Obstetrics: basic equipment needs.
The enunciation of equipment requirements has been attempted as needs appear today. Detailed and technical specifications for some of this equipment must be understood prior to major acquisitions. An awareness of current trends in clinical research can often be obtained from appropriate consultants which should forestall obsolescence. Finally, it must be reemphasized that the proper and intelligent use of equipment or diagnostic methods is essential. Likewise, the need to employ many of these techniques may become apparent only by paying close attention to the patient's clinical historical comments or as a result of skilled clinical observations.


Synthesis of N2, N6-bis(5-methylthiazol-2-yl)pyridine-2,6-dicarboxamide fluoroscent sensor for detection of Cu2+ and Ni2+ Ions.
This article reports an amide based Chemosensor used for selective detection of divalent Cu+2 and Ni+2 ions via Fluorescence turn off. The selective sensing ability of Chemosensor was investigated in presence of different metal ions Mg2+, Ag+, Fe2+, K+, Cu2+, Ni2+, Hg2+, Pb2+, Mn2+, Pd2+, Cd2+ and Mn3+ as competitive ions. The receptor i. e. Chemosensor formed complexes with metal ions in 1:1 stoichiometric ratio. The detection limit and binding constant calculated as 1.92×10-4 and 1.4×10-4 M and 2.16×103 M-1 and 3.09×103 M-1 for Cu2+ and Ni2+ions respectively. The complexes were characterized by UV/visible, FT-IR, 13C NMR and 1H NMR spectroscopy. Further the structure and Crystallinity were calculated by P-XRD spectral analysis. The crystallinity found to be 65.27 and 67.87% respectively.


Testicular defense systems: immune privilege and innate immunity.
The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation.


Cardiorespiratory response to exercise after modified Fontan operation: determinants of performance.
This study sought to measure the cardiorespiratory responses to exercise and to identify the perioperative determinants of exercise performance in children, adolescents and young adults who underwent the modified Fontan operation. Several studies of the cardiorespiratory responses to exercise after the Fontan operation have demonstrated subnormal maximal oxygen uptake and exercise heart rate, but the perioperative variables that ultimately affect exercise responses have not been assessed systematically. The study included 59 of the 548 patients who underwent a modified Fontan operation between January 1, 1984 and December 31, 1993 at the Mayo Clinic. Spirometry was performed at rest in all patients before exercise testing. The patients then exercised using a previously calibrated cycle ergometer and a 3-min incremental cycle exercise protocol. Multiple linear regression analysis was used to determine a subset of variables associated with oxygen uptake at peak exercise (VO2max), blood oxygen saturation (O2sat) and heart rate at peak exercise (HRmax). VO2max ranged from 29% to 95% of normal value; O2sat at peak exercise ranged from 77% to 96%; and HRmax ranged from 39.7% to 97.4% of normal value. Multivariate analysis showed that log VO2max/kg2/3 was associated with age at exercise, male gender, body surface area, preoperative confluent pulmonary arteries and rest VO2max/kg2/3. Preoperative left pulmonary artery stenosis, the presence of a classic Glenn anastomosis at exercise and rest O2sat were associated with O2sat at peak exercise. Age, body surface area at exercise, heart rate at rest and diastolic blood pressure were associated with HRmax at exercise. Subnormal VO2max and HRmax values were demonstrated at peak exercise. Several perioperative variables were associated with VO2max and O2sat at peak exercise. The presence of a classic Glenn anastomosis was associated with decreased O2sat at peak exercise, suggesting intrapulmonary shunting with the classic Glenn anastomosis.


Challenges of outcomes research for nurse practitioners.
To describe the numerous methodological challenges nurse practitioners (NPs) face in designing and conducting outcomes research and provide practical tips to implement an outcomes study within an institution. Review of world wide scientific literature on outcomes research. Nurse practitioners must be aware of the challenges of conducting outcomes research. Challenges associated with variable definition, designing outcomes studies, use of data sets, and instrument development and selection must be understood prior to undertaking an outcome study. Valuable studies have laid a foundation for evidence of quality care provision by NPs. Now is the time to measure patient outcomes of the NP care longitudinally over significant periods of time.


Plasma neurofilament light chain as a biomarker for fatal familial insomnia.
Fatal familial insomnia is a rare hereditary prion disease associated with the D178N-129M PRNP mutation. Early diagnosis is difficult, because the clinical syndrome may overlap with affective disorders. In addition, most known cerebrospinal fluid biomarkers for prion diseases and magnetic resonance imaging do not show a good diagnostic accuracy for fatal familial insomnia. In this context, data on plasma biomarkers are scarce. We analyzed levels of neurofilament light chain, glial fibrillary acidic protein, chitinase-3-like protein 1, calcium-binding protein B, and total tau protein in six serial plasma samples from a patient with fatal familial insomnia. Subsequently, plasma neurofilament light chain was analyzed in n = 25 patients and n = 19 controls. The diagnostic accuracy and associations with disease stage and duration were explored. Among all biomarker candidates in the case study, only neurofilament light chain levels showed a constant evolution and increased over time. They discriminated fatal familial insomnia from controls with an area under the curve of 0.992 (95% confidence interval [CI] = 0.974-1) in the case-control study. Higher concentrations were associated with methionine homozygosity at codon 129 PRNP (p = 0.006), shorter total disease duration (rho = -0.467, p = 0.019, 95% CI = -0.790 to -0.015), and shorter time from sampling to death (rho = -0.467, p = 0.019, 95% CI = -0.773 to -0.019). Plasma neurofilament light chain may be a valuable minimally invasive diagnostic biomarker for fatal familial insomnia after clinical onset. Most important, stage-related increase and association with disease duration indicate potential as a prognostic marker and as a surrogate marker in clinical trials.


Organizing multicenter trials: lessons from cardiovascular prevention trials.
Careful and thorough planning are essential aspects of a clinical trial that can make the difference and lead to a more successful trial. The value of feasibility studies should be recognized. The use of surrogate endpoints has justifiably come under increased scrutiny. The many complex issues of implementation demand experienced trial investigators. An openness to learn from lessons in previous trials is essential.


Keratin 14-dependent disulfides regulate epidermal homeostasis and barrier function via 14-3-3σ and YAP1.
The intermediate filament protein keratin 14 (K14) provides vital structural support in basal keratinocytes of epidermis. Recent studies evidenced a role for K14-dependent disulfide bonding in the organization and dynamics of keratin IFs in skin keratinocytes. Here we report that knock-in mice harboring a cysteine-to-alanine substitution at Krt14's codon 373 (C373A) exhibit alterations in disulfide-bonded K14 species and a barrier defect secondary to enhanced proliferation, faster transit time and altered differentiation in epidermis. A proteomics screen identified 14-3-3 as K14 interacting proteins. Follow-up studies showed that YAP1, a transcriptional effector of Hippo signaling regulated by 14-3-3sigma in skin keratinocytes, shows aberrant subcellular partitioning and function in differentiating Krt14 C373A keratinocytes. Residue C373 in K14, which is conserved in a subset of keratins, is revealed as a novel regulator of keratin organization and YAP function in early differentiating keratinocytes, with an impact on cell mechanics, homeostasis and barrier function in epidermis.


Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622.
Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression. The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay. Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo. Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.


Polymorphisms in the fetal progesterone receptor and a calcium-activated potassium channel isoform are associated with preterm birth in an Argentinian population.
To investigate genetic etiologies of preterm birth (PTB) in Argentina through evaluation of single-nucleotide polymorphisms (SNPs) in candidate genes and population genetic admixture. Genotyping was performed in 389 families. Maternal, paternal and fetal effects were studied separately. Mitochondrial DNA (mtDNA) was sequenced in 50 males and 50 females. Y-chromosome anthropological markers were evaluated in 50 males. Fetal association with PTB was found in the progesterone receptor (PGR, rs1942836; P=0.004). Maternal association with PTB was found in small conductance calcium activated potassium channel isoform 3 (KCNN3, rs883319; P=0.01). Gestational age associated with PTB in PGR rs1942836 at 32-36 weeks (P=0.0004). MtDNA sequencing determined 88 individuals had Amerindian consistent haplogroups. Two individuals had Amerindian Y-chromosome consistent haplotypes. This study replicates single locus fetal associations with PTB in PGR, maternal association in KCNN3, and demonstrates possible effects for divergent racial admixture on PTB.


Polyclonal increase in certain IgG subclasses in mice persistently infected with the 87V strain of scrapie.
Eight different combinations of seven strains of scrapie agent and the three known Sinc genotypes of mice were screened for changes in the concentration of IgG in serum. A single radial immunodiffusion assay was used to measure IgG throughout the incubation period which in different models ranged from an average of 125 days to longer than the maximum observation period of about 600 days. The only major changes occurred with the 87V strain of scrapie injected intracerebrally (i.c.) or intraperitoneally (i.p.) into mouse strains of the Sinc genotype p7p7. IgG concentration reached 1.5 to 2.0 times the control values in i.c. infected mice, which developed clinical disease after 270 to 320 days and also in i.p. infected mice, which did not develop the disease within the 600-day observation period. At very high IgG concentration, the increase was polyclonal; it involved the IgG 1 subclass more than the others and was accompanied by an increased rate of IgG clearance from serum. It is suggested that some scrapie infections of mice (and sheep) may upset the control of IgG production. The underlying mechanism may involve cell-pathogen interactions which are common to all scrapie infections, but only lead to gross changes in IgG in some combinations of agent strain and host genotype.


Malignant Peripheral Nerve Sheath Tumour in a Seba's Short-Tailed Bat (Carollia perspicillata).
There are few reports of tumours in bats, despite the fact that members of the Chiroptera order include 22.4% of all currently known mammal species. We now describe a case of malignant peripheral nerve sheath tumour (MPNST) in an adult female Seba's short-tailed bat (Carollia perspicillata) from a private zoo in Switzerland. The macroscopical and histological findings indicated that the MPNST originated from a dorsal spinal nerve root sheath in the lumbar region and metastasized to the spleen. Immunohistochemical labelling for glial fibrillary acid protein, S100 protein, neuron specific enolase and synaptophysin was negative. The cytoplasm of a few neoplastic cells labelled for smooth muscle actin and desmin. To our knowledge, this is the first report of a PNST in a member of the Chiroptera order.


Design and implementation of the first randomized controlled trial of coenzyme CoQ₁₀ in children with primary mitochondrial diseases.
We report the design and implementation of the first phase 3 trial of CoenzymeQ₁₀ (CoQ₁₀) in children with genetic mitochondrial diseases. A novel, rigorous set of eligibility criteria was established. The trial, which remains open to recruitment, continues to address multiple challenges to the recruitment of patients, including widely condoned empiric use of CoQ₁₀ by individuals with proven or suspected mitochondrial disease and skepticism among professional and lay mitochondrial disease communities about participating in placebo-controlled trials. These attitudes represent significant barriers to the ethical and scientific evaluation--and ultimate approval--of nutritional and pharmacological therapies for patients with life-threatening inborn errors of energy metabolism.


Taxometric analysis of helminthes of marine fishes. 1. Pedunculacetabulum spinatum n.sp., from Chorinemus mandetta and Wenyonia rhincodonti n.sp., from Rhincodon typus.
The investigations include report of two new worms from marine fishes of Central West Coast of Goa in Arabian Sea. A trematode, Pedunculacetabulum spinatum n.sp. from Chorinemusmandetta and Wenyonia rhincodoni n.sp. from sharks, Rhincodon typus have been described and compared with closer species. The systematics of genus Pedunculacetabulum Yamaguti (Japan J Zool 6:1-112, 1934) has been discussed with detailed evidence of taxometric significance to reinstate this genus.


Physical map and genetic early region of the T7-related coliphage, BA14.
The chromosome of the bacterial virus, BA14, a member of the T7 lytic coliphage group, was characterized by direct measurement of its length and construction of a restriction map. The chromosome (39.6 kb) is essentially the same size as T7 (39.9 kb), is devoid of a large number of restriction sites expected for a DNA of this size, and moreover, lacks modification sites for the Escherichia coli Dam and Dcm methyltransferases. The BA14 early region was assigned by testing the ability of specific chromosomal restriction fragments to direct RNA synthesis by E. coli RNA polymerase, and analysis of in vitro RNase III cleavage products of the transcripts. The data support and extend the previous assertion that BA14 is a representative of a distinct T7 subgroup, and limited nucleotide sequence analysis of the BA14 DNA ligase-encoding gene suggests a closer relationship of BA14 to T7 than to T3 phage, another member of the T7 group.


Polymer-hydroxyapatite composites for biodegradable bone fillers.
A number of composites made from biodegradable polymers and hydroxyapatite were studied in vivo and in vitro in an attempt to develop biodegradable artificial bone fillers. Histological observation in rats revealed that polylactic acid, of low molecular weight (PLAoligomer), was rapidly resorbed and replaced by newly formed bone tissue when incorporated with hydroxyapatite and this suggested that the incorporated hydroxyapatite seemed to play an active role in the new bone formation. In vitro testing revealed that the solubility of hydroxyapatite was markedly enhanced when mixed with PLAoligomer.


[Magnetic resonance tomography in suspected acoustic neurinoma: technic and differential diagnosis].
Sixty-five patients with suspected acoustic neuromas were examined by CT and MR; the optimal diagnostic procedures are discussed. Extrameatal acoustic neuromas (11 cases) were all diagnosed by CT and MR, but only 82% of intrameatal tumours could be diagnosed by CT combined with air cisternography. Using special surface coils and the paramagnetic contrast medium Gd-DTPA, the accuracy of MR was 100%. All tumours greater than 4 mm were demonstrated. Following clinical and neurological examination, MR is the primary diagnostic method in the investigation of acoustic neuromas.


Prenatal carbon monoxide exposure differentially affects postnatal weight and monoamine concentration of rat brain regions.
Regional weight, protein concentration, and monoamine concentration were determined in the pons/medulla, neocortex, hippocampus, and cerebellum of 21- and 42-day-old offspring of rats exposed to either air or 75, 150, or 300 ppm carbon monoxide (CO) throughout pregnancy. Norepinephrine and serotonin concentrations decreased linearly with increasing CO exposure concentrations in the pons/medulla of CO-exposed offspring at 21 days of age, but not by 42 days of age. Norepinephrine concentration increased linearly with increasing CO exposure concentrations in neocortex and tended to increase in hippocampus of CO-exposed offspring at 42 days of age, but not at 21 days of age. Regional weights and protein concentrations of the neocortex, hippocampus, or pons/medulla were not affected by CO exposure at either age. Cerebellar weights of CO-exposed offspring, however, decreased linearly with increasing CO exposure concentrations at both 21 and 42 days after birth. No significant effect of CO exposure on cerebellar monoamine concentrations was observed. The results suggest that prenatal CO exposure disrupts the development of noradrenergic and serotonergic neuronal systems, and the development of the cerebellum.


[Investigations for simplification of the clinical rotation test of irritability of the human vestibular organ (author's transl)].
Fifty ear-sound adolescents were rotated by constant acceleration and deceleration. These investigations yielded three results. 1. The nystagmus of acceleration and deceleration period permits a more exact statement about rotation irritability of peripheral vestibular organ than the per-rotatoric fading nystagmus during constant rotation. 2. The stop out of constant rotation causes only a fading nystagmus, the postrotatorius I. Consequently, deceleration should substitute the stop with regard to its greater exactness. 3. Statistical comparison shows that electronystagmograms of acceleration and deceleration correspond to electronystagmograms of right and left rotation. Therefore, the clinical rotation test is practicable with only one direction of rotation. In this case, deceleration has to be of the same strength and duration as the acceleration.


Early results of minimally invasive mitral valve surgery: initial series in a public hospital in Australia.
This study analyzes the initial experience with minimally invasive mitral valve surgery through a right minithoracotomy in a public teaching hospital in Australia and evaluates early surgical outcomes. A retrospective review of patients who underwent minimally invasive mitral valve surgery between November 2006 and March 2009 was performed. A total of 60 patients included 47 (78%) patients who had mitral valve plasty and 13 (22%) who had mitral valve replacement. The mean age was 61 ± 15 years; 33 (55%) patients were male; and 6 (10%) had had previous cardiac operations. The mean cardiopulmonary bypass and aortic cross-clamp times were 140 ± 46 and 93 ± 35 min, respectively. All patients who underwent mitral valve plasty left the operation room with no more than trivial residual mitral regurgitation. There was no operative mortality. Reoperation for bleeding and stroke occurred in 2 patients each. The mean intensive care unit and hospital stays were 3.1 ± 5.8 and 10.6 ± 8.9 days, respectively. Among the 47 patients with mitral valve plasty, 46 (98%) had mild or less mitral regurgitation on transthoracic echocardiography at discharge. There was one late death. No reoperation for the mitral valve has been observed so far. An echocardiography report was obtained for 34 of the 47 who had had mitral valve plasty at 12.1 ± 7.9 months postoperatively, and 27 (79%) of them had mild or less mitral regurgitation. Minimally invasive mitral valve surgery through a right minithoracotomy was safely performed with no early mortality.


External cervical resorption-a review of pathogenesis and potential predisposing factors.
External cervical resorption (ECR) refers to a pathological state in which resorption tissues penetrate into the dentin at the cervical aspect of the root. Despite being latent in its initial phase, ECR could cause severe damage to mineralized dental tissue and even involve the pulp if not given timely diagnosis and treatment. Nevertheless, the etiology of ECR is still poorly understood, which adds to the difficulty in early diagnosis. ECR has received growing attention in recent years due to the increasing number of clinical cases. Several potential predisposing factors have been recognized in cross-sectional studies as well as case reports. In the meantime, studies on histopathology and pathogenesis have shed light on possible mechanisms of ECR. This review aims to summarize the latest findings in the pathogenesis and potential predisposing factors of ECR, so as to provide pragmatic reference for clinical practice.


Human responses to bright light of different durations.
Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (<3 lux), and were then randomized for exposure to a bright light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.


Recent advances in stereoselective synthesis of 1,3-dienes.
The aim of this review is to present the latest developments in the stereoselective synthesis of conjugated dienes, covering the period 2005-2010. Since the use of this class of compounds is linked to the nature of their appendages (aryls, alkyls, electron-withdrawing, and heterosubstituted groups), the review has been categorized accordingly and illustrates the most representative strategies and mechanisms to access these targets.


Review of bioactivity and structure-activity relationship on baicalein (5,6,7-trihydroxyflavone) and wogonin (5,7-dihydroxy-8-methoxyflavone) derivatives: Structural modifications inspired from flavonoids in Scutellaria baicalensis.
Baicalein (5,6,7-trihydroxyflavone) and wogonin (5,7-dihydroxy-8-methoxyflavone), as typical flavonoids isolated from Scutellaria baicalensis, are well important precursors in drug discovery which produce diverse therapeutically related applications in pharmacological practices. Researches in medicinal chemistry field have synthesized baicalein and wogonin derivatives with multiple medicinal properties including antitumor, central nervous system (CNS), anti-inflammatory, antiviral, antimicrobial and hypoglycemic activities. Simultaneously, SAR (Structure-Activity Relationship) analysis has been gradually possessed, along with a great deal of derivatives have been derived for potential targets. In this article, we comprehensively summarize the biological activities and SAR for baicalein and wogonin derivatives, along with the featuring bioactive molecules reported in patents, wishing to provide an overall retrospect and prospect on baicalein and wogonin analogues.


Review of the bacterial composition of healthy milk, mastitis milk and colostrum in small ruminants.
Bacterial infections are the cause of many reproductive disorders of economic importance, such as mastitis, in livestock. Unfortunately, very little is known about the microbiota and the changes occurring during an infection state in small ruminants. The sequencing of regions of the 16S rRNA gene, is the useful tool to describe the whole dairy microbiome. Using this technique, studies have identified various phyla such as Firmicutes, Actinobacteria, Proteobacteria, Bacteroidetes, Fusobacteria and Cyanobacteria; and also several genera from raw milk of small ruminants. Nevertheless, there does not seem to be a consensus on the predominant genera nor phyla, even within the same breed. There is a lack of information about the mammary microflora in meat-oriented breeds, and about the microflora of colostrum and mastitis milk. Further studies comparing the microbiota between artificial and natural lactations and between healthy and mastitis milk are necessary. Considering the concerns arising from the use overuse of antibiotic therapy in Veterinary Medicine, it would be interesting to develop alternative strategies for the control of mastitis. Probiotics, such as lactic acid bacteria (LAB), have proven to be an interesting antibiotic-free strategy. Therefore, their presence in the dairy microflora of small ruminants and their interactions with other bacteria, such as mastitis-causing pathogens, should be scrutinized, given that the efficacy of probiotics increase when the bacterial strains used are specific to their host.


Egocentric path integration models and their application to desert arthropods.
Path integration enables desert arthropods to find back to their nest on the shortest track from any position. To perform path integration successfully, speeds and turning angles along the preceding outbound path have to be measured continuously and combined to determine an internal global vector leading back home at any time. A number of experiments have given an idea how arthropods might use allothetic or idiothetic signals to perceive their orientation and moving speed. We systematically review the four possible model descriptions of mathematically precise path integration, whereby we favour and elaborate the hitherto not used variant of egocentric cartesian coordinates. Its simple and intuitive structure is demonstrated in comparison to the other models. Measuring two speeds, the forward moving speed and the angular turning rate, and implementing them into a linear system of differential equations provides the necessary information during outbound route, reorientation process and return path. In addition, we propose several possible types of systematic errors that can cause deviations from the correct homeward course. Deviations have been observed for several species of desert arthropods in different experiments, but their origin is still under debate. Using our egocentric path integration model we propose simple error indices depending on path geometry that will allow future experiments to rule out or corroborate certain error types.


Using Drosophila Models and Tools to Understand the Mechanisms of Novel Human Cancer Driver Gene Function.
The formation, overgrowth and metastasis of tumors comprise a complex series of cellular and molecular events resulting from the combined effects of a variety of aberrant signaling pathways, mutations, and epigenetic alterations. Modeling this complexity in vivo requires multiple genes to be manipulated simultaneously, which is technically challenging. Here, we analyze how Drosophila research can further contribute to identifying pathways and elucidating mechanisms underlying novel cancer driver (risk) genes associated with tumor growth and metastasis in humans.


Clinical manifestations of treatment-naive patients with acquired immunodeficiency syndrome and responses to highly active antiretroviral therapy in the Taipei Veterans General Hospital: a 5-year prospective study.
Taipei Veterans General Hospital, one of the medical centers in Taiwan, has provided highly active antiretroviral therapy (HAART) to human immunodeficiency virus/AIDS patients for more than 10 years. Five years ago, we began a prospective follow-up of our patients' clinical manifestations and responses to HAART by collecting their clinical data. In this study, we analyzed the morbidity, mortality, and responses to HAART of treatment-naive AIDS patients. The purpose was to provide local data that may be valuable in Taiwan. Study cases were enrolled from January 1, 2004, to February 28, 2009, with inclusion criteria of newly diagnosed AIDS during hospitalization and being naive to HAART. Antiretroviral therapy was initiated. To evaluate the clinical responses to HAART, we excluded patients who were pregnant, died within 1 month after confirmation of an AIDS diagnosis, failed to initiate HAART, or were lost to follow-up for more than 6 months. Plasma viral loads and CD4(+) counts were quantified by reverse-transcriptase polymerase chain reaction and flow cytometry, respectively. Statistical analysis was performed using SPSS statistical software. A total of 49 patients were enrolled and 45 patients fulfilled the inclusion criteria for evaluating the efficacy of HAART. At 3 months, 12 months, and 30 months after the initiation of HAART, 64.4% (29 of 45), 88.2% (30 of 34), and 93.8% (15 of 16) had undetectable plasma viral loads, respectively, and 37.8% (17 of 45), 73.5% (25 of 34), and 81.2% (13 of 16) had CD4(+) counts of more than 200 cells/μL, respectively. Median CD4(+) counts increased from baseline at Month 3 by 171 cells/μL and at Month 30 by 375 cells/μL. The overall mortality was 22.4% (11 of 49). The virologic and immunologic responses after initiating HAART in this study demonstrated our achievements in providing care and treatment for AIDS patients during this 5-year period, which provides a strong evidence of the efficacy of HAART.


Formation and Electrochemical Evaluation of Polyaniline and Polypyrrole Nanocomposites Based on Glucose Oxidase and Gold Nanostructures.
Nanocomposites based on two conducting polymers, polyaniline (PANI) and polypyrrole (Ppy), with embedded glucose oxidase (GOx) and 6 nm size gold nanoparticles (AuNPs(6nm)) or gold-nanoclusters formed from chloroaurate ions (AuCl4-), were synthesized by enzyme-assisted polymerization. Charge (electron) transfer in systems based on PANI/AuNPs(6nm)-GOx, PANI/AuNPs(AuCl4-)-GOx, Ppy/AuNPs(6nm)-GOx and Ppy/AuNPs(AuCl4-)-GOx nanocomposites was investigated. Cyclic voltammetry (CV)-based investigations showed that the reported polymer nanocomposites are able to facilitate electron transfer from enzyme to the graphite rod (GR) electrode. Significantly higher anodic current and well-defined red-ox peaks were observed at a scan rate of 0.10 V s-1. Logarithmic function of anodic current (log Ipa), which was determined by CV-based experiments performed with glucose, was proportional to the logarithmic function of a scan rate (log v) in the range of 0.699-2.48 mV s-1, and it indicates that diffusion-controlled electrochemical processes were limiting the kinetics of the analytical signal. The most efficient nanocomposite structure for the design of the reported glucose biosensor was based on two-day formed Ppy/AuNPs(AuCl4-)-GOx nanocomposites. GR/Ppy/AuNPs(AuCl4-)-GOx was characterized by the linear dependence of the analytical signal on glucose concentration in the range from 0.1 to 0.70 mmol L-1, the sensitivity of 4.31 mA mM cm-2, the limit of detection of 0.10 mmol L-1 and the half-life period of 19 days.


Comparative Risk-Benefit Profiles of Individual Devices for Graft Fixation in Anterior Cruciate Ligament Reconstruction: A Systematic Review and Network Meta-analysis.
To compare the efficacy and safety of individual devices for femoral and/or tibial graft fixation in anterior cruciate ligament (ACL) reconstruction. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to December 12, 2018. Randomized controlled trials comparing individual devices for ACL graft fixation were included. Bayesian network meta-analysis was performed to assess the efficacy profile using the following outcomes: Lysholm score, International Knee Documentation Committee (IKDC) category, laxity, range of motion, and Tegner score. The incidence of infection, effusion, and graft rupture for each device was reported. We included 57 randomized controlled trials involving 4,304 patients aged 23.8 to 40.9 years. The female proportion ranged from 0% to 100%. The length of follow-up ranged from 6 to 144 months. Of the 13 studied femoral fixation devices, none was significantly different from the others regarding the Lysholm score, IKDC category, range of motion, and Tegner score. Bioabsorbable interference screws (standardized mean difference, 1.3; 95% credible interval, 0.0-2.5) showed higher laxity than the EndoPearl at a borderline level of statistical significance, but the difference varied substantially within multiple sensitivity analyses. Infection (2.0%) was most commonly seen with the EndoPearl, whereas the bone mulch screw had the highest incidence of effusion (5.5%) and graft rupture (5.5%). For the 9 studied tibial fixation devices, no significant difference was observed in the aforementioned efficacy measurements. Bioabsorbable interference screws with staples had the highest incidence of infection (11.1%) and effusion (15.6%), whereas graft rupture was most commonly seen with the bone plug (4.0%). Graft fixation devices in ACL reconstruction share a similar efficacy profile in terms of the Lysholm score, IKDC category, range of motion, and Tegner score but not laxity. On the other hand, safety profiles seem to vary among different devices. These findings can support surgeons, alongside their experience and preference, as well as the relative cost of each device, in delivering an individualized plan for an optimal operation. Level II, meta-analysis of Level I and II studies.


Response by gender of HIV-1-infected subjects treated with abacavir/lamivudine plus atazanavir, with or without ritonavir, for 144 weeks.
The 144-week results of the open-label, multicenter Atazanavir/Ritonavir Induction with Epzicom Study (ARIES) were stratified by gender to compare treatment responses. A total of 369 HIV-infected, antiretroviral-naïve subjects receiving once-daily abacavir/lamivudine + atazanavir/ritonavir (ATV/r) whose HIV-1 RNA was <50 copies/mL by week 30 were randomized 1:1 at week 36 to maintain or discontinue ritonavir for 108 subsequent weeks. Between- and within-treatment gender-related efficacy and safety differences were analyzed. Subjects were 85% male; 64% white; and had a mean age of 39 years, baseline median HIV-1 RNA of 114,815 copies/mL, and median CD4+ cell count of 198 cells/mm3. Gender (ATV [n=189]: 29 females/160 males; ATV/r [n=180]: 25 females/155 males) and most other demographics were similar between groups; more females than males were black (65% vs 25%) and fewer females had baseline HIV-1 RNA ≥100,000 copies/mL (41% vs 58%). At week 144, no significant differences between genders were observed in proportion maintaining HIV-1 RNA <50 copies/mL (ATV, 79% vs 77%; ATV/r, 60% vs 75%) or <400 copies/mL (ATV, 83% vs 84%; ATV/r, 68% vs 82%) (intent-to-treat-exposed: time to loss of virologic response analysis); median CD4+ change from baseline (ATV, +365 vs +300 cells/mm3; ATV/r, +344 vs +301 cells/mm3); proportion with treatment-related grade 2-4 adverse events (baseline to week 144: ATV, 41% vs 31%; ATV/r, 36% vs 43%; weeks 36 to 144: ATV, 14% vs 13%; ATV/r, 24% vs 23%); or proportion developing fasting lipid changes. Female and male virologic failure rates (ATV, 0 vs 5; ATV/r, 2 vs 4) and proportions completing the study were similar during the extension phase. Primary withdrawal reasons were loss to follow-up and pregnancy for females and loss to follow-up and other for males. Over 144 weeks, no significant gender differences were observed in efficacy, safety, or fasting lipid changes with abacavir/lamivudine +ATV or abacavir/lamivudine +ATV/r.


Outcome of patients with acute liver failure awaiting liver transplantation in Japan.
To clarify the outcome and predictive factors in patients with acute liver failure (ALF) awaiting deceased donor liver transplantation (DDLT) in Japan. Of the DDLT candidates in Japan between 2007 and 2016, 264 adult patients with ALF were retrospectively enrolled in this study. Factors associated with DDLT and waiting-list mortality were assessed using the Cox proportional hazard model. The DDLT and transplant-free survival probabilities were evaluated using Kaplan-Meier analysis and the log-rank test. The waiting-list registration year after the Transplant Law revision in 2010 was a significant factor associated with DDLT. The adjusted hazard ratio indicated that DDLT probability after 2010 was four times higher than that before, and the 28-day cumulative DDLT probability was more than 35%. The median survival time of the entire cohort was 40 days. Multivariate analysis identified the following three factors associated with waiting-list mortality: age, coma grade, and international normalized ratio. The transplant-free survival probabilities were significantly stratified by the number of risks, and patients with all three risks showed extremely poor short-term prognosis (median survival time = 23 days). The DDLT probability of ALF patients increased after the law revision in 2010; however, patients at high risk of short-term waiting-list mortality might need emergent living donor transplantation.


Effects of orally administered Clostridium butyricum MIYAIRI 588 on mucosal immunity in mice.
The activation of local mucosal immunity by Clostridium butyricum MIYAIRI 588 (CBM588) was investigated in germ-free mice. An increase of polyclonal IgA production in the small intestine or secretion into the intestinal lumen was observed in mice mono-associated with CBM588 and fed a diet containing killed vegetative cells of CBM588 (VCBM). However, fecal IgA of anti-CBM588 was rarely formed in mice administered CBM588 during 6 weeks from administration. Cholera toxin was administered orally to SPF mice fed a diet containing CBM588, and IgA secretion of anti-cholera toxin was enhanced in mice fed a VCBM diet. In addition, the production of IgA, IgM and IgG in Peyer's patch cell culture was increased in the presence of VCBM. These results suggest that oral administration of CBM588 stimulates polyclonal mucosal immune activity and shows adjuvant activity for anti-cholera toxin.


RYGB Is More Effective than VSG at Protecting Mice from Prolonged High-Fat Diet Exposure: An Occasion to Roll Up Our Sleeves?
Understanding the effects of Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) on adipose tissue physiology is important for the treatment of obesity-related metabolic disorders. By using robust mouse models of bariatric surgery that closely resemble those performed in humans, we can compare the effects of RYGB and VSG on adipose physiology in the absence of post-operative confounds such as diet and lifestyle changes. RYGB and VSG were compared using a diet-induced mouse model of obesity. High-fat diet (HFD) was administered post-operatively and changes to white and brown adipose tissue were evaluated, along with alterations to weight, glucose homeostasis, dyslipidemia, and insulin sensitivity. After prolonged exposure to high-fat diet post-operatively, RYGB was effective in achieving sustained weight loss, while VSG unexpectedly accelerated weight gain rates. The resolution of obesity-related comorbidities such as glucose and insulin intolerance, dyslipidemia, and insulin sensitivity was improved after RYGB, but not for VSG. In RYGB, there were improvements to the function and health of white adipose tissue, enhanced brown adipose metabolism, and the browning of subcutaneous white adipose tissue, with no comparable changes seen for these factors after VSG. Some markers of systemic inflammation improved after both RYGB and VSG. There are significantly different effects between RYGB and VSG when HFD is administered post-operatively and robust mouse models of bariatric surgery are used. RYGB resulted in lasting physiological and metabolic changes but VSG showed little difference from that of its sham-operated, DIO counterpart.


Clinical tests in shoulder examination: how to perform them.
This article describes the best clinical tests of shoulder function and injury as identified in a recent systematic review published in the British Journal of Sports Medicine. A description of the different tests is given, with photographs of the exact test procedure.


Hallucinations after preoperative baclofen discontinuation in spinal cord injury patients.
Baclofen is a muscle relaxant approved in this country for the treatment of muscle spasms secondary to multiple sclerosis, spinal cord injury, and other spinal diseases. Although baclofen is considered to have fewer side effects than alternative drugs, problems can occur when the dosage is changed abruptly. Two patients are presented who developed hallucinations after discontinuing baclofen as part of routine preoperative procedures. Both patients responded at 23 and 31 hours after reinstituting baclofen. If possible, patients should be withdrawn slowly from baclofen before surgery. Any patient withdrawn abruptly from baclofen should be restarted as soon as possible.


Interaction of acrylonitrile with hepatic microsomes of rats and men.
Acrylonitrile (AN) showed spectral interaction with hepatic microsomes from mouse, rat and man. Whereas human and rat liver microsomes resulted in ligand AN-binding spectra, mouse liver microsomes behaved differently. Hepatic microsomes from phenobarbital-treated mice with AN showed a type I substrate binding; ligand spectra are recorded with microsomes from benzo[a]pyrene-treated mice. Microsomes from untreated control mice showed a mixed type behaviour.


Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The DCCT Research Group.
The present study describes the epidemiology of severe hypoglycemia and identifies patient characteristics or behaviors associated with severe hypoglycemia in patients with insulin-dependent diabetes mellitus (IDDM) participating in the Diabetes Control and Complications Trial (DCCT). The DCCT is a multicenter randomized clinical trial designed to compare the benefits and risks of intensive therapy with those of conventional management of IDDM. The DCCT's feasibility phase demonstrated that intensive therapy, with the aim of achieving glucose levels as close to the non-diabetic range as possible, was accompanied by a threefold increase in severe hypoglycemia compared with conventional therapy. This report is based on the first 817 subjects who entered the DCCT, with a mean follow-up of 21 months. Two hundred sixteen subjects reported 714 episodes of severe hypoglycemia; 549 (77%) occurred in intensively treated subjects. The incidence of severe hypoglycemia in the intensive treatment group ranged from two to six times that observed with conventional treatment. Severe hypoglycemia occurred more often during sleep (55%); 43% of all episodes occurred between midnight and 8 AM. Of episodes that occurred while subjects were awake, 36% were not accompanied by warning symptoms. In intensively treated subjects, predictors of severe hypoglycemia included history of severe hypoglycemia, longer duration of IDDM, higher baseline glycosylated hemoglobin (HbA1c) levels, and a lower recent HbA1c. Multivariate analyses failed to yield predictive models with high sensitivity. In the DCCT, intensive treatment of IDDM increased the frequency of severe hypoglycemia relative to conventional therapy. Intensive treatment may cause even more frequent severe hypoglycemia when applied to less selected and less motivated populations in the clinical practice setting. These findings underscore the importance of determining the benefit-risk ratio of intensive and standard therapy of IDDM.


Efficient activation of peroxymonosulfate and degradation of Orange G in iron phosphide prepared by pickling waste liquor.
In this study, the low-cost preparation of iron phosphide by using pickling waste liquor as the initial material was performed through a two-step reaction. The degradation of Orange G was evaluated using iron phosphide coupled with peroxymonosulfate to construct a catalytic system. The removal efficiencies of Orange G and total organic carbon reached 97.4 and 58.4% at 60 min, respectively. Iron phosphide has dual-catalysis centers for the activation of PMS. Multiple free radicals (e.g., SO4•-, HO•, SO5•-, and O2•-) and singlet oxygen were involved in the pollutant degradation, of which sulfate radicals played the main role. The iron phosphide catalyst exhibited excellent recycling stability, and its catalytic efficiency reached 95% after five cycles. In summary, the Fe2P/PMS system-as a Fenton-like catalytic system-has certain advantages, including low cost, high efficiency, sufficient reusability, and good stability, all of which are favorable for its practical application.


The Medical Home Initiative in Italy: an Analysis of Changes in Healthcare Utilization.
Seventeen medical homes (MHs) were established in the Local Health Authority (LHA) of Parma (about 450,000 residents), Emilia Romagna, Italy, between 2011 and 2016. To estimate the effects of MH implementation on healthcare utilization. We conducted a longitudinal cohort study (01/2011-12/2017) using the Parma LHA administrative healthcare database. Residents for ≥1 year and older than 14 years of age with a documented primary care physician (PCP) in Parma LHA. MH exposure status was classified for each resident as either receiving care from a PCP that (1) eventually practices in an MH (pre-MH), (2) is currently in an MH (post-MH), or (3) does not join an MH (non-MH). Risks of ordinary inpatient hospital admissions, day hospital admissions, admissions for ambulatory care sensitive conditions (ACSCs), all-cause emergency department (ED) visits, and deferrable ED visits were compared using Cox proportional hazards regression and risks of all-cause 30- and 90-day readmissions for congestive heart failure (CHF) or chronic obstructive pulmonary disease (COPD) were compared using logistic regression. Prior to MH implementation, the risk of all-cause ED visits for pre-MH residents was 0.93 (95% CI: 0.92-0.94) that of non-MH residents. After MH implementation, the relative risk for post-MH versus non-MH was 0.86 (95% CI: 0.85-0.87) and, over time, post-MH versus pre-MH was 0.93 (95% CI: 0.92-0.94). Hospitalization risks were generally lower among the pre-MH and post-MH, compared to non-MH. However, hospitalizations and HF or COPD readmissions were not generally lower post-MH compared to pre-MH. This MH initiative was associated with a 7% reduction in risk of ED visits. More research is necessary to understand if ED visit risk will continue to improve and how other aspects of healthcare utilization might change as more MHs open and the length of exposure to MHs increases.


Do we get better outcomes from early treatment of Class III discrepancies?
Early orthodontic treatment in the mixed dentition aims to simplify definitive treatment in the permanent dentition. In Class III cases, this can be an effective strategy for the management of a local anterior crossbite, using either a removable or simple fixed appliance. For more significant Class III malocclusions, the decision to intervene early is a more difficult one. Traditionally, orthodontists in the UK have been reluctant to embark on early treatment in the presence of a skeletal Class III relationship but there is now some evidence that in selected cases, the use of protraction headgear can be a successful method of avoiding the need for later surgery. Although growth prediction in Class III cases is notoriously difficult, in the presence of maxillary retrognathia, the general dental practitioner should consider early referral of Class III cases to a specialist orthodontist.


Evidence of a gene-environment interaction that predisposes to spontaneous preterm birth: a role for asymptomatic bacterial vaginosis and DNA variants in genes that control the inflammatory response.
We determined whether an environmental exposure to bacterial vaginosis (BV) modified genetic susceptibilities for spontaneous preterm delivery within genes that regulate the inflammatory response. Maternal DNA samples and vaginal smears for Gram staining were collected from 743 women (68 preterm births). We used a 1536-single nucleotide polymorphism (SNP) custom chip to study associations between genotype distributions and preterm birth. For 8 SNPs in 3 genes (protein kinase C alpha, fms-like tyrosine kinase 1, and interleukin 6), the odds ratios for preterm birth ranged from 1.9-4.0 among women with susceptible genotypes who were BV positive. The odds ratios for preterm birth were 2.0-5.0 times greater among women who were BV positive than among women who were BV negative. The significance of these differences was demonstrated by logistic regression analyses for genotype/BV interaction. These results demonstrate that the risk of preterm delivery that is associated with tag SNPs in genes that regulate the inflammatory response is modified by an environmental exposure such as bacterial vaginosis.


[Chloroquine resistant malaria caused by P. falciparum in East Africa. Apropos of 2 cases].
The authors report two additional cases of malaria due to chloroquine-resistant Plasmodium falciparum, one from Tanzania, the other from Kenya. In addition to the in vivo observations, these strains were thoroughly investigated by chloroquine assay and evaluation of ED50 using an original method (in vitro semi-microtest).


The use of mitochondrial targeting resveratrol liposomes modified with a dequalinium polyethylene glycol-distearoylphosphatidyl ethanolamine conjugate to induce apoptosis in resistant lung cancer cells.
Intrinsic multidrug resistance (MDR) of cancers remains a major obstacle to successful chemotherapy. A dequalinium polyethylene glycol-distearoylphosphatidylethanolamine (DQA-PEG(2000)-DSPE) conjugate was synthesized as a mitochondriotropic molecule, and mitochondrial targeting resveratrol liposomes were developed by modifying DQA-PEG(2000)-DSPE on the surface of liposomes for overcoming the resistance. Evaluations were performed on the human lung adenocarcinoma A549 cells and resistant A549/cDDP cells, A549 and A549/cDDP tumor spheroids as well as the xenografted resistant A549/cDDP cancers in nude mice. The yield of DQA-PEG(2000)-DSPE conjugate synthesized was about 87% and the particle size of mitochondrial targeting resveratrol liposomes was approximately 70 nm. The mitochondrial targeting liposomes significantly enhanced the cellular uptake, and selectively accumulated into mitochondria when encapsulating coumarin as the fluorescent probe. Furthermore, mitochondrial targeting resveratrol liposomes induced apoptosis of both non-resistant and resistant cancer cells by dissipating mitochondria membrane potential, releasing cytochrome c and increasing the activities of caspase 9 and 3. They also exhibited significant antitumor efficacy in two kinds of cancer cells, in tumor spheroids by penetrating deeply into the core, and in xenografted resistant A549/cDDP cancers in nude mice. Mitochondrial targeting resveratrol liposomes co-treating with vinorelbine liposomes significantly enhanced the anticancer efficacy against the resistant A549/cDDP cells. In conclusion, mitochondrial targeting resveratrol liposomes would provide a potential strategy to treat the intrinsic resistant lung cancers by inducing apoptosis via mitochondria signaling pathway.


Red wine increases adipose tissue aromatase expression and regulates body weight and adipocyte size.
Obesity is an important component of the metabolic syndrome in constituting a risk factor for cardiovascular disease, diabetes, and cancer. Estrogens influence lipid accumulation in adipocytes, acting indirectly or directly on adipose tissue. In this study we aimed to investigate the influence of red wine ingestion on the expression of aromatase (estrogen synthase) in adipose tissue. Red wine or ethanol solution, in the concentration found in red wine, was provided to Wistar rats as the sole drinking fluid for 8 wk. Food and drink intakes and body weight were monitored throughout treatment and adipocyte size and aromatase expression in the adipose tissue were determined at the end of the experimental period. Red wine and ethanol increased aromatase expression in the adipose tissue and red wine decreased adipocyte size (P < 0.05). In addition, animals treated with red wine or ethanol had significantly lower weight gain than controls, despite a similar energy intake. Thus, the ingestion of red wine may alter the production of estrogens by adipose tissue, body weight gain, and adipocyte size. Some of these red wine effects are attributable to ethanol. This relation among estrogen availability, adipocyte biology, and weight gain is most interesting and deserves further study because it may lead to new strategies to reduce metabolic syndrome incidence.


The impact of metal pipe materials, corrosion products, and corrosion inhibitors on antibiotic resistance in drinking water distribution systems.
Drinking water distribution systems (DWDS) are unique engineering environments that are important routes for the acquisition and dissemination of antibiotic resistance. Antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in drinking water pose risks to human and environmental health. Metals are known stressors that can select for antibiotic resistance. The objective of this review was to assess the state of knowledge regarding the impact of metal pipe materials, corrosion products, and corrosion inhibitors on the prevalence of antibiotic resistance in DWDS. ARGs and mobile genetic elements (MGEs) have been detected in full-scale DWDS in concentrations ranging from ~ 101 to 1010 copies/L. Metal pipe materials can select for bacteria harboring ARGs and metal resistance genes (MRGs) through co-selection processes. Corrosion products that develop in metal drinking water pipes (Cu, Fe, and Pb oxides) may also stimulate antibiotic resistance selection during distribution. Different corrosion inhibitor regimes (phosphates, sodium silicates) may also have impacts on microbial communities and the abundance of resistance genes in DWDS. Research is needed to quantify how engineering decisions related to drinking water infrastructure and corrosion inhibitor practices impact the abundance and distribution of ARG, MRGs, and MGEs in potable water systems. KEY POINTS: • Lack of quantitative measurements of antibiotic and metal resistance genes in drinking water distribution systems. • Pipe materials and corrosion products that develop in pipe scales may impact antibiotic resistance. • Corrosion inhibitors with zinc or phosphate could alter antibiotic resistance. • Management decisions should consider antibiotic resistance ramifications. Graphical abstract.


Depolymerization of lignin using laccase from Bacillus sp. PCH94 for production of valuable chemicals: A sustainable approach for lignin valorization.
Lignin is the most abundant aromatic polymer in nature, and its depolymerization offers excellent opportunities to develop renewable aromatic chemicals. In the present study, Bacillus sp. PCH94 was investigated for laccase production and lignin depolymerization. Maximum production of laccase enzyme was achieved within 6.0 h at 50 °C on a natural lignocellulosic substrate. Furthermore, Bacillus sp. PCH94 was used to bioconvert lignin dimeric and polymeric substrates, validated using FT-IR, NMR (1H, 13C), and LCMS. Genome mining of Bacillus sp. PCH94 revealed laccase gene (lacBl) as multicopper oxidase (spore coat CotA). Further, lacBl from Bacillus sp. PCH94 was cloned, expressed, and kinetically characterized. LacBl enzyme showed activity for substrates ABTS (40.64 IU/mg), guaiacol (5.43 IU/mg), and DMP (11.93 IU/mg). The LacBl was active in higher temperatures (10 to 100 °C) and showed a half-life of 36 and 27 h at 50 and 60 °C, respectively. The purified LacBl was able to depolymerize kraft lignin into valuable products (ferulic acid and acetovanillone), which have applications in the pharmaceutical and food industries. Overall, the current study demonstrated the role of bacterial laccase in the depolymerization of lignin and opened a promising prospect for the green production of valuable compounds from recalcitrant lignin.


The chromosome-scale genome and the genetic resistance machinery against insect herbivores of the Mexican Toloache, Datura stramonium.
Plant resistance refers to the heritable ability of plants to reduce damage caused by natural enemies, such as herbivores and pathogens, either through constitutive or induced traits like chemical compounds or trichomes. However, the genetic architecture - the number and genome location of genes that affect plant defense and the magnitude of their effects - of plant resistance to arthropod herbivores in natural populations remains poorly understood. In this study, we aimed to unveil the genetic architecture of plant resistance to insect herbivores in the annual herb Datura stramonium (Solanaceae) through quantitative trait loci (QTL) mapping. We achieved this by assembling the species' genome and constructing a linkage map using an F2 progeny transplanted into natural habitats. Furthermore, we conducted differential gene expression analysis between undamaged and damaged plants caused by the primary folivore, Lema daturaphila larvae. Our genome assembly resulted in 6,109 scaffolds distributed across 12 haploid chromosomes. A single QTL region on chromosome 3 was associated with plant resistance, spanning 0 to 5.17 cM. The explained variance by the QTL was 8.44%. Our findings imply that the resistance mechanisms of D. stramonium are shaped by the complex interplay of multiple genes with minor effects. Protein-protein interaction networks involving genes within the QTL region and overexpressed genes, uncovered the key role of Receptor-like cytoplasmic kinases (RLCKs) in signaling and regulating tropane alkaloids and terpenoids, which serve as powerful chemical defenses against D. stramonium herbivores. The data generated in our study constitute important resources for delving into the evolution and ecology of secondary compounds mediating plant-insect interactions.


PAT-Seq: A Method for Simultaneous Quantitation of Gene Expression, Poly(A)-Site Selection and Poly(A)-Length Distribution in Yeast Transcriptomes.
Next-generation sequencing (NGS) and its application to RNA (RNA-seq) has opened up multiple aspects of RNA processing to deep transcriptome-wide analysis at nucleotide resolution. This has been useful in delineating the transcribed areas of the genome, and in quantitation of RNA isoforms. Such isoforms can diversify the regulatory repertoire of mRNAs. For example, the 3'-end of mRNA can vary in two important ways, in the position chosen for cleavage and polyadenylation, and in the length of the poly(A)-tail. Accordingly, the step-up in resolution made possible by NGS has revealed an unexpectedly high level of alternative polyadenylation (APA). Moreover, it has massively simplified the transcriptome-wide detection of poly(A)-tail length changes. Here we present our approach to the study of 3'-end dynamics using a 3'-focused RNA-seq method called PAT-seq (for poly(A)-test sequencing). The approach records gene expression, APA, and poly(A)-tail changes between transcriptomes to reveal complex interplay between transcriptional and posttranscriptional control mechanisms.


Transposon sequencing analysis of Bradyrhizobium diazoefficiens 110spc4.
Bradyrhizobium diazoefficiens USDA110 is one of the most effective nitrogen-fixing symbionts of soybeans. Here we carried out a large-scale transposon insertion sequencing (Tn-seq) analysis of strain Bd110spc4, which is derived from USDA110, with the goal of increasing available resources for identifying genes crucial for the survival of this plant symbiont under diverse conditions. We prepared two transposon (Tn) insertion libraries of Bd110spc4 with 155,042 unique Tn insertions when the libraries were combined, which is an average of one insertion every 58.7 bp of the reference USDA110 genome. Application of bioinformatic filtering steps to remove genes too small to be expected to have Tn insertions, resulted in a list of genes that were classified as putatively essential. Comparison of this gene set with genes putatively essential for the growth of the closely related alpha-proteobacterium, Rhodopseudomonas palustris, revealed a small set of five genes that may be collectively essential for closely related members of the family Bradyrhizobiaceae. This group includes bacteria with diverse lifestyles ranging from plant symbionts to animal-associated species to free-living species.


A method for karyotyping mouse blastocyst embryos developing from in vivo and in vitro fertilized eggs.
A method for karyotyping blastocyst-staged mouse embryos is described. The use of this protocol results in the recovery of a high percentage (greater than 70%) of readable karyotypes and can be completed rapidly.


Causal effect of lipoprotein-associated phospholipase A2 activity on ischemic stroke : a Mendelian randomization study.
Background The relationship between ischemic stroke (IS) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity is still unclear, and there is a dearth of stratified research on the relationship between Lp-PLA2 activity and different IS subtypes. Therefore, Mendelian randomization was used in this study to examine the relationship between genetically proxied Lp-PLA2 activity and the risks of IS and its subtypes. Methods Based on information from a meta-analysis of GWAS, which included 13,664 European people, five single-nucleotide polymorphisms related to Lp-PLA2 activity were chosen as instrumental variables. Summary statistics information about MEGESTROKE consortium with the European group (40,585 cases and 406,111 controls) include any ischemic stroke (AIS) (n = 34,217); large-artery stroke (LAS, n=4,373), cardioembolic stroke (CES, n=7,193) and small vessel stroke (SVS, n=5,386). In order to determine the causal relationships between Lp-PLA2 activity and IS as well as its subtypes, the inverse variance weighted (IVW) approach was chosen as the primary analysis. Significant estimates were then tested by sensitivity analysis to rule out heterogeneity and pleiotropy. Results IVW showed Lp-PLA2 activity was causally associated with LAS (OR=3.25, 95% CI=1.65-6.41, p=0.0007), but not with other subtypes of stroke. Sensitivity analysis for causal estimates between Lp-PLA2 activity and LAS showed no significant heterogeneity or pleiotropy. Conclusions These MR analyses support a causal effect of Lp-PLA2 activity on LAS but not on AIS, CES or SVS, which suggests that serum Lp-PLA2 activity might be a biomarker for prediction of LAS.


Validity of physical activity measures in individuals after total knee arthroplasty.
To determine the concurrent criterion-related validity of 2 activity monitors in comparison with the criterion method of indirect calorimetry in older adults after total knee arthroplasty (TKA). Validation study. Subjects completed 9 increasingly demanding daily activities in a research laboratory; each activity was performed for 7 minutes, for a total of 80 minutes, while the activity monitors and criterion method were used concurrently. Subjects (N=21, 67% women) had a mean age ± SD of 68±7 years and a body mass index of 29±4. Not applicable. Energy expenditure (in kcal/min) measured by accelerometer-based and multisensor-based monitors and by a criterion method. Validity was assessed by the paired t test, intraclass correlation coefficient (ICC), and Bland-Altman plots comparing the measurements from the activity monitors with those of the criterion method. Measurements from the accelerometer-based monitor were significantly lower than those of the criterion method across all walking and nonwalking activities. The underestimations ranged from 40% to 100%. The accelerometer-based monitor demonstrated small to moderate agreement compared with the criterion method (ICCs from 0 to .38). Measurements from the multisensor-based monitor were significantly lower than those of the criterion method during several nonwalking activities; yet, the differences were minor (2%-19%). Measurements from the multisensor-based monitor during walking activities were not different compared with the criterion method. The multisensor-based monitor demonstrated moderate to excellent agreement with the criterion method (ICCs from .48 to .81). The multisensor-based monitor showed better criterion-related validity than the accelerometer-based monitor and should be considered as a tool to measure physical activity in individuals after TKA.


Behavioral differences between C57BL/6J x FVB/NJ and C57BL/6J x NZB/B1NJ F1 hybrid mice: relation to control of ethanol intake.
C57BL/6J x FVB/NJ F1 (B6 x FVB) mice consume more alcohol than C57BL/6J x NZB/B1NJ F1 (B6 x NZB) mice and this high alcohol consumption is stable after abstinence whereas B6 x NZB show reduced consumption, thus providing models of Sustained Alcohol Preference (SAP) and Reduced Alcohol Preference (RAP). In female hybrids, we assessed several behavioral responses to define behaviors which might predict SAP and RAP. B6 x FVB exhibited less severe ethanol-induced conditioned taste aversion and were less sensitive to ethanol-induced loss of righting reflex than B6 x NZB. Both hybrids demonstrated ethanol-induced place preference and a low ethanol withdrawal severity. We found that these hybrids differ in their sensitivity to the aversive and sedative, but not rewarding, effects of ethanol. Results of elevated plus maze, mirror chamber, and locomotor tests reveal B6 x FVB mice are less anxious and more active than B6 x NZB mice. Results obtained offer insights about factors that determine SAP and RAP in these new genetic models of alcohol consumption.


Autoimmune destruction of pancreatic beta cells.
Type 1 diabetes results from the destruction of insulin-producing pancreatic beta cells by a beta cell-specific autoimmune process. Beta cell autoantigens, macrophages, dendritic cells, B lymphocytes, and T lymphocytes have been shown to be involved in the pathogenesis of autoimmune diabetes. Beta cell autoantigens are thought to be released from beta cells by cellular turnover or damage and are processed and presented to T helper cells by antigen-presenting cells. Macrophages and dendritic cells are the first cell types to infiltrate the pancreatic islets. Naive CD4+ T cells that circulate in the blood and lymphoid organs, including the pancreatic lymph nodes, may recognize major histocompatibility complex and beta cell peptides presented by dendritic cells and macrophages in the islets. These CD4+ T cells can be activated by interleukin (IL)-12 released from macrophages and dendritic cells. While this process takes place, beta cell antigen-specific CD8+ T cells are activated by IL-2 produced by the activated TH1 CD4+ T cells, differentiate into cytotoxic T cells and are recruited into the pancreatic islets. These activated TH1 CD4+ T cells and CD8+ cytotoxic T cells are involved in the destruction of beta cells. In addition, beta cells can also be damaged by granzymes and perforin released from CD8+ cytotoxic T cells and by soluble mediators such as cytokines and reactive oxygen molecules released from activated macrophages in the islets. Thus, activated macrophages, TH1 CD4+ T cells, and beta cell-cytotoxic CD8+ T cells act synergistically to destroy beta cells, resulting in autoimmune type 1 diabetes.


The Art of Medicine through the Humanities: an overview of a one-month humanities elective for fourth year students.
The purpose of incorporating humanities teaching into medical education is to encourage students to develop into more sensitive and caring doctors who communicate well with their patients and colleagues. A unique 4th year student elective at the Medical College of Wisconsin incorporates reflective and writing activities. Small group sessions are facilitated by faculty with specific interest and expertise in the humanities. Students keep a journal in which they record their reflections on personal issues, career planning and reactions to classroom discussions. Each student writes a poem and an essay or short story. The course is well received and oversubscribed. Students increase their understanding of the humanities through readings, small group discussions, journal keeping and formal writing. By incorporating humanism into their professional lives, medical students can learn to care for their patients in a more humane and thoughtful manner.


Clinical Characteristics of Myositis Associated with Graft-Versus-Host Disease.
Recipients of allogeneic hematopoietic stem cell transplantation (HSCT) are at increased risk for inflammatory myositis; histological subsets reported include dermatomyositis, necrotising myopathy and chronic graft-versus-host disease (cGVHD)-related myositis. Though corticosteroids and various immunosuppressive therapies have been used, there is a lack of consensus guidelines dictating therapy. Recent evidence suggests the fascia as a preferential target in cGVHD myositis, with conditioning regimens promoting fascial microtrauma. Positron emission tomography (PET) can be a useful diagnostic tool, and case reports suggest that the Bruton's tyrosine kinase inhibitor ibrutinib may have therapeutic potential. Emerging therapies include targeted B cell depletion with rituximab, and extracorporeal photophoresis. Clinicians need to be vigilant for the development of inflammatory myositis post-allogeneic HSCT as most patients respond to treatment. Advances in immunohistochemistry to determine the dominant cell type and cytokine profile may enable targeted and individualised therapies.


Activity of the alternative complement pathway after splenectomy: comparison to activity in sickle cell disease and hypogammaglobulinemia.
Patients with sickle cell disease and individuals who have undergone splenectomy share defects of certain host defense mechanisms and a predisposition to severe pyogenic bacterial infections. Since patients with sickle cell disease can have deficient activity of the alternative complement pathway, we have tested such activity in sera from splenectomized children and adults. A new kinetic hemolytic assay has been used, and we have compared results to those obtained with sera from patients with sickle cell disease or hypogammaglobulinemia. Sera from six of 58 splenectomized individuals (10%) had defective function of the alternative pathway, compared to 10 of 62 sera from patients with sickle cell disease (16%) and 10 of 18 sera from hypogammaglobulinemic patients (56%). Deficiency of antibody, a rate-influencing component of alternative pathway activity in this system, appears responsible for deficient activity in the hypogammaglobulinemic sera. The molecular basis for the deficiency found in sickle cell disease or after splenectomy is not clear. Defective function of the alternative complement pathway could contribute to the increased predisposition to bacterial infection that exists in these three patient groups.


Reactivity of proteins in ribosomes from Saccharomyces cerevisiae with trypsin.
The susceptibility of 40S and 60S ribosomal subunits from Saccharomyces cerevisiae to digestion with varying concentrations of trypsin was studied by two-dimensional electrophoresis and quantitative measurements of the protein remaining with the ribosomal particles after trypsin treatment. Proteins from both subunits can be classified into three groups according to their rate of digestion by trypsin. These results are in good agreement with those obtained on the order of ribosomal assembly in vivo, i.e., proteins which are most susceptible to trypsin digestion have been shown to associate with the ribosomal particles at a relatively late stage of ribosome assembly.


[Determination of 32 oxidative dyes by high performance liquid chromatography and confirmation by high performance liquid chromatography-tandem mass spectrometry].
Various types of oxidative dyes used in hair dye products possess poor stability and have varying frequency of use. Interference problems also frequently arise in actual sample measurements. Therefore, it is necessary to establish a simple, rapid, accurate, and specific method for the determination of common dyes in hair dye products for their effective regulation. In this study, dyes were grouped according to their frequency of use. Using a C18 column that minimizes the silanol effect and influence of metals, the quantitative high performance liquid chromatography (HPLC) method for 32 dyes listed in Safety and Technical Standards for Cosmetics (2015 edition) was optimized, and a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) confirmatory method for the dyes was established. The samples were extracted using a mixed solution of ethanol-water (1∶1, v/v) with 10 g/L sodium bisulfite solution as an antioxidant, vortexed and mixed, and then extracted by ultrasonication in an ice bath for 10 min. Methanol, acetonitrile, and phosphate buffer were used as the mobile phases in the HPLC analysis. Additionally, two different elution conditions (chromatographic gradient) were used for the separation of 32 oxidative dyes, which were detected at a wavelength of 280 nm. The HPLC separations were compared using columns of particle sizes 5 μm and 2.7 μm; 5 μm C18 columns with better anti-interference and antiblocking ability were selected. Satisfactory separation was achieved for all three commercial C18 columns with a particle size of 5 μm, and the method had good general usability. In condition 1, 17 commonly used dyes and three less commonly used dyes were assigned to group Ⅰ and separated by HPLC; in condition 2, eight banned dyes and four other less commonly used dyes were assigned to group Ⅱ and separated by HPLC. The HPLC-MS/MS method used 5 mmol/L ammonium acetate aqueous solution-acetonitrile and 5 mmol/L acetic acid aqueous solution-acetonitrile as mobile phases in the positive and negative ion modes, respectively. Multiple reaction monitoring (MRM) was performed for qualitative and quantitative analyses in the electrospray ionization mode. Under the examined conditions, six pairs of isomers were well resolved. For the HPLC and HPLC-MS/MS methods, the relative standard deviations (RSDs) of the intra-day precision and 48 h stability tests were less than 10%. The recoveries were between 82.6% and 114.9% (RSD<10%). In the HPLC method, 32 dyes showed good linearity in an approximate range of 10-500 mg/L (r2>0.99), and the limits of detection (LODs) were 9.7-40.1 μg/g. The linear range of hydroquinone in the HPLC-MS/MS method was 2.0-79.7 mg/L, and the LOD was 8.0 μg/g; the linear ranges of the other components were approximately 0.1-4 mg/L, and the LODs were 0.01-0.4 μg/g. The actual samples were simultaneously measured by HPLC, HPLC-MS/MS, and the standard method. Finally, 16 of the 32 dyes were detected, and the detected contents ranged from 58 to 25160 μg/g. The RSDs of the results obtained from the three detection methods were between 1.9% and 10.1%. All detected components were within the limits of group Ⅰ of this method. In comparison with methods reported in the literature and the standard method, this method covers all components for the routine regulatory inspection of oxidative dyes in cosmetics. The method can separate the commonly used dyes under the same HPLC conditions and avoid interference from 15 other commonly used dyes during the analysis of actual samples. A suitable HPLC-MS/MS confirmatory method was also established for the identification of currently unknown substances in the statutory inspection of cosmetics. The method is simple, rapid, accurate, and specific with general usability and good operability.


Draft Genome Sequence of Environmental Isolate Acinetobacter nosocomialis U20-HoPe-S34-3 from Germany.
The draft genome sequence of Acinetobacter nosocomialis U20-HoPe-S34-3, isolated from soil sampled from the banks of the river Holtemme in Germany, is provided. The strain has an average nucleotide identity of 98.3% to the type strain of the species.


Large dataset of octocoral mitochondrial genomes provides new insights into mt-mutS evolution and function.
All studied octocoral mitochondrial genomes (mt-genomes) contain a homologue of the Escherichia coli mutS gene, a member of a gene family encoding proteins involved in DNA mismatch repair, other types of DNA repair, meiotic recombination, and other functions. Although mutS homologues are found in all domains of life, as well as viruses, octocoral mt-mutS is the only such gene found in an organellar genome. While the function of mtMutS is not known, its domain architecture, conserved sequence, and presence of several characteristic residues suggest its involvement in mitochondrial DNA repair. This inference is supported by exceptionally low rates of mt-sequence evolution observed in octocorals. Previous studies of mt-mutS have been limited by the small number of octocoral mt-genomes available. We utilized sequence-capture data from the recent Quattrini et al. 2020 study [Nature Ecology & Evolution 4:1531-1538] to assemble complete mt-genomes for 94 species of octocorals. Combined with sequences publicly available in GenBank, this resulted in a dataset of 184 complete mt-genomes, which we used to re-analyze the conservation and evolution of mt-mutS. In our analysis, we discovered the first case of mt-mutS loss among octocorals in one of the two Pseudoanthomastus spp. assembled from Quattrini et al. data. This species displayed accelerated rate and changed patterns of nucleotide substitutions in mt-genome, which we argue provide additional evidence for the role of mtMutS in DNA repair. In addition, we found accelerated mt-sequence evolution in the presence of mt-mutS in several octocoral lineages. This accelerated evolution did not appear to be the result of relaxed selection pressure and did not entail changes in patterns of nucleotide substitutions. Overall, our results support previously reported patterns of conservation in mt-mutS and suggest that mtMutS is involved in DNA repair in octocoral mitochondria. They also indicate that the presence of mt-mutS contributes to, but does not fully explain, the low rates of sequence evolution in octocorals.


Golgi protein 73, hepatocellular carcinoma and other types of cancers.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a low survival rate. The identification of mechanisms underlying the development of HCC helps uncover cellular and molecular targets for the diagnosis, prevention, and treatment of HCC. Golgi protein 73 (GP73) level is upregulated in HCC patients and potentially can be a therapeutic target. Despite many studies devoted to GP73 as a marker for HCC early diagnosis, there is little discussion about the function of GP73 in HCC tumorigenesis. Given the poor response to currently available HCC therapies, a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC. The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis. Its roles in other types of cancer are also discussed.


Clinical-GAN: Trajectory Forecasting of Clinical Events using Transformer and Generative Adversarial Networks.
Predicting the trajectory of a disease at an early stage can aid physicians in offering effective treatment, prompt care to patients, and also avoid misdiagnosis. However, forecasting patient trajectories is challenging due to long-range dependencies, irregular intervals between consecutive admissions, and non-stationarity data. To address these challenges, we propose a novel method called Clinical-GAN, a Transformer-based Generative Adversarial Networks (GAN) to forecast the patients' medical codes for subsequent visits. First, we represent the patients' medical codes as a time-ordered sequence of tokens akin to language models. Then, a Transformer mechanism is used as a Generator to learn from existing patients' medical history and is trained adversarially against a Transformer-based Discriminator. We address the above mentioned challenges based on our data modeling and Transformer-based GAN architecture. Additionally, we enable the local interpretation of the model's prediction using a multi-head attention mechanism. We evaluated our method using a publicly available dataset, Medical Information Mart for Intensive Care IV v1.0 (MIMIC-IV), with more than 500,000 visits completed by around 196,000 adult patients over an 11-year period from 2008-2019. Clinical-GAN significantly outperforms baseline methods and existing works, as demonstrated through various experiments. Source code is at https://github.com/vigi30/Clinical-GAN.


Evaluation of strategies for increasing response rates to postal questionnaires in quality control of nasal septal surgery.
Postal questionnaires are often used to assess the results of nasal septoplasty, but response rates vary widely. This study assesses strategies designed to increase the response rate. Postoperative questionnaires using visual analogue scales (VAS) for nasal obstruction were mailed to 160 consecutive patients alternately allocated to one of two groups. Group A received the questionnaire in the usual manner and group B received a modified cover letter with hand-written name and signature and a hand-stamped return envelope. Of the 80 patients in each group, 47 (58.8%) in group A and 54 (67.5%) in group B returned the questionnaire (p = 0.25). There were no age or gender differences between the groups, nor did the pre- and postoperative VAS scores differ between the groups. The strategies used in this study increased the response rate to postal questionnaires by 8.7% points, but this was not a statistically significant or clinically meaningful improvement.


Standards for growth and final height in Turner's syndrome.
Data on birth, growth and final height were collected retrospectively for 78 women with Turner's syndrome born 1955-66. Seventy-one had received estrogen treatment from a mean age of 17.7 years (SD = 2.0 years), while 7 were spontaneously menstruating. At birth Turner girls were 440 g lighter (p less than 0.001) and 1.4 cm shorter (p less than 0.001) than 46,XX girls. Standards for untreated growth were established for the age period 6.5-17.5 years, while growth after 17.5 years was described in both untreated and estrogen treated women. Analysis of growth pattern showed that though no pubertal growth spurt was present, the steady decrease of height velocity (HV) was interrupted at the age of 9 years. HV was then constant until 12 years of age, whereafter it slowly decreased. Mean final height (FH) was 146.8 cm (SD = 5.8 cm, n = 76) compared to 166.8 cm in the general female population. No difference was found between 45,X women and women with other karyotypes (p greater than 0.7). Correlations between FH and parental heights, birthweight and birthlength were similar to those reported for normal women (19). FH varied with age at diagnosis. Those diagnosed after 17 years of age had a mean FH = 151.3 cm, while those diagnosed before had a mean FH = 145.8 cm (p less than 0.001).


A system of interpretation of infrared spectra of calculi for routine use in the clinical laboratory.
We have devised systematic schemes for objectives qualitative analysis of the IR spectra of calculi. These schemes are presented as flow charts based on questions each requiring a yes or no answer before going on to the next step. The specific question asked in each step concerns the similarity of a limited region of the spectrum to reference spectra. For renal calculi, 5 regions are evaluated and a maximum of 10 decisions is necessary to complete the analysis. Biliary calculi are treated similarily, with 5 spectral regions evaluated and a maximum of 8 yes-no decisions required. The method requires less technician time and is much less susceptible to differences in subjective judgment than the wet chemical procedure. Three percent of stones contain unusual components and are quickly recognized as such and identified using a library of reference spectra.


Outcomes of Drug-Eluting Stent Thrombosis After Treatment for Acute Versus Chronic Coronary Syndrome.
The primary objective of the current analysis was to assess the association between the clinical presentation at index procedure and mortality in patients with second-generation drug-eluting stent thrombosis (G2-ST). Patients with acute coronary syndrome (ACS) have a higher risk for stent thrombosis (ST) as compared with those with chronic coronary syndrome (CCS). However, clinical outcomes of patients with G2-ST after treatment for ACS and CCS remain poorly understood. From the REAL-ST (Retrospective Multicenter Registry of ST After First- and Second-Generation Drug-Eluting Stent Implantation) registry, this study evaluated 313 patients with G2-ST. According to baseline clinical presentation, patients were divided into the 2 groups: the ACS and CCS groups (n = 147 and n = 166, respectively). The primary endpoint was the cumulative 3-year incidence of all-cause death after the index ST events. Timing of ST, target lesion revascularization, and recurrent ST were also assessed. Early ST was more frequently observed in the ACS group (71.4% vs. 44.6%), while very late ST was less likely to occur in the ACS group than in the CCS group (11.6% vs. 30.7%). Cumulative 3-year incidence of all-cause death after the index ST events was comparable between the ACS and CCS groups (28.6% vs. 28.3%; hazard ratio: 1.14; 95% confidence interval: 0.75 to 1.73; p = 0.55). Compared with the CCS group, the ACS group showed higher incidences of target lesion revascularization and recurrent ST (23.8% vs. 17.2%; p = 0.06; and 9.9% vs. 1.4%; p = 0.001, respectively). Patients with G2-ST were associated with higher mortality irrespective of baseline clinical presentation.


A technique for the treatment of mandibular body fractures in young children.
Mandibular body fractures in young children are uncommon, yet their treatment and management often present several difficulties. The presence of developing dental follicles may lead to irregular fracture lines and precludes the use of intraosseus wiring. In addition, treatment of fractures in children of this age requires a technique that limits the number of separate procedures that they are subjected to. The technique outlined below for the treatment of mandibular body fractures in young children, uses a plastic impression tray as a splint and provides a simple means for their reduction and fixation.


In vitro degradation of neurotensin in human plasma.
To study the degradation of neurotensin in plasma in vitro, fresh human plasma was incubated with neurotensin in the presence and absence of the peptidase inhibitors pepstatin A, EDTA, PMSF and aprotinin. The half-time of disappearance of neurotensin at 37 degrees C was calculated to be 226 min in vitro as opposed to 1.4 min in vivo when measured by radioimmunoassay with a C-terminally directed neurotensin antiserum. Both gel filtration and reversed phase high-pressure liquid chromatography (HPLC) showed that the main degradation product of neurotensin in human plasma in vitro was chromatographically and immunologically identical to neurotensin 1-8 and HPLC also demonstrated the formation of neurotensin 1-11. The loss of neurotensin incubated in human plasma in vitro was greatly reduced by EDTA but not by the other peptidase inhibitors tested. In this respect peptidase(s) responsible for the degradation of neurotensin in plasma differ from those present in brain homogenates. EDTA may be of importance in the preservation of neurotensin in plasma samples.


BSA adsorption on titanium: ToF-SIMS investigation of the surface coverage as a function of protein concentration and pH-value.
The adsorption properties of bovine serum albumin (BSA) on pure titanium (99.99%+) were studied by time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). For this purpose, films consisting of BSA were prepared on cleaned titanium sheets in a phosphate buffered solution under different conditions and analysed by ToF-SIMS. The dependence of the surface coverage on the concentration of the protein solution could be determined from the secondary ion mass spectrometry signals. The results agree satisfactorily with the corresponding results obtained by XPS. The observed adsorption behaviour can be fitted by the well-known formula describing a Langmuir isotherm. The Langmuir constant for pH 7 was found to be K = 174 ± 99 lg(-)1.


Chorionic villus sampling in continuing pregnancies. II. Cytogenetic reliability.
Cytogenetic analysis was performed on 103 chorionic villus samples. Analysis of the 103 samples revealed six abnormalities. In three of the six the abnormalities were confirmed in fetal or neonatal tissue (47,XY, + 13; 46,XY, t(13q13q); 45,X). In three samples the abnormalities detected were not confirmed; in two of the three the abnormalities were detected only in long-term cultures, whereas in the other samples the abnormality was restricted to direct analysis of the villi after overnight incubation. Our initial experience leads us to conclude that certain abnormalities in chorionic villus sampling may not be indicative of fetal abnormalities; 45,X/46,XX or 45,X/46,XY mosaicism is such a complement. Discrepancies between cytogenetic analysis of intact villi processed soon after sampling and of cells grown in culture can be managed by adhering to several suggested guidelines and by liberal use of confirmatory amniocentesis.


Enhanced 129 Xe T1 relaxation in whole blood and in the presence of SPIONs at low magnetic field strengths.
To compare the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on the T1 of 129 Xe and 1 H and to measure the relaxation of 129 Xe in blood at low and high magnetic field strengths. 129 Xe and 1 H T1 relaxometry was performed at low- and high-field strengths in samples containing different SPION concentrations, while imaging was used to compare the contrast obtainable in these two field regimes. In vivo experiments at variable field strengths were performed to determine the depolarization of 129 Xe in blood and the feasibility of in vivo dissolved-phase spectroscopy and imaging at low field. The SPION relaxivity was substantially greater at low field for 1 H, increasing from 0.92 ± 0.06 mM s-1 at 11.7T to 31.5 ± 1.8 mM s-1 at 0.6 mT, and for 129 Xe, which increased from 0.13 ± 0.03 mM s-1 at 11.7T to 7.32 ± 0.71 mM s-1 at 2.1 mT. The additional MR signal loss increased from 0.7% at 9.4T to 20.6 ± 4.2% at 0.6 mT for 1 H and from -0.7 ± 3.4% at 9.4T to 12.7 ± 3.5% at 2.1 mT for 129 Xe. Blood was found to depolarize 129 Xe below 3T in a manner inversely proportional to the field strength. In vitro studies at 2.1 mT suggest 129 Xe relaxation times below 5 s in blood dilutions as low as 0.4% volume. SPIONs longitudinal relaxivity increases at low field both for 1 H and 129 Xe. The depolarization of xenon in blood, which is found to increase below 3T, effectively prevents in vivo dissolved-phase spectroscopy and imaging at low-field strengths.


Electron microscopic study on gut epithelium of the tench (Tinca tinca L.) with respect to its absorptive functions.
Few morphological differences are seen along the intestinal tract of the adult tench (Tinca tinca L.) a stomachless freshwater teleost. However, three segments can be distinguished, when function and structure of enterocytes are studied. The enterocytes of the proximal segment are found to be concerned with dietary lipids absorption. In the cell, absorbed fats are seen in two inclusion bodies: lipid particles and lipid droplets. Only lipid particles are involved in direct transport of absorbed fatty acids in the blood circulation, as in lymphatic vessels. Lipid droplets seem to be involved in temporary storage of fatty acids. Special features are found in enterocytes of the short middle segment; these cells show many invaginations and pinocytosis figures, a well-developed tubulo-vesicular network and large vacuoles in the supranuclear hyaloplasm. Such characters bear a resemblance to descriptions of the gut of some newborn mammals. The great permeability of this epithelium to macromolecules is demonstrated by the administration of horseradish peroxidase (HRP). Enterocytes of the distal segment show, at their basal pole, numerous invaginations of the plasma membrane, and a large mitochondrial population. Morphological similarity suggests a functional analogy with epithelia involved in water and ions transport.


The Prevalence and the Impact of Frailty in Hepato-Biliary Pancreatic Cancers: A Systematic Review and Meta-Analysis.
Frailty has been associated with increased mortality among hepatobiliary pancreatic (HBP) cancer patients. Nevertheless, estimates of frailty prevalence in HBP cancers and the precise average effect regarding mortality remains uncertain. The present systematic review and meta-analysis aimed to quantify: (1) the prevalence of frailty in patients with liver and pancreatic cancers and (2) the impact of frailty on mortality in patients affected by liver and pancreatic cancers. MEDLINE/PubMed database search was conducted from inception until 1 November 2021, the pooled prevalence and relative risk (RR) estimate were calculated. A total of 34,276 patients were identified and the weighted prevalence of frailty was 39%; (95% [C.I.] 23-56; I2 = 99.9%, p < 0.0001). Frailty was significantly associated with increased mortality RR 1.98 (95% [C.I.] 1.49-2.63; I2 = 75.9%, p = 0.006). Frailty prevalence is common among HBP cancer patients and exerts a significant negative impact on survival. These findings are characterized by significant heterogeneity and caution is warranted on their interpretation. However, stratification of patients with HBP cancer by frailty status may provide prognostic information and may inform priorities for decision-making strategy.


Citrate ligand-enhanced microscale zero-valent aluminum corrosion for carbon tetrachloride degradation with high electron utilization efficiency.
Carbon tetrachloride (CT) is highly toxic and recalcitrant in groundwater. In recent years, zero-valent aluminum (ZVAl) is highly reductive but limited by its surface passivation film. One of the effective ways to overcome this bottleneck is to add ligands. In this paper, compared with several other ligands, sodium citrate (SC), a natural organic ligand, was introduced to enhance microscale ZVAl (mZVAl) reactivity for the reductive degradation of CT. The results showed that the SC system could effectively reduce but not completely dechlorinate CT and electron utilization efficiency was as high as 94%. However, without ligands, mZVAl is chemically inert for CT degradation. Through SEM-EDS, BET, XRD, and XPS characterizations and H2 evolution experiments, enhanced mZVAl surface corrosion at the solid-liquid interface of mZVAl/SC system was verified. SC participated in the complexation corrosion reaction with surface inert film to form Al[Cit] complex, which made internal Al0 active sites exposed and then promoted mZVAl corrosion. In the five consecutive reuse experiments of mZVAl, CT can be completely degraded, which indicates that mZVAl, with the help of SC, has excellent sustainable utilization efficiency.