 5-min Apgar score < 7. No differences in the term of adverse effects of medications were recorded. Our results showed that DG adjuvant to magnesium sulfate could not be effective in improving the incidence of preterm labor, rate of recurrent UC, latency period, pregnancy outcomes, and maternal and neonatal outcomes when compared with the placebo group.


Social waves in giant honeybees (Apis dorsata) elicit nest vibrations.
Giant honeybees (Apis dorsata) nest in the open and have developed a wide array of strategies for colony defence, including the Mexican wave-like shimmering behaviour. In this collective response, the colony members perform upward flipping of their abdomens in coordinated cascades across the nest surface. The time-space properties of these emergent waves are response patterns which have become of adaptive significance for repelling enemies in the visual domain. We report for the first time that the mechanical impulse patterns provoked by these social waves and measured by laser Doppler vibrometry generate vibrations at the central comb of the nest at the basic (='natural') frequency of 2.156 ± 0.042 Hz which is more than double the average repetition rate of the driving shimmering waves. Analysis of the Fourier spectra of the comb vibrations under quiescence and arousal conditions provoked by mass flight activity and shimmering waves gives rise to the proposal of two possible models for the compound physical system of the bee nest: According to the elastic oscillatory plate model, the comb vibrations deliver supra-threshold cues preferentially to those colony members positioned close to the comb. The mechanical pendulum model predicts that the comb vibrations are sensed by the members of the bee curtain in general, enabling mechanoreceptive signalling across the nest, also through the comb itself. The findings show that weak and stochastic forces, such as general quiescence or diffuse mass flight activity, cause a harmonic frequency spectrum of the comb, driving the comb as an elastic plate. However, shimmering waves provide sufficiently strong forces to move the nest as a mechanical pendulum. This vibratory behaviour may support the colony-intrinsic information hypothesis herein that the mechanical vibrations of the comb provoked by shimmering do have the potential to facilitate immediate communication of the momentary defensive state of the honeybee nest to the majority of its members.


"Unattended, distracting or irrelevant": Theoretical implications of terminological choices in auditory selective attention research.
For seventy years, auditory selective attention research has focused on studying the cognitive mechanisms of prioritizing the processing a 'main' task-relevant stimulus, in the presence of 'other' stimuli. However, a closer look at this body of literature reveals deep empirical inconsistencies and theoretical confusion regarding the extent to which this 'other' stimulus is processed. We argue that many key debates regarding attention arise, at least in part, from inappropriate terminological choices for experimental variables that may not accurately map onto the cognitive constructs they are meant to describe. Here we critically review the more common or disruptive terminological ambiguities, differentiate between methodology-based and theory-derived terms, and unpack the theoretical assumptions underlying different terminological choices. Particularly, we offer an in-depth analysis of the terms 'unattended' and 'distractor' and demonstrate how their use can lead to conflicting theoretical inferences. We also offer a framework for thinking about terminology in a more productive and precise way, in hope of fostering more productive debates and promoting more nuanced and accurate cognitive models of selective attention.


Diagnostic value of ASVS for insulinoma localization: A systematic review and meta-analysis.
Previous studies on the diagnostic value of arterial calcium stimulation with hepatic venous sampling (ASVS) for the localization of insulinoma have reported inconsistent results. Here, we performed a meta-analysis of the relevant published studies. PubMed, Embase, Web of Science, the Cochrane Library, and Wanfang Data were searched for studies on the diagnostic value of ASVS in insulinoma localization published up to May 2019. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curve of ASVS in the localization of insulinoma. We included ten studies involving 337 patients in the study. The pooled sensitivity, specificity, PLR, and NLR were 0.93 (95% confidence interval [CI]: 0.83-0.97), 0.86 (95%CI: 0.75-0.93), 6.8(95%CI: 3.7-12.7), and 0.08 (95%CI: 0.03-0.19), respectively. The DOR was 84 (95%CI: 30-233), and the area under the ROC curve was 0.96 (95%CI: 0.94-0.97).The results of the heterogeneity of the studies (P = 0.00, I2 = 80.17) were calculated using forest plots of the DOR. ASVS is of significant value in localization of insulinoma. If a qualitative diagnosis of insulinoma is definite and the imaging examination results are negative, ASVS should be performed to confirm the localization of insulinoma.


AMPK and HIF signaling pathways regulate both longevity and cancer growth: the good news and the bad news about survival mechanisms.
The AMP-activated protein kinase (AMPK) and hypoxia-inducible factor (HIF) signaling pathways are evolutionarily-conserved survival mechanisms responding to two fundamental stresses, energy deficiency and/or oxygen deprivation. The AMPK and HIF pathways regulate the function of a survival network with several transcription factors, e.g. FOXO, NF-κB, NRF2, and p53, as well as with protein kinases and other factors, such as mTOR, ULK1, HDAC5, and SIRT1. Given that AMPK and HIF activation can enhance not only healthspan and lifespan but also cancer growth in a context-dependent manner; it seems that cancer cells can hijack certain survival factors to maintain their growth in harsh conditions. AMPK activation improves energy metabolism, stimulates autophagy, and inhibits inflammation, whereas HIF-1α increases angiogenesis and helps cells to adapt to severe conditions. First we will review how AMPK and HIF signaling mechanisms control the function of an integrated survival network which is able not only to improve the regulation of longevity but also support the progression of tumorigenesis. We will also describe distinct crossroads between the regulation of longevity and cancer, e.g. specific regulation through the AMPKα and HIF-α isoforms, the Warburg effect, mitochondrial dynamics, and cellular senescence.


Biochemical and Molecular Characterization of a Novel Cu/Zn Superoxide Dismutase from Amaranthus hypochondriacus L.: an Intrinsically Disordered Protein.
A novel Cu/ZnSOD from Amaranthus hypochondriacus was cloned, expressed, and characterized. Nucleotide sequence analysis showed an open reading frame (ORF) of 456 bp, which was predicted to encode a 15.6-kDa molecular weight protein with a pI of 5.4. Structural analysis showed highly conserved amino acid residues involved in Cu/Zn binding. Recombinant amaranth superoxide dismutase (rAhSOD) displayed more than 50 % of catalytic activity after incubation at 100 °C for 30 min. In silico analysis of Amaranthus hypochondriacus SOD (AhSOD) amino acid sequence for globularity and disorder suggested that this protein is mainly disordered; this was confirmed by circular dichroism, which showed the lack of secondary structure. Intrinsic fluorescence studies showed that rAhSOD undergoes conformational changes in two steps by the presence of Cu/Zn, which indicates the presence of two binding sites displaying different affinities for metals ions. Our results show that AhSOD could be classified as an intrinsically disordered protein (IDP) that is folded when metals are bound and with high thermal stability.


Sixteen discrete RNA components in the cytoplasmic ribosome of Euglena gracilis.
We have isolated cytoplasmic ribosomes from Euglena gracilis and characterized the RNA components of these particles. We show here that instead of the four rRNAs (17-19 S, 25-28 S, 5.8 S and 5 S) found in typical eukaryotic ribosomes, Euglena cytoplasmic ribosomes contain 16 RNA components. Three of these Euglena rRNAs are the structural equivalents of the 17-19 S, 5.8 S and 5 S rRNAs of other eukaryotes. However, the equivalent of 25-28 S rRNA is found in Euglena as 13 separate RNA species. We demonstrate that together with 5 S and 5.8 S rRNA, these 13 RNAs are all components of the large ribosomal subunit, while a 19 S RNA is the sole RNA component of the small ribosomal subunit. Two of the 13 pieces of 25-28 S rRNA are not tightly bound to the large ribosomal subunit and are released at low (0 to 0.1 mM) magnesium ion concentrations. We present here the complete primary sequences of each of the 14 RNA components (including 5.8 S rRNA) of Euglena large subunit rRNA. Sequence comparisons and secondary structure modeling indicate that these 14 RNAs exist as a non-covalent network that together must perform the functions attributed to the covalently continuous, high molecular weight, large subunit rRNA from other systems.


Sexuality after breast cancer, how to provide a global and contemporary approach.
Patients' sexuality is one of the major and most neglected impact of breast cancer (BC) and its treatment. Even though research is ongoing on the subject, sexuality issues are rarely taken into account and efficiently dealt with in clinical practice. The objective is to review the impact of BC and its treatment on modern women sexuality. In the literature, a heterogeneous level of advancement is notable in the different publishing countries depending on the cultural background; some countries simply do not publish on the matter, others mainly discuss the male partners and practicians experience, and lastly, the most progressive countries have moved up to studying niches of patients such as sexual and gender minorities. A multidisciplinary approach, including pharmacologic and nonpharmacologic management, appears most efficient. There is a need for greater inclusion of partners and for providing a specific training to first-line health care providers. This review provides a general contemporary worldwide overview of the state of the art in sexuality issues in BC patients and survivors.


Determination of intermolecular and intramolecular isotopic compositions of low-abundance gaseous hydrocarbons using an online hydrocarbon gas concentration method.
The stable isotopic composition of natural gas can be used to identify its origin and source. However, low concentrations of gaseous hydrocarbons in high-mature natural and shale gases hinder accurate determination of their compound- and position-specific isotopic compositions. In this study, an online C2+ hydrocarbon gas concentration system combined with gas chromatography-isotope ratio mass spectrometry (GC-IRMS) or gas chromatography-pyrolysis-gas chromatography-isotope ratio mass spectrometry (GC-Py-GC-IRMS) was developed to determine compound- and position-specific isotopic compositions of low-abundance gaseous hydrocarbons. The lower limit of the gas concentration required for isotope ratio determination using the online concentration system is 0.001% (0.003%) for compound-specific carbon (hydrogen) isotopes and 0.005% for position-specific carbon isotopes and is thus applicable to most natural gas samples. The online concentration technique does not cause significant isotopic fractionation effects, and the combination with GC-IRMS and GC-Py-GC-IRMS can accurately and precisely determine the compound-specific δ13C and δD values of low-content C2+ gaseous hydrocarbons and the position-specific δ13C values (δ13Ca, δ13Cb, and SP values) of propane in low-content propane samples, respectively. The application of our method to two natural gas samples from the Ordos and Sichuan basins further confirms that the online concentration method allows simple and rapid determination of the compound- and position-specific isotopic compositions of low-abundance gaseous hydrocarbons.


Cystic atypical mesoblastic nephroma.
Cystic variants of atypical mesoblastic nephromas are very rare. The present communication deals with two such cases encountered in 3- and 6-month-old patients. The literature is briefly reviewed. The need for proper diagnosis of this tumor to distinguish it from cystic nephroma and Wilms' tumor is highlighted.


Somatostatinergic projections from the central nucleus of the amygdala to the vagal nuclei.
In the rat, somatostatin immunoreactivity was identified in neurons of the central nucleus of the amygdala that were retrogradely labeled by injection of fluorescent dyes into the nucleus tractus solitarius and dorsal motor nucleus of the vagus nerve. The double-labeled neurons are located in the medial subdivision of the central nucleus and appear to comprise less than one fifth of the descending pathway. These results suggest that somatostatin may act as a neurotransmitter in a pathway which mediates cardiovascular and other autonomic responses to fear-producing and other emotional stimuli.


Comparing quantum versus Markov random walk models of judgements measured by rating scales.
Quantum and Markov random walk models are proposed for describing how people evaluate stimuli using rating scales. To empirically test these competing models, we conducted an experiment in which participants judged the effectiveness of public health service announcements from either their own personal perspective or from the perspective of another person. The order of the self versus other judgements was manipulated, which produced significant sequential effects. The quantum and Markov models were fitted to the data using the same number of parameters, and the model comparison strongly supported the quantum over the Markov model.


Attitudes and Actions Related to Racism: the Anti-RaCism (ARC) Survey Study.
Racism negatively impacts health and well-being. Members of the medical community must intervene to address racism. To assess whether attitudes about the impact of racism on health or society are associated with intervening around racism. Cross-sectional survey of a large department of medicine in an urban academic setting. Interns, residents, fellows, and faculty. The primary outcome was the likelihood of intervening around an observed racist encounter or a racist policy. Predictor variables included age, gender identity, race/ethnicity, and attitudes about racism. Although the majority of the 948 respondents endorsed the impact of racism on health and other societal effects, levels of endorsement were lower among older individuals, or those reporting male gender identity or selecting other race. Higher endorsement of the impact of racism on health was associated with increased odds of speaking up about a racist encounter or racist policy, with odds ratios from 1.18 to 1.30 across scenarios. Likelihood of speaking up about racism did not differ by racial or ethnic group, but older individuals were generally more likely to speak up and individuals between 20 and 29 years of age were more likely to speak with someone other than leadership or the source of a racist encounter. Awareness of the effects of racism on health is associated with increased likelihood of intervening when a racist encounter is observed or a racist policy is noted. Including information on the impact of racism on health and creating safe spaces to discuss racism may increase the likelihood of bystander intervention in anti-racism strategies.


Tendinous annulus of Zinn for a common origin of the extraocular rectus muscles: a histological study of the orbital apex from donated elderly cadavers.
The medial, inferior, lateral, and superior rectus muscles (MR, IR, LR, SR), levator palpebrae superioris (LPS), and superior oblique muscle (SO) seem to originate from the tendinous annulus of Zinn, ring-like fibrous tissue crossing the bony orbital fissure. We observed the histological annulus structure using semi-serial histological sections of the orbital apex from 30 elderly donated cadavers. Nearly frontal sections demonstrated a ring-like fibrous structure (a candidate annulus) connecting or embedding four rectus muscles. The candidate annulus did not contain the LPS and SO, and, in the anterior side, the latter muscles originated from the optic canal opening. Far posterior to the annulus, there was a common tendon of the MR, IR, and LR attached to the infero-medial wall of the bony orbital fissure. At the superior part, the annulus is tightly attached to the optic nerve sheath and the periosteum. Sagittal (or Horizontal) sections clearly exhibited parts of the annulus at the MR (SR) origin. Both sagittal and horizontal sections displayed (1) the common origin of the three rectus muscles near the oculomotor nerve in the bony fissure and (2) an accessory, independent muscle bundle of the MR originating from the superomedial margin of the optic canal near the origins of the LPS or SO. Consequently, the so-called tendinous annulus appeared not to provide origins of all six muscles.


Shared governance: a way to improve the care in an inpatient rehabilitation facility.
Rehabilitation care is specialized and individualized requiring effective and efficient communication to achieve optimal patient outcomes. To examine how effective implementation of shared governance could improve care delivery, promote patient-centered care, and improve patient outcomes. The shared governance approach included all members of the rehabilitation team (i.e., physical therapist, occupational therapist, speech therapist, registered nurse and nurse aide) and was implemented over 6 months. The major end products of this shared governance effort were improved staff communication, problem solving, patient outcomes, and staff satisfaction on our stroke and brain injury unit. When effectively implemented and sustained, shared governance between all rehabilitation team stakeholders can increase the effectiveness of communication along with more positive patient and staff outcomes.


An observational study of growth rate and body weight variance partition for United Kingdom dairy calves from birth to 20 weeks of age.
This study estimates the birth weight and growth rate for UK dairy calves and partitions unexplained variability in the weight of calves aged up to 20 wk. Raising replacements is a major contributor to the sustainability of dairying, but existing industry targets may not be applicable and achievable on all farms. For hierarchical data, variance partition coefficients (VPC) describe the proportion of unexplained variance residing at each level of the hierarchy due to clustering and indicate the potential to change outcomes through influencing variables acting at each level. This information could be used to inform the allocation of resources for further investigation. Calves were weighed according to farm-specific protocols. The data set analyzed contained records between June 5, 2014, and February 28, 2020, from 28 veterinary practices servicing 139 farms with 19,708 calves up to 20 wk of age, from which there were 59,588 weight recordings. Calves were Holstein-Friesian females. Calf weight was described using a multivariable mixed linear model with fixed effects for age. Mean birth weight was 41 kg. Mean growth rate increased from 0.59 kg/d at 1 d of age to 0.87 kg/d after 138 d. Cumulative mean growth rate up to 138 d of age was 0.73 kg/d. Birth weight and growth rate estimates are comparable with those made previously but are more precise due to larger sample size. Calf growth rate varied between farms, meaning that VPC at the calf, farm, and veterinary practice levels depended on calf age. Most unexplained variation in the weight of calves aged 66 d and over was due to differences between farms. At birth and 130 d of age, VPC at the farm level was 0.02 and 0.77, respectively. In contrast, most variation in neonatal calf weight was due to differences between calves. At birth and 130 d of age, VPC at the calf level was 0.84 and 0.20, respectively. The 0.025 to 0.975 quantile coverage of cluster-specific mean calf birth weight for combinations of veterinary practice and farm was 34 to 49 kg. The 0.025 to 0.975 quantile coverage of cluster-specific cumulative mean calf growth rate for combinations of veterinary practice and farm was 0.56 to 1.00 kg/d. Understanding reasons for these differences should be the basis of research into optimal calf management strategies to define economic targets for specific circumstances.


A case report of aneurysmal bone cyst of the thoracic spine treated by serial anterior and posterior fusion.
Aneurysmal bone cyst (ABC) is a benign, reactive, non-neoplastic, proliferative, highly vascular osseous lesion. Because of the rarity of aggressive ABC cases, diagnostic and treatment protocols remain controversial and problematic. Treatment of ABC includes surgery, radiotherapy, selective arterial embolization (SAE), and a combination of these modalities. Successful outcomes have been reported, but the technical requirements and complications of each modality are quite different. We report the clinical, radiological, and therapeutic aspects of ABC of the thoracic spine in an adolescent who was treated by circumferential fusion, and we review the published literature. An 18-year-old boy was transferred to our hospital complaining of a 2-month history of neck pain. ABC of the thoracic spine INTERVENTIONS:: Six days after SAE, T1 corpectomy was performed via an anterior approach. We performed the operation using the posterior approach 1 week after the anterior approach. Histopathological examination confirmed the diagnosis of ABC. No neurologic deterioration occurred during the postoperative period. Follow-up X-rays 2 year postoperative showed good bony fusion and alignment. Primary ABC of the spine is a benign lesion with a potential to be locally aggressive and a high rate of local recurrence. The optimal treatment of thoracic lesions is challenging due to their proximity to the spinal cord and nerve roots, and their frequent association with deformity. Surgical resection/curettage, SAE, and radiotherapy can be used alone or in combination. Complete exposure and resection is crucial to avoid the recurrence. Circumferential fusion and reconstruction of stability are also important for the treatment of thoracic ABC, especially in adolescent patient.


Vegetation-fire feedback reduces projected area burned under climate change.
Climate influences vegetation directly and through climate-mediated disturbance processes, such as wildfire. Temperature and area burned are positively associated, conditional on availability of vegetation to burn. Fire is a self-limiting process that is influenced by productivity. Yet, many fire projections assume sufficient vegetation to support fire, with substantial implications for carbon (C) dynamics and emissions. We simulated forest dynamics under projected climate and wildfire for the Sierra Nevada, accounting for climate effects on fuel flammability (static) and climate and prior fire effects on fuel availability and flammability (dynamic). We show that compared to climate effects on flammability alone, accounting for the interaction of prior fires and climate on fuel availability and flammability moderates the projected increase in area burned by 14.3%. This reduces predicted increases in area-weighted median cumulative emissions by 38.3 Tg carbon dioxide (CO2) and 0.6 Tg particulate matter (PM1), or 12.9% and 11.5%, respectively. Our results demonstrate that after correcting for potential over-estimates of the effects of climate-driven increases in area burned, California is likely to continue facing significant wildfire and air quality challenges with on-going climate change.


Unexpected intraoperative positive culture (UIPC) in presumed aseptic revision spine surgery: a systematic review and meta-analysis.
Unexpected intraoperative positive culture (UIPC) has recently become increasingly common in revision spine surgery, being implicated as an etiological factor in revision spine surgery indications such as implant failure or pseudoarthrosis. Utilizing the available literature, this study aimed to investigate the prevalence of UIPC, and its clinical importance in patients following presumed aseptic revision spine surgery. Meta-analysis and systematic review. Multiple databases and reference articles were searched until May 2022. The primary outcome was the pooled rate of UIPC, and the secondary outcomes were the microbiological profile of UIPC, the risk factors of UIPC, and the clinical fate of UIPC. Twelve studies were eligible for meta-analysis, with a total of 1,108 patients. The pooled rate of UIPC was 24.3% (95% CI=15.8%-35.5%) in adult patients, and 43.2% (95% CI=32.9%-54.2%) in pediatric patients. The UIPC rate was higher when both conventional wound culture and sonication were used together compared to sonication alone or conventional wound culture alone. The rates were 28.9%, 23.6%, and 15.5 %, respectively. In adult and pediatric patients, the most commonly cultured organism was Cutibacterium acnes (42.5% vs 57.7%), followed by coagulase-negative Staphylococcus (39.9% vs 30.5%). Male patients had a higher rate of UIPC (OR= 2.6, 95% CI=1.84-3.72, p<.001), as did patients with a longer fusion construct (MD=0.76, 95% CI=0.27-1.25, p<.001). The pooled rate of UIPC in aseptic spine revision surgery was 24.3% and 43.2% in adult and pediatric patients respectively. The most common organisms were C. acnes and coagulase-negative Staphylococcus. The impact of UIPC on patients` clinical outcomes is not fully understood. We are not able to recommend routine culture in revision spine surgery, however, adding sonication may aid in the diagnosis of UIPC. There is not enough evidence to recommend specific treatment strategies at this time, and further studies are warranted.


Mepanipyrim residues on pasteurized red must influence the volatile derived compounds from Saccharomyces cerevisiae metabolism.
The impact of mepanipyrim (Mep) and its corresponding commercial formulation (Mep Form) on Saccharomyces cerevisiae metabolites was assessed, separately, by using laboratory-scale wine fermentation assays on pasteurized red must. The presence of Mep did not alter the fermentation course. With regard to volatiles formed at the intracellular level by fermenting yeast cells, Mep residues affected mainly the acetate and ethyl ester biochemical pathways. In particular, the target acetates showed a notorious increment, >90%, in presence of commercial Mep Form at the higher dose assayed. The addition of Mep and Mep Form, at both tested levels, highly increased ethyl caprylate (between 42 and 63%) and ethyl caprate (between 36 and 60%) contents as the same as their respective fatty acid precursors. No important effects were observed on colour and non-volatile pyranoanthocyanins, probably due to the low anthocyanin content characteristic of pasteurized musts.


Neurophysiological effects of needle trauma and intraneural injection in a porcine model: a pilot study.
Neurophysiological data are lacking in the research of nerve injury during regional anaesthesia. The aim of this pilot study was to establish a large animal model in order to test the hypothesis that needle trauma alone or in combination with intraneural injection would result in measurable nerve injury. The experimental set-up was elaborated in four pre-test animals. In the remaining animals (n = 11), 22 sciatic nerves were randomly assigned to one of four groups: needle trauma (n = 5) generated by ultrasound-guided forced needle advancement; intraneural injection of 2.5 ml saline (n = 6); intraneural injection of 5 ml saline (n = 6); extraneural injection of 5 ml saline (n = 5) as control group. Compound muscle action potential (CMAP) amplitudes as well as latencies were taken as outcome parameter and monitored over 180 min. Sonographic assessments were performed simultaneously. Following needle trauma and intraneural injection, CMAP amplitudes declined significantly over 180 min (P < 0.001). The control group showed no electrophysiological alterations. At 60 min, decreases in amplitude were significant after needle trauma (P = 0.04) and intraneural injection of 2.5 ml (P = 0.045), and highly significant after injection of 5 ml (P = 0.006) when compared to controls. Sustained nerve swelling was observed after intraneural injection, but not after needle trauma and perineural injection. Isolated mechanical trauma caused by forced needle advancement alone or in combination with intraneural injection of saline was followed by a significant decline in CMAP amplitudes indicating conduction block due to disruption of myelin or axon loss (pseudo-conduction block).


Discontinuation of Oral Antiplatelet Agents before Dental Extraction - Necessity or Myth?
The risk of excessive bleeding often prompts physicians to interrupt the antiplatelet agents as acetylsalicilyc acid and clopidogrel before dental extractions which puts patients at risk of adverse thrombotic events. To assess the bleeding risk during dental extractions in patients with continued antiplatelet therapy. The study included 130 patients (64 men and 66 women) aged between 18 and 99 years old. Sixty-eight of the patients received 100 mg acetilsalicilic acid (ASA); these were divided into two groups: 34 patients continued taking ASA and 34 patients stopped it 72 hours before extraction. Sixty-two of the patients were treated with 75 mg clopidogrel; these were also divided into two groups: 31 continued taking clopidogrel and 31 patients stopped it 72 hours before extractions. Extraction was performed under local anaesthesia as no more than 3 teeth per visit were extracted. Local haemostasis with gelatine sponge and/or suturing was used to control bleeding. Mild bleeding was observed most frequently in the first 30 minutes, successfully managed by local haemostasis. Only 1 patient in the control and 1 in the experimental group receiving ASA reported mild bleeding in the first 24 hours, controlled by compression with gauze. No major haemorrhage requiring emergency or more than local haemostasis occurred. No statistically significant difference in bleeding between two groups was found. Single and multiple dental extractions in patients receiving acetylsalicylic acid or clopidogrel can be safely performed without discontinuation of the therapy with provided appropriate local haemostasis.


Dissociation of dorsal root ganglion neurons into afferent and efferent-like neurons.
Although the textbook function of dorsal root ganglion neurons is to signal information to the brain, a group of C-fibre and some A delta-fibre afferents have the capacity to release peptide transmitters from their peripheral terminations and thereby to regulate vascular and other tissue activities. Depending on the species under study, vasoactive dorsal root ganglion neurons in the skin belong to heat nociceptors or a subclass of polymodal nociceptors, and it has been a matter of long-standing discussion how the local effector role of dorsal root ganglion neurons is related to their afferent function. The observation that local vascular regulation may take place independently of nociception has commonly been explained by a number of transductional differences between peripheral peptide release and afferent nerve activity. However, the view that it is only one population of dorsal root ganglion neurons that can work in either mode is increasingly challenged, and after consideration of the available information we hypothesize that some dorsal root ganglion neurons are specialized in controlling peripheral effector mechanisms but have no role in sensation. These local effector neurons represent a novel class of autonomic neurons that lack a preganglionic input, but operate in an efferent-like mode after stimulation by internal or external stimuli.


Note on quantitative homogenization results for parabolic systems in R d.
In L 2 ( R d ; C n ) , we consider a semigroup e - t A ε , t ⩾ 0 , generated by a matrix elliptic second-order differential operator A ε ⩾ 0 . Coefficients of A ε are periodic, depend on x / ε , and oscillate rapidly as ε → 0 . Approximations for e - t A ε were obtained by Suslina (Funktsional Analiz i ego Prilozhen 38(4):86-90, 2004) and Suslina (Math Model Nat Phenom 5(4):390-447, 2010) via the spectral method and by Zhikov and Pastukhova (Russ J Math Phys 13(2):224-237, 2006) via the shift method. In the present note, we give another short proof based on the contour integral representation for the semigroup and approximations for the resolvent with two-parametric error estimates obtained by Suslina (2015).


Neuropsychological assessment through Coma Recovery Scale-Revised and Coma/Near Coma Scale in a sample of pediatric patients with disorder of consciousness.
The Coma Recovery Scale-Revised (CRS-R) has become a standard tool in assessing Disorders of consciousness (DoC) in adults. However, its measurement validity in pediatrics has only been ascertained in healthy cases. Increasing use of CRS-R in children with DoC imposes appropriate comparison against previously validated tools. The aims of the study were to describe the emergence to a conscious state (eMCS) in pediatric acquired brain injury (ABI); to explore the agreement between the CRS-R and Coma Near Coma Scale (CNCS) and to discuss the advantage of administering the CRS-R in pediatric age. In this observational prospective study, 40 patients were recruited. Inclusion criteria were age 5 to 18 years, Glasgow Coma Scale (GCS) score ≤ 8 at the insult, and unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS) at admission. Patients were assessed with CRS-R, and CNCS was used as standard. The agreement between scales was moderate (r = - 0.71). The analysis of the CRS-R domain scores also confirmed that decreasing CNCS levels (from a coma to eMCS) corresponded to concurrent increas of CRS-R scores in all domains. Moreover, CRS-R better defined patients' status in the emergency phase from MCS. Conversely, CRS-R had lower DoC scoring ability in the presence of severe motor impairment. We show that CRS-R can track changes in DoC in children as young as 5 years old, and we provide evidence that the agreement with CNCS scores is good.


Children's understanding of class inclusion hierarchies: the relationship between external representation and task performance.
Three experiments were designed to investigate children's understanding of class inclusion hierarchies and to determine whether such understanding may be related to children's ability to construct external representations for information that was hierarchical in nature. Understanding of hierarchies was studied through tasks designed to demonstrate children's ability with subset/superset classification and knowledge of asymmetric and transitive relations. Children were asked to construct their own external representations for passages containing information that could be represented hierarchically. It was hypothesized that the quality of children's external representations would be related to their ability to respond to questions related to the passages. Children's responses to questions, as well as their external representations, suggested that children as young as second grade have substantial understanding of hierarchical relations. Although the external representations were constructed in drawing, written, or structured modes, the data revealed a strong relationship between the quality of children's external representations and their performance on question tasks requiring both recognition and reasoning. Finally, children understood the relationships expressed in tree diagrams and could construct such diagrams to respond to questions. Implications of the findings, particularly as related to note-taking skills, and suggestions for further research are discussed.


Nondiabetic patients with either subclinical Cushing's or nonfunctional adrenal incidentalomas have lower insulin sensitivity than healthy controls: clinical implications.
The aim of this study was to estimate insulin sensitivity (IS) in nondiabetic patients with adrenal incidentalomas (AI): nonfunctional adrenal incidentalomas (NAI) and patients with AI and subclinical Cushing's syndrome (SCS). Based on the inclusion criteria (normal fasting glucose levels, no previous history of impaired fasting glucose and/or diabetes, and no medications or concomitant relevant diseases) and the exclusion criteria (pheochromocytoma, overt hypercortisolism, hyperaldosteronism, adrenal carcinoma, metastasis of extra-adrenal tumors, extra-adrenal malignancies), 142 subjects were drawn from a series of patients with AI. The subjects were age-, sex- and body mass index (BMI)-matched: 70 with NAI (50 women and 20 men), 37 with AI and SCS (31 women and 6 men) and 35 healthy control (HC) subjects (30 women and 5 men). The oral glucose tolerance test (OGTT) and several indices of insulin sensitivity (IS) were used: homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), triglycerides and glucose index (TyG), index of whole-body insulin sensitivity (ISI-composite) and glucose to insulin ratio (G/I). There was a significant difference in IS between subjects with NAI and HC (HOMA, p=0.049; QUICKI, p=0.036; TyG, p=0.002; ISI-composite, p=0.024) and subjects with SCS and HC (AUC insulin, p=0.01; HOMA, p=0.003; QUICKI, p=0.042; TyG, p=0.008; ISI-composite, p=0.002). There was no difference in the tested indices of IS between subjects with NAI and SCS (p>0.05). However, subjects with SCS had a significantly higher prevalence of impaired glucose tolerance and higher area under the curve for glucose than subjects with NAI (p=0.0174). The linear regression analysis showed that 1 mg-DST cannot be used as a predictor of HOMA (R(2)=0.004, F=0.407, p=0.525). Significant relationship was found between 1 mg-DST and ISI-composite (R(2)=0.042, F=4.981, p=0.028) but this relationship was weak and standard error of estimate was high. The linear regression model also showed that ACTH cannot be used as a predictor of HOMA (R(2)=0.001, F=0.005, p=0.943) or ISI-composite (R(2)=0.015, F=1.819, p=0.187). Insulin resistance is a major cardiovascular risk factor; therefore, the assessment of IS in patients with AI, even nonfunctional, has a valuable place in the endocrine workup of these patients.


[Myocardial infarction secondary to blunt chest trauma in a man of 25 years].
This paper describes the clinical case - anterior myocardial infarction after blunt chest trauma in a 25-year-old man.


Biofilm formation and exopolysaccharide (EPS) production by Cronobacter sakazakii depending on environmental conditions.
Biofilm matrices are formed largely of extracellular polymeric substance (EPS). This study was conducted to investigate biofilm formation and EPS production by Cronobacter sakazakii under various conditions (media, nutrition, and relative humidity (RH)) by quantification of EPS and cell populations, Field Emission Scanning Electron Microscope (FE-SEM), and colony observation. Various agar media conditions (TSA without dextrose (W/D), M9 minimum salt medium (MSM) agar, and M9 MSM agar with 3% glucose, 3% NaCl, 3% Tween 80, 3% sucrose, and adjusted to pH 5 with HCl) were prepared. C. sakazakii biofilm formed on the surface of stainless steel coupons (SSCs) immersed in TSB W/D and M9 MSM with or without 0, 1, 3, and 5% sucrose and subsequently exposed to various RH levels (23, 43, 68, 85, and 100%). EPS production by C. sakazakii on TSA W/D was significantly higher than that on other media after 1 and 2 days. However, C. sakazakii ATCC 12868 produced the highest levels of EPS (209.18 ± 16.13 and 207.22 ± 4.14 μg/mL after 1 and 2 days, respectively) on M9 MSM agar with 3% sucrose. Regarding C. sakazakii ATCC 12868 biofilm formed on the surface of SSCs immersed in M9 MSM with 0, 1, 3, and 5% sucrose and subsequently exposed to various RHs, populations were significantly different among the various RHs and sucrose concentrations, and EPS production was significantly higher (4.69 mg/L) compared to other sucrose concentrations (0%:0.71 mg/L and 1%:0.98 mg/L), except for M9 MSM with 3% sucrose (2.97 mg/L) (P ≤ 0.05). From these results, biofilm formation and EPS production by C. sakazakii differed depending on the nutrient or environmental conditions provided to the cells.


Neuroprotective effect of the novel Na+/Ca2+ channel blocker NS-7 on rat retinal ganglion cells.
To investigate whether NS-7, 4-(4-fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy) pyrimidine hydrochloride, a novel Na(+)/Ca(2+) channel blocker, can protect the rat retina subjected to ischemia-reperfusion insult. To evaluate the protective effect of NS-7 against retinal damage, the drug was administered before and after ischemia-reperfusion. Damage to the retina was assessed by measuring the thickness of the inner plexiform layer (IPL) and the outer nuclear layer (ONL) of each eye. In a subsequent experiment, electroretinographic (ERG) evaluation was also used. In histopathologic evaluation, ischemia-reperfusion injury caused a significant reduction of IPL thickness (measured as the IPL/ONL ratio). In the NS-7-treated group, retinal damage was partially prevented by a concentration of 0.25 mg/kg per day. In the ERG evaluation, ischemia-reperfusion injury caused a reduction of A- and B-wave amplitudes. NS-7 treatment significantly prevented the reduction of the B wave at a concentration of 0.1 or 0.3 mg/kg, while the reduction of the A wave was not significantly affected. NS-7 has neuroprotective effects against retinal damage resulting from subjection to ischemia. In addition, NS-7 can be used as an agent for treating acute ischemic retinopathy, including diseases associated with very high intraocular pressure, such as acute angle-closure glaucoma.


Comparison of the effects of isradipine and lisinopril on left ventricular structure and function in essential hypertension.
The effects on cardiac structure and function of antihypertensive regimens with different effects on the renin-angiotensin system were compared. In a 1-year study, 32 patients with essential hypertension were randomized to treatment with either the converting enzyme inhibitor lisinopril or the calcium antagonist isradipine; hydrochlorothiazide could be added. Blood pressure (BP) decreased significantly (p less than 0.001) and similarly in the 2 treatment groups. Left ventricular (LV) mass was already significantly reduced after 16 weeks of treatment (p less than 0.001) and remained decreased thereafter, with no difference in the response to the 2 treatment regimens. The change in LV mass was related to the decrease in systolic BP for the total study group (p less than 0.001) and for each treatment group separately. During the 3-week run-out period on placebo, BP and LV mass increased again (p less than 0.01). Afterload decreased during active treatment (p less than 0.001), and fractional shortening of the LV internal diameter was significantly increased (p less than 0.01) to a similar extent in both groups. The ratio of peak mitral flow velocities during atrial contraction and early filling was reduced after 1 year of active treatment in the total study group (p less than 0.01); this change was similar in both groups. The data suggest that the regression of LV mass during antihypertensive therapy is mainly related to the decrease in systolic BP.


Activity of germ-cell mutagens and nonmutagens in the rat spermatocyte UDS assay.
The ability of 13 chemicals of known germ-cell mutagenicity to induce unscheduled DNA synthesis (UDS) in rat spermatocytes was examined. At selected times following i.p. injection of test compounds, spermatocytes were isolated from Fischer 344 rats by enzymatic digestion of the seminiferous tubules and cultured for 24 h in the presence of [3H]thymidine. 7 compounds, methyl methanesulfonate, triethylenemelamine, cyclophosphamide, methylnitrosourea, ethylnitrosourea, procarbazine, and dibromochloropropane produced positive UDS responses in spermatocytes. These chemicals are also positive for specific locus mutations, heritable translocations, or dominant lethal mutations when administered to male rodents. Mitomycin C, which produces DNA interstrand crosslinks and induces heritable mutations and translocations in male germ cells, failed to stimulate UDS in rat spermatocytes. Germ-cell nonmutagens N-methyl-N'-nitro-N-nitrosoguanidine, dimethylnitrosamine, 4-nitroquinoline 1-oxide, and ethylene dibromide were negative in the rat spermatocyte UDS assay. Correlation of these results with those of other assays for heritable mutations in germ cells indicates that the in vivo/in vitro spermatocyte DNA repair assay is useful in predicting the mutagenic potential of chemicals in male germ cells.


Effects of melatonin on proliferation of cancer cell lines.
The pineal hormone melatonin has been reported to have in vitro antiproliferative effects on estrogen receptor-positive human breast cancer cell lines at concentrations near to plasma physiological concentrations (1 x 10(-11) to 1 x 10(-9) M). Its growth inhibitory actions have been thought to be linked to the estrogen-receptor system. We tested the cytotoxic effects of melatonin on MCF-7 and T47D human breast cancer cell lines by using the SRB (sulforhodamine-B), XTT-tetrazolium, and bromodeoxyuridine (BrdU) assays in 96-well microtiter plates. After a 3 or 4 day exposure, melatonin did not have any significant effect on breast cancer cell proliferation and survival in doses up to 1 x 10(-4) M. Doses higher than 1 mM exhibited a potent cytotoxic effect, which was not mediated by the estrogen-receptor or by protein tyrosine kinases and was not specific for breast cancer cell lines. Intracellular glutathione levels did not seem to play any role in the sensitivity of breast cancer cells to melatonin, since the addition of L-buthionine-[S,R]-sulfoximine, ethacrynic acid, or exogenous glutathione did not modify our results. We conclude that under our experimental conditions melatonin has no inhibitory effects on human breast cancer cells at low (physiological or supraphysiological) concentrations. The different experimental procedures that were utilized in the present study can partially explain the divergence between our results and the literature.


Urodynamic evaluation of ileal conduit function.
Bilateral hydroureteronephrosis following ileal conduit urinary diversion is not uncommon. It may be owing to ureteroileal stenosis, stomal stenosis or a poorly compliant ileal conduit. The standard evaluation of stoma size, conduit residual urine and a loopogram often fail to allow determination of the cause of ureteral dilatation. In addition to these standard tests, we have used conduit urodynamics to study conduit function with a triple lumen urodynamic catheter to measure simultaneously conduit pressure proximal and distal to the fascia during filling under fluoroscopy. In 4 control patients with normal upper tracts who were studied with this technique conduit leak point pressures ranged from 5 to 20 cm. water pressure. Six patients with bilateral hydroureteronephrosis were studied to evaluate conduit function. We found abnormalities in 5 patients, including functional stomal stenosis in 2, an atonic loop in 1, segmental obstruction in 1 and a high pressure noncompliant distal segment in 1.


Validation of the SenseWear Mini activity monitor in 5-12-year-old children.
This study aimed to validate SenseWear Mini software algorithm versions 2.2 (SW2.2) and 5.2 (SW5.2) for estimating energy expenditure (EE) in children. Laboratory-based validation study. 57 children aged 5-12 y completed a protocol involving 15 semi-structured sedentary (SED), light-intensity (LPA), and moderate- to vigorous-intensity (MVPA) physical activities. EE was estimated using portable indirect calorimetry (IC). The accuracy of EE estimates (kcal·min-1) from SW2.2 and SW5.2 were examined at the group level and individual level using the mean absolute percentage error (MAPE), Bland-Altman plots and equivalence testing. MAPE values were lower for SW5.2 (30.1±10.7%) than for SW2.2 (44.0±6.2%). Although mean differences for SW5.2 were smaller than for SW2.2 during SED (-0.23±0.22 vs. -0.61±0.20kcal·min-1), LPA (-0.69±0.76 vs. -1.07±0.46kcal·min-1) and MVPA (-2.22±1.15 vs. -2.57±1.15kcal·min-1), limits of agreement did not decrease for the updated algorithms. For all activities, SW2.2 and SW5.2 were not equivalent to IC (p>0.05). Errors increased with increasing intensity. The current SenseWear Mini algorithms SW5.2 underestimated EE. The overall improved accuracy for SW5.2 was not accompanied with improved accuracy at the individual level and EE estimates were not equivalent to IC.


Lipopolysaccharide inhibits the simultaneous establishment of LiCl-induced anticipatory nausea and intravascularly conditioned taste avoidance in the rat.
This study examined the effects of the bacterial endotoxin, lipopolysaccharide (LPS), on the establishment of anticipatory nausea and conditioned taste avoidance in a simultaneous conditioning paradigm using an intravascular/intraperitoneal saccharin taste. 83 naïve adult male Long-Evans rats were injected (intraperitoneal) with either 200 μg/kg LPS or 0.9% saline (NaCl), 90 min prior to ip treatment with either 64 mg/kg LiCl, 64 mg/kg LiCl+2.0% saccharin, 0.9% NaCl, or 0.9% NaCl+2.0% saccharin, and immediately placed into a distinctive context for 30 min (repeated over 4 conditioning days, spaced 72 h apart). 72 h following the final conditioning day, each animal was re-exposed to the context on a drug-free test day where orofacial responding was recorded. The next day, animals received a 24 h 2-bottle preference test with a choice between water and a palatable 0.2% saccharin solution. Results showed that LPS exposure, prior to LiCl or LiCl+Saccharin treatment, inhibited the establishment of anticipatory nausea, as evidenced by significantly lower conditioned gaping frequencies relative to animals pre-treated with NaCl followed by LiCl or LiCl+Saccharin. LPS pre-treatment also inhibited the formation of LiCl-induced taste avoidance, as evidence by significantly higher saccharin preferences in Group LPS-LiCl+Saccharin relative to Group NaCl-LiCl+Saccharin. The results of the current study provide additional evidence for the deleterious effects of LPS on learning and memory in aversive conditioning.


Obesity Prevention and Weight Maintenance After Loss.
Obesity is one of the most prevalent medical diseases in pets. Outcomes are often disappointing; many animals either fail to reach target weight or regain weight. This article discusses managing obesity, focusing on prevention. It gives guidance on establishing monitoring programs that use regular body weight and condition assessments to identify animals at risk of inappropriate weight gain, enabling early intervention. Weight management in obese animals is a lifelong process. Regular weight and body condition monitoring are key to identifying animals that rebound early, while continuing to feed a therapeutic weight loss diet can help prevent it from happening.


Mid-term clinical results and patient satisfaction after uterine artery embolization in women with symptomatic uterine fibroids.
To evaluate the mid-term clinical results and patient satisfaction following uterine artery embolization (UAE) in women with symptomatic fibroids. Between August 1998 and December 2002, 135 patients had UAE for symptomatic uterine fibroids. All patients were asked to fill in a questionnaire. Questions were aimed at changes in bleeding, pain, and bulk-related symptoms. Symptoms after UAE were scored as disappeared, improved, unchanged or worsened. Adverse events were noted, such as vaginal dryness and discharge, menopausal complaints or fibroid expulsion. Patient satisfaction after UAE was assessed. Patient satisfaction of women embolized with polyvinyl alcohol (PVA) particles was compared with satisfaction of women embolized with calibrated microspheres. The questionnaire was returned by 110 of 135 women (81%) at a median time interval of 14 months following UAE. In 10 women additional embolization or hysterectomy had been performed. Of the 110 responders, 86 (78%) were satisfied with the result of UAE. The proportion of satisfied women was higher in the group embolized with calibrated microspheres than in women embolized with PVA, although this difference was not statistically significant (p = 0.053). UAE in women with symptomatic uterine fibroids leads to improvement of symptoms and patient satisfaction is good in the vast majority after a median follow-up period of 14 months.


Echocardiography in the diagnosis of apical non-compaction associated with congenital heart diseases.
Isolated left ventricular non-compaction has been reported extensively. However, apical non-compaction of both ventricles and the interventricular septum (IVS) is not often reported in the literature. The objective of our study is to evolve the echocardiographic diagnostic criteria and to assess the types and impact of the associated lesions in "apical non-compaction". Seventy consecutive cases that fulfilled standard echocardiographic criteria for non-compaction of the left ventricle and, in addition, N/C ratio of >3 for the right ventricle and apical IVS formed the material. The age of patients ranged from 3 days to 35 years, with 37 males and 33 females. The associated lesions were present in all 70 cases: 62 had acyanotic (88.6 %) and 8 had cyanotic congenital heart diseases (11.4 %). Of the 70 cases, 18 had pump failure (25.7 %): 8 cases had left ventricular dysfunction, 7 had right ventricular dysfunction, and 3 had biventricular dysfunction; 33 (47.1 %) had pulmonary hypertension, 2 (2.9 %) had thrombus, and 1 (1.4 %) had tachyarrhythmia. Pump failure was worsened by volume overload in 33.9 % and by pressure overload in 8.1 % of cases. Some very rare lesions were detected. All 70 cases had Swiss cheese appearance of the apical half of the IVS, looking like the delta of a river. All of the apical non-compaction syndrome cases had associated lesions, mostly acyanotic congenital heart disease with volume overload, rather than obstructive lesions. Transthoracic echocardiography plays an important role in the diagnosis of apical non-compaction syndrome and associated lesions that worsen the pump failure.


Reducing mortality in severe sepsis: the Surviving Sepsis Campaign.
This article traces the history and evolution of the Surviving Sepsis Campaign as a public health initiative through its several stages of development. The literature that has characterized clinical experiences with interventions related to the campaign is reviewed and conclusions discussed.


Rat somatostatin sst2(a) and sst2(b) receptor isoforms mediate opposite effects on cell proliferation.
We have investigated the actions of somatostatin (SRIF) and angiopeptin on cell proliferation of CHO-K1 cells expressing the recently cloned rat sst2(b) receptor (CHOsst2(b)) and compared these to their effects in cells expressing the sst2(a) receptor (CHOsst2(a)). In contrast to the sst2(a) receptor, the sst2(b) receptor did not mediate inhibition of bFGF (10 ng ml(-1))-stimulated re-growth and cell proliferation. Rather, SRIF (0.1-1000 nM) and angiopeptin (0.1-1000 nM) stimulated basal re-growth and proliferation of CHOsst2(b) cells in a concentration-dependent manner (estimated pEC50 values of 7.8 and 7.9, respectively). The opposite effects of SRIF on cell proliferation mediated through the two sst2 receptor isoforms were both abolished by 18 h pre-treatment with pertussis toxin. The proliferative effect via the sst2(b) receptor was also abolished by the tyrosine kinase inhibitor, genistein. In conclusion, the present study shows that the rat sst2(a) and sst2(b) receptor splice variants mediate opposite effects on cell proliferation.


Development of acute frost drought in Rhododendron ferrugineum at the alpine timberline.
Acute winter frost drought in Rhododendron ferrugineum at the alpine timberline was provoked by removing the snow that had covered the shrubs and by irradiating and rewarming the twigs in situ in a climatized chamber simulating snow melt conditions. Water potential decreased to -2.3 MPa within three days. After activation of photosynthesis on the 1st day, the COr-uptake decreased during the 2nd day and approached zero at the 3rd day. With advanced desiccation, the internal COr concentration of the leaves increased indicating an impairment of chloroplast functions. The procedure of the disturbances appears to be similar to that of other acute drought events.


Embryonic lethalities and endothelial tumors in chimeric mice expressing polyoma virus middle T oncogene.
The effect of the middle T oncogene of polyoma virus was studied in vivo using a replication-defective selectable retrovirus. Injection of virus into newborn and adult mice resulted in the rapid appearance of cavernous hemangiomas. Infection of embryos did not yield transgenic mice; therefore, embryonal stem (ES) cells were used as an alternative system. Several infected ES cell clones were established that constitutively expressed middle T and its associated tyrosine kinase activity. Chimeric embryos obtained by blastocyst injection of individual ES cell clones were specifically arrested at midgestation, when multiple hemangiomas disrupted blood vessel formation. From these tumors endothelial cell lines were established that retained expression of von Willebrand factor yet were tumorigenic in vivo. These results suggest that middle T acts in endothelial cells as a single-step oncogene and that ES cells provide a valuable system for the study of growth control during embryogenesis.


Mechanisms of support: coping with loss in a major children's hospital.
Employment in a children's hospital of a major medical center can be stressful for healthcare providers, especially when faced with potential losses of pediatric and adolescent patients. Although it seems natural to believe that emotional distress following the death of a patient would be addressed, this is not always the case. The current manuscript presents results of a survey of healthcare providers at Shands Children's Hospital at the University of Florida, a not for profit teaching hospital. Hospital staff (N=94) responded to the survey with a 100% return rate. Responses identified situations considered to be stressful, and described how healthcare providers in this setting dealt with these incidents. Regarding existing hospital resources, respondents reported using multidisciplinary patient care conferences, social workers, and co-workers most often, as sources of support. Respondents also provided a lengthy listing of recommendations for improvement. Addressing the issues presented in this study may result in improved employee retention and lower overall turnover rates.


Effect of photodynamic therapy on surface decontamination in clinical orthodontic instruments.
The objective was to develop, characterize and test a box containing light emission diode (LED), Patent Deposit MU-BR20.2017.002297-3, which was named "Photodynamic Inactivation Device" (PID) and verify if it's suitable in microbial reduction or disinfection action of solid surfaces using PID. The equipment was made in a container of polypropylene with a lid of the same material and, for a better use of irradiation the internal part was covered with a layer of reflective aluminum. In addition, sixty boards of red LED 660 nm wavelength, containing three radiators each, for which the distribution of irradiation and spectral irradiance in all of the six internal faces were calculated in this device. That way, a low cost alternative was tested over three types of microorganisms present on the human microbiota: two strains Gram-positive (Gram +), Staphylococcus aureus and Streptococcus mutans and one strain Gram-negative (Gram -), Escherichia coli, inoculated in orthodontic instruments previously autoclaved. To assess the Photodynamic Inactivation (PDI) over these bacteria, instruments were contaminated by bacterial suspensions (3 × 10⁸ CFU/mL) and ulterior treatment with a solution of 100 μmol/L of MB for 20 min, and irradiated for another 20 min (energy density of 026 J/cm²). Microbial reduction was assessed by number counting of Colony Forming Units (CFU). At the end, microbial reduction of the surface of orthodontic metal instruments was compared with the positive group of each group. Results showed that PID caused a significant reduction (p < 0.05) of the microbial charge stuck in the orthodontic instruments. Thus, the photo prototype of the drawing is appropriate for phototherapy studies, granting it´s advantageous to the low level light therapy as well as for the antimicrobial photodynamic therapy. The perspective is that PID may potentialize the dissemination of phototherapy studies for determining its proper use in health science. And, thus, propose a low cost and atoxic alternative for disinfection of biomedical appliances as non-critical instruments, allowing also for use in the food industry.


Small nodules (≤ 6 mm in diameter) of multiple primary lung cancers: prevalence and management.
Synchronous multiple primary lung cancers associated with small non-dominant nodules are commonly encountered. However, the incidence, follow-up, and treatment of small non-dominant tumors have been but little studied. We explored the prevalence and management of small non-dominant tumors and factors associated with interval growth. This observational, consecutive, retrospective single-center study enrolled patients diagnosed with synchronous multiple primary lung cancers and small non-dominant tumors (≤ 6 mm in diameter) who underwent resection of the dominant tumor. The incidence, follow-up, and management of small non-dominant tumors and predictors of nodule growth were analyzed. There were 88 patients (12% of all lung cancer patients) with pathological diagnoses of synchronous multiple primary lung cancers. A total of 131 (18%) patients were clinically diagnosed with at least one small (≤ 6 mm in diameter) multiple primary lung cancer non-dominant tumor. 94 patients with 125 small-nodule non-dominant tumors clinically diagnosed as multiple primary lung cancers were followed-up for at least 6 months. A total of 29 (29/125, 23.2%) evidenced small pulmonary nodules (≤ 6 mm in diameter) that exhibited interval growth on follow-up computed tomography (CT). On multivariate analysis, a part-solid nodule (compared to a pGGN) (OR 1.23; 95% CI 1.08-1.40) or a solid nodule (compared to a pGGN) (OR 3.50; 95% CI 1.94-6.30) predicted small nodule interval growth. We found a relatively high incidence of multiple primary lung cancers with small non-dominant tumors exhibiting interval growth on follow-up CT, suggesting that resection of non-dominant tumors at the time of dominant tumor resection, especially when the nodules are part-solid or solid, is the optimal treatment.


The airway fungal microbiome in asthma.
Fungal involvement in asthma is associated with severe disease. The full spectrum of fungal species in asthma is not well described and is derived largely from insensitive culture techniques. To use high-throughput sequencing to describe the airway mycobiota in asthmatics with and without fungal sensitization and healthy controls; to compare samples representing different airway compartments; to determine whether the mycobiota was influenced by the fungal composition of outdoor air; and to compare findings with clinically relevant outcomes. We amplified the internal transcribed spacer region 2 of the nuclear ribosomal operon to identify the fungal species present. Ninety-seven subjects were recruited and provided sputum (83 asthmatics; 14 healthy subjects), with 29 also undergoing a bronchoscopy. A subset of airway samples were compared with matched outdoor air and mouthwash samples. Two hundred and six taxa at the species level were identified in sputum, most at low relative abundance. Aspergillus fumigatus, Candida albicans and Mycosphaerella tassiana had the highest relative abundances and were the most prevalent species across all subjects. The airway mycobiota consisted of a complex community with high diversity between individuals. Notable shifts in the balance of fungi detected in the lung were associated with asthma status, asthma duration and biomarkers of inflammation. Aspergillus tubingensis, a member of the Aspergillus niger species complex, was most prevalent from bronchoscopic protected brush samples and significantly associated with a low sputum neutrophilia. Cryptococcus pseudolongus, from the Cryptococcus humicola species complex, was more abundant from bronchoscopy samples than sputum, and differentially more abundant in asthma than health. The airway mycobiota was dominated by a relatively small number of species, but was distinct from the oropharyngeal mycobiota and air samples. Members of the A. niger and C. humicola species complexes may play unexpected roles in the pathogenesis of asthma.


Autoinflammatory Skin Disorders: The Inflammasomme in Focus.
Autoinflammatory skin disorders are a group of heterogeneous diseases that include diseases such as cryopyrin-associated periodic syndrome (CAPS) and familial Mediterranean fever (FMF). Therapeutic strategies targeting IL-1 cytokines have proved helpful in ameliorating some of these diseases. While inflammasomes are the major regulators of IL-1 cytokines, inflammasome-independent complexes can also process IL-1 cytokines. Herein, we focus on recent advances in our understanding of how IL-1 cytokines, stemming from inflammasome-dependent and -independent pathways are involved in the regulation of skin conditions. Importantly, we discuss several mouse models of skin inflammation generated to help elucidate the basic cellular and molecular effects and modulation of IL-1 in the skin. Such models offer perspectives on how these signaling pathways could be targeted to improve therapeutic approaches in the treatment of these rare and debilitating inflammatory skin disorders.


Designed formation of Co3O4@NiCo2O4 sheets-in-cage nanostructure as high-performance anode material for lithium-ion batteries.
Structural and compositional control of functional nanoparticles is considered to be an efficient way to obtain enhanced chemical and physical properties. A unique Co3O4@NiCo2O4 sheets-in-cage nanostructure is fabricated via a facile conversion reaction, involving subsequent hydrolysis and annealing treatment. Such hollow nanoparticles provide an excellent property for Li storage.


Langerhans Cell Histiocytosis in a Pediatric Patient with Simultaneous Gastrointestinal and Skin Involvement: A Case Report and Literature Review.
Background: Langerhans cell histiocytosis (LCH) has heterogeneous presentations involving single or multiple systems, but simultaneous isolated skin and gastrointestinal involvement is not common. Case report: A female infant with intermittent bloody diarrhea was unresponsive for treatment of food allergy. Histology of gastric and colonic tissues demonstrated Langerhan's cell histiocytosis. The infant also had red rashes that were histologically proven Langerhan's cell histiocytosis. Chemotherapy utilized vincristine, cytarabine and prednisone. The bloody diarrhea and rash completely resolved with no recurrence in the 11 months of follow-up. Conclusion: Langerhan cell histiocytosis may present with simultaneous gastrointestinal and skin involvement.


Three-dimensional culture of sebaceous gland cells revealing the role of prostaglandin E2-induced activation of canonical Wnt signaling.
Prostaglandin E2 (PGE2) is a proinflammatory mediator and activates the canonical Wnt-β-catenin signaling pathway in hematopoietic stem cells. The SZ95 cell line was established from human sebaceous gland cells and is studied as a model system for these cells. Given that 2D culture of SZ95 cells does not recapitulate the organization of sebaceous glands in situ, we developed a 3D culture system for these cells and examined the effects of PGE2 on cell morphology and function. SZ95 cells maintained in 3D culture formed organoids that mimicked the organization of sebaceous glands in situ, including the establishment of a basement membrane. Organoids exposed to PGE2 were larger and adopted a more complex organization compared with control organoids. PGE2 activated the canonical Wnt signaling pathway as well as increased cell viability and proliferation, mitochondrial metabolism, and lipid synthesis in the organoids. Culture of SZ95 cells in 3D culture system recapitulates the structure and susceptibility to PGE2 of sebaceous glands in situ and should prove useful for studies of the response of these glands to inflammation and other environmental stressors. Our results also implicate PGE2-induced activation of canonical Wnt signaling pathway in regulation of the morphology,proliferation, and function of "semi-vivo" sebaceous glands.


Depressive symptoms during the different phases of a migraine attack: A prospective diary study.
The relationship between migraine and depression has been thoroughly investigated, indicating a bidirectional comorbidity. The exact temporal relationship between acute depressive symptoms (mood changes) and the various phases of the migraine attack has not yet been examined. We performed a prospective diary study in n = 487 participants with migraine. Participants filled out a daily diary on migraine and acute depressive symptoms during a 1-month period. We randomly selected one migraine attack per participant, consisting of six days around an attack, including the interictal, premonitory, ictal, and postdromal phases. Acute depressive symptoms covered five major items from the DSM-5 classification. Primary analysis was performed using a mixed model with post-hoc testing. We also tested whether lifetime depression influenced the presence of acute depressive symptoms. During a migraine headache day, patients scored higher on acute depressive symptoms than on all other days of the migraine attack (p < 0.001). There were no early warning signs for an upcoming headache attack through acute depressive symptomatology. Migraine patients with lifetime depression scored overall higher during the migraine attack than those without lifetime depression (p < 0.001). Migraine attacks were based on self-reported migraine and one migraine attack per patient was randomly selected. We now clearly demonstrate that during the migraine headache phase, but not in the prodromal phase, patients report increased depressive symptomatology. No evidence was found for mood changes as an early warning sign for an upcoming migraine attack.


Distribution characteristics and potential ecological risk assessment of heavy metals (Cu, Pb, Zn, Cd) in water and sediments from Lake Dalinouer, China.
The concentrations of Cu, Pb, Zn and Cd were measured in water and sediment to determine their distribution characteristics and potential ecological risks of the Lake Dalinouer. The results revealed that the dominate form of Cu, Pb, Cd and Zn in surface sediments respectively were organic sulfides, Fe-Mn oxides, carbonates and Fe-Mn oxides, with a mean content of 4.28mgkg(-1), 0.76mgkg(-1), 7.84μgkg(-1) and 1.77mgkg(-1), respectively; the concentrations of bio-available metals had an increase tendency from the northeast to the southwest part of this lake. Acid volatile sulfides (AVS) and simultaneously extracted metal (SEM) were used to predict the potential bioavailability of heavy metals. The horizontal distribution of AVS (0.15-2.4μmolg(-1), mean 0.53μmolg(-1)) in surface sediments shows an increasing trend from southwest to northeast of the lake, whereas SEM (0.02-0.99μmolg(-1), mean 0.37μmolg(-1)) had an opposite pattern. The relative high salt and pH which restrained the bioactivities of sulfate-reducing bacteria (SRB) were the main controlling factor in AVS concentrations. The vertical variation of AVS concentration in sediment core increased with depth and different from SEM. Potential ecological risk index (PERI) and geo-accumulation index (Igeo) were used to assess heavy metals accumulation. The results indicated that moderate contamination of most heavy metals was prevalent and presented a decreased trend from southern to northern of the lake, and element Cd emerged the greatest potential ecological risk. The pollution of heavy metal in the southern of the Lake Dalinouer should be taken into consideration seriously.


Vascular endothelial growth factor gene delivery for revascularization in transplanted human islets.
Islet transplantation is limited by islet graft failure because of poor revascularization, host immune rejection, and nonspecific inflammatory response. Human vascular endothelial growth factor (hVEGF) gene delivery is likely to promote islet revascularization and survival. We evaluated gene expression from a bicistronic plasmid encoding hVEGF and enhanced green fluorescent protein (EGFP) (pCMS-EGFP-hVEGF). Glucose responsiveness of islets was evaluated both in vitro and in vivo, and revascularization in islet graft was evaluated by immunohistochemistry. After transfection, hVEGF and EGFP expression levels were comparable with original monocistronic plasmids in Jurkat cells but higher and prolonged hVEGF expression in islets transfected with the bicistronic plasmid was observed, possibly as the result of differences in promoter strength and hypoxia response. The 3:1 w/w complexes showed little toxicity to islets at a dose of 5 microg DNA per 2000 islets. On glucose challenge, insulin release from transfected islets as well as secretion from islets after transplantation under the mouse kidney capsules in response to glucose stimulation, increased with time. Immunohistochemical staining of transplanted islets using mouse anti-human insulin, mouse anti-human von Willebrand factor, and rat anti-mouse CD31 antibodies suggests that islets are functional and there is new blood vessel formation. These findings suggest that transient hVEGF gene expression by the islets may promote islet revascularization and prolong islet survival after transplantation.


Evaluating mRNA expression of tax, B chain of PDGF and PDGF-β receptors as well as HTLV-I proviral load in ATL patients and healthy carriers.
Adult T-cell leukemia (ATL) is a life-threatening malignant neoplasm of CD4+ T cells resulted from human T-cell leukemia virus type I (HTLV-I). Tax1 protein of HTLV-I can induce malignant proliferation of T-cells by modulating the expression of growth factors such as platelet-derived growth factor (PDGF). Here, we aimed to investigate the proviral load (PVL) of HTLV-I in ATL and also to evaluate the mRNA expression of B chain of PDGF and PDGF-β receptors in ATL patients and HTLV-I-infected healthy carriers. To this end, peripheral blood mononuclear cells (PBMCs) were isolated by using Ficoll-Histophaque density centrifugation. The mean of HTLV-I PVL in ATL patients (42,759 ± 15,737 copies/104 cells [95% CI, 9557-75962]) was significantly (p = .01) higher than that in healthy carriers (650 ± 107 copies/104 cells [95% CI, 422-879], respectively. The HTLV-I PVL in ATL patients exhibited a significant correlation with PBMC count (R = .495, p = .001). The mRNA expression of Tax, B chain of PDGF, and PDGF-β receptor genes was significantly higher in healthy carriers than in patients with ATL. In conclusion, the expression of the canonical PDGFβ and its receptor, and their correlation with Tax expression cannot be a suitable indicator and/or prognostic factor for progression of ATL in HTLV-I carriers.


Chemo-selection with docetaxel, cisplatin and 5-fluorouracil (TPF) regimen followed by radiation therapy or surgery for pharyngeal and laryngeal carcinoma.
Induction chemotherapy for patients with head and neck cancer is widely performed, and several advantages of induction chemotherapy have been reported. However, there is currently insufficient evidence to strongly recommend induction chemotherapy. In this study, we analyzed the outcomes for patients treated with induction chemotherapy and subsequent definitive treatments. Operable patients with untreated oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinoma treated with induction chemotherapy were included in this retrospective study. We conducted induction chemotherapy using docetaxel, cisplatin and 5-fluorouracil and performed subsequent surgical treatment or radiotherapy according to the response to induction chemotherapy. A total of 65 patients were included in this study, and 50 patients (76.9%) had Stage IV tumors. The response to induction chemotherapy was CR in two patients, PR in 55 patients, and SD in eight patients. The subsequent definitive treatment was radiotherapy in 60 patients, and surgery in five patients. The 3-year overall survival rates for patients who received radiotherapy and surgery were 88.4% and 75.0%, respectively (P = 0.30). The 3-year disease-free survival rates for patients who received radiotherapy and surgery were 68.0% and 0%, respectively (P = 0.01). The 3-year laryngeal dysfunction free survival rates for patients who received RT and surgery were 77.8% and 0%, respectively (P < 0.01). We achieved favorable survival outcomes and high larynx preservation rates. Our results suggest that induction chemotherapy using TPF regimen is one of the optimal treatment strategies when treating head and neck cancers. Further prospective studies with a larger cohort are required to confirm our findings.


Normal Sleep in Children and Adolescence.
Adequate sleep is essential for healthy development in childhood and adolescence. Healthy sleep contributes to good physical health, immune function, mental health, and academic performance. The regulation and architecture of sleep change greatly across childhood and adolescence, and the ability to obtain sufficient sleep is impacted by a range of factors that change with maturation. This article describes normal sleep across childhood and adolescence and discusses some of the most common barriers to adequate sleep, including early school start times, technology use, and changes to circadian rhythms, and sleep homeostasis across puberty.


Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities.
Six new compounds, including a tetralone 1, two xanthones 2 and 3, a flavan derivative 4, and two nor-diterpenoids 7 and 8, accompanied by two known flavan derivatives 5 and 6 and a known olefine acid (9) were isolated from whole bodies of Kronopolites svenhedini (Verhoeff). The structures of the new compounds were determined by 1D and 2D nuclear magnetic resonance (NMR) and other spectroscopic methods, as well as computational methods. Selected compounds were evaluated for their biological properties against a mouse pancreatic cancer cell line and inhibitory effects on iNOS and COX-2 in RAW264.7 cells.


The molecular size of natural organic matter (NOM) determined by diffusivimetry and seven other methods.
The objectives of this work are to (1) determine the diffusion coefficients of natural organic matter (NOM) by diffusivimetry, (2) compare the results with diffusion coefficients determined by two other methods (fluorescence correlation spectroscopy (FCS) and dynamic adsorption experiments (DAM), (3) compare molecular weights derived from the diffusion coefficients to molecular weights determined by three different ultrafiltration experiments and high perfomance size exclusion chromatography (HPSEC). The diffusion coefficients determined in this work (stirred diffusion cell) are about 70% higher than that determined by DAM, and agree well with diffusion coefficients determined by FCS. Molecular weights determined by HPSEC are of the same magnitude as molecular weights derived from diffusion coefficients. Molecular weights determined by ultrafiltration vary considerably depending on the choice of membrane types. Membranes made of cellulose acetate generate results similar to results derived from diffusion coefficients. Membranes made of regenerated cellulose and polyether sulfone appear to retain too much of NOM, resulting in artificially high molecular weights.


Differences in the impact of impaired glucose status on clinical outcomes in younger and older adults: Over a decade of follow-up in the Tehran lipid and glucose study.
Studies found that the impact of dysglycemia on microvascular, macrovascular events and mortality outcomes were different between the younger vs. older population. We aimed to investigate the age-specific association of prediabetes with clinical outcomes including type 2 diabetes (T2DM), hypertension, chronic kidney disease (CKD), cardiovascular disease (CVD), and mortality. A total of 5,970 Iranians (3,829 women) aged ≥30 years, without T2DM, were included. The age-specific (<60 and ≥60 years; minimum p-value for interaction = 0.001) multivariable-adjusted Cox regression was done to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the impaired glucose status including impaired fasting glucose (IFG) vs. normal fasting glucose (NFG), impaired glucose tolerance (IGT) vs. normal glucose tolerance (NGT), and IFG&IGT vs. NFG/NGT with each outcome. Among individuals aged ≥60 years, the prevalence of impaired glucose status (IFG, IGT, or both) was about 2 times higher compared to those aged <60. Age-specific association between prediabetes and incident hypertension was found for those aged <60 years; [HR (95% CI); IFG: 1.38 (1.16-1.65), IGT: 1.51 (1.26-1.81), and IFG&IGT: 1.62 (1.21-2.12)]. For CVD, in all impaired glycemic states, those aged <60 were at higher significant risk [IFG: 1.39 (1.09-1.77), IGT: 1.53 (1.19-1.97), and IFG&IGT: 1.60 (1.14-2.25)]. Stratified analyses showed similar associations for IFG and IGT with non-CV mortality 1.71 (1.04-2.80) and 2.12 (1.30-3.46), respectively, and for all-cause mortality among those aged <60 years [IFG: 1.63 (1.08-2.45) and IGT: 1.82 (1.20-2.76)]. In both age groups, all glycemic status groups were significantly associated with T2DM but not with CKD and CV mortality. The high prevalence of prediabetes particularly among the elderly population, limited resources, and the observed significant age differences in the impact of prediabetes states on different clinical outcomes calls for multicomponent intervention strategies by policy health makers, including lifestyle and possible pharmacological therapy, with the priority for the young Iranian population.


Resurgence of Autologous Fascial Slings in a Challenging Climate for Sling Surgery: A 20-Year Review of Comparative Data.
Since the US Food and Drug Administration's 2016 ban of transvaginal mesh use in vaginal prolapse surgery, there has been growing public scrutiny over the use of synthetic mesh slings (SSs) for the surgical management of female stress urinary incontinence (SUI). Although long considered the mainstay of current practice, interest in biological alternatives has grown. This article reviews the last 20 years of data comparing the success of autologous fascial slings (AFSs) and SSs in the treatment of female SUI. We reviewed the literature for randomized controlled trials comparing autologous pubovaginal sling and SS for the primary surgical treatment of female SUI using several search engines and databases between January 1, 2000, and March 31, 2020. Data were retrieved and compared across studies. Trials were evaluated for study setting, type, population characteristics, sample size, success definition and rate, recurrence rate, operative time, length of hospital stay, complications, and quality of life. Of the 1382 articles reviewed, 8 met eligibility criteria, representing 6 distinct cohorts and 726 subjects. Synthetic slings available for review were either tension-free vaginal tape (TVT) or minisling. The vast majority of studies demonstrated similar short- and long-term success rates of AFS and SS procedures utilizing a range of outcome measures. Both AFS and TVT sling had low recurrence rates in short- and long-term follow-up. However, AFS had significantly longer operative time, and longer hospital stay. Bladder perforation, on the other hand, occurred more commonly in TVT sling. Health-related quality-of-life scores, including sexual function, were similar between groups. Autologous fascial sling and SS are both highly effective surgical procedures for the treatment of female SUI. Although success rates are comparable, AFS is associated with less favorable operative measures. This review supports the effectiveness of AFS in treating female SUI as concerns over the use of synthetic materials in vaginal surgery rise. However, clinicians must weigh the risks conferred by this nonsynthetic alternative.