The impact of substance use disorder comorbidity on cognition of individuals with bipolar disorder: A systematic review.
The aim of this study is to describe whether Bipolar Disorder (BD) with Substance Use Disorder (SUD) comorbidity is associated with an increased cognitive impairment as compared to BD without SUD comorbidity. This is a systematic review. The literature search was conducted in three databases: PubMed, PsycINFO and Embase. A total of 2032 studies were screened after removing duplicates. 29 articles were included for full text screening, and a total of 14 articles were included in the systematic review. Multiple cognitive domains were assessed, including verbal, spatial and visual memory, and psychomotor and executive functioning. Over half the articles (64.3%, n=9) identified cognitive impairments in individuals with BD+SUD comorbidity as compared to individuals with BD without SUD comorbidity. In addition, individuals with the comorbidity exhibited more severe impairments on tests of executive functioning, and greater impairments in verbal and visual memory. The studies included in this systematic review reinforce that individual with comorbidity of BD and SUD have increased cognitive impairment as compared to individuals with BD without SUD comorbidity. Executive functioning was the most impaired cognitive domain found across the studies included in this review. Intervention strategies focused on executive functioning would be beneficial for this specific population.


Comparison of 3 Knee-Specific Quality-of-Life Instruments for Patients With Meniscal Tears.
Meniscal tears are a common cause of knee pain and disability. The objective measurement of the health-related quality of life of patients with meniscal tears plays a key role in clinical evaluation and therapeutic decision making. Several evaluation tools have been used to measure the effects of meniscal tears on knee function and quality of life. However, most of these tools are nonspecific for meniscal pathology. The purpose of the present study was to compare the capability of 3 commonly used knee assessment tools to measure the impact of meniscal tears on knee function and quality of life: the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Western Ontario Meniscal Evaluation Tool (WOMET). Our null hypothesis was that no difference would exist among the 3 assessment tools. Cohort study (diagnosis); Level of evidence, 2. A total of 207 consecutive patients (mean ± SD: age, 52.6 ± 14.3 years) with arthroscopically confirmed meniscal tear were included. Preoperatively, 3 knee function and quality-of-life scores were obtained: KOOS, WOMAC, and WOMET. The relative outcome scores of the questionnaires were compared postoperatively. The sum scores (relative scores) were as follows: 234.2 ± 92.5 (55.7%) for the KOOS, 132.6 ± 54.3 (55.5%) for the WOMAC, and 113 ± 30.8 (71%) for the WOMET. The relative score results for the WOMET were significantly higher than those for the WOMAC and the KOOS (both P < .01), while no significant difference was found between the WOMAC and the KOOS (P = .735). A greater impact on health-related quality of life for patients with meniscal tears can be measured with the WOMET when compared with the WOMAC and the KOOS. Therefore, using the WOMET can be recommended for the evaluation of knee function and quality-of-life impairment of patients with meniscal tears.


A mass spectrometry and DFT study of pyrithione complexes with transition metals in the gas phase.
2-Mercaptopyridine N-oxide (pyrithione, PTOH) along with several transition metal ions forms coordination compounds displaying notable biological activities. Gas-phase complexes formed between pyrithione and manganese (II), cobalt (II), nickel (II), copper (II), and zinc (II) were investigated by infusion in the electrospray source of a quadrupole-time of flight mass spectrometer. Remarkably, positive ion mode spectra displayed the singly charged metal adduct ion [C10 H8 MN2 O2 S2 ]2+ ([M(PTO)2 ]+• or [M(DPTO)]+• ), where DPTO is dipyrithione, 2,2'-dithiobis(pyridine N-oxide), among the most abundant peaks, implying a change in the oxidation state of whether the metal ion or the ligands. In addition, doubly charged ions were recognized as metal adduct ions containing DPTO ligands, [M(DPTO)n ]2+ . Generation of [M(PTO)2 ]+• / [M(DPTO)]+• could be traced by CID of [M(DPTO)2 ]2+ , by observation of the sequential losses of a charged (PTO+ ) and a radical (PTO• ) deprotonated pyrithione ligand. The fragmentation pathways of [M(PTO)2 ]+• / [M(DPTO)]+• were compared among the different metal ions, and some common features were noticed. Density functional theory (DFT) calculations were employed to study the structures of the observed adduct ions, and especially, to decide in the adduct ion [M(PTO)2 ]+• / [M(DPTO)]+• whether the ligands are 2 deprotonated pyrithiones or a single dipyrithione as well as the oxidation state of the metal ion in the complex. Characterization of gas-phase pyrithione metal ion complexes becomes important, especially taking into account the presence of a redox-active ligand in the complexes, because redox state changes that produce new species can have a marked effect on the overall toxicological/biological response elicited by the metal system.


Selection of in-phase or out-of-phase synchronization in a model based on global coupling of cells undergoing metabolic oscillations.
On the basis of experimental observations, it has been suggested that glycolytic oscillations underlie the pulsatile secretion of insulin by pancreatic beta cells, with a periodicity of about 13 min. If beta cells within an islet are synchronized through gap junctions, the question arises as to how beta cells located in different islets of Langerhans synchronize to produce oscillations in plasma levels of insulin. We address this question by means of a minimal model that incorporates the secretion of insulin by cells undergoing glycolytic oscillations. Global coupling and synchronization result from the inhibition exerted by insulin on the production of glucose, which serves as the substrate for metabolic oscillations. Glycolytic oscillations are described by a simple two-variable model centered on the product-activated reaction catalyzed by the allosteric enzyme phosphofructokinase. We obtain bifurcation diagrams for the cases in which insulin secretion is controlled solely by the product or by the substrate of the metabolic oscillator. Remarkably, we find that the oscillating cells in these conditions synchronize, respectively, in phase or out of phase. Numerical simulations show that in-phase and out-of-phase synchronization can sometimes coexist when insulin release is controlled by both the substrate and the product of the metabolic oscillator. The results provide an example of a system in which the selection of in-phase or out-of-phase synchronization is governed by the nature of the coupling between the intracellular oscillations and the secretion of the biochemical signal through which the oscillating cells are globally coupled.


Common human melanoma-associated antigen(s) detected by monoclonal antibodies.
Hybridoma cells have been derived from a fusion between mouse myeloma cells (P3-NSI/1Ag4) and spleen cells from a mouse immunized with membrane-enriched fractions from the human melanoma cell line Me-43. Of the 26 hybrids obtained, seven secreted antibodies which reacted with the melanoma cell line used for immunoassay. The specificity of the antibodies produced by the seven positive hybrids was further investigated on 16 melanoma cell lines, 15 other tumors, and 14 lymphoblastoid cell lines. The antibodies from four positive hybrids showed a broad reactivity, whereas those from three hybrids reacted exclusively with melanoma cells. The antibodies from two of these three hybrids, alpha-Mel/5 and alpha-Mel/14, seem to be directed against common melanoma antigen(s) since they reacted with all (with one exception) of the 16 melanoma cell lines tested only with five of the 16 melanoma lines. Reciprocal binding inhibition tests using [3H]leeucine-labeled antibodies showed that alpha-Mel/5 and alpha-Mel/14 antibodies were directed against different antigenic determinants.


Screening for thyroid malignancy: the role of fine-needle biopsy.
Cytological examination of the aspirate of fine-needle biopsy is becoming more widely accepted as a screening test for malignancy in thyroid nodules. However, it tends to be used in addition to, rather than instead of, more traditional methods. In this five-year prospective evaluation we performed fine-needle biopsy in 618 euthyroid patients with nodular thyroid enlargement, 86% of whom also underwent radionuclide scans and 55% of whom underwent ultrasound scans. In 19% of patients fine-needle biopsy yielded insufficient material for diagnosis, and in 14% of patients normal follicular cells were found (which indicated that the clinical lesion was not sampled). To date, a histological diagnosis has been obtained in 258 (42%) patients, 44 of whom had malignancies. The results of the radionuclide and ultrasound scans did not alter the odds in favour of the detection of malignancy. The cytological diagnosis of malignancy was falsely-positive in two patients and falsely-negative in four patients (three cases of which probably were sampling errors). If, in addition to overtly-malignant cells, atypical Hürthle cells and follicular neoplasms were considered to be potentially malignant, fine-needle biopsy alone had a sensitivity of 87% and a specificity of 72%. This good accuracy would be reduced by sampling failures, but a policy of operating on all patients with potentially-malignant cells, or on those in whom satisfactory aspirates could not be obtained, would yield high rates of the diagnosis of malignancy and would reduce the number of operations. Our data indicate that the most-appropriate method of screening thyroid nodules for malignancy is fine-needle biopsy without pertechnetate scanning or ultrasound examinations.


Orthotopic neobladder: a 22-year experience.
To analyze the outcome of orthotopic ileal neobladder related to complications and quality of life. From 1985 to 2006, 75 patients with mean age of 57 years, (41-75) underwent radical cystectomy and orthotopic ileal neobladder substitution. The mean follow up was 72 months (6-144). Mean operative time was 240 minutes. Intraoperative blood loss ranged from 250 to 2810 ml. Ureteral stents were removed on 14th postoperative day, and patients were discharged at 2st day, average. Complications appeared in 23 patients. There were two recurrent TCC in the neobladder. Three patients died from pulmonary embolism. Vesicoureteral reflux appeared in three patients, and it was bilateral in two patients. Total of 98% patients have daytime continence. Continent urinary reservoirs represent the state of the art in urinary diversion. Surgeons who perform these operations are urgent to institute requirements for careful long-term follow-up of these patients.


Upgrade of far infrared three-wave polarimeter-interferometer system on Joint-TEXT.
The far infrared polarimeter-interferometer system (POLARIS) on the Joint-TEXT has been upgraded recently. A new support structure has been applied to the mixer array of the POLARIS for adjusting the position of the mixers precisely. Five detection chords have been added to the system on the low field side by optimizing the utilization efficiency of the laser beams on both sides of the beam splitting grid. The spatial resolution can be improved from 3 to 1.5 cm. A better measurement on plasma electron density and current density has been obtained after the system is upgraded. The initial experimental result will be introduced along with the upgrade details.


[Evaluation of positive cases with peritoneal lavage cytology in gastric cancer].
Peritoneal dissemination with advanced gastric cancer is of significant problem. Peritoneal lavage cytology has been an effective method for the detection of early peritoneal dissemination since 1999. The accurate evaluation of peritoneal lavage cytology is unclear except for the same prognosis of peritoneal dissemination. We examined the clinical findings and the prognosis with positive cases in peritoneal lavage cytology. The prognosis of cases with P1CY1 or P2P3 group was poorer than in the P0CY1 or P0, CY1 group. We thus review the evaluation of peritoneal lavage cytology with gastric cancer in the Japanese and English literature. In addition, we describe the diagnosis of early peritoneal dissemination using peritoneal lavage tumor markers or molecular markers of peritoneal lavage.


The meaning of concepts related to breast reconstruction.
Information is presented from a psychometric study using a semantic differential to measure the meaning of concepts related to breast reconstruction. One hundred five women participated. All were experiencing breast reconstruction subsequent to mastectomy. The average woman was married, middle-aged, and had 11/2 years of education beyond high school. Results from the semantic differential demonstrated that the women viewed themselves, their bodies, and their femininity positively. They valued themselves, and their self-concepts were closer in meaning to health than to mastectomy, death, or cancer.


A neurosurgical presentation of patent foramen ovale with atrial septal aneurysm.
We describe a case of cerebral abscess in a 53-year-old lady with a background of congenital heart defect. She has an atrial septal defect with atrial septal aneurysm, which remained undiagnosed until this clinical presentation. She presented with a short history of right-sided hemiplaegia and neuroimaging revealed a heterogeneous lesion in the left frontoparietal region. Neuronavigation-guided left frontoparietal craniotomy was performed to debulk the lesion and preoperatively frank pus was drained, which grew Streptococcus constellatus. She was successfully treated with antibiotics for 6 weeks and her clinical condition improved. We believe that the patients' previous dental extraction has possibly resulted in a paradoxical embolism through the atrial septal defect bypassing the pulmonary circulation. The MRI scan picture was misleading, as it was initially thought to be a high-grade brain tumour.


Nurses' Intentions to Initiate an Antipsychotic or Behavioral Intervention with Nursing Home Residents: The Role of Norms and Being Evaluated.
To examine whether exposure to a message to avoid antipsychotic medications and a salient sense of managerial oversight influenced nurses' treatment intentions. 158 nurses from 28 long-term care facilities were randomized to one of four conditions within a 2 × 2 between-participants design. The nurses responded to a case study depicting a resident with dementia-related behavioral problems with their intent to initiate an antipsychotic or a psychosocial intervention. Self-efficacy, descriptive norms, and attitudes were measured via self-report. Perceived local antipsychotic prevalence was related to the nurses' treatment intentions. There were no main or interactive effects of the avoid antipsychotic or manager oversight conditions on the nurses' treatment intentions. However, there was a significant interaction of actual facility antipsychotic prevalence and the avoid antipsychotics message on intentions to initiate an antipsychotic. Nurses' perceptions of local antipsychotic prevalence were positively associated with intentions to initiate an antipsychotic and negatively associated with intentions to initiate a psychosocial intervention. However, a salient message to avoid antipsychotics had limited influence on nurses' treatment intentions and was associated with increased intentions to initiate antipsychotics in facilities with higher rates of antipsychotic use. The oversight condition did not demonstrate adequate internal validity, which may have caused its lack of effect on treatment intentions. Nurses' perceptions of the local prevalence of antipsychotic use is associated with their treatment intentions. However, increasing the visibility of a message discouraging antipsychotic use may have limited utility in influencing nurses' intentions to initiate an antipsychotic or psychosocial intervention.


An incidental finding of pleomorphic adenoma of the minor salivary glands in the skin area of the lower lip.
Salivary gland tumors are uncommonly seen and account for less than 3% of the head and neck tumors. Pleomorphic adenoma is a well-described benign tumor of the salivary glands, originating from myoepithelial and intercalated duct cells. It is most commonly found in major salivary glands. We present a rare and unusual case of pleomorphic adenoma of the minor salivary glands in the lower lip. The tumor was diagnosed upon excision of 1.5 × 1.2 cm(2) well-circumscribed nodule at the junction of the lower lip and chin in a 46-year-old man. The histopathological analysis confirmed presence of an epithelial salivary gland tumor with islands of plasmacytoid cells, and duct-like structures within a variable and mixed stroma.


[The death of foundlings, a drama in two acts].
Around 1750 society grows aware of the high mortality of abandoned infants: enlightened physicians and administrators attempt to remedy this disaster and put the blame on the country wet nurses who took in the foundlings. A large number of contemporary historians have incritically contented themselves with repeating these reproaches. This article constitutes an attempt to rehabilitate country wet nurses. According to the authors, the infants were victims of the circumstances of being abandoned. An analysis based on a list of names does show that the most obvious causes for the high mortality rate of the foundlings were the close incidents surrounding the fact of being abandoned whereas it can rarely be explained by the living conditions at a wet nurse's. In the background, an original rural society emerges in a poor country taking in infants constitutes a real business. This study represents but one stage at the core of a developing research.


Acetylcholine and Alzheimer's disease.
The hypothesis that cognitive impairment in Alzheimer's disease is related to cholinergic degeneration in the brain is still, a decade after its formulation, subject to critical evaluation. In marked contrast to the monoamine hypotheses of affective disorders or schizophrenia--based primarily on the mechanisms of action of therapeutic drugs, and yet lacking convincing pathological data on the human brain itself--the cholinergic hypothesis of Alzheimer's disease currently rests largely on evidence of neurochemical pathology in affected tissue, but still depends on effective therapy for its ultimate validation. The urgent need for a means of countering cognitive impairment in degenerative dementias such as Alzheimer's disease (probably the most important cause of intellectual decline in old age) hardly needs emphasising. In this annotation, a number of key questions specifically relating to the cholinergic involvement in Alzheimer's disease are considered. These questions are already being answered both within and, as so often in the history of biological psychiatry, outside the immediate area of investigation.


Effect of an adenosine deaminase inhibitor on the uptake and metabolism of arabinosyl adenine (Vidarabine) by intact human erythrocytes.
Tritium-labeled vidarabine was incubated with fresh citrated human blood in the absence and presence of an adenosine deaminase inhibitor, co-vidarabine was rapidly deaminated to form ara-Hx with minimal incorporation into the erythrocytes. Ara-HxMP was identified as the major component in the erythrocytic nucleotide pool, together with small amounts of IMP, adenosine nucleotides and traces of arabinosyl nucleotides. Addition of the inhibitor completely protected vidarabine from enzymatic deamination and resulted in much greater accumulation of vidarabine 5'-mono-, di-, and triphosphates in the erythrocytes.


The impact of the repair of staple line dehiscence in post-RYGB patients on glucose homeostasis and gut hormones--a preliminary study.
Staple-line disruption (SLD) following Roux-en-Y gastric bypass (RYGB) results in weight regain. This study evaluated glucose homeostasis and gut hormonal changes following surgical repair of gastrogastric fistula. Three patients with SLD underwent an oral 75 g glucose tolerance test (OGTT) before (baseline) and one week after gastric pouch restoration. Plasma glucose, insulin and glucagon glucose-dependent insulinotropic polypeptide (GIP) and glucagonlike peptide-1 (GLP-1) were measured in the OGTT samples. Fasting plasma levels of ghrelin and leptin were assessed. Restoration of gastric pouch provided moderate amelioration of glucose metabolism and gut hormones, yet without complete normalisation of glucose homeostasis at one week after surgery. Duodenal passage exclusion resulted in early improvement of control fasting plasma glucose with decrease of glucagon from 18.5 to 15 (ng/mL, by 19%), relatively stable insulin and decline of incretin hormones (GIP and GLP-1). Post-challenge measurements confirmed amelioration of glycaemic control with decrease of plasma glucose from 182 to 158 mg/dL at 60 minutes. Surgical re-intervention resulted in exacerbation of GIP response with brisk rise in plasma level, accompanied by considerable increase of peak insulin concentration. The overall post-challenge glucagon and GLP-1 responses were decreased. Marked decrease in fasting plasma ghrelin and leptin were observed. Our report gives further insight into the hormonal mechanisms underlying the effects of surgically altered anatomy of different parts of the small intestine on glucose homeostasis that is highly important, since it may facilitate novel conservative therapies of diabetes without the need for surgery.


The release of As, Cr and Cu from contaminated soil stabilized with APC residues under landfill conditions.
The aim of this study was to investigate the stability of As, Cr and Cu in contaminated soil treated with air pollution control residues under landfill conditions. The influence of landfill gas and temperature on the release of trace elements from stabilized soil was simulated using a diffusion test. The air pollution control residues immobilized As through the precipitation of Ca-As minerals (calcium arsenate (Ca5H2(AsO4)3 × 5H2O), weilite (CaAsO4) and johnbaumite (Ca5(AsO4)3(OH)), incorporation of As into ettringite (Ca6Al2(SO4)3(OH)12 × 26H2O) and adsorption by calcite (CaCO3). The air pollution control residues generally showed a high resistance to pH reduction, indicating high buffer capacity and stability of immobilized As in a landfill over time. Generation of heat in a landfill might increase the release of trace elements. The release of As from stabilized soil was diffusion-controlled at 60 °C, while surface wash-off, dissolution, and depletion prevailed at 20 °C. The air pollution control residues from the incineration of municipal solid waste immobilized Cr, indicating its stability in a landfill. The treatment of soil with air pollution control residues was not effective in immobilization of Cu. Contaminated soils treated with air pollution control residues will probably have a low impact on overall leachate quality from a landfill.


Observation of the Decay Ξ_{b}^{-}→pK^{-}K^{-}.
Decays of the Ξ_{b}^{-} and Ω_{b}^{-} baryons to the charmless final states ph^{-}h^{'-}, where h^{(')} denotes a kaon or pion, are searched for with the LHCb detector. The analysis is based on a sample of proton-proton collision data collected at center-of-mass energies sqrt[s]=7 and 8 TeV, corresponding to an integrated luminosity of 3 fb^{-1}. The decay Ξ_{b}^{-}→pK^{-}K^{-} is observed with a significance of 8.7 standard deviations, and evidence at the level of 3.4 standard deviations is found for the Ξ_{b}^{-}→pK^{-}π^{-} decay. Results are reported, relative to the B^{-}→K^{+}K^{-}K^{-} normalization channel, for the products of branching fractions and b-hadron production fractions. The branching fractions of Ξ_{b}^{-}→pK^{-}π^{-} and Ξ_{b}^{-}→pπ^{-}π^{-} relative to Ξ_{b}^{-}→pK^{-}K^{-} decays are also measured.


The conquest of cesarean section-related infections: a progress report.
More than a century ago, Robert P. Harris demonstrated convincingly that death from infection after cesarean section could be reduced significantly by operating early, rather than after several days of labor, by using aseptic surgical technique, and by closing the uterine incision. For the most part, his advice was ignored and the mortality rate remained high, except in hospitals with well-organized and well-controlled obstetric services. Although the incidence of total infections has been decreased by the use of prophylactic antibiotics, too many serious infections and maternal deaths still occur. These can be reduced by proper management of labor, by recognizing the need for cesarean section early, by using alternative methods for delivery when appropriate, by meticulous surgical technique, and by selective use of prophylactic antibiotics. These changes are not likely to occur unless care of obstetric patients is assumed by experienced obstetricians who are prepared to recognize and correct abnormal labor early and to perform instrumental extraction and vaginal breech deliveries rather than cesarean section in carefully selected patients.


It's worth the ... risk.
Sharing risk with HMOs requires the patience of a kindergarten teacher, the finesse of a U.N. negotiator, and the agility of a fighter pilot. Intimidated yet? Neither are these executives. Our exclusive data show how hospitals handle risk contracts.


Ypt11 functions in bud-directed transport of the Golgi by linking Myo2 to the coatomer subunit Ret2.
A yeast class V myosin Myo2 transports the Golgi into the bud during its inheritance. However, the mechanism that links the Golgi to Myo2 is unknown. Here, we report that Ypt11, a Rab GTPase that reportedly interacts with Myo2, binds to Ret2, a subunit of the coatomer complex. When Ypt11 is overproduced, Ret2 and the Golgi markers, Och1 and Sft2, are accumulated in the growing bud and are lost in the mother cell. In a ret2 mutant that produces the Ret2 protein with reduced affinity to Ypt11, no such accumulation is observed upon overproduction of Ypt11. At a certain stage of budding, it is known that the late Golgi cisternae labeled with Sec7-GFP show polarized distribution in the bud. We find that this polarization of late Golgi cisternae is not observed in the ypt11Delta mutant. Indeed, analyses of Sec7-GFP dynamics with spatio-temporal image correlation spectroscopy (STICS) and fluorescence loss in photobleaching (FLIP) reveals that Ypt11 is required for the vectorial actin-dependent movement of the late Golgi from the mother cell toward the emerging bud. These results indicate that the Ypt11 and Ret2 are components of a Myo2 receptor complex that functions during the Golgi inheritance into the growing bud.


[Effect of intravenous infusion with lidocaine on rapid recovery of laparoscopic cholecystectomy].
Objective: To investigate the effect of intravenous infusion with lidocaine on rapid recovery of laparoscopic cholecystectomy. Methods: This study was a prospective randomized controlled trial. From February to August 2016 in Affiliated Yiwu Hospital of Wenzhou Medical University, 60 patients scheduled for laparoscopic cholecystectomy under general anesthesia were involved and randomly divided into control group (n=30) and lidocaine group (n=30). Patients in lidocaine group received lidocaine 1.5 mg/kg intravenously before induction and followed by 2.0 mg·kg(-1)·h(-1) to the end of surgery. Patients in control group received equal volumes of saline intravenously. Anesthesia induction in both groups were given intravenous midazolam 0.03 mg/kg, sufentanil 0.2 μg/kg, propofol 2.0 mg/kg and cisatracuium 0.2 mg/kg. Anesthesia was maintained with propofol 0.05-0.20 mg·kg(-1)·min(-1) and remifentanil 0.1-0.5 μg·kg(-1)·min(-1) for laryngeal mask airway which bispectral index (BIS) value maintained at 40-60. BIS, heart rate(HR) and mean arterial pressure(MAP) were recorded before anesthesia induction, before and immediately after laryngeal mask implantation, intraoperative 30 min and anesthesia awake. Pain scores were assessed using visual analogue scales (VAS) at postoperation immediately, 30 min during postanesthesia care unit (PACU), 2, 6, 12, and 24 h after surgery. The time of PACU retention, postoperative ambulation, first intestine venting and discharge were recorded. The dosage of propofol and remifentanil, the frequency of sufentanil used, the incidence of postoperative nausea and vomiting were also recorded. Patient satisfaction was evaluated by using Simple Restoration Quality Score (QoR-9). Results: BIS values before and after laryngeal mask implantation in lidocaine group were 50.50±3.47 and 54.63±1.25 respectively, which was lower than those in control group(54.30±4.78, 55.80±2.33; t=3.542, 2.423, all P<0.05). The VAS score at postoperation immediately, PACU 30 min, postoperative 2, 6, 12 h in lidocaine group were 2.76±0.97, 2.37±0.93, 2.10±1.12, 1.76±0.97, 1.20±0.76 respectively, which was lower than those in control group (3.83±1.34, 3.27±1.26, 3.06±1.20, 2.63±0.88, 1.90±0.84; t=3.528, 3.154, 3.217, 3.603, 3.372, all P<0.05 ). The frequency of additional sufentanil at postoperation immediately and PACU 30 min in lidocaine group was 5(17%), 3(10%), which were less than those in control group(12(40%), 9(30%); χ(2)=4.022, 3.950, all P<0.05). The dosage of propofol and remifentanil in lidocaine group were (4.33±0.75) mg·kg(-1)·h(-1) and (9.00±1.66) μg·kg(-1)·h(-1) respectively, which were less than those in control group ((5.20±1.39) mg·kg(-1)·h(-1) and (10.43±2.20) μg·kg(-1)·h(-1;) t= 2.982, 2.842, all P<0.05). The time of PACU retention, postoperative ambulation and first intestine venting were (39.90 ± 8.06) min, (11.93±1.68) h and (10.16±1.05) h respectively in lidocaine group, which were shorter than those in control group ((48.23±10.04) min, (13.16±1.58) h and (11.13±1.30) h; t=3.514, 2.931, 3.156, all P<0.05). The QoR-9 score in lidocaine group was 15.60±1.07, which was higher than that in control group(14.73±0.74, t=-3.649, P<0.05). There was no significant difference in the incidence of postoperative nausea/vomiting and the discharge time between two groups (all P>0.05). Conclusion: Intravenous infusion of lidocaine can effectively reduce the dosages of propofol and remifentanil, postoperative early VAS score, postoperative ambulation time and first intestine venting time which could improve the satisfaction of patients.


The MYB46 transcription factor is a direct target of SND1 and regulates secondary wall biosynthesis in Arabidopsis.
We demonstrate that the Arabidopsis thaliana MYB46 transcription factor is a direct target of SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1), which is a key transcriptional activator regulating the developmental program of secondary wall biosynthesis. The MYB46 gene is expressed predominantly in fibers and vessels in stems, and its encoded protein is targeted to the nucleus and can activate transcription. MYB46 gene expression was shown to be regulated by SND1, and transactivation analysis demonstrated that SND1 as well as its close homologs were able to activate the MYB46 promoter. Electrophoretic mobility shift assays and chromatin immunoprecipitation experiments revealed that SND1 binds to the MYB46 promoter. Dominant repression of MYB46 caused a drastic reduction in the secondary wall thickening of fibers and vessels. Overexpression of MYB46 resulted in an activation of the biosynthetic pathways of cellulose, xylan, and lignin and concomitantly led to ectopic deposition of secondary walls in cells that are normally nonsclerenchymatous. In addition, the expression of two secondary wall-associated transcription factors, MYB85 and KNAT7, was highly upregulated by MYB46 overexpression. These results demonstrate that MYB46 is a direct target of SND1 and is another key player in the transcriptional network involved in the regulation of secondary wall biosynthesis in Arabidopsis.


Generation of induced pluripotent stem cells from Asian patients with chronic neurodegenerative diseases.
Induced pluripotent stem (iPS) cells derived from disease patients are an invaluable resource for biomedical research and may provide a source for replacement therapies. In this study, we have generated iPS cells from Asian patients with chronic degenerative diseases of the nervous system, including spinal muscular atrophy (SMA), Parkinson disease (PD) and amyotrophic lateral sclerosis (ALS) by transduction with four factors (KLF4, SOX2, OCT4 and c-MYC). All of the iPS cells showed pluripotency similar to that of human embryonic stem cells (hESCs) and were able to differentiate into various somatic cell types in vitro and in vivo. Furthermore, the iPS cells also can be committed to differentiate into neural cells, the cell type that is affected in chronic degenerative diseases. Therefore, the patient-specific iPS cells we generated offer a cellular model in which to investigate disease mechanisms, discover and test novel drugs and develop new therapies for chronic neurodegenerative diseases.


Fluoroquinolone adverse effects and drug interactions.
Extensive pharmacologic and clinical development of quinolone antimicrobial agents has resulted in improved antimicrobial activity, pharmacokinetic features, toxicity, and drug-drug interaction profiles. Nalidixic acid and other early quinolones had limited use due to poor pharmacokinetics, relatively narrow antimicrobial spectrum of activity, and frequent adverse effects. Beginning with the development of fluoroquinolones, such as norfloxacin and ciprofloxacin, in the 1980s, the agents assumed a greatly expanded clinical role because of their broad antimicrobial spectrum of action, improved pharmacokinetic properties, and more acceptable safety profile. Although the pharmacokinetics and efficacy of the drugs have improved significantly, a major area of continued emphasis is to further reduce the frequency and severity of adverse events and drug-drug interactions. Older agents such as ciprofloxacin and ofloxacin are still extensively prescribed, but the focus of this article is on the newer fluoroquinolones (levofloxacin and other drugs that have been approved or have been under investigation since approximately 1997).


[Controlled respiration in patients with severe neurological diseases. Syndrome of functional changes].
The investigations were carried out on a group of neurological patients treated by means of assisted or controlled respiration from respirators. Volumetric and gasometric measurements were performed and radiological examinations of the chest were done periodically. The obtained results suggest that neurological patients constitute a specific group with a more rapid fall in the values of VC and PaO2, increased alveolar-capillary gradient (PA-a) and decreased actual compliance delta t/ delta p.


Feasibility and acceptability of peer-delivered interventions using mHealth for PrEP services among adolescent girls and young women in DREAMS program in Botswana.
Adolescent girls and young women accounted for 25% of all new HIV infections despite representing only 10% of the population in Sub Saharan Africa. PEPFAR has launched the Determined, Resilient, Empowered, AIDS-free, Mentored, and Safe (DREAMS) initiative, a comprehensive HIV prevention program including PrEP services. Among adolescent girls and young women, PrEP adherence is currently sub-optimal. Tailored strategies for adolescent girls and young women to improve access and use of PrEP delivery are urgently needed to maximise its potential. Recommended interventions include peer-delivered interventions using mobile technology. However, data on the feasibility and acceptability of this approach is limited for SSA. We assessed the feasibility and perceived acceptability of providing mHealth peer-delivered interventions to support PrEP services among adolescent girls and young women in Botswana. This cross-sectional study included HIV-negative women aged 18-24 years old seeking health services at DREAMS-supported facilities. Participants completed a survey assessing the feasibility and perceived acceptability of the mHealth peer-delivered interventions, which included the Acceptability of Intervention Measure (AIM). Descriptive analyses were performed. A total of 131 participated in the study. Overall, 89% owned a mobile phone (feasibility). There was no difference in cell phone ownership between participants from rural and urban settings. Among participants, 85% reported interest in participating in a mHealth peer-delivered intervention if it was available to them. Regarding perceived acceptability for mHealthpeer support groups for PrEP, the average score on the AIM was 3.8 out of 5 (SD = 0.8). mHealthpeer-delivered interventions appear to be feasible and perceived acceptable among adolescent girls and young women in Botswana. This modality should be incorporated into PEPFAR's programmatic toolkit of implementation strategies to improve PrEP services.


Quantitative Mapping of Endosomal DNA Processing by Single Molecule Counting.
Extracellular DNA is engulfed by innate immune cells and digested by endosomal DNase II to generate an immune response. Quantitative information on endosomal stage-specific cargo processing is a critical parameter to predict and model the innate immune response. Biochemical assays quantify endosomal processing but lack organelle-specific information, while fluorescence microscopy has provided the latter without the former. Herein, we report a single molecule counting method based on fluorescence imaging that quantitatively maps endosomal processing of cargo DNA in innate immune cells with organelle-specific resolution. Our studies reveal that endosomal DNA degradation occurs mainly in lysosomes and is negligible in late endosomes. This method can be used to study cargo processing in diverse endocytic pathways and measure stage-specific activity of processing factors in endosomes.


Remimazolam tosylate's long-term sedative properties in ICU patients on mechanical ventilation: effectiveness and safety.
This study compared remimazolam tosylate with propofol or midazolam to assess its safety and effectiveness for long-term sedation of intensive care unit (ICU) patients requiring mechanical ventilation. Adult patients in the ICU receiving sedation and mechanical ventilation for longer than 24 h were included in this single-center, prospective, observational study. Depending on the sedatives they were given, they were split into two groups (midazolam or propofol group; remimazolam group). ICU mortality was the main result. Laboratory tests, adverse events, and the length of ICU stay were considered secondary outcomes. A total of 106 patients were involved (46 received propofol or midazolam versus 60 received remimazolam). Age (P = 0.182), gender (P = 0.325), and the amount of time between being admitted to the ICU and receiving medication infusion (P = 0.770) did not substantially differ between the two groups. Multivariate analysis revealed no statistically significant difference in ICU mortality between the two groups. The remimazolam group showed less variability in heart rate (P = 0.0021), pH (P = 0.048), bicarbonate (P = 0.0133), lactate (P = 0.0002), arterial blood gas analyses, liver, and kidney function. The Richmond Agitation and Sedation Scale scores, length of ICU stay, and occurrence of adverse events did not exhibit significant differences between the two groups. Remimazolam tosylate did not increase the total inpatient cost, the incidence of adverse events, and ICU mortality in patients with mechanical ventilation. These findings suggest that remimazolam may represent a promising alternative for sedation in the ICU setting.


Both ciliary and non-ciliary functions of Foxj1a confer Wnt/β-catenin signaling in zebrafish left-right patterning.
The Wnt/β-catenin pathway is implicated in left-right (LR) axis determination; however, the underlying mechanism remains elusive. Prompted by our recent discovery that Wnt signaling regulates ciliogenesis in the zebrafish Kupffer's vesicle (KV) via Foxj1a, a ciliogenic transcription factor, we decided to elucidate functions of Foxj1a in Wnt-regulated LR pattern formation. We showed that targeted injection of wnt8a mRNA into a single cell at the 128-cell stage is sufficient to induce ectopic foxj1a expression and ectopic cilia. By interrogating the transcription circuit of foxj1a regulation, we found that both Lef1 and Tcf7 bind to a consensus element in the foxj1a promoter region. Depletion of Lef1 and Tcf7 inhibits foxj1a transcription in the dorsal forerunner cells, downregulates cilia length and number in KV, and randomizes LR asymmetry. Targeted overexpression of a constitutively active form of Lef1 also induced an ectopic protrusion that contains ectopic transcripts for sox17, foxj1a, and charon, and ectopic monocilia. Further genetic studies using this ectopic expression platform revealed two distinct functions of Foxj1a; mediating Wnt-governed monocilia length elongation as well as charon transcription. The novel Foxj1a-charon regulation is conserved in KV, and importantly, it is independent of the canonical role of Foxj1a in the biosynthesis of motile cilia. Together with the known function of motile cilia movement in generating asymmetric expression of charon, our data put forward a hypothesis that Foxj1a confers both ciliary and non-ciliary functions of Wnt signaling, which converge on charon to regulate LR pattern formation.


Pipping muscle and liver metabolic profile changes and relationships in broiler embryos on days 15 and 19 of incubation.
The relative proportions and relationships of pipping muscle and liver nutrients in broiler embryos on d 15 and 19 of incubation were determined. Ninety hatching eggs obtained from a 30-wk-old broiler breeder flock were incubated on 3 replicate tray levels (30 eggs per tray) for 19 d. On 15 and 19 d of incubation, 10 live embryos per tray level were necropsied to collect pipping muscle and liver samples. As the broiler embryo developed between d 15 and 19 of incubation, the glycogen and protein concentrations of the pipping muscle increased, whereas those of the liver decreased, and the fat concentration of the pipping muscle decreased, whereas that of the liver increased. Across d 15 and 19, pipping muscle glycogen was negatively correlated with liver fat, whereas on d 15, pipping muscle glucose was negatively correlated with liver fat, and pipping muscle glycogen was negatively correlated with liver glucose and glycogen. Pipping muscle fat was negatively correlated with liver glucose on d 15 but positively correlated with liver glycogen on d 19. In conclusion, in preparation for hatch between d 15 and 19 of incubation, weights of the liver and pipping muscle of broiler embryos increased relative to their BW. This occurred in association with the accumulation of glucose, glycogen, and protein and with the loss of fat in the pipping muscle. The carbohydrate stores in the pipping muscle were supported by the active metabolism of the liver before 19 d of incubation, which included the transfer of glucose and fatty acids to the pipping muscle via the circulation. Despite the liver's active supply of these nutrient subunits for assimilation and oxidation by the pipping muscle, there was an overall accumulation of hepatic fat between d 15 and 19 of incubation. These data suggest that the integrated changes in the energy profiles of pipping muscle and liver between 15 and 19 d of embryogenesis are integral to the broiler embryo's preparation for hatch.


The essential function of the Trypanosoma brucei Trl1 homolog in procyclic cells is maturation of the intron-containing tRNATyr.
Trypanosoma brucei, the etiologic agent of sleeping sickness, encodes a single intron-containing tRNA, tRNA(Tyr), and splicing is essential for its viability. In Archaea and Eukarya, tRNA splicing requires a series of enzymatic steps that begin with intron cleavage by a tRNA-splicing endonuclease and culminates with joining the resulting tRNA exons by a splicing tRNA ligase. Here we explored the function of TbTrl1, the T. brucei homolog of the yeast Trl1 tRNA ligase. We used a combination of RNA interference and molecular biology approaches to show that down-regulation of TbTrl1 expression leads to accumulation of intron-containing tRNA(Tyr) and a concomitant growth arrest at the G1 phase. These defects were efficiently rescued by expression of an "intronless" version of tRNA(Tyr) in the same RNAi cell line. Taken together, these experiments highlight the crucial importance of the TbTrl1 for tRNA(Tyr) maturation and viability, while revealing tRNA splicing as its only essential function.


[Embracing cultural diversity in child-care facilities].
In child-care facilities, taking into account the cultural diversity of families in migration is essential. Professionals can then review their references and habits to meet families and build a trust relationship. This exchange forms a respectful accompaniment of the values and habits of each, favouring the development of young children.


Complete nucleotide sequence of sugarcane streak Monogeminivirus.
The complete nucleotide sequence of the genome of the Monogeminivirus sugarcane streak virus (SSV) was determined from cloned replicative form DNA. The genome is contained in one DNA circle of 2,758 nucleotides, and has four open reading frames with the potential to encode proteins of MW > 10 kDa: two in the viral (+) sense and two in the complementary (-) sense. Each open reading frame has a counterpart among the open reading frames reported for other Monogeminiviruses. A potential binding site for a DNA replication primer and potential transcriptional control sequences were identified on the (+) strand, and a possible intron on the (-) strand. Phylogenetic analysis of coat protein and replication-associated protein sequences of SSV and other grass-infecting geminiviruses indicate that SSV, although distinct from any other virus, is part of an "African streak virus subgroup" of Monogeminiviruses.


Naloxone-Induced Acute Pulmonary Edema is Dose-Dependent: A Case Series.
BACKGROUND Naloxone remains the mainstay for the treatment of opioids overdose both in the clinical and public settings. Naloxone has been showing relative safety, leading to trivial adverdse effects which are mostly due to acute withdrawal effects, but when used in patients with known long-term addiction, it usually requires additional dosing or rapid infusion to achieve detoxification effects in a timely manner or to sustain the effects after they fade away. In some patients this has resulted in fatal adverse effects, including non-cardiogenic pulmonary edema (NCPE), which may require intensive care for those patients. Whether the higher dose is the cause has been debatable and not enough studies have looked into this subject. CASE REPORT Here, we report a series of 2 cases where 2 young patients were given naloxone following opioid overdose. Both our patients required frequent dosing due to insufficient response or owing to the washout of the naloxone effect shortly after, given its short half-life. Although the administered doses were different, both patients developed the adverse effect of NCPE and required ventilator support. CONCLUSIONS Evidence suggests that such a catastrophic adverse effect following the administration of such a critical medication, which is known to be relatively safe and is being publicized for saving lives, might limit its use and would require more attention and further studies to standardize a safe dose, limiting these life-threatening events and decreasing the need for unnecessary invasive respiratory support as well as admissions to intensive care units, which might create an additional burden on the health care system.


Magnetic resonance imaging in ischaemic heart disease.
Magnetic resonance imaging has an increasing role in the assessment of ischaemic heart disease. Its superb spatial and temporal resolution currently allows accurate assessment of cardiac function, regional wall motion, and the extent of myocardial infarction. Regional myocardial perfusion can also be assessed, most commonly by a first-pass technique. Non-invasive imaging of the coronary arteries by various magnetic resonance imaging techniques represents a major advance in recent years. In the foreseeable future, magnetic resonance imaging may become a single, comprehensive examination for the assessment of ischaemic heart disease.


New Early Cenozoic ghost shrimps (Decapoda, Axiidea, Callianassidae) from Pakistan and their palaeobiogeographic implications.
A new set of Paleocene and Eocene decapod crustaceans is described from the Kirthar Range of Pakistan. Two new ghost shrimps (Crustacea, Decapoda, Callianassidae) are described: Neocallichirus khadroensis Hyžný & Charbonnier, n. sp. from the Paleocene (Danian, Khadro Formation) of Gawar Band, Ranikot District, and Neocallichirus lakhraensis Hyžný & Charbonnier, n. sp. from the Early Eocene (Ypresian, Lakhra Formation) of Rbod Nala, Jhirak District. Both new species exhibit chelipeds which are morphologically surprisingly close to extant Neocallichirus karumba (Poore & Griffin, 1979) from the Indo-West Pacific. A group of species sharing this same cheliped morphology is provisionally called the "karumba group" based on Neocallichirus karumba, best documented species. The "karumba group" encompasses seven fossil species: the two new Pakistani species, Neocallichirus tuberculatus (Lőrenthey in Lőrenthey & Beurlen, 1929) n. comb. from the Eocene of Hungary, Neocallichirus borensis Beschin, De Angeli, Checchi & Mietto, 2006 from the Eocene of Italy, Neocallichirus birmanicus (Noetling, 1901) n. comb. from the Miocene of Myanmar, Neocallichirus dijki (Martin, 1883) from the Miocene of Java and Philippines, and the subfossil Neocallichirus maximus (A. Milne-Edwards, 1870) from Thailand. Based upon the extant and fossil occurrences, it is difficult to reconstruct migration pattern of the "karumba group". For now, it can be concluded, that at the genus level, a relative homogeneity of the ghost shrimps is observed between the Eastern and the Western Tethyan regions, as already suggested by Merle et al. (2014) for the assemblage of volutid gastropods from the Lakhra Formation.


Structural requirements for action of cholecystokinin on enzyme secretion from pancreatic acini.
Using dispersed acini prepared from guinea pig pancreas, we found that the structural requirements for cholecystokinin-induced stimulation of amylase secretion are the same as those for cholecystokinin-induced desensitization of amylase secretion. 1) The relative potencies with which various C-terminal fragments of cholecystokinin cause stimulation are the same as their relative potencies for causing desensitization. 2) With each fragment tested, desensitization occurs with peptide concentrations that are supramaximal for causing stimulation of amylase secretion. 3) Fragments of cholecystokinin less efficacious in causing supramaximal inhibition of amylase secretion are also less efficacious in causing desensitization of amylase secretion. In contrast, there is no obvious fixed relation between the ability of a cholecystokinin fragment to cause stimulation of enzyme secretion and its ability to cause residual stimulation of enzyme secretion. Cholecystokinin and its C-terminal hexadecapeptide are 25-40% more efficacious than the C-terminal decapeptide, octapeptide, and heptapeptide in causing residual stimulation, and the C-terminal pentapeptide and tetrapeptide caused no detectable residual stimulation. The C-terminal tetrapeptide, however, can prevent as well as reverse the residual stimulation caused by other cholecystokinin fragments, and the ability of the tetrapeptide to prevent cholecystokinin-induced residual stimulation is itself fully reversible.


Changes in GABA and glutamate receptors on auditory cortical excitatory neurons in a rat model of salicylate-induced tinnitus.
Tinnitus is associated with neural hyperactivity, which is regulated by neuronal plasticity in the auditory central system, especially the auditory cortex (AC). Excitatory neurons constitute approximately 70-85% of the total populations of neuronal cells. However, few reports have focused on the AMPA receptor (AMPAR) and the GABAA receptor (GABAAR) on the excitatory neuron in animal model of tinnitus. In this study, we gave rats a single or long-term of salicylate administrations. The tinnitus-like behavior was assessed by combination of the gap prepulse inhibition of acoustic startle (GPIAS) and the pre-pulse inhibition (PPI) tests. Using immunofluorescent staining, we examined whether the AMPAR and the GABAAR on the calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) -labeled excitatory neurons in the auditory cortex underwent changes following salicylate treatment. The rats with 14 days of salicylate administration showed evidence of experiencing tinnitus, while the rats receiving a single dose of salicylate manifested no tinnitus-like behavior. Furthermore, the AMPAR and GABAAR responded in a homeostatic manner after a single dose of salicylate while those showing in a Hebbian way after long-term salicylate administration. Thus, the different patterns of plasticity change in cortical excitatory neurons might affect the generating of salicylate-induced tinnitus.


Expression of miR-9 and miR-200c, ZEB1, ZEB2 and E-cadherin in Non-Small Cell Lung Cancers in Iran.
MicroRNAs (miRNAs) exert a critical influence on physiological and pathological processes through posttranscriptional modification of their mRNA targets. They play important roles in tumorigenesis and are considered to be potential diagnostic and prognostic biomarkers with various cancers. MiR-200c and miR-9 are regulatory elements that can have dual impacts as oncogenes and/or tumor suppressor genes. MiR-200c regulates two transcription factors, ZEB1 and ZEB2, while miR-9 is a regulatory factor for the E-cadherin protein which has a critical function in cell-cell junctions and is inhibited by two transcription factors ZEB1 and ZEB2. In this study, expression levels of miR-200c and miR-9, ZEB-1, ZEB-2 and E-cadherin were assessed in 30 non-small cell lung cancers (NSCLCs) by real-time qPCR. MiR-9 was down-regulated significantly in tumor tissues compared to normal adjacent tissues, while there was no significant change in expression level of miR-200c. On the other hand, ZEB1 demonstrated significant increase and ZEB2a decrease at the mRNA level. These results indicate roles for miR-9 and ZEB1 in genesis of lung cancer, although clinico-pathological associations were not evident. Further studies are necessary to assess implications for treatment of lung cancer.


Partial compensation to delayed auditory feedback: An analysis of syllable duration.
Altered feedback perturbation studies have shown that speakers only partially compensate for shifts in vocal pitch, intensity, or spectral content. The partial compensation generally plateaus around 30%-40% of the non-shifted, baseline production and is proposed to reflect the integrated effect of altered (auditory) and non-altered (somatosensory) sensory feedback. The authors hypothesized that the same pattern should hold for changes in syllable duration with delayed auditory feedback. To test this, the authors calculated average syllable duration from 21 young adults who read a standard passage as auditory feedback was delayed by 0, 10, 50, 100, 200, 300, and 600 ms. Given the complex nature of speech errors elicited under delayed auditory feedback, the authors compared durational effects across two broad error categories: prolongations and repetitions. Average syllable duration increased non-linearly and reached a peak near 40% of baseline durations. Separated by error type, prolongations, and distortions made up 89% of perceived errors. Only 9% of perceived errors were identified as repetitions. Unlike prolongations, however, the duration of repeated tokens ranged from 74% to 110% of the target syllable and compensated fully for the delay. These results are consistent with the notion that increasing syllable duration compensates partially for delays in auditory feedback. The compensation pattern resembles that of responses to other forms of altered auditory feedback, which suggests that this may be a general attribute of low-level, sensorimotor compensation. The higher frequency of prolongation occurrences further suggests that these may be the primary means of compensation for delayed auditory feedback. Repetitions, on the other hand, likely reflect compensatory mechanisms of higher-level motor planning or sequencing processes.


Activity-based intervention in motor skill development.
This study assessed the effectiveness of an activity-based intervention program and a direct instruction program for preschool children with disabilities. Two groups of preschool students (average age=4.1 yr.), classified as having developmental delays or at risk for such delays, were selected. They were provided 15 weeks of physical education through activity-based intervention and 15 weeks of physical education by direct instruction. Instruction was provided three times a week for 30-min. each session. In the fall semester the morning group received physical education through activity-based intervention, while the afternoon group received physical education through direct instruction. In the spring semester delivery of instruction was reversed for each group. The curriculum and activities provided to each group were identical with only the instructional delivery format altered. Two sets of pre- and post-tests using the Test of Gross Motor Development were administered before and after each 15-wk. instructional period. Group improvement in skills was compared between instructional methods. Significant improvement in both locomotor and object control skills through the activity-based intervention was found compared to direct instruction. Activity-based intervention was shown to be easily adapted to a naturalistic educational setting befitting that of preschool education.


Undescended testes: Diagnosis and timely treatment in Australia (1995-2014).
Routine primary care checks in infants and prepubertal boys aim for early detection and intervention of undescended testes (UDT). Congenital and acquired UDT cause infertility, and congenital UDT also increases testicular cancer risk. We examined 20 years of Australian orchidopexy data (1995-2014) to explore the national orchidopexy operation rates over time. Orchidopexy and population data were collected from the Australian Bureau of Statistics (ABS) for 1995-2014, and census data for each age group were also collected. Poisson regressions were used to analyse the data. For patients aged DISCUSSION: The rate of orchidopexy per age has decreased in patients aged 5-14 years over the past 20 years, possibly indicating that acquired UDT is not being diagnosed and treated in some boys, risking infertility in adulthood.


Expression and site-directed mutagenesis of human dihydrofolate reductase.
A procaryotic high-level expression vector for human dihydrofolate reductase has been constructed and the protein characterized as a first step toward structure-function studies of this enzyme. A vector bearing the tac promoter, four synthetic oligodeoxynucleotides, and a restriction fragment from the dihydrofolate reductase cDNA were ligated in a manner which optimized the transcriptional and translational frequency of the enzyme mRNA. The reductase, comprising ca. 17% of the total soluble protein in the host bacteria, was purified to apparent homogeneity as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and characterized by amino acid composition, partial amino acid sequence, and steady-state kinetic analysis. This expression vector has been used as a template for double-stranded plasmid DNA site-specific mutagenesis. Functional studies on a Cys-6----Ser-6 mutant enzyme support the contention that Cys-6 is obligatory for organomercurial activation of human dihydrofolate reductase. The Ser-6 mutant enzyme was not activated to any extent following a 24-h incubation with p-(hydroxymercuri)benzoate and nicotinamide adenine dinucleotide phosphate (reduced) (NADPH), whereas the kcat for Cys-6 reductase increased 2-fold under identical conditions. The specific activities of the Cys-6 and Ser-6 enzymes were virtually identical as determined by methotrexate titration as were the Km values for both dihydrofolate and NADPH. The Ser-6 mutant showed a decreased temperature stability and was more sensitive to inactivation by alpha-chymotrypsin when compared to the wild-type enzyme. These results suggest that the Ser-6 mutant reductase is conformationally altered relative to the Cys-6 native enzyme.


Ectopic ACTH-syndrome due to a thymic carcinoid tumor.
Investigating a recently developed Cushing Syndrome, we diagnosed in a 47-year-old woman an ectopic ACTH syndrome due to a metastatic carcinoid tumor, most likely a thymic carcinoid tumor. Combined therapy with sandostatin and nizoral and later on with sandostatin, metopirone and orimeten, was not able to suppress the hypercortisolism. A few weeks after surgical adrenalectomy, clinical deterioration ensued, culminating in the patient's death 7 months after diagnosis.


Oxysterols are potential physiological regulators of ageing.
Delaying and even reversing ageing is a major public health challenge with a tremendous potential to postpone a plethora of diseases including cancer, metabolic syndromes and neurodegenerative disorders. A better understanding of ageing as well as the development of innovative anti-ageing strategies are therefore an increasingly important field of research. Several biological processes including inflammation, proteostasis, epigenetic, oxidative stress, stem cell exhaustion, senescence and stress adaptive response have been reported for their key role in ageing. In this review, we describe the relationships that have been established between cholesterol homeostasis, in particular at the level of oxysterols, and ageing. Initially considered as harmful pro-inflammatory and cytotoxic metabolites, oxysterols are currently emerging as an expanding family of fine regulators of various biological processes involved in ageing. Indeed, depending of their chemical structure and their concentration, oxysterols exhibit deleterious or beneficial effects on inflammation, oxidative stress and cell survival. In addition, stem cell differentiation, epigenetics, cellular senescence and proteostasis are also modulated by oxysterols. Altogether, these data support the fact that ageing is influenced by an oxysterol profile. Further studies are thus required to explore more deeply the impact of the "oxysterome" on ageing and therefore this cholesterol metabolic pathway constitutes a promising target for future anti-ageing interventions.


Alcohol-induced severe acute pancreatitis followed by hemolytic uremic syndrome managed with continuous renal replacement therapy.
Acute kidney injury in patients with acute pancreatitis carries a poor prognosis. Hemolytic uremic syndrome (HUS) is characterized by non-immune hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney, and though rare in adults it is associated with high mortality and a high rate of chronic renal failure. Herein, we report a case of alcohol-induced acute pancreatitis in a 38-year-old Chinese female complicated by HUS. Her renal function progressively deteriorated in 2 days, and daily continuous renal replacement therapy (CRRT) was thus performed for a total of 13 treatments. She also received intermittent transfusions of fresh frozen plasma. Her renal failure was successfully managed, with subsequent return of normal renal function. She was discharged 1 month after admission and follow-up at 3 months revealed normal urea and creatinine. CRRT was shown to be useful for the treatment of HUS following acute pancreatitis. Prior case reports and our case should remind clinicians that HUS is a possible complication of acute pancreatitis. This study highlights the importance of early diagnosis and prompt initiation of CRRT to prevent mortality and improve outcomes.


[Intraocular lens implantation in the glaucomatous eye].
Cataract extraction with intraocular lens implantation was performed in 32 eyes of 32 patients in the years 1990-1992. Surgery was performed in 10 eyes with well-controlled intraocular pressure without any antiglaucomatous operation, in 10 because of inadequate control with simultaneous trabeculectomy, in 7 after earlier filtering procedures and in 5 with secondary glaucoma. Surgical technics, intra- and postoperative complications and the results are discussed. Visual acuity in 18 eyes was 0.5-1.0, in 10 eyes 0.1-0.4 and in 2 it was 0.05. The follow-up for all the eyes yielded normal intraocular pressure, in most cases without additional pharmacological treatment.


Adjuvant doxorubicin hydrochloride and radiation in stage D bladder cancer: a preliminary report.
The prognosis of patients with stage D bladder cancer is dismal. This report expands the results of our efforts to modify the clinical course of such patients by administration of doxorubicin hydrochloride sandwiched around pelvic radiation. Pathologic stage D bladder cancer was recognized in 19 patients by evaluation of tissue obtained by radical cystectomy and pelvic lymphadenectomy (8), pelvic lymph node dissection (5) or biopsies (3), ileal conduit and pelvic lymph node biopsy (1), or transurethral biopsy of the bladder and prostate (2). Treatment of these patients with doxorubicin hydrochloride before and after radiation was initiated 3 to 4 weeks postoperatively. The treatment regimen consisted of 1) 60 mg. per M.2 doxorubicin intravenously every 3 weeks for 3 cycles, 2) 5,000 rad external radiation to the entire pelvis in 5 to 6 weeks and 3) doxorubicin for 5 cycles. The observed survival rates were 37 per cent at 3 years and 28 per cent at 5 years. The median survival time was 16 months. Five patients had no evidence of disease 13 to 63 months postoperatively. One patient underwent salvage cystectomy for recurrent bladder carcinoma at 33 months and had no evidence of disease at 74 months. One patient was alive with recurrent disease at 13 months. Three patients who died did not complete the protocol owing to metastatic disease, 8 lived 6 to 52 months without recognized disease and died of metastases, and 1 died of a second primary. The extent of surgical excision was not associated significantly with survival. Of 8 patients treated with radical cystectomy 7 suffered a significant obstruction of the small bowel that required decompression or bypass surgery and all 7 recovered completely. These preliminary observations indicate encouraging results with a high but manageable morbidity for this regimen.


Interactions of muscle beta-connectin with myosin, actin, and actomyosin at low ionic strengths.
The interaction of the muscle elastic protein connectin with myosin and actin filaments was investigated by turbidimetry, viscosity, flow birefringence measurements, and electron microscopic observations. In KCl concentrations lower than 0.15 M at pH 7.0 at 25 degrees C, both myosin and actin filaments were aggregated by connectin. Myosin filaments were entangled with each other in the presence of connectin. Actin filaments were assembled into bundles under the influence of connectin just as under that of alpha-actinin. The physiological significance of the interactions of connectin with myosin and actin filaments is discussed in relation to the localization of connectin in myofibrils. The Mg2+-activated ATPase activity of actomyosin was appreciably enhanced by connectin in the presence of KCl concentrations lower than 0.1 M. The extent of activation by connectin was smaller than by alpha-actinin. The enhancement of the ATPase activity may be due to acceleration of the onset of superprecipitation of actomyosin.


[Recommendations of the Croatian Society for Rheumatology for prevention, diagnostics and treatment of post-menopausal osteoporosis].
Osteoporosis is a disease characterized by loss of bone mass and the structural deterioration of bone tissue leading to increased bone fragility and fractures. Preventive measures for osteoporosis and osteoporotic fractures include adequate calcium and vitamine D intake, adequate physical activity and reduction of the risk factors can be influenced. Currently, measurement of bone mineral density using dual energy x-ray absorptiometry (DXA) is still the gold standard for the diagnosis of osteoporosis. Non-pharmacological therapy is the integral part of the management ofosteoporosis. Nitrogen-containing bisphosphonates in weekly or more prolonged (monthly) dosing intervals are now the firstline osteoporosis therapy. Oral bisphosphonates show, generally, similar efficacy on vertebral fractures risk reduction. There, might be some differences among bisphosphonates, regarding risk reduction of non-vertebral, hip and glucocortiocoid related fratures. On behalf of Croatian Society of Rheumatology of Croatian Medical Association we propose recommendations for the prevention, diagnosis and management ofpostmenopausal osteoporosis.


Ultrasonic backscatter from flowing whole blood. II: Dependence on frequency and fibrinogen concentration.
Earlier studies showed that ultrasonic backscatter from erythrocytes suspended in saline is a function of hematocrit and frequency and that it can be affected by flow disturbance. The experimental data agree well with the theories. Recently, studies have been extended to flowing whole blood. The results indicated that ultrasonic backscatter from flowing whole blood differs from that from saline suspensions of erythrocytes in that it is shear-rate dependent and species dependent. In the present article, data on the dependence of ultrasonic backscatter from flowing whole blood on frequency and on fibrinogen concentration are reported. It was found that ultrasonic backscatter from flowing whole blood also depends on fibrinogen concentration when red blood cell (RBC) aggregation exists. Moreover, when the blood is under conditions that favor RBC aggregation such as low shear rates, high fibrinogen concentration, or high hematocrits, Rayleigh scattering apparently is no longer sufficient to describe its scattering behavior.


Association between cardiovascular diseases and COVID-19 pneumonia outcome in Indonesia: a multi-center cohort study.
COVID-19 is a pandemic affecting 185 countries, including Indonesia. Cardiovascular diseases (CVD) in COVID-19 patients were linked to worse clinical outcomes. However, the association remained inconclusive due to limited data in Indonesia. This study aimed to determine the association between CVD in COVID-19 pneumonia patients with its clinical outcomes. This retrospective cohort study was conducted in four Indonesian hospitals, enrolling 584 adult COVID-19 pneumonia patients from September 2020 to July 2021. Patients were categorized into two groups: non-CVD and CVD [hypertension, coronary artery disease (CAD), chronic heart failure (CHF), hypertensive heart disease (HHD), arrhythmia, cardiomegaly, left ventricular hypertrophy (LVH), mitral regurgitation (MR), and myocardial injury (MI)]. Clinical outcomes include in-hospital mortality, intensive care unit admission, ventilator use, earlier death, and prolonged hospital stay. Mann-Whitney test was used for analysis. The most common CVD was hypertension (48.1%), followed by MI (10.6%), CAD (9.2%), CHF (6.8%), HHD (3.1%), arrhythmia (1.7%), and others (0.7%). The in-hospital mortality rate was 24%, and patients were hospitalized for a median of 12 days. MI was the only CVD that increased in-hospital mortality (RR 2.105). It was also significantly increased in patients with diabetes mellitus (RR 1.475) and chronic kidney disease (RR 2.079). Meanwhile, prolonged hospital stay was associated with any CVD (RR 1.553), hypertension (RR 1.511), MI (RR 1.969), CHF (RR 1.595), diabetes mellitus (RR 1.359), and cerebrovascular disease (RR 2.203). COVID-19 pneumonia in patients with CVD, specifically MI and hypertension, worsens the COVID-19 clinical outcomes.


Surgical Indications and Techniques for Adrenalectomy.
Indications for adrenalectomy are malignancy suspicion or malignant tumors, non-functional tumors with the risk of malignancy and functional adrenal tumors. Regardless of the size of functional tumors, they have surgical indications. The hormone-secreting adrenal tumors in which adrenalectomy is indicated are as follows: Cushing's syndrome, arises from hypersecretion of glucocorticoids produced in fasciculata adrenal cortex, Conn's syndrome, arises from an hypersecretion of aldosterone produced by glomerulosa adrenal cortex, and Pheochromocytomas that arise from adrenal medulla and produce catecholamines. Sometimes, bilateral adrenalectomy may be required in Cushing's disease due to pituitary or ectopic ACTH secretion. Adenomas arise from the reticularis layer of the adrenal cortex, which rarely releases too much adrenal androgen and estrogen, may also develop and have an indication for adrenalectomy. Adrenal surgery can be performed by laparoscopic or open technique. Today, laparoscopic adrenalectomy is the gold standard treatment in selected patients. Laparoscopic adrenalectomy can be performed transperitoneally or retroperitoneoscopically. Both approaches have their advantages and disadvantages. In the selection of the surgery type, the experience and habits of the surgeon are also important, along with the patient's characteristics. The most common type of surgery performed in the world is laparoscopic transabdominal lateral adrenalectomy, which most surgeons are more familiar with. The laparoscopic anterior transperitoneal approach is the least preferred laparoscopic method in adrenalectomy. Retroperitoneal laparoscopic adrenalectomy can be performed with a posterior or lateral approach. In addition to conventional laparoscopy, laparoscopic surgery is robot-assisted, which can be administered by transperitoneal or retroperitoneal approach. In addition, conventional or robot-assisted laparoscopic adrenalectomy can be performed transabdominally or retroperitoneally using the single-port method. Today, partial adrenalectomy can be performed using laparoscopic techniques in bilateral adrenal masses, hereditary diseases with the risk of developing multiple adrenal tumors, and solitary masses of the adrenal gland. Open surgery is indicated in the case of malignancy or suspected malignancy and large tumors when laparoscopic surgery is contraindicated. The risk of conversion to open surgery is low (approximately 5%). The open transperitoneal anterior approach is the most common open intervention, especially in large tumors with malignancy or suspected malignancy. This procedure can be performed using a midline incision, bilateral or unilateral subcostal incision, Makuuchi or modified Makuuchi incision. Thoracoabdominal incision may be required, especially in the removal of large malignant lesions as a block. The open retroperitoneal approach can be applied posteriorly or laterally.


Diagnosis of herpes simplex virus by direct immunofluorescence and viral isolation from samples of external genital lesions in a high-prevalence population.
One hundred thirty specimens from 108 consecutive patients with a history of recurrent genital ulcerations were used in a study comparing herpes simplex virus (HSV) isolation with a direct fluorescent-antibody (DFA) technique using mouse monoclonal antibodies. HSV was isolated from 70% of vesicular lesions, 67% of pustular lesions, 32% of ulcerative lesions, and 17% of crusted lesions, whereas the DFA technique detected HSV antigen in 87, 67, 30, and 10% of lesions in similar stages, respectively. When both methods were used, HSV was identified in 97, 79, 45, and 17% of vesicles, pustules, ulcers, and crusted lesions, respectively. The overall sensitivity and specificity of the DFA technique in comparison with virus isolation (VI) were 74 and 85%, respectively. Of the 17 patients from whom DFA-positive, VI-negative samples were obtained, HSV was subsequently isolated from a genital lesion in 14, suggesting that they were not DFA false-positives. Similarly, of the 46 patients whose initial lesion samples were DFA and VI negative, 37 (80%) had HSV identified from subsequent genital lesions during follow-up. Thus, a single sample for VI or DFA testing from a recurrent genital lesion had a sensitivity of only 53 and 51%, respectively. Combining the DFA technique and VI increased the sensitivity of laboratory diagnosis of a single recurrent episode of genital HSV; however, repetitive laboratory testing was often required to confirm the diagnosis of recurrent genital HSV infection.


Sons and parental cognition in mid-life and older adulthood.
Prior research suggests a relationship between number of sons and maternal long-term health outcomes, including dementia. We assessed the relationship between having sons and parental cognitive aging. Specifically, we investigated the relationship between having at least 1 son and parental baseline cognition level and rate of cognitive decline, accounting for life course sociodemographic characteristics in a cohort of 13 222 adults aged ≥50 years from the US Health and Retirement Study. We included only participants with at least one child. We further explored whether this relationship varies by parental sex and whether the magnitude of the relationship increases with each additional son. Cognition was assessed biennially for a maximum of nine times as a sum of scores from immediate and delayed 10-noun free recall tests, a serial 7s subtraction test, and a backwards counting test. Associations were evaluated using linear mixed-effects models, stepwise adjusting for sociodemographic and health-related factors. In our analytic sample of parents, a total of 82.3% of respondents had at least 1 son and 61.6% of respondents were female. Parents of at least 1 son had a faster rate of cognitive decline in comparison to parents without any son. Our results also suggest that cognitive decline was faster among parents of multiple sons, compared to parents with only daughters. Thus, the results support the theory that having sons might have a long-term negative effect on parental cognition.


Molecular analysis of BRCA1 and BRCA2 genes by next generation sequencing and ultrastructural aspects of breast tumor tissue.
In this paper, we focus our interest on the dynamics alterations of the tumor-stroma interface at the ultrastructural level and to detect BRCA1 and BRCA2 mutations using next generation sequencing (NGS) of breast tumor tissue. Electron microscopic investigation revealed some peculiar infrastructural alterations of the tumor cells per se as well as of the tumor-stroma interface: invadopodia, shedding microvesicles, altered morphology and reduced number of telocytes, different abnormalities of the microvasculature. Tumor suppressor genes BRCA1 and BRCA2 are the genes with most hereditary predisposition to breast and ovarian cancer. An early identification of mutation within these genes is essential for determining classification and therapeutic approach to patients. Genetic tests used to determine mutations in BRCA1 and BRCA2 genes are laborious analysis methods which include, among others, NGS. We analyzed a total of eight samples, in which genomic DNA was amplified using Ion AmpliSeq panel BRCA1 and BRCA2. DNA libraries were created, amplified and sequenced with Ion Torrent Personal Genome Machine. The bio-information data obtained allow us to detect all known pathogenic mutation and uncertain polymorphisms.


On-task distractors associated with totball baseball games: a preliminary study.
Two totball baseball leagues in southern Louisiana were monitored to judge what type of parental involvement yielded the highest on-task behaviors among participants. 39 children ages 3 to 5 years participated in 3- or 4-inning baseball games with parents on the field. In the Parent on Bases League, a parent stood on first, second, and third base only. In the Parent with Every Child League, a parent stood next to every child on the field. Children were observed on the field at three different dates at 1-min. intervals during the first two innings of one game in both leagues. On-task behaviors were defined as standing in the correct field position and watching the ball. Off-task behaviors consisted of sitting, rolling on the field, talking to a coach or parent, and not watching the ball. A statistically significant difference in the percent of time children spent on-task favored the Parents on Bases League (75.7) versus the other league (50.3). Having fewer parents on the field in these baseball games kept players on-task more effectively than having a parent with each child.


Biophysical basis for airway hyperresponsiveness.
Airway hyperresponsiveness is the excessive narrowing of the airway lumen caused by stimuli that would cause little or no narrowing in the normal individual. It is one of the cardinal features of asthma, but its mechanisms remain unexplained. In asthma, the key end-effector of acute airway narrowing is contraction of the airway smooth muscle cell that is driven by myosin motors exerting their mechanical effects within an integrated cytoskeletal scaffolding. In just the past few years, however, our understanding of the rules that govern muscle biophysics has dramatically changed, as has their classical relationship to airway mechanics. It has become well established, for example, that muscle length is equilibrated dynamically rather than statically, and that in a dynamic setting nonclassical features of muscle biophysics come to the forefront, including unanticipated interactions between the muscle and its time-varying load, as well as the ability of the muscle cell to adapt (remodel) its internal microstructure rapidly in response to its ever-changing mechanical environment. Here, we consider some of these emerging concepts and, in particular, focus on structural remodeling of the airway smooth muscle cell as it relates to excessive airway narrowing in asthma.


Routine use of laser Doppler flowmetry for monitoring autologous tissue transplants.
This is a report of a prospective study in which 41 consecutive autologous tissue transplants were monitored using the Laserflo BPM model 403 laser Doppler monitor (TSI Inc., St. Paul, MN). Flaps were monitored both intraoperatively and postoperatively, and clinical flap monitoring was compared with laser Doppler monitoring. Twenty-nine flaps had no problems as indicated by clinical or Doppler measurement. Twelve flaps underwent 13 reexplorations; one flap was explored twice. Five venous and five arterial anastomoses were corrected, with complete survival of the flaps. Three hematomas were evacuated. Two of these flaps failed. There were no instances where the laser Doppler indicated a problem with flap viability that subsequently did not merit reexploration. There were no instances of flap failure undetected by the laser Doppler. In comparison to the clinical monitoring, laser Doppler monitoring was more rapid and more precise in identifying problems with the flap. The use of this monitor has improved our salvage rate for flap reexploration from 50 to 85% and has provided a more objective standard for both nurses and physicians to evaluate flaps in the perioperative period.


Prevalence of atypical mycobacteriosis in slaughtered swine in Gunma Prefecture and the serovars of the isolates.
Atypical mycobacteriosis was detected in 4,919 (0.28%) of 1,776,294 swine slaughtered at the G slaughter house in Gunma Prefecture during the period 1988-1990. The tuberculous lesions were mainly observed in the submaxillary (64.4%) and mesenteric lymph nodes (29.0%). The enzootic and sporadic infections were detected in 4 and 870 of 1,200 piggeries, respectively. Of the 2,076 infected swine detected between September, 1988 and December, 1989, 231 swine were submitted to the isolation of Mycobacterium avium-intracellulare complex (MAIC). MAIC was isolated from 141 of 219 swine that had tuberculous lesions only in the lymph nodes and from all of the remaining 12 swine that had lesions in the liver or in both the lymph nodes and organs. MAIC was also isolated from 11 gastric and 6 cecal contents of the 231 swine. Of 431 strains isolated, 336 were classified into 13 serovars. M. intracellulare serovar 6 (34.6%) was the most predominant, followed by serovars 8 (21.8%), 4 (8.6%) and 10 (6.5%). Four strains (0.9%) were identified as M. avium serovar 3. In 16 swine, each individual harbored plural serovars. The results of the investigation suggested that the atypical mycobacteriosis due to MAIC was widely distributed in swine in Gunma Prefecture.


Evaluation of demineralized dentin contraction by stereo measurements using environmental and conventional scanning electron microscopy.
Numerous investigations of etched human dentin are performed using scanning electron microscopy (SEM). Usually specimens are fractured and cross sections of etched layers with underlying unaffected dentin are observed. Results from this study showed that the edge of the etched layer contracted and became curved after fracture of wet specimens and that tensile stresses were developed in this layer by acid etching. The degree of contraction was determined utilizing profiles of the specimen edges obtained with the help of stereo measurements. Fixation in glutaraldehyde decreased the contraction in wet specimens prepared for environmental scanning electron microscopy (ESEM). Fixation also decreased shrinkage of the demineralized layer due to gradual desiccation in the ESEM during observation. For conventional SEM, the contraction was minimized if specimens of etched and fixed dentin were fractured in the dry condition after dehydration.


Survival and perioperative outcomes of octo- and nonagenarians with resectable esophageal carcinoma.
The outcomes of different treatment modalities for patients aged 80 and above with locally advanced and resectable esophageal carcinoma are not well described. The aim of this study was to explore survival and perioperative outcomes among this specific group of patients. A retrospective, cohort analysis was performed on a prospectively maintained esophageal cancer database from the McGill regional upper gastroinestinal cancer network. Between 2010 and 2020, all patients ≥80 years with cT2-4a, Nany, M0 esophageal carcinoma were identified and stratified according to the treatment modality: Neoadjuvant chemotherapy (nCT) or chemoradiotherapy (nCRT); definitive CRT (dCRT); upfront surgery; palliative CT/RT; or best supportive care (BSC). Of the 162 patients identified, 79 were included in this study. The median age was 83 years (80-97), most were cT3 (73%), cN- (56%), and had adenocarcinoma (62%). Treatment included: nCT/nCRT (16/79, 20%); surgery alone (19/79, 24%); dCRT (12/29, 15%); palliative RT/CT (27/79, 34%); and BSC (5/79, 6%). Neoadjuvant treatment was completed in 10/16 (63%). Of the 35/79 who underwent surgery, major complications occurred in 13/35 (37%) and 90-day mortality in 3/35 (9%). Overall survival (OS) for the cohort at 1- and 3-years was 58% and 19%. Among patients treated with nCT/nCRT, this was 94% and 46% respectively. Curative intent treatment (nCT/nCRT/upfront surgery/dCRT) had significantly increased 1- and 3- year OS compared with non-curative treatment (76%/31% vs. 34%/3.3%). Multimodal standard of care treatment is feasible and safe in select octo/nonagenarians, and may be associated with improved OS. Age alone should not bias against treatment with curative intent.


Biosensing application of multiwall boron nitride nanotube-based nanoresonator for detecting various viruses.
This study explores the suitability of biosensors using multi-walled boron nitride nanotubes (MW-BNNTs) with virus/bacterium attached at the free end of cantilever through vibration analysis. Various viruses/bacteria having mass of the order of zeptogram level are considered for obtaining resonance frequencies of cantilevered triple-walled boron nitride nanotube (TW-BNNT) by means of a continuum mechanics-based analytical approach. The simulation with various viruses/bacteria attached at the tip of cantilevered TW-BNNT is carried out for different lengths. The finite element method simulated resonance frequency values are compared with results obtained from the analytical method by taking into account the effective wall thickness of tubes and van der Waals interaction between various BNNTs. A close proximity is observed between results obtained from the two approaches, which further confirms the validity of the proposed model. The obtained results suggest that shorter length TW-BNNT is more sensitive for detecting viruses/bacteria having mass of zeptogram order.


Function of abnormal corpora lutea in vitro after GnRH-induced ovulation in the anoestrous ewe.
Normal and abnormal corpora lutea were recovered from anoestrous Romney Marsh ewes on Days 3, 4, 5 and 6 after treatment with small-dose (250 ng) multiple injections of GnRH followed by a bolus injection (125 micrograms) with (+P) and without (-P) progesterone pretreatment and a study made of their characteristics in vitro. Plasma progesterone concentrations initially rose concurrently in all animals but abnormal luteal function occurred in 70% of the -P ewes and was defined on Day 5 when plasma progesterone concentrations declined relative to those in the +P ewes. All corpora lutea recovered on Days 3 and 4 appeared macroscopically similar and there were no significant differences between the +P and -P groups in terms of luteal weight, progesterone content and binding of 125I-labelled hCG on these days. However, corpora lutea from the -P animals only exhibited a decline in progesterone production in vitro on Day 4 (P less than 0.01), and morphological differences became apparent on Days 5 and 6 when the abnormal corpora lutea from the -P animals also decreased in weight (P less than 0.01) and progesterone content (P less than 0.001). Binding of 125I-labelled hCG increased on Day 5 in the normal corpora lutea only. These results show that, although abnormal luteal function induced by GnRH treatment of anoestrous ewes could not be distinguished from normal corpora lutea before Day 5 by measurement of progesterone in peripheral plasma, a significant decline in progesterone production in vitro occurred on Day 4 in the abnormal corpora lutea. This was followed by significant decreases in weight and progesterone content and a failure to increase 125I-labelled hCG binding. Abnormal corpora lutea are therefore capable of some initial growth and progesterone production, before undergoing a rapid and premature regression from Day 4, which has similar characteristics to natural luteolysis.


Comparing comfort and wearability between Type III single-layered and double-layered EVA mouthguards.
This study compared two Type III ethylene vinyl acetate (EVA) mouthguards for wearability, comfort, fit, and patient preference. Twenty-two athletes each received two custom-fabricated athletic mouthguards, a single-layered vacuum-formed EVA mouthguard and a double-layered heat- and pressure-laminated EVA type. Athletes wore each type of mouthguard for a two-week period while playing basketball. At the end of each two-week period, the athletes completed questionnaires that evaluated 17 characteristics of each mouthguard type. Data were analyzed using the binomial test for small numbers. The double-layered heat- and pressure-laminated EVA mouthguard performed as well as or better than the single-layered vacuum-formed type in 14 of the 17 categories. There was a statistically significant patient preference for the double-layered heat- and pressure-laminated mouthguard.


Electrochemical Detection of Ultratrace (Picomolar) Levels of Hg2+ Using a Silver Nanoparticle-Modified Glassy Carbon Electrode.
Ultratrace levels of Hg2+ have been quantified by undertaking linear sweep voltammetry with a silver nanoparticle-modified glassy carbon electrode (AgNP-GCE) in aqueous solutions containing Hg2+. This is achieved by monitoring the change in the silver stripping peak with Hg2+ concentration resulting from the galvanic displacement of silver by mercury: Ag(np) + 1/2Hg2+(aq) → Ag+(aq) + 1/2Hg(l). This facile and reproducible detection method exhibits an excellent linear dynamic range of 100.0 pM to 10.0 nM Hg2+ concentration with R2 = 0.982. The limit of detection (LoD) based on 3σ is 28 pM Hg2+, while the lowest detectable level for quantification purposes is 100.0 pM. This method is appropriate for routine environmental monitoring and drinking water quality assessment since the guideline value set by the US Environmental Protection Agency (EPA) for inorganic mercury in drinking water is 0.002 mg L-1 (10 nM).


[Surgery for bronchiectasis. Operative indications and results. 48 observations].
Forty-eight patients: 27 women and 21 men, with mean age of 36 +/- 14 years were operated on for bronchiectasis from 1976 to 1989. In 20 cases bronchiectasis was the sequelae of acute bronchopathy of childhood, 6 cases of tuberculosis and 5 cases of inhalated foreign bodies. The bronchiectasis was apparently primitive in 12 occasions. Five varied etiologies were found of which 2 congenital hypogammaglobulinemias. The anatomic extension of the lesions was precised in 47 cases by bronchography and CT scan in 6 cases, in 1 case with CT scan only. The lesions were bilateral in 5 cases. One pneumonectomy, 42 lobectomies (of which 10 bilobectomies) and 5 segmentectomies were performed. The operative mortality was nil. The morbidity (14 cases among 48, i.e. 29%) was not negligible and was comparable with the literature data. The evalued results for 36 patients (mean post-operative follow-up: 54 +/- 58 months) showed that 24 patients (67%) were asymptomatic, 34 have taken their normal professional activities.


Single-Cell Analysis of the Expression of Pseudomonas syringae Genes within the Plant Tissue.
A plethora of pathogenic microorganisms constantly attack plants. The Pseudomonas syringae species complex encompasses Gram-negative plant-pathogenic bacteria of special relevance for a wide number of hosts. P. syringae enters the plant from the leaf surface and multiplies rapidly within the apoplast, forming microcolonies that occupy the intercellular space. The constitutive expression of fluorescent proteins by the bacteria allows for visualization of the microcolonies and monitoring of the development of the infection at the microscopic level. Recent advances in single-cell analysis have revealed the large complexity reached by clonal isogenic bacterial populations. This complexity, referred to as phenotypic heterogeneity, is the consequence of cell-to-cell differences in gene expression (not linked to genetic differences) among the bacterial community. To analyze the expression of individual loci at the single-cell level, transcriptional fusions to fluorescent proteins have been widely used. Under stress conditions, such as those occurring during colonization of the plant apoplast, P. syringae differentiates into distinct subpopulations based on the heterogeneous expression of key virulence genes (i.e., the Hrp type III secretion system). However, single-cell analysis of any given P. syringae population recovered from plant tissue is challenging due to the cellular debris released during the mechanical disruption intrinsic to the inoculation and bacterial extraction processes. The present report details a method developed to monitor the expression of P. syringae genes of interest at the single-cell level during the colonization of Arabidopsis and bean plants. The preparation of the plants and the bacterial suspensions used for inoculation using a vacuum chamber are described. The recovery of endophytic bacteria from infected leaves by apoplastic fluid extraction is also explained here. Both the bacterial inoculation and bacterial extraction methods are empirically optimized to minimize plant and bacterial cell damage, resulting in bacterial preparations optimal for microscopy and flow cytometry analysis.


Role of infant feeding practice, sex, and age on fatness and subcutaneous fat distribution in infancy: Longitudinal analysis of multiple skinfold measurements.
The aim of this study was to determine whether subcutaneous fatness and fat distribution differ on the basis of feeding practice and sex during the first 6 months of life. Longitudinal principal components analysis (PCA) was done on skinfolds measured at five sites in 45 breast-fed and 41 formula-fed infants. The first component represented fatness, the second component change in fatness, and the third component upper body/lower body fat distribution. Analysis of the components indicated that fatness and the proportion of lower body fat were greater in breast-fed than in formula-fed infants; however, when race was included as a predictor, the differences in lower body fat did not persist. The interpretation of components and the group differences were confirmed by repeated measures analysis of variance (ANOVA) on the sum of skinfolds (fatness) or simple skinfold ratios (fat distribution). Group differences for fatness and upper body/lower body fat persisted when race was included as a predictor. Longitudinal PCA of another indicator, the Rohrer index, suggested that fatness was greater in formula-fed than breast-fed infants. Collectively, these findings suggest that formula-fed infants have less subcutaneous fat than breast-fed infants; however, formula-fed infants may have either more internal fat or more lean body mass. Am. J. Hum. Biol. 9:179-190, 1997. © 1997 Wiley-Liss, Inc.