High-resolution photo-mosaic time-series imagery for monitoring human use of an artificial reef.
Successful marine management relies on understanding patterns of human use. However, obtaining data can be difficult and expensive given the widespread and variable nature of activities conducted. Remote camera systems are increasingly used to overcome cost limitations of conventional labour-intensive methods. Still, most systems face trade-offs between the spatial extent and resolution over which data are obtained, limiting their application. We trialed a novel methodology, CSIRO Ruggedized Autonomous Gigapixel System (CRAGS), for time series of high-resolution photo-mosaic (HRPM) imagery to estimate fine-scale metrics of human activity at an artificial reef located 1.3 km from shore. We compared estimates obtained using the novel system to those produced with a web camera that concurrently monitored the site. We evaluated the effect of day type (weekday/weekend) and time of day on each of the systems and compared to estimates obtained from binocular observations. In general, both systems delivered similar estimates for the number of boats observed and to those obtained by binocular counts; these results were also unaffected by the type of day (weekend vs. weekday). CRAGS was able to determine additional information about the user type and party size that was not possible with the lower resolution webcam system. However, there was an effect of time of day as CRAGS suffered from poor image quality in early morning conditions as a result of fixed camera settings. Our field study provides proof of concept of use of this new cost-effective monitoring tool for the remote collection of high-resolution large-extent data on patterns of human use at high temporal frequency.


Head and Neck Tumor Resection and Free Flap Reconstruction in Low-Volume Center.
To determine the surgical outcomes of free tissue transfer surgery following head and neck tumor extirpation in a low-volume medical center. Retrospective chart review of patients who underwent free tissue transfer surgery for head and neck cancer at Moanalua Medical Center from 2015 to 2018. Free flap failure rate and free flap-related complications. From 2015 to 2018, there were 27 free tissue transfer surgery (mean 6.75 flap surgery/year). There were 2 events of partial flap necrosis, and no cases of total flap loss. One patient required leech therapy for venous congestion. One patient required additional free flap surgery. Two patients developed orocutaneous fistula that resolved with local wound care. One patient developed malocclusion following mandible reconstruction using fibular free flap. Overall free flap success rate was 96%. This study supports the ability of small-volume centers to produce positive outcomes with few complications in head and neck cancer free flap reconstructive surgery. While the data are limited to a single surgical team in one care center, it provides additional support for the idea that there are factors beyond the surgical volume that determine outcome.


Body mass index, waist-to-hip ratio, waist circumference and waist-to-height ratio cannot predict male semen quality: a report of 1231 subfertile Chinese men.
There were controversial results between obesity-associated markers and semen quality. In this study, we investigated the correlations between age, obesity-associated markers including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and waist circumference (WC), the combination of age and obesity-associated markers, semen parameters and serum reproductive hormone levels in 1231 subfertile men. The results showed that BMI, WC, WHR and WHtR were positively related to age, and there were also positive relations between BMI, WHR, WC and WHtR and between sperm concentration (SC), total sperm count (TSC), progressive motility (PR), sperm motility and per cent of normal sperm morphology (NSM). However, age, each of obesity-associated markers and the combination of obesity-associated markers and age were unrelated to any of semen parameters including total normal-progressively motile sperm count (TNPMS). Age, BMI, WHR, WC and WHtR were negatively related to serum testosterone and SHBG levels. However, only serum LH and FSH levels were negatively related to sperm concentration, NSM and sperm motility. In a conclusion, although age and obesity have significant impacts on reproductive hormones such as testosterone, SHBG and oestradiol, semen parameters related to FSH and LH could not be influenced, indicating that obesity-associated markers could not predict male semen quality.


Sequential updating of a new dynamic pharmacokinetic model for caffeine in premature neonates.
Caffeine treatment is widely used in nursing care to reduce the risk of apnoea in premature neonates. To check the therapeutic efficacy of the treatment against apnoea, caffeine concentration in blood is an important indicator. The present study was aimed at building a pharmacokinetic model as a basis for a medical decision support tool. In the proposed model, time dependence of physiological parameters is introduced to describe rapid growth of neonates. To take into account the large variability in the population, the pharmacokinetic model is embedded in a population structure. The whole model is inferred within a Bayesian framework. To update caffeine concentration predictions as data of an incoming patient are collected, we propose a fast method that can be used in a medical context. This involves the sequential updating of model parameters (at individual and population levels) via a stochastic particle algorithm. Our model provides better predictions than the ones obtained with models previously published. We show, through an example, that sequential updating improves predictions of caffeine concentration in blood (reduce bias and length of credibility intervals). The update of the pharmacokinetic model using body mass and caffeine concentration data is studied. It shows how informative caffeine concentration data are in contrast to body mass data. This study provides the methodological basis to predict caffeine concentration in blood, after a given treatment if data are collected on the treated neonate.


Coherent 2 microm differential absorption and wind lidar with conductively cooled laser and two-axis scanning device.
A coherent 2 microm differential absorption and wind lidar (Co2DiaWiL) was developed to measure CO(2) concentration and line-of-sight wind speed. We conductively cooled a pumping laser head to -80 degrees C and diode arrays to approximately 20 degrees C. A Q-switched laser outputs an energy of 80 mJ (pulse width 150 ns (FWHM), pulse repetition frequency up to 30 Hz). CO(2) measurements made over a column range (487-1986 m) for 5 min accumulation time pairs achieved 0.7% precision. Line-of-sight wind speeds for ranges up to approximately 20 km and returns from a mountainside located 24 km away from the Co2DiaWiL were obtained.


[Hypnotherapy for Irritable Bowel Syndrome].
Irritable bowel syndrome (IBS) is a functional disorder of the lower digestive tract. Based on the biopsychosocial model, there is a wide range of therapeutic interventions to deal with the symptoms of IBS and to improve the quality of life of those who are affected. In this context, hypnotherapy and in particular gut-directed hypnosis represents a psychotherapeutic intervention with great empirical evidence for its efficacy.


Development of calcaneal gait without prior triceps surae lengthening: an examination of predictive factors.
Although equinus is more common in cerebral palsy (CP), the prevalence of calcaneal gait (CG) has been reported at more than 30% among patients with CP, even in the absence of prior surgical intervention. The goal of this study was to identify patient characteristics predictive of the development of CG in patients without prior triceps surae lengthening. Gait data were reviewed for 58 participants with bilateral involvement owing to CP (116 limbs) who had 2 gait analysis tests with no triceps surae lengthening between tests. None of the patients exhibited CG at the initial gait study. Patients were grouped according to whether or not they exhibited CG patterns at the second test. Factors potentially predictive of calcaneal gait patterns were compared statistically between groups. CG was shown by 24/116 extremities (21%) at the second study. The CG group experienced greater increase in body weight and body mass index between tests (P=0.006 and 0.03 respectively). Passive dorsiflexion range with the knee flexed was significantly greater in the CG group (P=0.008). The CG group also showed a tendency toward greater plantarflexor weakness, although this only approached statistical significance (P=0.08) likely owing to small sample size. Age, CP subtype, time to follow-up, hamstring range, selective motor control, and gross motor functional level were not predictive. Patients who undergo (or have potential to undergo) significant weight gain, and have tendencies toward excessive passive dorsiflexion with the knee flexed may be at risk for development of CG over time. In such patients, treatment regimens should include therapy to maintain or improve plantarflexor strength, and methods to prevent overstretching the plantarflexors. Nonsurgical treatments for triceps surae contractures, such as serial casting, may be preferable, to avoid hastening development of calcaneal crouch gait over time. Prognostic study---Level III (case-control).


[Jan Marian Dobrowolski--botanist and expert in herbalism (1886-1958)].
A botanist by education, Jan M. Dobrowolski devoted his whole life to the advancement of pharmacy. Working at the universities of Warsaw and Poznań, he organized medicinal herbs cultivation projects, for which he developed a theoretical basis. He also gave lectures for students of pharmacy, taking care to provide them with a comprehensive and modern eduction. Some of the less known episodes of his life include his participation in the formation of the scouting movement in Poland, his religious and ethical activity, his journalistic experiences, and his role in organizing mass-scale collection of medicinal herbs in the years of the Second World War. After the war he continued his research as well as organizational and didactic work at the University of Poznań.


A Deep Learning Approach for Histopathological Diagnosis of Onychomycosis: Not Inferior to Analogue Diagnosis by Histopathologists.
Onychomycosis is common. Diagnosis can be confirmed by various methods; a commonly used method is the histological examination of nail clippings. A deep learning system was developed and its diagnostic accuracy compared with that of human experts. A dataset with annotations for fungal elements was used to train an artificial intelligence (AI) model. In a second dataset (n=199) the diagnostic accuracy of the AI was compared with that of dermatopathologists. The results show a non-inferiority of the deep learning system to that of analogue diagnosis (non-inferiority margin 5%) with respect to specificity and the area under the receiver operating characteristic curve (AUC). The AI achieved an AUC of 0.981. One limitation of this system is the need for a large number of training images. The AI had difficulty recognizing spores and confused serum or aggregated bacteria with fungal elements. Use of this deep learning system in dermatopathology routine might help to diagnose onychomycosis more efficiently.


The global burden of chronic respiratory disease in adults.
With an aging global population, chronic respiratory diseases are becoming a more prominent cause of death and disability. Age-standardised death rates from chronic obstructive pulmonary disease (COPD) are highest in low-income regions of the world, particularly South Asia and sub-Saharan Africa, although airflow obstruction is relatively uncommon in these areas. Airflow obstruction is, by contrast, more common in regions with a high prevalence of cigarette smoking. COPD mortality is much more closely related to the prevalence of a low forced vital capacity which is, in turn, associated with poverty. Mortality from asthma is less common than mortality from COPD, but it is also relatively more common in poorer areas, particularly Oceania, South and South-East Asia, the Middle East and Africa. Again this contrasts with the asthma prevalence among adults, which is highest in high-income regions. In high-income areas, mortality due to asthma, which is predominantly an adult problem, has fallen substantially in recent decades with the spread of new guidelines for treatment that emphasise the use of inhaled steroids to control the disease. Although mortality rates have been falling, the prevalence of atopy has been increasing between generations in Western Europe. Changes in the prevalence of wheeze among adults has been more varied and may have been influenced by the reduction in smoking and the increase in the use of inhaled steroids.


Heparin/heparan sulfate anticoagulant glycosaminoglycans in human plasma of healthy donors: preliminary study on a small group of recruits.
Glycosaminoglycans in normal human plasma, mainly represented by chondroitin sulfates and heparan sulfates/heparin (HSGAGs), show a specific distribution in the Cohn-Oncley fractions of human plasma. In the present study we investigated their effects on coagulation. Plasma was fractionated following the procedure of Cohn-Oncley, and each fraction was treated for extraction of glycosaminoglycans after extensive proteolysis; the anticoagulant activity in the extracted samples was measured by activated partial thromboplastin time (APTT). The effects of the samples containing HSGAGs on factor II and factor X activities, before and after treatment with heparinase I, were also measured. The molecular weight of HSGAGs was determined by polyacrylamide gel-electrophoresis. Cryoprecipitate and fraction I, fraction II+III, and fraction IV-1 (the fractions containing HSGAGs) prolonged the APTT, whereas fractions IV-4 and V had no effect on the APTT. Fractions containing HSGAGs showed effects on factor II and factor X activities that were sensitive to heparinase I treatment. The molecular weight of HSGAGs recovered in cryoprecipitate and fraction I was 15-18 kDa; that of HSGAGs recovered in fraction IV-1 was 12.0 kDa. In conclusion, these results demonstrate that HSGAGs of different molecular weight, endowed with anticoagulant activity, circulate in normal human plasma in association with specific proteins involved in the regulation of hemostasis; and that endogenous HSGAGs play a role in maintaining the antithrombotic/hemostatic balance in normal human plasma.


Scale-Up of Phytosterols Bioconversion into Androstenedione.
Phytosterols, generated as a by-product of vegetable oils or wood pulp, contain the cyclopentane-perhydro-phenanthrene nucleus, and can be converted into steroid intermediates by removing the C17 side chain. This chapter shows the scale-up, from flask to fermentor, of the phytosterols bioconversion into 4-androstene-3,17-dione (androstenedione; AD) with Mycobacterium neoaurum B-3805. Due to the fact that phytosterols and AD are nearly insoluble in water, two-phase systems and the use of chemically modified cyclodextrins have been described as methods to solve it. Here we use a water-oil two-phase system that allows for the bioconversion of up to 20 g/L of phytosterols into AD in 20 L fermentor.


[Inpatient psychotherapeutic health care services in northern Germany--Results of an expertise].
In Germany health care services for patients with psychosomatic disorders are characterized by three specific features: A large amount of inpatient facilities, which have been developed outside psychiatric institutions and which are mainly rehabilitation clinics instead of acute clinics. We have tried to analyze whether (1) there is a sufficient number of inpatient facilities in Northern Germany, whether (2) the treatment of psychosomatic disorders should be conducted in large-scale outpatient clinics or in minor departments of community hospitals and (3) to what extent therapy should preferably be offered in acute rather than in rehabilitative settings. By means of different methodological approaches our analysis shows (1) a need for more facilities for the treatment of patients with psychosomatic disorders than legally established by the government, (2) the necessity to differentially allocate patients to appropriate clinics and (3) to encourage clinics to develop or to expand those therapeutic elements which aim more at rehabilitative or acute care.


Two native plasmids of Pseudomonas syringae pathovar tomato strain PT23 share a large amount of repeated DNA, including replication sequences.
Strain PT23 of Pseudomonas syringae pv. tomato contains four native plasmids, designated A, B, C, and D. By DNA hybridization of genomic and plasmid DNA digests from the wild type and a plasmid-cured strain, we determined that c. 61 kb (c. 74%) of pPT23B is repeated in pPT23 A and only c. 17 kb (c. 21%) is in single copy in strain PT23. pPT23B also contains DNA repeated in the chromosome that occurs in three DNA fragments of 0.6, 4.6, and 9.6 kb that might be transposable elements. Additionally, the 9.6 kb fragment also shares sequences with the three other plasmids of strain PT23. By DNA hybridization with the origin of replication from a native plasmid of P. syringae pv. syringae and in vivo replication tests, we identified the origins of replication of plasmids A, B, and D and showed that they cross-hybridize. The putative par region from pPT23 A has also been identified and is not conserved in the other three native plasmids from strain PT23. By using the defined minimal origin of replication from pPT23 A as a probe, we showed that it is highly conserved in 14 strains belonging to nine different pathovars of P. syringae and that as many as five different native plasmids with closely related origins of replication coexist in the same cell. The duplication and reorganization of plasmids might therefore occur at high frequency and could be responsible for the existence of large numbers of native plasmids in P. syringae strains.


Bacterial adhesion to protein-coated hydrogels.
Extended wear soft contact lenses have been implicated in the increased occurrence of corneal bacterial infections. This research investigated the effects of polymer chemistry, water content, and pre-sorbed proteins upon the adherence of Pseudomonas aeruginosa to model hydrogels with chemistries similar to those of extended wear soft contact lenses. The hydrogels were exposed to washed suspensions of P. aeruginosa in a laminar flow cell. Albumin, fibrinogen, desialylated fibrinogen, or mucin were deposited on the hydrogels before exposure to the bacteria. Results showed that with or without protein pre-exposure, bacterial adhesion decreased as water content increased. In the presence of the sorbed protein, the number of adherent bacteria increased by about 45%, and all four proteins caused similar increases in adhesion. Bacterial adhesion was not significantly influenced by the presence of sialic acid residues in the pre-sorbed protein.


The Unexpected Death of a Child and The Experience of Emergency Service Personnel.
In 2013, 55,000 infants and children, aged 0 to 14, died in the United States. Nearly 7,000 of those deaths were attributed to traumatic causes. A child's death significantly affects emergency service personnel (ESP) caring for children and families. This study explores the lived experience of ESP involved in unsuccessful pediatric resuscitation efforts and how this experience affects them professionally and personally. A phenomenologic approach guided this study. Using an open-ended format, an interview was conducted with a purposive sample of ESP who experienced unexpected pediatric death. Eight ESP participated in semistructured, face-to-face interviews, ranging in length from 35 to 75 minutes. The research question asked: "What is it like for you when a child dies after an unsuccessful resuscitation attempt?" Data were analyzed using thematic analysis. Van Manen's 4 existentials guided this study, and 10 subthemes emerged that included: "what if," "dying before my eyes," "team," "what if it was were my child?/being a parent," "the environment," "being trapped," "wounded healer," "education," "anger," and "coping." This study explores the experience of ESP involved in unsuccessful pediatric resuscitation that resulted in unexpected pediatric death and ESP's perceptions of this experience: thoughts of loss, a sense of anger, and a lack of preparation to cope with unexpected pediatric death and the unknowns of life.


Clearance and metabolism of circulating pancreatic proelastase in the rat.
A rat model has been employed to study the mechanism of clearance of pancreatic proelastase from the circulation. The clearance of 125I-labeled proelastase was shown to be biphasic, with a half-life for clearance of free 25,000-dalton proelastase of approximately 7-10 min. A slow component of clearance possibly due to proelastase associated with plasma protease inhibitors was also observed. At 10 min after injection of 125I-labeled proelastase into the circulation, the major fraction of the 125I was found to be localized in the kidney. However, appearance of 125I in urine is slow, with 16 h being required for excretion of 50% of the injected 125I as acid-soluble material. Subcellular localization experiments on homogenates of kidneys removed at 10 min postinjection revealed that the majority of the 125I-labeled material was associated with the mitochondrial and lysosomal fraction. Sucrose-gradient centrifugation studies of this fraction demonstrated that the labeled material passes from the membrane fraction to the lysosomal fraction with time. These data demonstrate that the rat kidney constitutes the major site for both circulatory clearance and catabolism of circulating pancreatic proelastase.


A simple and effective method for cancer immunotherapy by inactivated allogeneic leukocytes infusion.
Allogeneic mixed leukocytes reaction has been reported to activate vast numbers of T lymphocytes and produce large amounts of type 1 cytokines that are linked to an initiation of antitumor immunity. Using poor immunogeneic B16-F10 and Lewis lung carcinoma (LLC) tumor model, we evaluated the effects of inactivated allogeneic leukocytes infusion (ALI) on the generation of antitumor immune response, as well as its effect on the primary and metastatic tumor. Allogeneic response promoted the generation of both specific and nonspecific antitumor immunity in an in vitro mixed lymphocytes-tumor cell culture system. Introveinous infusion of mitotically inactivated allogeneic leukocytes resulted in increased type-1 cytokines (including IL-2 and IFN-gamma) release, proliferation of various lymphocyte subsets, and generation of both specific and nonspecific antitumor immune response. As a result of such immune response, ALI caused a delayed tumor growth and a prolonged survival in established B16-F10 melanoma model. In LLC pulmonary spontaneous metastases model, ALI treatment significantly reduced postoperative tumor metastasis as the lung weights were far smaller than control group (0.16 vs. 0.34 g). Furthermore, after primary tumor resection and ALI treatment, 62.5% mice obtained long-term survival (>120 days) and there were no tumor growths in these mice when they were rechallenged with the same tumor. These experiments demonstrate that inactivated ALI could activate innate and adoptive antitumor immune response. It would be a simple, effective and secured method for cancer immunotherapy.


The Validity and Reliability of the Persian Version of Nomophobia Questionnaire.
Nomophobia is the fear of being disconnected from one's mobile phone, prevailing in modern area. To the best of our knowledge, no Persian psychometric scales are available for investigating nomophobia among Iranians. Therefore, we here aimed to translate and validate the Nomophobia Questionnaire (NMP-Q) for being used in Iran. The NMP-Q was translated from English to Persian using a classical "backward and forward" procedure. Exploratory factor analysis (EFA) was carried out to explore the underlying factor structure of the translated questionnaire. A principal component analysis (PCA) approach with varimax rotation was further performed. 425 volunteer students were included. Among them, 80.2% were 20-30 years old. Men and women constituted 187 (44.0%) and 238 (56.0%) of the participants, respectively. 100 (23.5%) of the subjects were medicine graduates. Using mobile phones for more than 5 years was noted in 215 (50.6%) subjects. Also, 422 (99.3%) subjects connected to the Internet via their cellphones. Regarding cellphone usage, 301 (70.8%) subjects used them less than 5 hours a day, 158 (37.2%) subjects checked their cellphones less than 10 times a day, and 92 (21.6%) subjects checked their cellphones every 20 minutes. Eigenvalues and the scree-plot supported a 3-factorial nature of the translated questionnaire. NMP-Q showed an overall Cronbach's alpha coefficient of 0.93 (the coefficients of 0.90, 0.77, and 0.71 for the three factors, respectively). The first, second, and third factors explained 26.30%, 20.84%, and 17.60% of the variance, respectively. The total score of NMP-Q correlated with the hours spent with mobile phones, the years of using them, and the age. Our findings showed that the Persian version of the NMP-Q was a valid and reliable tool for evaluating nomophobia among Iranians.


Incidental covariation learning leading to strategy change.
As they approach a traffic light, drivers and pedestrians monitor the color (instructed stimulus feature) and/or the position of the signal (covarying stimulus feature) for response selection. Many studies have pointed out that instructions can effectively determine the stimulus features used for response selection in a task. This leaves open whether and how practice with a correlating alternative stimulus feature can lead to a strategy change from an instructed to a learned variant of performing the task. To address this question, we instructed participants to respond to the position of a stimulus within a reference frame, at the same time, during task performance, an unmentioned second stimulus feature, the color, covaried with stimulus position and allowed the use of an alternative response strategy. To assess the impact of the non-instructed stimulus feature of color on response selection throughout practice, the spatial position of the stimulus was ambiguous on some trials. Group average increases in color usage were based on a mixture of (1) participants who, despite extended practice on the covariation, exclusively relied on the instructed stimulus feature and (2) those who abruptly started to rely heavily on stimulus color to select responses in ambiguous trials. When the instructed and uninstructed feature predicted different actions, choices were still biased by the uninstructed color feature, albeit more weakly. A second experiment showed that the influence of color generalized across frequently and infrequently presented combinations of position and color. Strategy changes were accompanied by awareness in both experiments. The results suggest that incidental covariation learning can trigger spontaneous voluntary strategy change involving a re-configuration of the instructed task set.


Self-Folding Liquid Crystal Network Filaments Patterned with Vertically Aligned Mesogens.
Fibrous soft actuators with high molecular anisotropy are of interest for shape morphing from 1D to 2D and 3D in response to external stimuli with high actuation efficiency. Nevertheless, few have fabricated fibrous actuators with controlled molecular orientations and stiffness. Here, we fabricate filaments from liquid crystal networks (LCNs) with segmental crosslinking density and gradient porosity from a mixture of di-acrylate mesogenic monomers and small-molecule nematic or smectic liquid crystals (LCs) filled in a capillary. During photopolymerization, phase separation between the small-molecule LCs and LCN occurs, making one side of the filament considerably denser than the other side. To direct its folding mode (bending or twisting), we control the alignment of LC molecules within the capillary, either along or perpendicular to the filament long axis. We show that the direction of UV exposure can determine the direction of phase separation, which in turn direct the deformation of the filament after removal of the small-molecule LCs. We find that the vertical alignment of LCs within the filament is essential to efficiently direct bending deformation. By photopatterning the filament with segmental crosslinking density, we can induce a reversible folding/unfolding into 2D and 3D geometries triggered by deswelling/swelling in an organic solvent. Moreover, by taking advantage of the large elastic modulus of LCNs and large contrast of the modulus before and after swelling, we show that the self-folded LCP filament could act as a strong gripper.


Incidence and time course of subsyndromal symptoms in patients with bipolar I disorder: an evaluation of 2 placebo-controlled maintenance trials.
Subsyndromal symptoms in bipolar disorder can cause significant functional impairment and are associated with relapse. In this post hoc analysis from 2 randomized, double-blind, 18-month, placebo-controlled maintenance trials for bipolar I disorder (both trials were conducted between August 1997 and August 2001 and used DSM-IV criteria), the incidence, time course, and impact of pharmacotherapy on subsyndromal symptoms were examined. Subsyndromal symptoms occurred in approximately 25% of all visits. Compared with placebo (54.8%), a significantly higher mean percentage of visits in remission were observed with lamotrigine treatment (63.0%, p = .020) but not with lithium treatment (60.0%, p = .165). The median time to onset of subsyndromal symptoms for lamotrigine (N = 223), lithium (N = 164), and placebo (N = 188) was 15, 15, and 9 days, respectively. Compared with placebo, both lamotrigine and lithium significantly delayed the time from randomization to onset of subsyndromal symptoms (p = .046, lamotrigine vs. placebo; p = .033, lithium vs. placebo; p = .763, lamotrigine vs. lithium) and the time from onset of subsyndromal symptoms to subsequent mood episode (p = .037, lamotrigine vs. placebo; p = .023, lithium vs. placebo; p = .845, lamotrigine vs. lithium). Agreement between the polarities of the first-observed subsyndromal symptom and subsequent intervention for mood episode was statistically significant (p < .001). Subsyndromal symptoms are common during maintenance treatment and appear to be associated with relapse into an episode of the same polarity. Both lithium and lamotrigine delayed the onset of subsyndromal symptoms and the time from onset of subsyndromal symptoms to subsequent relapse. Further study to assess whether treatment intervention can minimize subsyndromal symptoms or prevent relapse is encouraged.


Growth arrest and apoptosis in adult T cell leukemia cell lines following IL-2 deprivation.
Adult T-cell leukemia (ATL) is a peripheral T-cell neoplasm caused by human T-cell leukemia virus type-I (HTLV-I). Since ATL cells often require IL-2 for their proliferation and survival, we examined the effect of IL-2 deprivation on the IL-2-dependent ATL cells established from ATL patients. After IL-2 withdrawal, these cells were arrested in the G1 phase and then underwent apoptosis. p27Kip1 was observed to act as a cell cycle inhibitor. A decrease in the amount of Bcl-xL was more distinct than that of Bcl-2, while Bax increased slightly during IL-2 withdrawal. The activation of caspase-3 and the loss of mitochondrial membrane potential were also observed. An overexpression of Bcl-xL protein in the KK1, one of the ATL cell lines, suppressed apoptosis by the 3rd day, however, apoptosis could not be prevented completely. Thereafter, a decrease in Bcl-xL and an activation of caspase-3 were observed even under the overexpression of Bcl-xL. The mitochondrial membrane potential and the intra-cellular levels of reactive oxygen species (ROS) also changed due to IL-2 deprivation. From these results, the IL-2 signals are considered to be essential for the survival of ATL cells, and the interruption of IL-2 signaling might thus be useful as a potentially new treatment for ATL.


Relationships between the use of Embden Meyerhof pathway (EMP) or Phosphoketolase pathway (PKP) and lactate production capabilities of diverse Lactobacillus reuteri strains.
The aims of this study is to compare the growth and glucose metabolism of three Lactobacillus reuteri strains (i.e. DSM 20016, DSM 17938, and ATCC 53608) which are lactic acid bacteria of interest used for diverse applications such as probiotics implying the production of biomass, or for the production of valuable chemicals (3-hydroxypropionaldehyde, 3-hydroxypropionic acid, 1,3-propanediol). However, the physiological diversity inside the species, even for basic metabolisms, like its capacity of acidification or glucose metabolism, has not been studied yet. In the present work, the growth and metabolism of three strains representative of the species diversity have been studied in batch mode. The strains were compared through characterization of growth kinetics and evaluation of acidification kinetics, substrate consumption and product formation. The results showed significant differences between the three strains which may be explained, at least in part, by variations in the distribution of carbon source between two glycolytic pathways during the bacterial growth: the phosphoketolase or heterolactic pathway (PKP) and the Embden-Meyerhof pathway (EMP). It was also shown that, in the context of obtaining a large amount of biomass, DSM 20016 and DSM 17938 strains were the most effective in terms of growth kinetics. The DSM 17938 strain, which shows the more significant metabolic shift from EMP to PKP when the pH decreases, is more effective for lactate production.


Coadministration of interleukin 2 plasmid DNA with combined DNA vaccines significantly enhances the protective efficacy against Mycobacterium tuberculosis.
Coadministration of interleukin 2(IL-2) plasmid DNA with combined DNA vaccines enhanced Th1-type cellular responses by producing higher amounts of IFN-gamma with a higher ratio of antigen-specific IgG2a/IgG1. The IFN-gamma specific for Ag85B, MPT64, and MPT83 in this group was 415, 267, and 255 U/ml, respectively, and was 1.6-, 1.8-, and 2.5-fold higher than that of the same vaccine without adding IL-2. The IgG2a/IgG1 ratio for Ag85B, MPT64, and MPT83 was 4, 8, and 4, respectively, upon addition of the genetic adjuvant in the DNA vaccine, which was four times higher for every antigen when IL-2 was not included. Fluorescence activated cell sorter (FACS) analysis showed that, in the presence of IL-2, CD8+ and CD4+ T cells increased significantly, whereas in the absence of the genetic adjuvant, only a mild increase was observed for CD8+ T cells compared to the vector DNA-treated group. Bacterial CFU was reduced to less than 1/100 in the lung and to about 1/10 in the spleen relative to the same combined DNA vaccine without IL-2. The lungs of this group of mice showed much less damage due to an influx of epithelioid macrophages and less lymphocytes. RT-PCR showed that antigen genes could be detected in more organs and for a longer period of time when treated with combined DNA vaccine formulated in IL-2. We suggest that IL-2 enhanced the immunigencity and protective efficacy in immunized mice by improving the Th1-type response and also by prolonging the antigen gene expression in different organs.


Bacterial Epigenomics: Coming of Age.
Epigenetic DNA methylation in bacteria has been traditionally studied in the context of antiparasitic defense and as part of the innate immune discrimination between self and nonself DNA. However, sequencing advances that allow genome-wide analysis of DNA methylation at the single-base resolution are nowadays expanding and have propelled a modern epigenomic revolution in our understanding of the extent, evolution, and physiological relevance of methylation. Indeed, as the number of mapped bacterial methylomes recently surpassed 4,000, increasing evidence supports roles for methylation in gene expression regulation, virulence, and host colonization, among others. In this paper, I summarize lessons taken from high-dimensional methylome data analyses and recent efforts that we and others are developing to leverage such findings into meaningful biological insights and overarching frameworks. Ultimately, I highlight anticipated research avenues and technological developments likely to unfold in the coming years.


Use of cholesterol-lowering therapy by elderly adults after myocardial infarction.
Use of cholesterol-lowering drugs reduces mortality and adverse cardiac events among people aged 65 to 75 years with coronary heart disease, but previous studies have shown that most patients have not received this treatment. We conducted a telephone survey during 1999 and 2000 of 815 Medicare beneficiaries aged 65 to 74 years hospitalized for an acute myocardial infarction in California, Florida, Massachusetts, New York, or Pennsylvania during 1994 and 1995. Outcome measures included use of cholesterol-lowering drugs, beliefs about the importance of lowering cholesterol levels, and knowledge of personal cholesterol levels, adjusting for demographic and clinical factors using logistic regression. Among respondents, 59.4% reported taking a cholesterol-lowering drug, but most were not aware of potential adverse effects. In adjusted analyses, drug treatment was significantly more common among women, patients aged 65 to 69 years, and those who reported that a cardiologist was mainly responsible for their cholesterol management. Lowering cholesterol levels was viewed as "very important" by 77.2% of respondents, but significantly less often by men, older patients, and those with diabetes mellitus or congestive heart failure. Only 33.1% of respondents knew their cholesterol level, and this knowledge was significantly less common among black patients and those with diabetes mellitus or congestive heart failure. Use of cholesterol-lowering drugs was much greater than in previous studies of elderly patients after myocardial infarction, demonstrating increased attention to secondary prevention. However, most patients were unaware of their cholesterol level or potential adverse effects of drug treatment, indicating that they may benefit from greater education about cholesterol testing and treatment.


Pellet charge exchange helium measurement using neutral particle analyzer in large helical device.
It is very important to investigate the confinement of alpha particles, which will be produced by nuclear reactions in ITER and fusion reactors. The pellet charge exchange (PCX) measurement is one of the most powerful methods because it can directly provide the profile of the alpha particle energy spectra in a plasma. In the large helical device, PCX using tracer encapsulated solid pellet (TESPEL) has been tried in many hydrogen and helium plasmas, including helium accelerated by using the cyclotron resonance heating. In the PCX, we use the compact neutral particle analyzer without simultaneous mass separation ability. The helium particle measurement can be achieved by the application of voltage in the condenser plate. The scattering of hydrogen particle is carefully considered during the estimation of the helium amount. The radial helium profiles can also be obtained by comparing four TESPEL injection shots with/without higher harmonic fast wave heating and at applied plate voltages for He or H, respectively.


Shared genetics and bidirectional causal relationships between type 2 diabetes and attention-deficit/hyperactivity disorder.
Type 2 diabetes (T2D) is a chronic metabolic disorder with high comorbidity with mental disorders. The genetic links between attention-deficit/hyperactivity disorder (ADHD) and T2D have yet to be elucidated. We aim to assess shared genetics and potential associations between ADHD and T2D. We performed genetic correlation, two-sample Mendelian randomisation and polygenic overlap analyses between ADHD and T2D. The genome-wide association study (GWAS) summary results of T2D (80 154 cases and 853 816 controls), ADHD2019 (20 183 cases and 35 191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38 691 cases and 275 986 controls from the 2022 GWAS ADHD dataset) were used for the analyses. The T2D dataset was obtained from the DIAGRAM Consortium. The ADHD datasets were obtained from the Psychiatric Genomics Consortium. We compared genome-wide association signals to reveal shared genetic variation between T2D and ADHD using the larger ADHD2022 dataset. Moreover, molecular pathways were constructed based on large-scale literature data to understand the connection between ADHD and T2D. T2D has positive genetic correlations with ADHD2019 (rg=0.33) and ADHD2022 (rg=0.31). Genetic liability to ADHD2019 was associated with an increased risk for T2D (odds ratio (OR): 1.30, p<0.001), while genetic liability to ADHD2022 had a suggestive causal effect on T2D (OR: 1.30, p=0.086). Genetic liability to T2D was associated with a higher risk for ADHD2019 (OR: 1.05, p=0.001) and ADHD2022 (OR: 1.03, p<0.001). The polygenic overlap analysis showed that most causal variants of T2D are shared with ADHD2022. T2D and ADHD2022 have three overlapping loci. Molecular pathway analysis suggests that ADHD and T2D could promote the risk of each other through inflammatory pathways. Our study demonstrates substantial shared genetics and bidirectional causal associations between ADHD and T2D.


A Systematic Review of Outcomes Associated With Withholding or Continuing Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Before Noncardiac Surgery.
The global rate of major noncardiac surgical procedures is increasing annually, and of those patients presenting for surgery, increasing numbers are taking either an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin receptor blocker (ARB). The current recommendations of whether to continue or withhold ACE-I and ARB in the perioperative period are conflicting. Previous meta-analyses have linked preoperative ACE-I/ARB therapy to the increased incidence of postinduction hypotension; however, they have failed to correlate this with adverse patient outcomes. The aim of this meta-analysis was to determine whether continuation or withholding ACE-I or ARB therapy in the perioperative period is associated with mortality and major morbidity. This meta-analysis was prospectively registered on PROSPERO (CRD42017055291). A comprehensive search of MEDLINE (PubMed), CINAHL (EBSCO host), ProQuest, Cochrane database, Scopus, and Web of Science was conducted on December 6, 2016. We included adult patients >18 years of age on chronic ACE-I or ARB therapy who underwent noncardiac surgery in which ACE-I or ARB was either withheld or continued on the morning of surgery. Primary outcomes included all-cause mortality and major cardiac events (MACE). Secondary outcomes included the risk of congestive heart failure, acute kidney injury, stroke, intraoperative/postoperative hypotension, and the length of hospital stay. After abstract review, the full text of 25 studies was retrieved, of which 9 fulfilled the inclusion criteria: 5 were randomized control trials, and 4 were cohort studies. These studies included a total of 6022 patients on chronic ACE-I/ARB therapy before noncardiac surgery. A total of 1816 patients withheld treatment the morning of surgery and 4206 continued their ACE-I/ARB. Preoperative demographics were similar between the 2 groups. Withholding ACE-I/ARB therapy was not associated with a difference in mortality (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.62-1.52; I = 0%) or MACE (OR, 1.12; 95% CI, 0.82-1.52; I = 0%). However, withholding therapy was associated with significantly less intraoperative hypotension (OR, 0.63; 95% CI, 0.47-0.85; I = 71%). No effect estimate could be pooled concerning length of hospital stay and congestive heart failure. This meta-analysis did not demonstrate an association between perioperative administration of ACE-I/ARB and mortality or MACE. It did, however, confirm the current observation that perioperative continuation of ACE-I/ARBs is associated with an increased incidence of intraoperative hypotension. A large randomized control trial is necessary to determine the appropriate perioperative management of ACE-I and ARBs.


Premarital hemoglobinopathy screening in Kocaeli, Turkey: a crowded industrial center on the north coast of Marmara Sea.
Premarital hemoglobinopathy screening is one of the important procedures of hemoglobinopathy control program. This is the first report about the prevalence of hemoglobinopathies in Kocaeli. Study covered screening from July 2005 to the end of the December 2008. Under the auspices of the Ministry of Health and Regional Health authorities blood samples of the couples were obtained during admission to the wedding office. Complete blood counts and hemoglobin variant analysis were performed with automatic counter and high pressure liquid chromotography technique. A genetic counseling was given to carriers of abnormal hemoglobins. A total of 88888 people were screened. The frequency of β -thalassemia trait and sickle cell anemia trait were 0.89% and 0.05% respectively. The frequency of high risk couples was 0.01%. The prevalence of β -thalassemia trait and sickle cell anemia trait was quite low as a reflection of the frequency of eastern and northern Anatolia and migration to Kocaeli from these geographic regions. Although frequency is low, chronic transfusion requirement, high cost of chelating, organ damage, painful crisis and other crisis, availability of stem cell transplantation for a limited number of patients with compatible sibling donors justify premarital screening studies even in less prevalent regions as Kocaeli.


Interactions between Genetic and Ecological Effects on the Evolution of Life Cycles.
Sexual reproduction leads to an alternation between haploid and diploid phases, whose relative length varies widely across taxa. Previous genetical models showed that diploid or haploid life cycles may be favored, depending on dominance interactions and on effective recombination rates. By contrast, niche differentiation between haploids and diploids may favor biphasic life cycles, in which development occurs in both phases. In this article, we explore the interplay between genetical and ecological factors, assuming that deleterious mutations affect the competitivity of individuals within their ecological niche and allowing different effects of mutations in haploids and diploids (including antagonistic selection). We show that selection on a modifier gene affecting the relative length of both phases can be decomposed into a direct selection term favoring the phase with the highest mean fitness (due to either ecological differences or differential effects of mutations) and an indirect selection term favoring the phase in which selection is more efficient. When deleterious alleles occur at many loci and in the presence of ecological differentiation between haploids and diploids, evolutionary branching often occurs and leads to the stable coexistence of alleles coding for haploid and diploid cycles, while temporal variations in niche sizes may stabilize biphasic cycles.


Distal Femoral Oblique Fracture in a Young Male Soldier: Case Report of an Unusual Presentation.
Here, we report a case of a distal femoral fracture in a 23-year-old male army cadet who presented to the Accident and Emergency department following a twisting injury while participating in a routine military marching exercise. A pathological fracture was considered but this suspicion was put to rest following thorough investigations, leaving only a diagnosis of a nontraumatic spontaneous femoral fracture.To our knowledge, there have been no reported cases of distal femoral fractures associated with nontraumatic military exercises, with the majority of injuries instead related to stress fractures. A vigilant literature search yielded no cases of similar injury nature, which is the primary reason we believe that those interested in orthopaedics or military doctors would find themselves drawn to this case.The patient presented with severe pain in his left thigh and on examination there was a deformity of his left thigh.In terms of investigations, a bone profile, plain film radiographs, C-reactive protein, erythrocyte sedimentation rate, and tumor markers were all preformed and proved unremarkable. The definitive treatment was by open reduction and internal fixation.Femoral fractures often require significant amounts of force, particularly in young, healthy individuals. Generally, these injuries in this demographic follow high-energy traumas, with the lion's share occurring following a road traffic accident or other high-speed impact. More often than not, the treatment is surgical. Given the extraordinary manner of this such, one must be attentive and exhaustive in their investigation of such presentations.


Measuring attachment and parental bonding in psychosis and its clinical implications.
Attachment theory proposes that psychological functioning and affect regulations are influenced by the attachment we form with others. Early relationships with parents or caregivers lay the foundations for attachment styles. These styles are proposed to influence how we relate to others during our life can be modified by the relationships and events we experience in our lifespan. A secure attachment style is associated with a capacity to manage distress, comfort with autonomy and the ability to form relationships with others, whereas insecure attachment can lead to dysfunctional relationships, emotional and behaviour avoidance. Attachment theory provides a useful framework to inform our understanding of relationship difficulties in people with psychosis. This paper aims to complement recent systematic reviews by providing an overview of attachment theory, its application to psychosis, including an understanding of measurement issues and the clinical implications offered. A narrative review was completed of the measures of attachment and parental bonding in psychosis. Its clinical implications are also discussed. The paper also explores the link between insecure attachment styles and illness course, social functioning and symptomatology. The following questions are addressed: What are the key attachment measures that have been used within the attachment and psychosis literature? What are the results of studies that have measured attachment or parental bonding in psychosis and what clinical implications can we derive from it? What are some of the key questions for future research from these findings in relation to the onset of psychosis research field? The most commonly used measures of attachment in psychosis research are reviewed. Self-report questionnaires and semi-structured interviews have mainly been used to examine attachment styles in adult samples and in recent years comprise a measure specifically developed for a psychosis group. The review suggests that insecure attachment styles are common in psychosis samples. Key relationships were observed between insecure, avoidant and anxious attachment styles and psychosis development, expression and long-term outcome. Attachment theory can provide a useful framework to facilitate our understanding of interpersonal difficulties in psychosis that may predate its onset and impact on observed variability in outcomes, including treatment engagement. Greater attention should be given to the assessment of attachment needs and to the development of interventions that seek to compensate for these difficulties. However, further investigations are required on specifying the exact mechanisms by which specific attachment styles impact on the development of psychosis and its course.


Rapidly dissolving microneedle patch for synergistic gene and photothermal therapy of subcutaneous tumor.
The synergistic combination of gene therapy and photothermal therapy (PTT) has been widely investigated as a promising strategy for cancer treatment. To deliver genes and photothermal agents simultaneously and accurately to a tumor site, a microneedle (MN) patch co-loaded with p53 DNA and IR820 was fabricated by a two-step casting method. Hyaluronic acid was chosen as a matrix and p53 DNA and IR820 were mainly loaded into the tips to enhance utilization and reduce waste. The MN patch could efficiently penetrate the stratum corneum, and dissolve rapidly to release p53 DNA and IR820 in the subcutaneous tumor site. Due to the efficient photothermal efficacy of IR820, the temperature of the tumor site where the MN patch was applied increased by 14.7 °C under near-infrared light irradiation. The MN patch showed excellent antitumor effects in vivo owing to the synergistic effect of gene therapy and PTT. Consequently, the p53 DNA/IR820 MN patch may be a promising synergistic strategy for subcutaneous tumor treatments.


Implementation of a single sign-on system between practice, research and learning systems.
Multiple specialized electronic medical systems are utilized in the health enterprise. Each of these systems has their own user management, authentication and authorization process, which makes it a complex web for navigation and use without a coherent process workflow. Users often have to remember multiple passwords, login/logout between systems that disrupt their clinical workflow. Challenges exist in managing permissions for various cadres of health care providers. This case report describes our experience of implementing a single sign-on system, used between an electronic medical records system and a learning management system at a large academic institution with an informatics department responsible for student education and a medical school affiliated with a hospital system caring for patients and conducting research. At our institution, we use OpenMRS for research registry tracking of interventional radiology patients as well as to provide access to medical records to students studying health informatics. To provide authentication across different users of the system with different permissions, we developed a Central Authentication Service (CAS) module for OpenMRS, released under the Mozilla Public License and deployed it for single sign-on across the academic enterprise. The module has been in implementation since August 2015 to present, and we assessed usability of the registry and education system before and after implementation of the CAS module. 54 students and 3 researchers were interviewed. The module authenticates users with appropriate privileges in the medical records system, providing secure access with minimal disruption to their workflow. No passwords requests were sent and users reported ease of use, with streamlined workflow. The project demonstrates that enterprise-wide single sign-on systems should be used in healthcare to reduce complexity like "password hell", improve usability and user navigation. We plan to extend this to work with other systems used in the health care enterprise.


Comorbidity of Migraine and Epilepsy in Pediatrics: A Review.
Migraine and epilepsy are classified as chronic paroxysmal neurologic disorders sharing many clinical features, as well as possible treatment options. This review highlights the similarities between migraine and epilepsy in pediatrics, focusing on epidemiologic, pathophysiological, genetic, clinical, and pharmacologic aspects. Despite the fact that several syndromes share symptoms of both migraine and epilepsy, further research is needed to clarify the pathophysiological and genetic basis of their comorbidity. Drugs used for prophylactic therapy of migraine and epilepsy have similar pharmacologic properties. The role of epileptic pharmacotherapy in the prophylaxis of migraine is assessed, including the use of conventional antiepileptic drugs, calcium channel blockers, and nonpharmacologic methods such as dietary therapy, supplements, and vagal nerve stimulation. Further randomized, controlled clinical trials assessing pharmacologic and nonpharmacologic methods for the treatment of both disorders are essential, in order to initiate new therapeutic approaches.


Regulation of P-element transposase activity in Drosophila melanogaster by hobo transgenes that contain KP elements.
Fusions between the Drosophila hsp70 promoter and three different incomplete P elements, KP, SP, and BP1, were inserted into the Drosophila genome by means of hobo transformation vectors and the resulting transgenic stocks were tested for repression of P-element transposase activity. Only the H(hsp/KP) transgenes repressed transposase activity, and the degree of repression was comparable to that of a naturally occurring KP element. The KP transgenes repressed transposase activity both with and without heat-shock treatments. Both the KP element and H(hsp/KP) transgenes repressed the transposase activity encoded by the modified P element in the P(ry(+), Delta2-3)99B transgene more effectively than that encoded by the complete P element in the H(hsp/CP)2 transgene even though the P(ry(+), Delta2-3)99B transgene was the stronger transposase source. Repression of both transposase sources appeared to be due to a zygotic effect of the KP element or transgene. There was no evidence for repression by a strictly maternal effect; nor was there any evidence for enhancement of KP repression by the joint maternal transmission of H(hsp/KP) and H(hsp/CP) transgenes. These results are consistent with the idea that KP-mediated repression of P-element activity involves a KP-repressor polypeptide that is not maternally transmitted and that KP-mediated repression is not strengthened by the 66-kD repressor produced by complete P elements through alternate splicing of their RNA.


The influence of the suppression of gastrooesophageal reflux on the gene expression pattern in Barrett's oesophagus.
About 10% of Barrett's patients develop an adenocarcinoma in the course of life. There is increasing evidence that persistent gastrooesophageal reflux is involved in carcinogenesis. We investigated whether the gene expression pattern of Barrett's epithelium cells changes upon suppression of gastrooesophageal reflux compared to unsuppressed reflux. Biopsies from various regions of Barrett's segments and, further, during and without proton pump inhibitor therapy were collected in 5 patients. The reflux profile was assessed by simultaneous 24-h oesophageal pH and bile reflux testing. m-RNA was extracted from the specimens, and integrity and absence of DNA proven by gel electrophoresis and ALU-PCR. Using the micro array technique 1,176 genes were analysed and assigned an expression level. The number of genes detected in each experiment varied from 86 to 136. There was a 91% concordance of the gene expression pattern in distal and proximal biopsies from an individual Barrett's segment. Concordance was much less (68%) between biopsies of the same patient taken during and without proton pump inhibitor therapy. The gene expression pattern in a Barrett's oesophagus varies dependent upon different reflux situations. Other factors like the location of biopsy are of minor importance. The micro array technique allows for selection of candidate genes important in carcinogenesis.


Raman Optical Activity of N-Acetyl-L-Cysteine in Water and in Methanol: The "Clusters-in-a-Liquid" Model and ab Initio Molecular Dynamics Simulations.
Raman and Raman Optical Activity (ROA) spectra of N-acetyl-L-cysteine (NALC), a flexible chiral molecule, were measured in water and in methanol to evaluate the solvent effects. Two different solvation approaches, that is, the DFT based "clusters-in-a-liquid" solvent model and the ab initio molecular dynamics (AIMD) simulations, were applied to simulate the Raman and ROA spectra. Systematic conformational searches were carried out using a recently developed conformational searching tool, CREST, with the inclusion of polarizable continuum model of water and of methanol. The CREST candidates of NALC and the NALC-solvent complexes were re-optimized and their Raman and ROA simulations were done at the B3LYP-D3BJ/def2-TZVP and the B3LYP-aug-cc-pVDZ//cc-pVTZ levels. Also, AIMD simulations, which includes some anharmonic effects and all intermolecular interactions in solution, were performed. By empirically weighting the computed Raman and ROA spectra of each conformer, good agreements with the experimental data were achieved with both approaches, while AIMD offered some improvements in the carbonyl and in the low wavenumber regions over the static DFT approach. The pros and cons of these two different approaches for accounting the solvent effects on Raman and ROA of this flexible chiral system will also be discussed.


Optical design study of an infrared visible viewing system for Wendelstein 7-X divertor observation and control.
For the Wendelstein 7-X stellarator, which will allow quasicontinuous operation (tau < or = 30 min) with 10 MW of electron cyclotron radiation heating power, a conceptual design study for an IR/visible viewing system (IVVS) has been elaborated. Ten such systems, as part of the machine protection system, will be required for real time monitoring of all ten discrete, water cooled divertor modules with high spatial (< 10 mm) resolution, in order to prevent local overheating of the target tiles, which could easily lead to their destruction. On the physics side, the systems will be used for divertor symmetry investigations by studying the power load distribution on all targets modules and by observing the island divertor plasmas in the light of H alpha, C II, and C III using the visible imaging section of the systems. The optics of the system can be divided into three parts: a mirror based optical head, creating an intermediate image, a Cassegrain telescope system, and individual lens based imaging optics adapted to the various detectors for IR (3-5 microm and 8-14 microm) and visible observations, with their optical light paths being separated by in-vacuum dichroic beam splitters.


Randomized controlled trial of oral versus intravenous fluid supplementation on serum bilirubin level during phototherapy of term infants with severe hyperbilirubinaemia.
To compare the rates of decrease in serum bilirubin levels in severely jaundiced healthy term infants given oral or intravenous fluid supplementation during phototherapy. A randomized controlled study was carried out in the neonatal intensive care unit (NICU) of Hospital Universiti Kebangsaan Malaysia over a 12-month period. Fifty-four healthy term infants with severe hyperbilirubinemia were randomized to receive either solely enteral feeds (n = 27) or both enteral and intravenous (n = 27) fluid during phototherapy. There were no significant differences in the mean birthweight, mean gestational age, ethnic distribution, gender distribution, modes of delivery and types of feeding between the two groups. Similarly, there was no significant difference in the mean indirect serum bilirubin (iSB) level at the time of admission to the NICU between the enteral (359 +/- 69 micromol/L [mean +/- SD]) and intravenous group (372 +/- 59 micromol/L; P = 0.4). The mean rates of decrease in iSB during the first 4 h of phototherapy were also not significantly different between the enteral group (10.4 +/- 4.9 micromol/L per h) and intravenous group (11.2 +/- 7.4 micromol/L per h; P = 0.6). There was no significant difference in the proportion of infants requiring exchange transfusion (P = 0.3) nor in the median duration of hospitalization (P = 0.7) between the two groups. No infant developed vomiting or abdominal distension during the study period. Severely jaundiced healthy term infants had similar rates of decrease in iSB levels during the first 4 h of intensive phototherapy, irrespective of whether they received oral or intravenous fluid supplementation. However, using the oral route avoided the need for intravenous cannulae and their attendant complications.


25-hydroxy-Vitamin D status: limitations in comparison and clinical interpretation of serum-levels across different assay methods.
Background: Over the last decade, clinical interest to evaluate human 25-hydroxy-vitamin D (25[OH]D) serum levels has increased exponentially. In the present study, four chemiluminescence immunoassays (CLIA), one radioimmunoassy (RIA), and one high performance liquid chromatography (HPLC) method were compared and also with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method in view of 25(OH)D serum level determination. Methods: For the method comparison, blood samples from 133 consecutive patients were prospectively collected. All participants gave written informed consent for their blood samples to be used in this study. They came to the Department of Nuclear Medicine of the Central Hospital Steyr (Austria) for osteodensidometric measurement as part of their preventive medical check-up. Pearson's correlation coefficients, Bland-Altman plots, and paired t-tests were calculated. Assay-specific reference ranges were considered using blood samples from persons with normal parathormone, calcium, and total-protein values (n = 97). Results: The highest correlation was between the HPLC and the LC-MS/MS method (r = 0.96). The lowest correlation was between the cobas Vitamin D3 assay (Roche) and any of the evaluated assays (r = 0.46 - 0.63). Bland-Altman plots revealed a big negative mean bias in three assays (cobas Vitamin D3 assay [Roche]: -22.8; DiaSorin LIAISON [25[OH]D total CLIA [Diasorin]: -18.4; Diasorin 25[OH]D125 I RIA [Diasorin]: -23.8 [nmol/L]) and a much smaller positive mean bias in the other assays (ClinRep complete 25[OH]D2/D3 HPLC kit [Recipe]: 2.7; ADVIA Centaur Vitamin D total assay [Siemens]: 8.2; IDS total vitamin D assay [Immunodiagnostic Systems]: 12.1 [nmol/L]) compared to the LC-MS/MS method. Meanwhile, the manufacturer has withdrawn the cobas Vitamin D3 assay from the market. Conclusions: Poor antibody specificity with cross-reactivity to other vitamin D metabolites, incomplete extraction of the 25(OH)D analyte from the vitamin D-binding protein (DBP), and confounding matrix substances such as lipids could be potential reasons for the unacceptable performance of the cobas Vitamin D3 assay (Roche) and also the significant differences in the 25(OH)D determination between various assays. Standardization and harmonization of 25(OH)D measurements are therefore urgently needed. The widespread introduction of well standardized assays in clinical laboratories is the challenge in the next years. (Clin. Lab. 2014;60:1541-1550. DOI: 10.7754/Clin.Lab.2014.131114)


Rate of growth of intraabdominal metastases from colorectal cancer.
Monitoring the progression or regression of intraabdominal metastatic disease is required for knowledgeable management of chemotherapeutic regimens designed to treat metastases. Computerized tomography (CT) and CT with EOE-13, a liver contrast agent, allowed precise measurement of metastatic disease. The tumor doubling time of colorectal metastases in four patients was determined from serial CT scans of individual patients. Tumor doubling times of untreated patients varied from 50 to 95 days, and were in the same range for hepatic, lymph node, or intraperitoneal metastatic disease. These data may indicate that metastatic disease of colorectal cancer progresses at a faster rate in the peritoneal cavity than is reported for colorectal cancer metastatic to the lungs. The response to chemotherapy or progression of disease was also determined in treated patients. High resolution CT scanning with EOE-13 allowed calculation of tumor doubling times, and therefore more precise management of cancer patients with metastases.


Abdomino-scrotal hydrocele in 35 years old: a case report.
Abdomino-scrotal hydrocele is a condition usually affecting children. It is unusual to find an abdomino-scrotal hydrocele in middle aged adult. Most of the patients are asymptomatic except cystic abdominal mass and discomfort occasionally. We hereby report an unusual presentation of abdomino-scrotal hydrocele at age of 35 years and presenting as large cystic abdominal mass extending into scrotum.


Interventions for improving adherence to airway clearance treatment and exercise in people with cystic fibrosis.
Cystic fibrosis (CF) is a life-limiting genetic disorder predominantly affecting the lungs and pancreas. Airway clearance techniques (ACTs) and exercise therapy are key components of physiotherapy, which is considered integral in managing CF; however, low adherence is well-documented. Poor physiotherapy adherence may lead to repeated respiratory infections, reduced exercise tolerance, breathlessness, reduced quality of life, malaise and reduced life expectancy, as well as increased use of pharmacology, healthcare access and hospital admission. Therefore, evidence-based strategies to inform clinical practice and improve adherence to physiotherapy may improve quality of life and reduce treatment burden. To assess the effects of interventions to enhance adherence to airway clearance treatment and exercise therapy in people with CF and their effects on health outcomes, such as pulmonary exacerbations, exercise capacity and health-related quality of life. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 1 March 2023. We also searched online trials registries and the reference lists of relevant articles and reviews. Date of last search: 28 March 2023. We included randomised controlled trials (RCTs) and quasi-RCTs of parallel design assessing any intervention aimed at enhancing adherence to physiotherapy in people with CF versus no intervention, another intervention or usual care. Two review authors independently checked search results for eligible studies and independently extracted data. We used standard procedures recommended by Cochrane and assessed the certainty of evidence using the GRADE system. Two RCTs (77 participants with CF; age range 2 to 20 years; 44 (57%) males) met the inclusion criteria of this review. One study employed an intervention to improve adherence to exercise and the second an intervention to improve adherence to ACT. Both studies measured outcomes at baseline and at three months, but neither study formally assessed our primary outcome of adherence in terms of our planned outcome measures, and results were dependent on self-reported data. Adherence to ACTs One RCT (43 participants) assessed using specifically-composed music alongside ACTs compared to self-selected or no music (usual care). The ACT process consisted of nebuliser inhalation treatment, ACTs and relaxation or antibiotic nebuliser treatment. We graded all evidence as very low certainty. This study reported adherence to ACTs using the Morisky-Green questionnaire and also participants' perception of treatment time and enjoyment, which may influence adherence (outcome not reported specifically in this review). We are uncertain whether participants who received specifically-composed music may be more likely to adhere at six and 12 weeks compared to those who received usual care, risk ratio (RR) 1.75 (95% confidence interval (CI) 1.07 to 2.86) and RR 1.56 (95% CI 1.01 to 2.40) respectively. There may not be any difference in adherence when comparing specifically-composed music to self-selected music at six weeks, RR 1.21 (95% CI 0.87 to 1.68) or 12 weeks, RR 1.52 (95% CI 0.97 to 2.38); or self-selected music to usual care at six weeks, RR 1.44 (95% CI 0.82 to 2.52) or 12 weeks, RR 1.03 (95% CI 0.57 to 1.86). The music study also reported the number of respiratory infections requiring hospitalisation at 12 weeks, with no difference seen in the risk of hospitalisation between all groups. Adherence to exercise One RCT (24 participants) compared the provision of a manual of aerobic exercises, recommended exercise prescription plus two-weekly follow-up phone calls to reinforce exercise practice over a period of three months to verbal instructions for aerobic exercise according to the CF centre's protocol. We graded all evidence as very low certainty. We are uncertain whether an educational intervention leads to more participants in the intervention group undertaking increased regular physical activity at three months (self-report), RR 3.67 (95% CI 1.24 to 10.85), and there was no reported difference between groups in the number undertaking physical activity three times per week or undertaking at least 40 minutes of physical activity. No effect was seen on secondary outcome measures of spirometry, exercise capacity or any CF quality of life domains. This study did not report on the frequency of respiratory infections (hospitalised or not) or adverse events. We are uncertain whether a music-based motivational intervention may increase adherence to ACTs or affect the risk of hospitalisation for a respiratory infection. We are also uncertain whether an educational intervention increases adherence to exercise or reduces the frequency of respiratory infection-related hospital admission. However, these results are largely based on self-reported data and the impact of strategies to improve adherence to ACT and exercise in children and adolescents with stable CF remains inconclusive. Given that adherence to ACT and exercise therapy are fundamental to the clinical management of people with CF, there is an urgent need for well-designed, large-scale clinical trials in this area, which should conform to the CONSORT statement for standards of reporting and use appropriate, validated outcome measures. Studies should also ensure full disclosure of data for all important clinical outcomes.


Transcriptional Regulation of Pine Male and Female Cone Initiation and Development: Key Players Identified Through Comparative Transcriptomics.
With long reproductive timescales, large complex genomes, and a lack of reliable reference genomes, understanding gene function in conifers is extremely challenging. Consequently, our understanding of which genetic factors influence the development of reproductive structures (cones) in monoecious conifers remains limited. Genes with inferred roles in conifer reproduction have mostly been identified through homology and phylogenetic reconstruction with their angiosperm counterparts. We used RNA-sequencing to generate transcriptomes of the early morphological stages of cone development in the conifer species Pinus densiflora and used these to gain a deeper insight into the transcriptional changes during male and female cone development. Paired-end Illumina sequencing was used to generate transcriptomes from non-reproductive tissue and male and female cones at four time points with a total of 382.82 Gbp of data generated. After assembly and stringent filtering, a total of 37,164 transcripts were retrieved, of which a third were functionally annotated using the Mercator plant pipeline. Differentially expressed gene (DEG) analysis resulted in the identification of 172,092 DEGs in the nine tissue types. This, alongside GO gene enrichment analyses, pinpointed transcripts putatively involved in conifer reproductive structure development, including co-orthologs of several angiosperm flowering genes and several that have not been previously reported in conifers. This study provides a comprehensive transcriptome resource for male and early female cone development in the gymnosperm species Pinus densiflora. Characterisation of this resource has allowed the identification of potential key players and thus provides valuable insights into the molecular regulation of reproductive structure development in monoecious conifers.


Cardiovascular sex-differences: insights via physiology-based modeling and potential for noninvasive sensing via ballistocardiography.
In this study, anatomical and functional differences between men and women in their cardiovascular systems and how these differences manifest in blood circulation are theoretically and experimentally investigated. A validated mathematical model of the cardiovascular system is used as a virtual laboratory to simulate and compare multiple scenarios where parameters associated with sex differences are varied. Cardiovascular model parameters related with women's faster heart rate, stronger ventricular contractility, and smaller blood vessels are used as inputs to quantify the impact (i) on the distribution of blood volume through the cardiovascular system, (ii) on the cardiovascular indexes describing the coupling between ventricles and arteries, and (iii) on the ballistocardiogram (BCG) signal. The model-predicted outputs are found to be consistent with published clinical data. Model simulations suggest that the balance between the contractile function of the left ventricle and the load opposed by the arterial circulation attains similar levels in females and males, but is achieved through different combinations of factors. Additionally, we examine the potential of using the BCG waveform, which is directly related to cardiovascular volumes, as a noninvasive method for monitoring cardiovascular function. Our findings provide valuable insights into the underlying mechanisms of cardiovascular sex differences and may help facilitate the development of effective noninvasive cardiovascular monitoring methods for early diagnosis and prevention of cardiovascular disease in both women and men.


Hemoglobin Is a Vital Determinant of Arterial Oxygen Content in Hypoxemic Patients with Pulmonary Arteriovenous Malformations.
PaO2 and SaO2 are commonly measured in respiratory practice, but arterial oxygen content (CaO2) refers to the volume of oxygen delivered to the tissues per unit blood volume. CaO2 is calculated from SaO2 and the hemoglobin concentration in blood, recognizing that each gram of hemoglobin can transport approximately 1.34 ml of oxygen when fully saturated. To prospectively evaluate serial changes in CaO2 in humans, incorporating and excluding dynamic changes to oxygenation and hemoglobin parameters that may occur during life. A cohort of 497 consecutive patients at risk of both hypoxemia and anemia were recruited. The patients had radiologically proven pulmonary arteriovenous malformations (PAVMs), which result in hypoxemia due to right-to-left shunting, and concurrent hereditary hemorrhagic telangiectasia, which placed them at risk of iron deficiency anemia due to recurrent hemorrhagic iron losses. Presentation SaO2 (breathing room air, by pulse oximetry), hemoglobin, red cell and iron indices were measured, and CaO2 calculated as SaO2 × hemoglobin × 1.34 ml/g. Serial measurements were evaluated in 100 cases spanning up to 32.1 (median, 10.5) years. Presentation CaO2 ranged from 7.6 to 27.5 (median, 17.6) ml/dl. CaO2 did not change appreciably across the SaO2 quartiles. In contrast, hemoglobin ranged from 5.9 to 21.8 g/dl (median, 14.1 g/dl), with a linear increase in CaO2 across hemoglobin quartiles. After PAVM embolization and an immediate increase in SaO2, hemoglobin fell and CaO2 was unchanged 1.6-12 (median, 4) months later. When hemoglobin fell because of iron deficiency, there was no change in SaO2. Similarly, when hemoglobin rose after iron treatment, there was no change in SaO2, and the expected CaO2 increment was observed. These relationships were not evident during pregnancy when hemoglobin fell, and PAVMs usually deteriorated: in pregnancy SaO2 commonly increased, and serial CaO2 values (incorporating hemodilution/anemia) more accurately reflected deteriorating PAVM status. An apparent fall in CaO2 with age in females was attributable to the development of iron deficiency. There was an unexplained increase in CaO2 with age in follow-up of males after embolization. Hemoglobin/CaO2 should be further incorporated into oxygenation considerations. More attention should be given to modest changes in hemoglobin that substantially modify CaO2.


Intraplant movement of generalist slug caterpillars (Limacodidae: Lepidoptera): effects of host plant and light environment.
Insect herbivores frequently move about on their host plants to obtain food, avoid enemies and competitors, and cope with changing environmental conditions. Although numerous plant traits influence the movement of specialist herbivores, few studies have examined movement responses of generalist herbivores to the variable ecological conditions associated with feeding and living on an array of host plants. We tested whether the movement patterns of two generalist caterpillars (Euclea delphinii Boisduval and Acharia stimulea Clemens, Limacodidae) differed on six different host tree species over 10 d. Because these tree species vary in the range of light environments in which they commonly grow, we also compared the movement responses of E. delphinii caterpillars to two contrasting light environments, sun and shade. For both caterpillar species, multiple measures of movement varied significantly among host tree species. In early censuses, movement rates and distances were highest on red oak and black cherry and lowest on white oak. Site fidelity was greatest on white oak and lowest on black cherry. Movement of both caterpillar species varied inversely with mean predator density on five of the six host trees. Other ecological predictors (e.g., leaf size and the density of other herbivores) were unrelated to movement. Light environment altered behavior such that caterpillars in the shade moved and fed more often, and moved greater distances, than caterpillars in the sun. Although the mechanism(s) promoting or inhibiting movement under these different conditions requires further study, the consequences of increased movement for caterpillar development and mortality from natural enemies are discussed.


Floral meristem indeterminacy depends on flower position and is facilitated by acarpellate gynoecium development in Impatiens balsamina.
* Floral meristems are generally determinate. Termination of their activity varies with species, occurring after carpel or ovule development, depending on the placentation type. In terminal flowering Impatiens balsamina (cv. Dwarf Bush Flowered) some flowers exhibit meristem indeterminacy; they produce organs from the placenta after ovule development. * Here we provide a detailed description of gynoecium development in this line and explore the basis of the indeterminate nature of some of its floral meristems. * We find that the placenta is sometimes established without complete carpel fusion. Proliferative growth derives from meristematic remnants of the placenta and is more common in the terminal inflorescence. RNA in situ hybridization reveals that IbLFY (Impatiens LFY homologue) is expressed in all meristem states, even in proliferating meristems. Expression of IbAG in axillary flowers is as expected in the meristem, stamens and carpels but absent from the proliferating meristem. * We conclude that I. balsamina has cauline placentation. Incomplete suppression of inflorescence identity in flowers of the terminal inflorescence leads to floral meristem proliferation after ovule development in this species.


The curse of relieving pain.
A 39-year-old woman with a history of chronic back pain due to spinal haemangiomas, multiple malignancies and depression was brought by Emergency medical servicesS to the emergency centre (EC) after being found unresponsive on the bathroom floor. The patient had an exacerbation of her back pain the previous day for which she admitted to taking double her usual dose of oxycodone, in addition to alprazolam, lorazepam, diphenhydramine and a glass of wine. She reported that she lost consciousness and was down for over 8 hours. In the EC, she complained of right forearm pain which was accompanied by mild diffuse soft-tissue swelling and decreased sensation in the right hand. Radial pulse was intact. Creatine kinase was found to be at 4663 U/L. The patient was found to have acute compartment syndrome and underwent emergent forearm fasciotomy. She eventually regained full function of the right arm.


The Firepower Sweep Test: A novel approach to cookstove laboratory testing.
Emissions from solid-fuel cookstoves have been linked to indoor and outdoor air pollution, climate forcing, and human disease. Although task-based laboratory protocols, such as the Water Boiling Test (WBT), overestimate the ability of improved stoves to lower emissions, WBT emissions data are commonly used to benchmark cookstove performance, estimate indoor and outdoor air pollution concentrations, estimate impacts of stove intervention projects, and select stoves for large-scale control trials. Multiple-firepower testing has been proposed as an alternative to the WBT and is the basis for a new standardized protocol (ISO 19867-1:2018); however, data are needed to assess the value of this approach. In this work, we (a) developed a Firepower Sweep Test [FST], (b) compared emissions from the FST, WBT, and in-home cooking, and (c) quantified the relationship between firepower and emissions using correlation analysis and linear model selection. Twenty-three stove-fuel combinations were evaluated. The FST reproduced the range of PM2.5 and CO emissions observed in the field, including high emissions events not typically observed under the WBT. Firepower was modestly correlated with emissions, although the relationship varied between stove-fuel combinations. Our results justify incorporating multiple-firepower testing into laboratory-based protocols but demonstrate that firepower alone cannot explain the observed variability in cookstove emissions.


Concomitant Crohn's Disease and Anti-Glutamic Acid Decarboxylase (GAD)-Associated Autoimmune Encephalitis: A Case Report.
Crohn's disease is an inflammatory, autoimmune disorder that predominantly affects the intestines but can also affect extraintestinal organs. Certain neurological conditions, such as autoimmune encephalitis, can develop along with this disease. In this case report, we present a case of anti-glutamic acid decarboxylase (GAD) antibody-associated autoimmune encephalitis that occurred shortly after the diagnosis of Crohn's disease and was unrelated to the treatment and nutritional deficiencies. After a significant weight loss (24 kg) and persistent diarrhea, the patient was diagnosed with Crohn's disease by colonoscopy and biopsy. Within two weeks after the diagnosis, he experienced altered consciousness and memory impairment, followed by a rapid deterioration in consciousness and respiratory distress, leading to intubation and admission to the intensive care unit. His brain MRI revealed asymmetrical diffuse cortical diffusion restrictions, hyperintense signals on fluid-attenuated inversion recovery (FLAIR) sequences, and diffuse pachymeningeal contrast enhancement involving both cingulate gyri, bilateral insular cortices, amygdalae, hippocampi, and the right precuneus. Analysis of cerebrospinal fluid (CSF) revealed a slight elevation of CSF proteins, and the patient tested positive for serum anti-GAD antibodies. The patient responded favorably to a seven-day course of intravenous methylprednisolone, five days of intravenous immunoglobulin (IVIG), and oral corticosteroids. Subsequent treatment consisted of monthly IVIG, azathioprine, and vedolizumab, resulting in no neurologic sequelae except mild amnesia. A follow-up MRI at three months showed a nearly complete disappearance of the lesions. This is the first reported case of anti-GAD-associated encephalitis occurring in the presence of Crohn's disease.


Effect of sodium molybdate on the interaction of androgens and progestins with binding proteins in human hyperplastic prostatic tissue.
A reliable measurement of steroid hormone receptors is essential for attempts to correlate receptor levels with response to endocrine therapy in prostatic carcinoma. Evidence that receptors in many tissues are stabilized by sodium molybdate prompted the examination of the effects of this salt on the measurement of steroid-binding sites in human prostatic tissue. The presence of molybdate (10 mmol/l) during tissue homogenization, cytosol or nuclear extract preparation and binding-site assay led to a threefold increase in the amount of high-affinity androgen binding detected in cytosol, and a slight increase in the number of cytosol progestin-binding sites. The apparent binding affinity for steroids was increased in both cases. No effect of molybdate was observed on androgen-binding sites in nuclear extracts.


Change in plasma volume from a state of hyper-, normo- or hypovolemia with or without noradrenalin infusion in the rat.
Fluid substitution is important in critically ill patients to maintain normovolemia, but there is always a risk that the treatment is too aggressive resulting in fluid overload, or is insufficient with maintenance of hypovolemia. The present study on the rat aims at evaluating the change in plasma volume after 2.5 h from a state of hyper- and hypovolemia. The analysis was made without and with noradrenalin infusion, based on the fact that noradrenalin infusion is a common drug to maintain an adequate arterial pressure, and noradrenalin may induce transcapillary filtration. Plasma volume was determined at baseline and at the end of the experiments with a (125)I-albumin tracer technique. Arterial and central venous pressure, and urine output were recorded. We showed that induction of hypervolemia with a 5% albumin solution (15 ml/kg) resulted in successive loss of plasma volume, which was aggravated with noradrenalin infusion. Hypovolemia induced by hemorrhage (15 ml/kg) resulted in transcapillary absorption, an absorption almost abolished during noradrenalin infusion. There was no plasma volume loss in the sham group. Urine output was higher under hypervolemia than under normovolemia, which in turn was higher than under hypovolemia. We conclude that hypervolemia induces plasma volume loss, which is aggravated by noradrenalin infusion. The compensatory absorption effect after hemorrhage is counteracted by noradrenalin. The results can be explained by differences in hydrostatic capillary pressure via alterations in arterial and venous pressure, according to the 2-pore theory of transcapillary fluid exchange.


The periphery of the avian retina: specializations of the layer of ganglion cells and their axons.
Ganglion cells and their axons were studied in the retinas of chicken, quails and pigeons. Retinal flat mounts were examined with light microscopy after cresyl violet or silver impregnation procedures. Silver-impregnated specimens were also examined with scanning electron microscopy. Significant differences were observed between ganglion cells of the central region and those lying along the temporal and nasal margins of the retina. These peripheral ganglion cells formed belt-like structures where groups of cell bodies were arranged in stripes. Their axons did not make a straight course and they reached the nerve head after an arciform path. Axon bundles and stripes of cells were similarly oriented. Consequently, axons originating in the same region of the retina did not necessarily arrive to the same point of the nerve head. Both the nasal and the temporal belts contained the largest neuronal bodies found in the retina. However, there were more cellular stripes in the temporal belt than along the nasal margin. In some birds, the belts developed after hatching.


Epidemiological study of antimicrobial-resistant bacteria in healthy free-ranging bantengs (Bos javanicus) and domestic cattle.
Antimicrobial-resistant microorganisms (ARMs) have been increasing among wild animals. Interactions occurring at the interface between wildlife, humans, and livestock can lead to the transmission of ARMs. Thus, the prevalence of ARMs in wild and domestic animals should be determined to address and prevent this issue. This study aimed to determine the resistance patterns of cefotaxime (CTX)-resistant Escherichia coli and identify the presence of extended-spectrum beta-lactamase (ESBL) genes in ESBL-producing E. coli among a population of wild banteng (Bos javanicus) and domestic cattle kept on farms located close to the Lam Pao non-hunting area, Kalasin province, Thailand. Forty-five fecal samples were taken from wild bantengs inhabiting the Lam Pao non-hunting area in Thailand, alongside 15 samples from domestic cattle. Bacterial culture, triple sugar iron, and motile indole lysine tests were conducted to identify E. coli. A polymerase chain reaction (PCR) was conducted for specific confirmation. MacConkey agar supplemented with 2 μg/mL of CTX was used to identify CTX-resistant E. coli, which would be used to identify ESBL production based on a double-disk synergy test. Extended-spectrum beta-lactamase-producing samples were subjected to disk diffusion tests to determine resistant patterns, and the sizes of PCR bands and DNA sequencing were used to differentiate ESBL gene types. All samples tested positive for E. coli. Forty-five isolates from 15 banteng samples and three isolates from one domestic cattle sample displayed CTX-resistant and ESBL-producing traits. The banteng and domestic cattle populations exhibited nine and three distinct resistant patterns, respectively. The PCR results indicated that the banteng isolates harbored the following genes: Cefotaxime-M1 (n = 38), CTX-M9 (n = 5), and the SHV group (n = 2). All three isolates from the domestic cattle sample contained the CTX-M1 gene. Classification of ESBL genes based on the DNA sequences of the banteng isolates showed the characteristics of CTX-M15 (n = 20), CTX-M55 (n = 6), CTX-M14 (n = 5), and CTX-M79 (n = 1). The three domestic cattle isolates exhibited the characteristics of CTX-M15, CTX-M55, and CTX-M79. Despite no previous antibiotic applications, approximately one-third of the banteng samples displayed CTX resistance, indicating ARM contamination within the ecosystem. The similarity in ESBL genes between the banteng and domestic cattle populations suggests potential gene transmissions between these animal groups. However, the initial source of ARMs remains unclear, as the banteng population exhibited more ESBL genes than the domestic cattle, suggesting the possibility of multiple ARM sources. These findings raise concerns because the banteng population inhabits an area that is an important source of freshwater and nourishes the entire north-east region of Thailand and other South-east Asian countries, including Laos, Cambodia, and Southern Vietnam.


[Continuous intraportal chemotherapy for prevention of metachronous hepatic metastasis in colorectal cancer].
Fifty-five colorectal cancer patients who had continuous intraportal chemotherapy between 1990 and 1993 (treated group) and 130 colorectal cancer patients who did not have portal chemotherapy between 1982 and 1993 (untreated group) were studied to clarify the effects of continuous intraportal chemotherapy on the prognosis. After a catheter was placed in the portal vein through the right gastroepiploic vein at the time of radical operation, 10 mg of MMC was continuously infused for 4 hours at operation and 500 mg/day of 5-FU was continuously infused for 7 days postoperatively. The toxicities of this therapy were not serious. The five-year survival rate was 65.3% in the treated group and 65.6% in the untreated group. The five-year disease-free survival rate was 69.8% in the treated group and 58.6% in the untreated group, with no significant difference. In stage II patients, however, the five-year disease-free survival rate in the treated group was slightly higher than in the untreated group (90.0% vs 70.3%, p = 0.073), and the rate of hepatic recurrence in the treated group was significantly lower than in the untreated group. These results suggest that continuous intraportal chemotherapy may prevent metachronous hepatic metastases in stage II colorectal cancer patients.


Tubulin Resists Degradation by Cereblon-Recruiting PROTACs.
Dysregulation of microtubules and tubulin homeostasis has been linked to developmental disorders, neurodegenerative diseases, and cancer. In general, both microtubule-stabilizing and destabilizing agents have been powerful tools for studies of microtubule cytoskeleton and as clinical agents in oncology. However, many cancers develop resistance to these agents, limiting their utility. We sought to address this by developing a different kind of agent: tubulin-targeted small molecule degraders. Degraders (also known as proteolysis-targeting chimeras (PROTACs)) are compounds that recruit endogenous E3 ligases to a target of interest, resulting in the target's degradation. We developed and examined several series of α- and β-tubulin degraders, based on microtubule-destabilizing agents. Our results indicate, that although previously reported covalent tubulin binders led to tubulin degradation, in our hands, cereblon-recruiting PROTACs were not efficient. In summary, while we consider tubulin degraders to be valuable tools for studying the biology of tubulin homeostasis, it remains to be seen whether the PROTAC strategy can be applied to this target of high clinical relevance.