Molecular cloning and characterization of a gene for rat U2 small nuclear RNA.
Six phage clones that contain sequences hybridizable with the small nuclear RNA U2 were isolated from a rat gene library. Of these clones, one which includes a candidate for a functional U2 RNA gene was selected and characterized. The sequence within the clone which hybridizes with rat U2 RNA was completely co-linear with that of the RNA. A T-A-T-A box was not found in the region of more than 400 base-pairs which lies upstream of the gene. However, several block homologies were found with the upstream sequences of a rat U1 RNA gene candidate cloned in our laboratory. An "identifier sequence", which was reported to be an element of gene regulation related to differentiation, was found downstream of the coding region at the same distance and with the same orientation as the identifier sequence located downstream of the U1 RNA gene candidate. We detected a presumed U2 RNA precursor elongated by about 11 nucleotides at the 3' end by S1 nuclease mapping using a fragment from the clone. A potential termination signal for transcription was found within the elongated region of the presumed precursor. Southern blot analysis suggests that families of U2 RNA genes that have conserved flanking sequences are present in the genomes of rat, mouse, man, calf and chicken.


Hydroxycamptothecin-loaded nanoparticles enhance target drug delivery and anticancer effect.
Hydroxycamptothecin (HCPT) has been shown to have activity against a broad spectrum of cancers. In order to enhance its tissue-specific delivery and anticancer activity, we prepared HCPT-loaded nanoparticles made from poly(ethylene glycol)-poly(gamma-benzyl-L-glutamate) (PEG-PBLG), and then studied their release characteristics, pharmacokinetic characteristics, and anticancer effects. PEG-PBLG nanoparticles incorporating HCPT were prepared by a dialysis method. Scanning electron microscopy (SEM) was used to observe the shape and diameter of the nanoparticles. The HCPT release characteristics in vitro were evaluated by ultraviolet spectrophotometry. A high-performance liquid chromatography (HPLC) detection method for determining HCPT in rabbit plasma was established. The pharmacokinetic parameters of HCPT/PEG-PBLG nanoparticles were compared with those of HCPT. The HCPT-loaded nanoparticles had a core-shell spherical structure, with a core diameter of 200 nm and a shell thickness of 30 nm. Drug-loading capacity and drug encapsulation were 7.5 and 56.8%, respectively. The HCPT release profile was biphasic, with an initial abrupt release, followed by sustained release. The terminal elimination half-lives (t 1/2 beta) of HCPT and HCPT-loaded nanoparticles were 4.5 and 10.1 h, respectively. Peak concentrations (Cmax) of HCPT and HCPT-loaded nanoparticles were 2627.8 and 1513.5 microg/L, respectively. The apparent volumes of distribution of the HCPT and HCPT-loaded nanoparticles were 7.3 and 20.0 L, respectively. Compared with a blank control group, Lovo cell xenografts or Tca8113 cell xenografts in HCPT or HCPT-loaded nanoparticle treated groups grew more slowly and the tumor doubling times were increased. The tumor inhibition effect in the HCPT-loaded nanosphere-treated group was significantly higher than that of the HCPT-treated group (p < 0.01). Tumor inhibition in the control group by PEG-PBLG nanoparticles was not observed (p > 0.05). Compared to the HCPT- and control-treated groups, the HCPT-loaded nanoparticle-treated group showed a more sustained release, a longer circulation time, increased delivery to tissue, and an enhanced anticancer effect. HCPT-loaded nanoparticles appear to change the pharmacokinetic behavior of HCPT in vivo.


Demonstrating analytical similarity of a biosimilar HLX04 to bevacizumab with a panel of state-of-the-art methods and tiering of quality attributes.
Therapeutical monoclonal antibodies are structurally and functionally complex, whereas the innovator's manufacturing processes are proprietary. With respect to the similarity assessment, a proposed biosimilar product needs to demonstrate a side-by-side comparison between the reference product (RP) and candidate product in terms of physicochemical properties and biological activities, as well as nonclinical and clinical outcomes. Here, a comprehensive analytical similarity assessment was performed for in-depth comparison of HLX04, China-sourced Avastin® (CN-Avastin®), and Europe-sourced Avastin® (EU-Avastin®) following a tier-based quality attribute (QA) evaluation. A series of orthogonal and state-of-the-art analytical techniques were developed for the assessment. Ten lots of HLX04 were compared with 29 lots bevacizumab RP. Referred to the characterization results, HLX04 is highly similar to the RPs with respect to physicochemical properties and biological functions. In addition, HLX04 was found with similar stability and degradation behaviors upon multiple stressed conditions to bevacizumab. Minor differences were observed in glycosylation, aggregates, FcγRIIIa(F), and FcγRIIIa(V) binding activities; nevertheless, they were evaluated and demonstrated not to impact clinical outcomes. According to the reported clinical results, the totality of evidence, including the pharmacokinetic, efficacy, safety, and immunogenicity, further shows that HLX04 is similar to CN-/EU-Avastin®.


Pilocytic astrocytomas.
Pilocytic astrocytoma (PA) is the most common pediatric brain tumor in children. PAs are a distinct histologic and biologic subset of glioma that have a slow growth rate and may even spontaneously regress. These tumors tend to arise in the cerebellum and chiasmatic/hypothalamic region, but can also occur in other regions of the central nervous system. Dissemination is uncommon, but may occur in newly diagnosed PAs. Alterations in the Ras/RAF/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway (Ras/ERK) have been discovered in a majority of PAs, with KIAA1549-BRAF fusions being the most commonly identified alteration. Children with neurofibromatosis 1 are predisposed to developing PAs, primarily within the optic pathway. When required, treatment consists of surgery, chemotherapy, and/or radiation, although new molecular agents targeting the Ras/ERK and related signaling pathways are promising new approaches. The 10-year survival rates are greater than 90% in pediatric patients; however, they are poorer in adults. Tumors that are amenable to complete resection (i.e., cerebellum and cortex) have the best overall survival.


Mitochondrially targeted tamoxifen alleviates markers of obesity and type 2 diabetes mellitus in mice.
Type 2 diabetes mellitus represents a major health problem with increasing prevalence worldwide. Limited efficacy of current therapies has prompted a search for novel therapeutic options. Here we show that treatment of pre-diabetic mice with mitochondrially targeted tamoxifen, a potential anti-cancer agent with senolytic activity, improves glucose tolerance and reduces body weight with most pronounced reduction of visceral adipose tissue due to reduced food intake, suppressed adipogenesis and elimination of senescent cells. Glucose-lowering effect of mitochondrially targeted tamoxifen is linked to improvement of type 2 diabetes mellitus-related hormones profile and is accompanied by reduced lipid accumulation in liver. Lower senescent cell burden in various tissues, as well as its inhibitory effect on pre-adipocyte differentiation, results in lower level of circulating inflammatory mediators that typically enhance metabolic dysfunction. Targeting senescence with mitochodrially targeted tamoxifen thus represents an approach to the treatment of type 2 diabetes mellitus and its related comorbidities, promising a complex impact on senescence-related pathologies in aging population of patients with type 2 diabetes mellitus with potential translation into the clinic.


Prior event uncertainty reduction under two different levels of time uncertainty of foreperiod duration in schizophrenia.
Schizophrenic and alcoholic Ss judged stimulus durations of .50 and .55 seconds. Stimulus was 1, 3 or 5 dark dots and was preceded by variable foreperiod duration of 1, 3 or 5 seconds. Judgment of stimulus duration was found to be a monotonically increasing function of both foreperiod duration and numerosity of dots. When pitch of sound, which functioned as a warning signal, was correlated with numerosity of dots, the monotonic relation between numerosity of dots and estimation of stimulus duration was eliminated for alcoholics, but not for schizophrenics, only when foreperiod duration was constant from trial to trial. The effect of prior information as to numerosity of dots was negligible for both schizophrenics and alcoholics when foreperiod duration was variable from trial to trial.


Mycobacterium tuberculosis protease Rv3090 is associated with late cell apoptosis and participates in organ injuries and mycobacterial dissemination in mice.
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb). Mtb can overcome macrophage intracellular killing and lead to persistent infections. The proteases of Mtb are critical virulence factors that participate in immune responses. We determined that Rv3090 is a cell wall-associated protease and a potential pathogenic factor. To characterize the role of Rv3090 in Mtb, recombinant Msg_Rv3090 and Msg_pAIN strains were constructed to infect macrophages and mice. Lactate dehydrogenase assays and flow cytometry results showed that Rv3090 induces late macrophage apoptosis. In vivo infection experiments indicated that Rv3090 could induce hepatocyte and lung cell apoptosis and cause pathological damage to the spleen, livers and lungs. Msg_Rv3090 specifically stimulated the secretion of inflammatory cytokines including TNF-α, IL-6 and IL-1β. Overexpression of Rv3090 significantly promoted the survival of Msg in livers and lungs. Thus, Rv3090 protease triggered late cell apoptosis and contributed to the pathogenicity and dissemination of Mtb.


13-Oxyingenol dodecanoate, a cytotoxic ingenol derivative, induces mitochondrial apoptosis and caspase-dependent Akt decrease in K562 cells.
13-Oxyingenol dodecanoate (13OD) is an ingenol derivative prepared from Chinese traditional medicine Euphorbia kansui without any report about its bioactivity. The present study demonstrated for the first time that 13OD displayed potent cytotoxicity against chronic myeloid leukemia K562 cells in vitro. 13OD inhibited proliferation, induced G2/M phase arrest, and exhibited potent apoptotic activity in K562 cells. In K562 cells, 13OD disrupted the mitochondrial membrane potential and induced high level of ROS, which played an indispensable role in 13OD-induced apoptosis. Further investigations on the molecular mechanisms revealed that total Akt protein level was decreased in a caspase-dependent way after treatment with 13OD; in addition, ERK was activated by 13OD, and this activation played a protective role in 13OD stimulation. Altogether, these results revealed that the cytotoxic ingenol derivative 13OD induced apoptosis with novel mechanisms for the proapoptotic function in cancer cells, and suggested that 13OD may serve as a lead template for rational drug design and for future anticancer agent development.


The importance of size and growth in infancy: integrated findings from systematic reviews of scientific evidence and lay perspectives.
Associations between growth and size during infancy and adult disease have led some to recommend that interventions in infancy might benefit lifelong health. Any such recommendations should be informed by both the scientific evidence for relationships between infancy and later outcomes and the views and opinions of those who care for babies. Separate, but interlinked, systematic reviews were conducted of the epidemiological evidence relating infant size or growth to later health and of lay perspectives on infant size and growth. Findings were compared and integrated to consider policy implications. Lay and scientific perspectives both cast infant growth and size as an indicator of other aspects of an infant's life, rather than being of fundamental importance. While the scientific literature is most often concerned with infants at the extreme ends of the population distribution, and towards long-term outcomes, the literature on lay perspectives suggests a focus on defining the 'normal' range, and on current health. Differences and similarities between scientific and lay perspectives on health can highlight areas of agreement, as well as areas of potential misunderstanding or miscommunication.


Charge transfer between tryptophan and tyrosine in casein: a pulse radiolysis study.
Charge transfer from tyrosine to tryptophan radicals in bovine milk casein, as observed using pulse radiolysis technique, is reported. The reactions of casein with hydroxyl, azide, Br(2)(*-) and CCl(3)O(2)(*) radicals have also been studied. Radical transformation was found to take place at a rate of 1.5 x10(4) s(-1). The effect of pH, oxidising radical and the proximity of tyrosine and tryptophan on this radical transformation, as well as repair of the casein radical by ascorbate, have also been studied.


Influencing factors of sense of responsibility among undergraduate nursing students: A cross-sectional study.
Nursing students are critical in responding to public health emergencies like the COVID-19 pandemic. Their ability to fulfill their responsibilities is influenced by their sense of responsibility, which holds profound cultural significance, particularly in traditional Chinese culture. However, limited research has specifically explored the sense of responsibility among undergraduate nursing students in China and globally. This study aimed to determine the sense of responsibility among undergraduate nursing students and identify potential factors associated with it. We conducted a cross-sectional study and recruited 526 nursing students from June to July 2022 in Guizhou province in southwest China. Participants completed the General Information Questionnaire, Sense of Responsibility, and Self-esteem Scale. We analyzed the relationship between a sense of responsibility and self-esteem using Spearman correlation analysis. Then we determined factors that affect undergraduate nursing students' sense of responsibility using multiple linear stepwise regression. Nursing students' total sense of responsibility scores were 96(84,106). The study found a positive association between self-esteem and a sense of responsibility (r = 0.433, P < 0.001) and its four dimensions: altruism (r = 0.381, P < 0.001), self-control (r = 0.378, P < 0.001), courage (r = 0.300, p < 0.001), and commitment (r = 0.361, P < 0.001). Self-esteem (β = 1.532, p < 0.001), personality (extroverted personality β = 7.263, P < 0.001; neutral personality β = 3.221, P = 0.029), and social practice experience (β = -3.156, P = 0.010) significantly influenced undergraduate nursing students' sense of responsibility (R2 = 0.268, F = 17.065, P < 0.001). The study highlights the importance of nursing students' sense of responsibility and suggests room for improvement in its level. Higher self-esteem was associated with a stronger sense of responsibility. Additionally, self-esteem, personality, and social practice experience emerged as significant influencing factors. Nursing educators should prioritize students' sense of responsibility and explore targeted interventions, such as social practice activities, particularly for students with low self-esteem and introversion.


Clinical evaluation of the efficacy of a new bone cement-injectable cannulated pedicle screw in the treatment of spondylolysis-type lumbar spondylolisthesis with osteoporosis: a retrospective study.
To investigate the clinical efficacy and safety of a bone cement-injectable cannulated pedicle screw (CICPS) in the treatment of spondylolysis-type lumbar spondylolisthesis with osteoporosis. A retrospective study was conducted on 37 patients (Dual-energy X-ray bone density detection showed different degrees of osteoporosis) with spondylolysis-type lumbar spondylolisthesis who underwent lumbar spondylolisthesis reduction and fusion using a new type of injectable bone cement screw from May 2011 to March 2015. Postoperative clinical efficacy was evaluated by the Visual Analogue Scale (VAS) scores and the Oswestry Disability Index (ODI). Imaging indexes were used to evaluate the stability of internal fixation of the devices 1, 3, 6, and 12 months after surgery and annually thereafter. The safety of the CICPS was assessed by the prevalence of intraoperative and postoperative complications. A total of 124 CICPS were implanted intraoperatively. Bone cement leakage occurred in 3 screws (2.42%), and no clinical discomfort was found in any patients. All 37 patients were followed up with an average follow-up time of 26.6 ± 13.4 months (12-58 months). In the evaluation of the clinical effects of the operation, the average postoperative VAS score of the patients decreased from 4.30 ± 1.58 before surgery to 0.30 ± 0.70 after surgery (P < 0.001), and the ODI decreased from 47.27% ± 16.97% before surgery to 3.36% ± 5.70% after surgery (P < 0.001). No screw was loose, broken or pulled out. CICPS is safe and effective in the treatment of spondylolysis-type lumbar spondylolisthesis complicated by osteoporosis.


In vitro regeneration and its histological characteristics of Dioscorea nipponica Makino.
Dioscorea nipponica Makino is an optimal candidate to develop the diosgenin industry in North China. Due to its increasing demand in the medicine industry, it is urgent to apply new biotechnological tools to foster breeds with desirable traits and enhanced secondary metabolite production. The production of useful metabolites by the in vitro cultured rhizomes can be explored successfully for utilization by various food and drug industries. In this study, we reported callus formation and plantlet regeneration of the medicinal plant D. nipponica. Explants of leaves, stem segments and rhizomes of aseptic seedlings were cultured on Murashige and Skoog (MS) medium containing various combinations of auxin and cytokinin to find the optimal PGRs of each type of explant for callus induction and shoot regeneration of D. nipponica. The paraffin section technique was also used to observe of the morphogenesis of callus and adventitious bud. Explants of seeds and rhizomes formed calli at high frequency in all lines we examined. However, the explant of leaves rarely formed callus. Three kinds of callus were detected during the induction phase. Here, we describe three types of callus (Callus I-III) with different structure characteristics. Greenish in color and a nodule-like protrusion surface (Callus type III) were arranged more closely of cells with less interstitial substance, cell differentiation ability stronger than other callus types. The optimum combination was the maximum shoot differentiation frequency of 90% in callus derived from seeds cultured on MS medium with 2.0 mg L-16-BA + 0.2 mg L-1NAA. The shoot differentiation frequency (88.57%) of rhizome-induced callus was obtained by the combination of MS medium supplemented with 3.0 mg L-16-BA + 2.0 mg L-1NAA. 1/2 MS medium plus 0.5 mg L-1NAA resulted in a higher root regeneration frequency of 86.70%. In vitro propagated plantlets with healthy roots were domesticated and transplanted into small plastic pots containing sterile soil rite under greenhouse conditions with 80% survivability. Bud differentiation is mostly of exogenous origin, mostly occurring on the near callus surface. Therefore, it may be surmised that in vitro morphogenesis of D. nipponica is mainly caused by indirect organogenesis (adventitious bud).


The global burden of urinary bladder cancer: an update.
Bladder cancer is among the top ten most common cancer types in the world, with approximately 550,000 new cases annually. The highest burden of bladder cancer is currently falling on most developed communities across the globe. But with an anticipated shift in world demographics with growing and aging populations mainly on the African continent, and important shifts in exposure to different risk factors across the world, this is likely to change over the next decades. In this review, we provide an overview of the current incidence, mortality, prevalence, survival, risk factors and costs of bladder cancer worldwide.


Acenocoumarol therapy in pediatric patients.
To determine guidelines for administering and monitoring acenocoumarol therapy in children, 93 patients (median 5.1 years, range: 0.2-18 years) were prospectively evaluated over a 33-month period. The loading doses used were: <1 year, 0.20 mg x kg-1; >1-5 years, 0.09 mg x kg-1; 6-10 years, 0.07 mg x kg-1; 11-18 years, 0.06 mg x kg-1. In this study, the loading dose and the dose to achieve and maintain target therapeutic range (TTR) for acenocoumarol are age-dependent, with infants having the highest and teenagers having the lowest requirements. The use of a different loading dose according to age has allowed most of the children (80%) in all the age groups to achieve TTR in less than 1 week. No patients had serious bleeding or thrombotic complications. We conclude that there is an age-dependent response to acenocoumarol in pediatric patients. The implementation of an age-adjusted loading dose regimen reduces the length of hospitalization required to achieve effective anticoagulant therapy.


Non-typeable Haemophilus influenzae Osteomyelitis and Discitis of the Cervical Vertebrae in an Elderly Adult: A Case Report and Literature Review.
While Haemophilus influenzae type B (Hib) is well described in the literature to cause osteomyelitis, non-typeable H. influenzae has not. In areas where vaccination is routine, the prevalence of Hib has declined, whereas, in contrast, the prevalence of non-typeable H. influenza has increased. Generally, the non-typeable strains are less invasive but can access the vascular system by transmural migration through epithelial tight junctions or by an independent intercellular mechanism. Herein, we described a case of a 79-year-old man with the first case of non-typeable H. influenzae causing cervical osteomyelitis with associated bacteremia in an elderly adult.


Pre-pregnancy BMI is associated with offspring body composition in adulthood before adiposity-related disorders: a retrospective cohort.
To investigate the association between maternal pre-pregnancy BMI and offspring body composition in adulthood. Retrospective cohort. Undergraduates of nutrition or nutritionists were recruited at the baseline of the Nutritionists' Health Study between 2014 and 2017. Maternal pre-pregnancy BMI and current life aspects were self-reported through online questionnaires. Three body compartments were dual-energy x-ray absorptiometry-determined. The following variables were obtained: body fat (%), fat mass index (FMI) (kg/m2), android-to-gynoid fat ratio, visceral adipose tissue (VAT) (cm3), appendicular skeletal muscle mass index (ASMI) (kg/m2), total bone and femur mineral content (g) and density (g/cm2). Linear regression adjusted according to directed acyclic graphs recommendation was performed. São Paulo, Brazil. Healthy non-pregnant women (aged 20-45 years) (n 150). Median age and BMI were 22 years (IQR = 20, 29) and 22·3 kg/m2 (IQR = 20·4, 25·3), respectively. Pre-pregnancy BMI ≥ 25 kg/m2 was reported by 14·7 % of mothers. In fully adjusted models, maternal pre-pregnancy BMI was associated with their daughters' body fat % (β = 0·31; 95 % CI 0·0004, 0·63), FMI (β = 0·17; 95 % CI 0·03, 0·30), android-to-gynoid ratio (β = 0·01; 95 % CI 0·004, 0·02) and VAT (β = 0·09; 95 % CI 0·02, 0·16), but not with total bone density (β = 0·001; 95 % CI -0·003, 0·006) and content (β = 7·13; 95 % CI -4·19, 18·46). Direct association with ASMI was also detected, but lost statistical significance when participants whose mothers were underweight were excluded. Maternal pre-pregnancy BMI was directly associated with offspring general and visceral adiposity but seems not to be associated with bone mass. Results reinforce importance of avoiding excess of maternal adiposity, as an attempt to break the vicious cycle of obesity transmission.


Quantitative determination of domperidone in rat plasma by high-performance liquid chromatography with fluorescence detection.
A sensitive and selective analytical method for the determination of domperidone in rat plasma is described. The procedure involves liquid-liquid extraction followed by reversed-phase high-performance chromatographic analysis with fluorometric detection at 282 nm for excitation and 328 nm for emission. The detection limit was 1 ng ml(-1) using 1 ml of plasma. This assay procedure should be useful for the pharmacokinetic study of domperidone in small animals such as rats.


CRF-containing neurons of the rat hypothalamus.
The immunoreactive CRF-neurons of the rat hypothalamus have been examined immunohistochemically employing anti-rat CRF serum. These neurons are confined to the paraventricular nucleus, dorsomedial-lateral hypothalamic area, and suprachiasmatic nucleus, and are, respectively, also immunoreactive to anti-Met-enk, -alpha-MSH, and -VIP sera. Intraventricular administration of colchicine (50 micrograms/5 microliters/rat) induces a dramatic enhancement of the immunostainability of the cell somata, and also accelerates the development of immunoreactivity of other stored peptides, especially in the paraventricular nucleus. The CRF-neurons respond to adrenalectomy by showing increased immunoreactivity and an increase in the number of cell bodies; in the dorsomedial-lateral area and suprachiasmatic nucleus, there is also an enhanced immunoreactivity for alpha-MSH and VIP, respectively. CRF-cells in the paraventricular nucleus become markedly hypertrophied, but do not show any enhanced immunoreactivity for Met-enk. Since the axons of the paraventricular neurons run to the median eminence, it is probable that they are involved with the endocrine control of hypophysial ACTH release. It is concluded that the CRF-containing neurons in rat hypothalamus consist of three types which are functionally and morphologically different.


Synthesis and acetylcholinesterase inhibitory activity of (+/-)-14-fluorohuperzine A.
The synthesis of (+/-)-14-Fluorohuperzine A has been accomplished and the ability of this agent to inhibit acetylcholinesterase has been measured. Taking into account its racemic form, this compound exhibits 62 times less potent activity than natural (-)-huperzine A.


A new model for chronic in vivo analysis of the periosteal microcirculation.
Microvascular perfusion is indispensable for the growth and remodulation of membrane bone. Trauma, inflammation and surgical interventions may alter periosteal perfusion. However, there is not much known about periosteal perfusion in membrane bones. Therefore, the aim of this study was to establish a new chronic model that permits the repeated in vivo analysis of the microcirculation of periosteum. A circular skin island with a diameter of 6 mm was excised at the forehead of six Lewis rats. Then a newly developed chamber was implanted, containing a coverglass to protect the periosteum. Intravital microscopy (IVM) enables a quantitative analysis of periosteal microcirculation immediately as well as 3, 5 and 10 days after chamber implantation. At the end of the experiment the calvaria and periosteum were removed for histological examination. Six unoperated Lewis rats served as histological controls. The periosteal microcirculation remained stable over 10 days. The implantation of the chamber did not result in any substantial inflammatory response. The functional microvascular density was 131.2+/-19.3 cm/cm(2). The histological examinations revealed a regular anatomical structure of periosteum and bone including an intact interface. The presented model allows for the first time to conduct a repetitive, quantitative in vivo analysis of the periosteal microcirculation in membrane bone. Future studies may thus evaluate novel strategies to influence the periosteal perfusion.


Neuroendocrine basis of thermally regulated maternal responses to young in the rat.
Over the first two weeks postpartum there is a decline in the amount of time that the rat dam spends with her young, resulting from a decrease in the duration of each nest bout. The duration of each nest bout is limited by the rate of rise of maternal temperature when she huddles with her litter. This pattern of mother-young contact is dependent on the dam's hormonal status, because adrenalectomised dams fail to show the expected decline in mother-young contact over time. Ovariectomy, on the other hand, does not have any effect on this behavior. Replacement therapy with glucocorticoids or placing the dam in a warm (25 degrees C) ambience reinstates the normal pattern of mother-litter contact in adrenalectomised-ovariectomised dams. These data suggest that the elevated level of serum glucocorticoids in lactating dams affects maternal behavior by increasing maternal heat load, thereby making the dam vulnerable to an acute rise in temperature when huddling with her young. Prolactin suppression also results in an increase in contact time between mother and young, but only in the second week postpartum. The effects of prolactin suppression are reversed by progesterone replacement or placing prolactin-suppressed females in a warm ambience. However, progesterone is ineffective in restoring the normal pattern of mother-litter contact in adrenalectomised females. These findings suggest that progesterone raises the thermal set point, thereby permitting the thermogenic effects of glucocorticoids to occur.


Psychological confounds in medical research: the example of excessive cough in asthma.
This experiment tested the hypothesis that the setting in which research is conducted may dominate symptom magnitude. Cough was induced with inhaled citric acid and its magnitude was influenced by changing the setting in 30 adolescents with asthma. Cough thresholds for citric acid were determined. The participants were assigned to a condition emphasising asthma, or a control condition, described as estimation of lemon flavors. All participants inhaled (in different order) thresholds for citric acid, 50% of these thresholds, or placebo. Results showed that both cough frequency and subjective 'cough tendency' were significantly higher in the asthma condition. State anxiety was higher in the asthma condition, but correlated only moderately with cough. Lung function, severity of asthma, trait anxiety, age or sex did not correlate with cough. It was concluded that patients with asthma cough more often in a situation which they have learned to associate with asthma.


Changes in mammary function at the onset of lactation in the goat: correlation with hormonal changes.
1. Changes in mammary function and plasma hormone concentrations during late pregnancy and the onset of lactation have been studied in conscious goats.2. Mammary blood flow, oxygen consumption and glucose uptake increased markedly and significantly between 2 days and 0.5-1 day pre-partum.3. The increase in mammary glucose uptake was relatively greater than that of oxygen consumption or blood flow.4. The concentration of citrate in mammary secretion increased; the first significant change was apparent 0.5-1 day pre-partum but the main rise occurred after this time.5. It is concluded that the marked increase in mammary glucose uptake 0.5-1 day before parturition indicates the time of onset of copious milk secretion.6. The first significant increase in the concentration of unconjugated oestrogens in arterial plasma occurred 3 days pre-partum, whereas the first significant decrease in progesterone and increase in 13,14-dihydro-15-oxoprostaglandin F(2alpha) occurred 0.5-1 day pre-partum, thus coinciding with the mammary changes; there was also a peak in prolactin concentrations at the latter time.7. The hormonal changes are discussed in relation to current concepts of the initiation of parturition and the onset of copious milk secretion in this species. It is suggested that the fall in plasma progesterone concentrations triggers milk secretion at high rates.


[Treatment of cancer of the breast with Patey's modified radical mastectomy].
Patey's operation was used to treat breast cancer in 658 cases between 1956 and 1976 at the Bologna University Surgical Clinic. Follow-up in 562 cases revealed 5-yr and 10-yr survival rates substantially similar to those obtained by Halsted and others. It is felt that the type of operation used is of relative importance for survival, since breast cancer is dependent on other factors that require careful appraisal in each case.


Household Social Needs, Emotional Functioning, and Stress in Low-Income Latinx Children and their Mothers.
Latinx families may be particularly vulnerable to emotional dysfunction, due to higher rates of economic hardship and complex social influences in this population. Little is known about the impact of environmental stressors such as unmet social needs and maternal stress on the emotional health of Latinx children from low-income families. We conducted secondary analyses using survey and biomarker data from 432 Latinx children and mothers collected in a separate study. We used binomial and multinomial logistic regression to test if household social needs, or maternal perceived stress or hair cortisol concentration (HCC), predicted child measures of emotional functioning or child HCC, independent of relevant sociodemographic factors. Approximately 40% of children in the sample had symptoms consistent with emotional dysfunction, and over 37% of households reported five or more social needs. High perceived maternal stress predicted higher odds of child emotional dysfunction (OR = 2.15; 95% CI [1.14, 4.04]; p = 0.01), and high maternal HCC was positively associated with high child HCC (OR = 10.60; 95% CI [4.20, 26.74]; p < 0.01). Most individual household social needs, as well as the level of household social need, were not independently associated with child emotional dysfunction or child HCC. Our findings begin to define a framework for understanding emotional health, stress, and resilience when caring for Latinx children and mothers living with high levels of social need, and the need for integrated mental health and social needs screening and interventions in settings that serve this population.


The integrated luteal progesterone: an assessment of luteal function.
An integrated luteal progesterone (ILPL) was calculated on the basis of a luteal progesterone (P) level with the assumption that the daily plasma P level in the luteal phase closely approximates a sine curve. The midluteal P-amplitude (K) was also obtained mathematically. Daily luteal P levels from five normal ovulatory cycles were assessed for the biologic variation of ILPL and K, then compiled to construct a normogram of the ILP during the luteal phase. The coefficient of variation of K and total ILPL in each cycle ranged from 9.7% to 24.3% and 3.5% to 13.2%, respectively. Fifty-two infertility patients were evaluated for their luteal function by the luteal P and estradiol (E2) level, K, ILPL, endometrial biopsy (EBX)-lag-day, as well as the lengths of follicular phase, luteal phase (L#), and cycle. Thirty-nine patients had EBX-lag day less than or equal to 2 days and were designated as infertile-normal (INF-NL) luteal phase, while the remaining 13 patients who had EBX-lag day greater than 2 days were considered as luteal phase defect (LPD). Significant (P less than 0.05) differences were observed between INF-NL and LPD in: luteal length (13.2 +/- 0.31 versus 11.0 +/- 0.58 days, respectively), and total ILPL (170 +/- 8.3 versus 113 +/- 8.5 ng/ml-day, respectively). No differences were seen in luteal P, E2 and K levels, nor in follicular and cycle length. Significant (P less than 0.05) correlations were observed between total ILPL and luteal P, E2, L#, and K; while a negative correlation was noted between follicular and luteal length.(ABSTRACT TRUNCATED AT 250 WORDS)


Polymorphism of the ADIPOQ gene and its association with productive traits in Awassi Ewes.
Adiponectin (ADIPOQ) plays a critical role in energy and lipid metabolism, indicating that adiponectin could affect livestock productivity. There is an association between polymorphisms in the ADIPOQ gene and variations in livestock productive traits. Therefore, this study investigated the relationship between ADIPOQ polymorphism and productive traits in Awassi ewes. This study included 200 sexually mature ewes, aged 2.5 to 5 years, non-pregnant and not lactating. A phenotypic measurement consisting of live weight and body dimensions, was taken. Samples of blood were taken for extraction of genomic DNA and PCR-SSCP based genotyping, followed by sequencing to confirm variants in amplified fragments. A novel c.198,473,337 C > A SNP was found in exon 1 of the ADIPOQ gene confirming heterogeneity with genotypes AA, CC, and CA. The AA genotype differed significantly (P < 0.05) by comparison with the CA and CC genotypes concerning live body weight and body measurements. An association between productive traits and the c.198,473,337 C > A SNP revealed a significant association of the A allele (odds ratio: 2.22 (95% CI: 0.94-5.30) in the additive genetic model. Sheep with the AA genotype were heavier and had larger body dimensions, implying superior production and reproduction. Further studies are required in other breeds to prove the results.


Amantadine stimulates sexual behavior in male rats.
The effects of amantadine on sexual behavior, penile erection, and seminal emission of male rats was studied. Amantadine significantly decreased latency of mounts in all doses (1.25 to 50 mg/kg), and decreased the number of mounts and intromission latency at the highest doses used. The lowest dose of amantadine significantly increased ejaculation latency and intromission frequency, while higher doses significantly reduced it, which indicates a biphasic response of the drug. Additionally, seminal emission, erections, and genital grooming were significantly induced by amantadine. Amantadine-induced seminal emissions were impaired by spinal cord transection, which suggests the involvement of supraspinal structures in the drug action. Haloperidol and atropine sulphate significantly reduced seminal emissions and penile erections induced by amantadine. These results demonstrate that amantadine stimulates sexual behavior and genital reflexes in male rats and suggest a facilitatory effect of the drug that probably involves different mechanisms of action.


Escin exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vivo and in vitro.
Escin, a natural mixture of triterpenoid saponins isolated from the seed of the horse chestnut (Aesculus hippocastanum), had been demonstrated to possess anti-edematous and anti-inflammatory effects. The present study was designed to investigate whether escin exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. The carrageenan-induced paw edema and pleuritis in bilaterally adrenalectomized rats were used to investigate the anti-inflammatory effects of escin and glucocorticoid alone or combined. The carrageenan-induced paw edema was inhibited only when escin and corticosterone (Cort) were administered together. Co-administration of escin with Cort significantly reduced the volume of exudates and the number of white blood cells of exudates in bilaterally adrenalectomized rats with pleuritis, but treatment with escin or Cort alone at a suboptimal concentration did not show any effect on the pleuritis rats. After the murine macrophagic RAW264.7 cells stimulated by lipopolysaccharide (LPS), they were treated with escin, Cort or escin and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) of cell culture supernatants were analyzed. Escin or Cort markedly reduced the content of NO, TNF-α and IL-1β secreted by LPS-stimulated RAW264.7 macrophage cells. The combination of suboptimal concentrations of escin with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO, TNF-α and IL-1β in LPS-stimulated RAW264.7 macrophage cells. The findings suggest escin can synergize with glucocorticoids to enhance their anti-inflammatory effect.


Patient advocacy in the perioperative setting.
A descriptive study was undertaken to define patient advocacy and perioperative nurses' role as advocates and to investigate perioperative nurses' perceptions of behaviors that represent advocacy in the perioperative setting. A purposive sample of 163 perioperative RNs from upstate New York was invited to participate in the study. A total of 57 responses were returned, and 33 individuals participated in audiotaped interviews. The four overarching themes that emerged from the interviews include protection, communication/giving voice, doing, and comfort and caring. These interrelated, overlapping themes represent nurses' definition, role, and experiences of patient advocacy in the perioperative setting.


Dietary restriction initiated in late adulthood can reverse age-related alterations of protein and protein metabolism.
Many reports have been published on the effects of lifelong dietary restriction (DR) on a variety of parameters such as life span, carcinogenesis, immunosenescence, memory function, and oxidative stress. There is, however, limited available information on the effect of late onset DR that might have potential application to intervene in human aging. We have investigated the effect of DR initiated late in life on protein and protein degradation. Two months of DR in 23.5-month-old mice significantly reduced heat-labile altered proteins in the liver, kidney, and brain. DR reversed the age-associated increase in the half-life of proteins, suggesting that the dwelling time of the proteins is reduced in DR animals. In accordance with this observation, the activity of proteasome, which is suggested to be responsible for degradation of altered proteins, was found increased in the liver of rats 30 months of age subjected to 3.5 months of DR. Thus, DR can increase turnover of proteins, thereby possibly attenuating potentially harmful consequences by altered proteins. Likewise, DR in old rats reduced carbonylated proteins in liver mitochondria, although the effect was not observed in cytosolic proteins. Fasting induced apoA-IV synthesis in the liver of young mice for efficient mobilization of stored tissue fats, while it occurred only marginally in the old. DR for 2 months from 23 months of age partially restored inducibility of this protein, suggesting the beneficial effect of DR. Taking all these findings together, it is conceivable that DR conducted in old age can be beneficial not only to retard age-related functional decline but also to restore functional activity in young rodents. Interestingly, recent evidence that involves DNA array gene expression analysis supports the findings on the age-related decrease in protein turnover and its reversion by late-onset DR.


Taste buds in vallate papillae grafted to the anterior chamber of the eye.
Vallate papillae from rats were grafted to the anterior chamber of the eye of the same animal. Longterm grafts showed small taste buds located in epitelial cavities which were probably the remnants of trench walls. These grafts have been reinnervated by local nerves. Excretory ducts and serous acini of Von Ebner's glands were also present. The latter showed secretory granules in their cells. The specificity of the nerve fibers and of the epithelium in relation to the induction of taste bud differentiation are discussed.


Effect of glyburide on hepatic glucose metabolism.
Glyburide, along with the other second-generation oral hypoglycemic agent glipizide, has been used as adjunctive therapy for the treatment of non-insulin-dependent diabetes mellitus. After glyburide therapy, basal glycemia and glucose response to a meal are greatly improved. The mechanism for the glucose-lowering effect of the drug remains controversial. Glyburide is generally thought to exert two major actions: stimulation of pancreatic insulin secretion and enhancement of insulin action in hepatic and extrahepatic tissues. Studies in patients with non-insulin-dependent diabetes mellitus indicate that the action of glyburide on the liver plays a central role in decreasing glucose. With short-term therapy, glyburide decreases hepatic glucose production by elevating pancreatic insulin secretion. However, this increase in pancreatic insulin secretion is not sustained as therapy is continued, suggesting that glyburide then acts directly on the liver. The mechanism for the improvement in hepatic glucose metabolism after long-term treatment is not known. In vitro, glyburide has been shown to inhibit gluconeogenesis as well as glycogenolysis and to enhance hepatic glucose uptake, thus providing possible explanations for the action of the drug on the liver.


Transportation can cancel out the ecological advantages of producing organic cacao: The carbon footprint of the globalized agrifood system of ecuadorian chocolate.
Under the hypothesis that organically managed cacao agroforestry systems report a lower global warming potential (GWP) and reduce other environmental pressure indicators compared with conventionally managed systems and monocultures, this work discusses how global transportation can cut back the ecological advantage of the production phase. For this purpose, the life cycle assessment (LCA) of 1 kg of dark chocolate manufactured with Ecuadorian cacao has been performed (cradle-to-retailer approach), including the indirect impacts of transportation and estimating the equilibrium distances beyond which organic chocolate would have a higher impact than chocolate manufactured from cacao grown in monocultures and/or conventionally managed systems. To articulate the discussion, the carbon footprint (CF) of cacao/chocolate was analyzed together with 10 additional LCA-related impact categories. Three management systems-conventional monoculture (CM) and agroforestry (CA), and organic agroforestry (OA)-and three different supply chain scenarios with different weights in the transportation phase were studied. Expanding on the concept of "food miles", the equivalent kilometers of the impact of emissions (km-eq) (or cumulated energy demand, eutrophication, etc.) were defined as the variable distance that a certain means of transportation can travel in relation to a fixed level of GHG emissions (or MJ, kg PO4-eq, etc.). The CF of the life cycle of cacao/chocolate was estimated at between 2.04 and 4.66 kg CO2-eq kg-1. The relative weight of transportation in relation to the total GHG emissions ranged between 8.9% and 51.1%, with cacao/chocolate traveling between 1380 and 9155 km-eq. The CF of chocolate made from cacao grown in OA systems was 22.7%-34.2% and 6.3%-10.7% lower than the CF of chocolate produced from cacao grown in CM and CA and manufactured and transported under the same conditions. The equilibrium distances between managements were estimated at 1213 and 5275 km-eq. Beyond those equivalent kilometers, organic chocolate would have a larger CF than chocolate manufactured from cacao grown, respectively, in CA and CM systems. Our results indicate that transportation would cancel out this and most other comparative ecological advantages of producing organic cacao analyzed in this work. Directly exporting chocolate from cacao-producing countries and relocating chocolate manufacture would help reduce GHG emissions and other environmental impacts of the supply chain.


Antenatal therapy with corticosteroids and postpartum complications.
In a group of patients receiving dexamethasone antenataly, there was no difference in incidence of postpartum complications when compared to a group treated with a placebo. It is concluded that, from the maternal point of view, selected pregnant patients may safely receive corticosteroids to minimize the incidence of respiratory distress syndrome.


Ozonation/UV irradiation of dispersed Ag/AgI nanoparticles in water resources: stability and aggregation.
Proliferation of nanoparticles (NPs) as aqueous pollutants is a matter of growing concern today. The aggregation kinetics of colloidal bare silver (Ag, 20.5 nm) and silver iodide (AgI, 15.3 nm) NPs were investigated during ozone/ultraviolet (O3/UV) oxidation. Dynamic light scattering was applied to monitor the aggregation of NPs, and the z-average of treated samples was considered aggregate diameter. The effect of temperature, pH, and initial concentration of NPs was investigated on the aggregation rate constant and stability ratio. At a short oxidation period of approximately 1 min, the lower stability ratio was achieved for Ag NPs (< 50) than AgI NPs (> 100). Under acidic conditions, the negative surface charge of both NPs was neutralized that resulted in faster aggregation. In contrast, the impact of temperature and initial concentration of NPs on the aggregation rate was different for both NPs, which was due to the type of O3/UV interaction with the surface of NPs and the thickness of the electrical double layer surrounding the NPs. The aggregation behavior of Ag NPs obeyed diffusion-limited regime, while an intermediate regime between diffusion- and reaction-limited was observed for AgI NP aggregation. The resulting aggregate morphologies showed that the clusters were ramified for Ag and compressed for AgI NPs. Applying the O3/UV oxidation process for water treatment purposes leads to a significant reduction in aggregation time for inherently unstable Ag and stable AgI toxic NPs from several hours or days to several minutes.


Eating behavior dimensions and 9-year weight loss maintenance: a sub-study of the Finnish Diabetes prevention study.
Behavioral processes through which lifestyle interventions influence risk factors for type 2 diabetes (T2DM), e.g., body weight, are not well-understood. We examined whether changes in psychological dimensions of eating behavior during the first year of lifestyle intervention would mediate the effects of intervention on body weight during a 9-year period. Middle-aged participants (38 men, 60 women) with overweight and impaired glucose tolerance (IGT) were randomized to an intensive, individualized lifestyle intervention group (n = 51) or a control group (n = 47). At baseline and annually thereafter until nine years body weight was measured and the Three Factor Eating Questionnaire assessing cognitive restraint of eating with flexible and rigid components, disinhibition and susceptibility to hunger was completed. This was a sub-study of the Finnish Diabetes Prevention Study, conducted in Kuopio research center. During the first year of the intervention total cognitive (4.6 vs. 1.7 scores; p < 0.001), flexible (1.7 vs. 0.9; p = 0.018) and rigid (1.6 vs. 0.5; p = 0.001) restraint of eating increased, and body weight decreased (-5.2 vs. -1.2 kg; p < 0.001) more in the intervention group compared with the control group. The difference between the groups remained significant up to nine years regarding total (2.6 vs. 0.1 scores; p = 0.002) and rigid restraint (1.0 vs. 0.4; p = 0.004), and weight loss (-3.0 vs. 0.1 kg; p = 0.046). The first-year increases in total, flexible and rigid restraint statistically mediated the impact of intervention on weight loss during the 9-year study period. Lifestyle intervention with intensive and individually tailored, professional counselling had long-lasting effects on cognitive restraint of eating and body weight in middle-aged participants with overweight and IGT. The mediation analyses suggest that early phase increase in cognitive restraint could have a role in long-term weight loss maintenance. This is important because long-term weight loss maintenance has various health benefits, including reduced risk of T2DM.


GABA in the insula - a predictor of the neural response to interoceptive awareness.
The insula has been identified as a key region involved in interoceptive awareness. Whilst imaging studies have investigated the neural activation patterns in this region involved in intero- and exteroceptive awareness, the underlying biochemical mechanisms still remain unclear. In order to investigate these, a well-established fMRI task targeting interoceptive awareness (heartbeat counting) and exteroceptive awareness (tone counting) was combined with magnetic resonance spectroscopy (MRS). Controlling for physiological noise, neural activity in the insula during intero- and exteroceptive awareness was confirmed in an independent data sample using the same fMRI design. Focussing on MRS values from the left insula and combining them with neural activity during intero- and exteroceptive awareness in the same healthy individuals, we demonstrated that GABA concentration in a region highly involved in interoceptive processing is correlated with neural responses to interoceptive stimuli, as opposed to exteroceptive stimuli. In addition, both GABA and interoceptive signal changes in the insula predicted the degree of depressed affect, as measured by the Beck Hopelessness Scale. On the one hand, the association between GABA concentration and neural activity during interoceptive awareness provides novel insight into the biochemical underpinnings of insula function and interoception. On the other, through the additional association of both GABA and neural activity during interoception with depressed affect, these data also bear potentially important implications for psychiatric disorders like depression and anxiety, where GABAergic deficits, altered insula function and abnormal affect coincide.


Effects of substance P on neurones in the dorsal horn of the spinal cord of the cat.
The activity of single, physiologically identified neurones has been recorded both extra- and intracellularly in the 6th and 7th lumbar segments of the pentobarbitone-anaesthetized cat. In the majority of dorsal horn neurones studies (laminae 4 and 5 of Rexed) microiontophoretically applied synthetic substance P and the active fragment, substance P (4--11), were found to cause a slow and prolonged increase of the spontaneous firing rate and/or an enhancement of L-glutamate induced activity. Intracellular studies revealed that substance P caused a reversible depolarization of both dorsal horn neurones and motoneurones without a detectable alteration of the membrane resistance, antidromic action potential or postsynaptic potentials. These results are compatible with a possible role of substance P in sensory transmission in the spinal cord of the cat.


Genetic evidence that a Y-linked gene in man is homologous to a gene on the X chromosome.
The mammalian sex chromosomes are thought to be related to each other by sharing a common origin. That is, the X and Y chromosomes originally evolved from a pair of chromosomes that only differed at the locus determining sexual differentiation. For example, this evolutionary relationship is reflected during meiosis in chromosomal pairing between the tip of the human X chromosome short arm and the Y chromosome which presumably implies sequence homology. However, compelling genetic evidence for functional homology between the mammalian X and Y chromosome is lacking. We describe here the localization of a gene to the tip of the short arm of the human X chromosome and evidence for a related gene on the Y chromosome.


Lymphocutaneous nocardiosis and cutaneous pheohyphomycosis in a liver transplant recipient.
Infections are the leading cause of morbidity and mortality in transplanted patients. The increasing number of immunocompromised patients has not only augmented infections by specific pathogens, but also by opportunistic microbial agents. A mixed cutaneous infection caused by Nocardia brasiliensis and Exophiala jeanselmei is reported in a liver transplant patient. The cutaneous lesions were painful nodules which drained purulent material. They were located on the right lower limb, with lymphadenopathies in the groin. The patient was treated with itraconazole (600 mg/day) plus trimethoprim (1600 mg/day)-sulfamethoxazole (320 mg/day) for 8 weeks, with complete remission of the lesions.


Near-Infrared Light Triggered the Shape Memory Behavior of Polydopamine-Nanoparticle-Filled Epoxy Acrylate.
Through the effective combination of photothermal conversion agent polydopamine (PDA) nanoparticles and epoxy acrylate polymer (EA), a new kind of near-infrared (NIR) light-triggered shape memory polymer (PDA/EA) is developed. Due to the outstanding photothermal effect of PDA, even with a very low concentration of PDA (0.1 wt.%), when exposed to an 808 nm NIR light with a power of 1 W/cm2, the temporary shapes can be fully light-responsive, recovered in 60 s. Based on dynamic thermomechanical analysis and thermal gravimetric analysis, it can be seen that the introduction of PDA is beneficial for improving dynamic mechanical properties and thermal resistance compared to EA. As an environmentally friendly and highly efficient photoactive SMP, PDA/EA has a great application prospect.


When State Policy Makes National Politics: The Case of "Obamacare" Marketplace Implementation.
State governments have been powerful sites of Republican resistance to the implementation of the Affordable Care Act (ACA), the Democratic Party's signature 2010 law. By influencing how citizens experience the ACA, state-level implementation can affect the national-level political implications of the law. I examine three largely unstudied areas of marketplace implementation: navigator laws, transitional plan termination, and rating area configurations. For each policy area, I use linear probability models to investigate the determinants of state lawmakers bolstering or eroding marketplaces. In each case, Democrat-controlled states were more likely to bolster marketplaces than Republican-controlled states were, with decisions more polarized in those policy areas-navigator laws and transitional plan termination-and with greater potential for national-level feedback. For navigator laws, where Republican state lawmakers were most cross-pressured by national party interests and local interests, marketplace eroding policy was highly associated with strength of conservative networks. Crafters of federal legislation cannot expect state lawmakers to universally implement federal law to maximize the direct benefits to their constituents. Rather, we should expect state lawmakers to, in many instances, implement federal law in ways that benefit their parties.


Plasma osteopontin increases after bariatric surgery and correlates with markers of bone turnover but not with insulin resistance.
Osteopontin (OPN) is a multifunctional protein involved in bone metabolism, cardiovascular disease, diabetes, and obesity. OPN levels are elevated in the plasma and adipose tissue of obese subjects, and are decreased with diet-induced weight loss. We investigated the effect of bariatric surgery on plasma OPN concentrations in morbidly obese patients. The study was performed at a university hospital. We investigated 40 obese patients aged 43.1 +/- 1.8 yr, scheduled to undergo bariatric surgery. Roux-en-Y gastric bypass (RYGB) was performed in 30 subjects (27 females, three males), and laparoscopic adjustable gastric banding (LAGB) in 10 subjects (eight females, two males). All patients were studied before and 1 yr (10.3-14.8 months) after the intervention. OPN, leptin, C-reactive protein, insulin, the homeostatic model assessment insulin resistance index, calcium, 25-hydroxyvitamin D, C telopeptide, and osteocalcin were determined. Both bariatric procedures significantly reduced body weight, body mass index, insulin, leptin, and C-reactive protein 1 yr after surgery. Plasma OPN increased from 31.4 +/- 3.8 to 52.8 +/- 3.7 ng/ml after RYGB (P < 0.001) and from 29.8 +/- 6.9 to 46.4 +/- 10.6 ng/ml after LAGB (P = 0.042). Preoperative OPN correlated with age, insulin, the homeostatic model assessment insulin resistance index, and postoperative OPN. Postoperative OPN correlated with C telopeptide and osteocalcin. One year after RYGB and LAGB, plasma OPN levels significantly increased and correlated with biomarkers of bone turnover. Unlike other proinflammatory cytokines, OPN does not normalize but increases further after bariatric surgery.


Securing the premises while advancing your future.
One of the country's leading corporate leadership motivators and trainers focuses in this article on what healthcare security directors can do to advance their careers.


Studies of isolated and enriched rat antral mucosa gastrin cells.
A technique has been developed to obtain viable, isolated and enriched populations of gastrin cells (G-cells) from the rat stomach. Restricted tissue samples from a small area of the pyloric antrum known to be particularly rich in G-cells, were sequentially digested with pronase followed by mechanical agitation, to remove the epithelial cells. This technique resulted in a significant enrichment of G-cells (3-4 fold) since the surface epithelial cells and upper portions of the glands were discarded before the initial G-cell fraction was collected. These cells in suspension were then isolated from each other by gentle pipetting in a DNase containing solution and designated the crude preparation (CP). The G-cells were then purified further by separating the cells according to size by velocity sedimentation. The greatest concentration of G-cells (15-25%) was found in the fraction containing cells with diameters of 10 to 12 micrometer. The effectiveness of the technique was evaluated by counting G-cells as identified by electron microscopy and immunofluorescence and assessing gastrin activity by radioimmunoassay. All three methods indicated that cell separation by gravity velocity sedimentation enriched the G-cell population 15-20 fold over their concentration in the CP. The combined techniques of selective pronase digestion followed by gravity velocity sedimentation resulted in an isolated cell preparation containing a 50-100 fold increase of G-cells over their normal distribution in the intact gastric mucosa. Since these isolated G-cells retain features indicating viability, their usefulness for in vitro studies is suggested.


[Hypertrophic cardiomyopathy with two episodes of recuperated sudden death. Report of the first implantable defibrillator cardioverter inserted in Chile].
We report a 29 years old male with a non obstructive hypertrophic cardiomyopathy that survived two episodes of cardiac arrest and with a familiar history of the disease and sudden death. He had an implant of an automatic implantable cardioverter defibrillator by a left anterior thoracotomy with intraoperative electrophysiology. The postoperative outcome was uneventful. After one year of follow up, the patient is in good functional capacity and the implanted device has not performed defibrillations.


[Results of mammographic screening at the Mammary Center of Debrecen in 1999 and 2000].
The screening mammography decreases the mortality of female breast cancer. A complex, independent centre of screening mammography has been operating in Debrecen since 1999. The number of the examinations were 10,399 in 1999 and 13,800 in 2000. The number of explored breast cancer cases were 43 (0.41%) in 1999 and 62 (0.45%) in 2000. Although the mortality reduction can be exactly measured after several years, we are convinced that the chances for a better life of these 107 women operated on with breast cancer in early state increased thanks to our project. The results of the breast cancer screening program in Debrecen fulfilled the professional requirements of mammographic service-screening.


Morphomic Signatures Derived from Computed Tomography Predict Hepatocellular Carcinoma Occurrence in Cirrhotic Patients.
Computed tomography (CT) provides scans of the human body from which digitized features can be extracted. The aim of this study was to examine the role of these digital biomarkers for predicting subsequent occurrence of hepatocellular carcinoma (HCC) in cirrhotic patients. A cohort of 269 patients with cirrhosis were recruited and prospectively followed for the occurrence of HCC in Taiwan. CT scans were retrospectively retrieved and computationally processed using analytic morphomics. A predictive score was constructed using Cox regression and the generalized iterative modeling method, maximizing the log likelihood of the time to HCC development. An independent cohort of 274 patients from University of Michigan was utilized to examine the predictive validity of this score in a Western population. Of the 27 digitized features at the 12th thoracic vertebral level, six features were significantly associated with HCC occurrence. Two digitized features (fascia eccentricity and the bone mineral density) were able to stratify patients into high- and low-risk groups with distinct cumulative incidence of HCC in both the training and validation cohorts (P = 0.015 and 0.044, respectively). When the two digitized features were tested in the Michigan cohort, only bone mineral density remained an effective predictor. Digitized features derived from the CT were effective in predicting subsequent occurrence of HCC in cirrhosis patients. The bone mineral density measured on CT was an effective predictor for patients in both Taiwan and USA.


Physiological and behavioral effects of interpersonal validation: A multilevel approach to examining a core intervention strategy among self-injuring adolescents and their mothers.
The current study examined how teaching an interpersonal validation-oriented skill from dialectical behavior therapy affects behavioral and biological indices of self-inflicted injury (SII) risk among self-injuring adolescents and their mothers (n = 30 dyads), and typical control mother-daughter dyads (n = 30). Behavioral indicators of family functioning (e.g., cohesion, coercion, and invalidation) and a physiological index of emotion dysregulation (respiratory sinus arrhythmia [RSA]) were examined across two conflict tasks (pre- and postskills training). Dyads' subjective affect and observed behavior generally improved when practicing validation. Findings indicate mother-, daughter-, and dyad-level behavior accounted for significant variance in RSA reactivity. Results demonstrate that teaching a single skill on one occasion can have detectable effects on biosocial functioning, with important implications for the etiology and treatment of SII.


Correction to: Predictors of Dropout in Disordered Gamblers in UK Residential Treatment.
The original version of this article contained errors in Table 1. The numbers (N) and percentages (%) in the 'completed treatment' column were incorrect. It is now corrected with this erratum.


Role of cyclosporin A in the treatment of kidney disease and nephrotoxicity.
The clinical use of cyclosporin A (CsA) has led to significant advances and achievements in the field of transplantation and immune diseases. However, the nephrotoxicity of CsA is a major concern in current immunosuppression regimens. CsA causes abnormal kidney function while treating kidney disease, causing problems for clinicians and patients. Evidence of CsA nephrotoxicity is almost always present in transplant recipients after long-term CsA administration (up to 10 years), and similar phenomena occur with other calcineurin inhibitors. In this review, we summarize the mechanisms and influencing factors of CsA for the treatment of primary nephrotic syndrome. The mechanisms of CsA nephrotoxicity, clinical-pathological features, diagnosis, prevention strategies, and risk factors are summarized. We discuss the correlates and mechanisms of the switch between kidney disease prevention and nephrotoxicity of CsA to better understand the function of CsA in the kidney and to provide a basis for the prevention and treatment of CsA nephrotoxicity.


Persistent sodium current and Na+/H+ exchange contributes to the augmentation of the reverse Na+/Ca2+ exchange during hypoxia or acute ischemia in ventricular myocytes.
The increases in persistent sodium currents (I (Na.P)) and Na(+)/H(+) exchange (NHE) causes intracellular Ca(2+) overload. The objective of this study was to determine the contribution of I (Na.P) and NHE on the hypoxia- or acute ischemia-induced increase in the reverse Na(+)/Ca(2+) exchange current (HIR- or AIR-I (NCX)). I (Na.P) and I (NCX) in rabbit ventricular myocytes were recorded during hypoxia or acute ischemia, combination of acidosis (pH values were 6.0 intracellularly and 6.8 extracellularly) and hypoxia, using whole-cell patch-clamp techniques. The results indicate that (1) under hypoxic condition, the augmentation of both HIR-I (NCX) and I (Na.P) was inhibited by TTX (2 to 8 μM) in a concentration-dependent manner. The inhibitions of I (Na,P) and HIR-I (NCX) reached maximum in the presence of either 4 μM TTX or 10 μM KR-32568 (a NHE inhibitor), respectively. The maximal inhibitions of HIR-I (NCX) by 4 μM TTX and 10 μM KR-32568 were 72.54% and 16.89%, respectively. (2) Administration of 2 μM TTX and 10 μM KR-32568 in either order in the same cells decreased HIR-I (NCX) by 64.83% and 16.94%, respectively. (3) I (Na.P) and the reverse I (NCX) were augmented during acute ischemia. TTX (4 μM) and KR-32568 (10 μM) reduced AIR-I (NCX) by 73.39% and 24.13%, respectively. (4) Under normoxic condition, veratridine (20 μM) significantly increased I (Na.P) and the reverse I (NCX), which was reversed by 4 μM TTX. In conclusion, during hypoxia or acute ischemia, both increased I (Na.P) and NHE contribute to the HIR- or AIR-I (NCX) with the former playing a major role comparing with the latter.


Post-traumatic endophthalmitis prophylaxis: a systematic review and meta-analysis.
The goal of this study is to determine if certain aspects of endophthalmitis prophylaxis strategies are superior to others. This investigation is a systematic review and meta-analysis. All studies specifying a type of prophylaxis strategy and resulting rates of endophthalmitis were included. Time course, method of administration, and antibiotic regimen, and confounding factors were collected and included for meta-regression. Time courses greater than 24 h did not significantly improve outcomes. Likewise, intraocular and/or intravenous antibiotic administration methods did not significantly outperform oral administration. No antibiotic regimens performed differently from vancomycin/ ≥ 3rd generation cephalosporin except for ciprofloxacin monotherapy which yielded significantly worse outcomes. Future antibiotic strategies should strongly consider the risks of antibiotic treatment > 24 h and administration methods other than the oral antibiotic forms. In addition, providers should be wary of using ciprofloxacin monotherapy for endophthalmitis prophylaxis when treating open globe injuries.


An acidic arabinogalactan-protein from the roots of Baptisia tinctoria.
An acidic arabinogalactan-protein (AGP) isolated from an aqueous extract of the roots of wild indigo [ Baptisia tinctoria (L.) R. Br.] by precipitation with beta-glucosyl Yariv reagent consists of L-arabinose (34.0 %) and D-galactose (58.7 %) (1 : 1.7), minor amounts of D-glucuronic acid (4.0 %) and traces of D-rhamnose (2.3 %) and D-glucose (<1 %). The protein part of the AGP mainly contains asparagine/aspartic acid (11.3 %), glutamine/glutamic acid (10.8 %), alanine (8.0 %), serine (8.0 %), leucine (7.0 %) and hydroxyproline (6.3 %). Methylation analysis revealed that the carbohydrate moiety of the glycoprotein has a highly branched structure. The core consists of 3-linked beta- D-galactopyranose units carrying side chains of 6-linked beta- D-galactopyranose in position C(O)6, partly substituted in position C(O)3 by side chains of 5- and 3-linked alpha- L-arabinofuranosyl residues and 4-linked beta- D-galactopyranose units. Galactose and arabinose as well as glucose, rhamnose and glucuronic acid occur in terminal positions. The presence of these glycosyl linkage types was confirmed by (13)C-NMR data. The AGP was separated into two fractions by SEC. The major peak corresponded to a hydrodynamic volume of 5.6 x 10 (4) Da (AGP-F2) and the minor peak to a hydrodynamic volume of 1.2 x 10 (6) Da (AGP-F1). MALLS revealed apparent weight average molecular masses of 1.4 x 10 (5) Da and >1.0 x 10 (7) Da, respectively. Both fractions show corresponding carbohydrate compositions and structural features with regard to the carbohydrate moiety. Mild acid hydrolysis of the AGP leads to loss of terminal arabinofuranosyl units. The residual galactan backbone does not react with the Yariv reagent in gel diffusion tests while the total AGP still interferes with the reagent following reduction of terminal glucuronic acid residues.


Antimalarial and safety evaluation of Pluchea lanceolata (DC.) Oliv. & Hiern: in-vitro and in-vivo study.
Many of the effective therapeutic strategies have been derived from ethnopharmacologically used natural products. Pluchea lanceolata is an herb employed in Indian folk medicine for malaria like fever but it lacks proper pharmacological intervention. To evaluate antimalarial and safety profile of Pluchea lanceolata: an in-vitro, in-vivo for its ethnopharmacological validation. Methanol, butanol, ethyl acetate, chloroform, hexane extracts and its isolate, taraxasterol acetate (TxAc) were obtained from air dried aerial part of Pluchea lanceolata. These were tested in-vitro against chloroquine-sensitive strain of Plasmodium falciparum NF54 by measuring the parasite specific lactate dehydrogenase activity. The most potent hexane extract and TxAc were further validated for in-vivo antimalarial and safety evaluation. TxAc, a pentacyclic-triterpene isolated from the most active fraction was further evaluated with special emphasis on inflammatory mediators involved in malaria pathogenesis. Murine malaria was induced by intra-peritoneal injection of Plasmodium berghei infected red blood cells to the male Swiss inbred mice. Mice were orally treated following Peters 4-Day suppression test. In-vivo antimalarial efficacy was examined by evaluating the parasitaemia, percent survival, mean survival time, blood glucose, haemoglobin and pro-inflammatory mediators involved in malaria pathogenesis. Hexane extract and TxAc showed promising antimalarial activity in-vitro and in-vivo condition. TxAc attributed in inhibition of the pro-inflammatory cytokines as well as afford to significant increase in the blood glucose and haemoglobin level when compared with vehicle treated infected mice. We have not observed the synergistic action of combinations of chloroquine and TxAc from our experimental results. In-vitro and in-vivo safety evaluation study revealed that hexane extract is non toxic at higher concentration. Present study further validates the ancient Indian traditional knowledge and use of Pluchea lanceolata as an antimalarial agent. Study confirms the suitability of Pluchea lanceolata as a candidate for further studies to obtain a prototype for antimalarial medicine.


Adaptability evaluation of switchgrass (Panicum virgatum L.) cultivars on the Loess Plateau of China.
In the study, the growth traits, photosynthesis and morphology characteristics of several cultivars of switchgrass (Panicum virgatum L.) have been assessed the yield potential and adaptability in diverse environments (Yangling, Dingbian of Shaanxi province, Guyuan of Ningxia) on the Loess Plateau of China. Alamo was the best adapted switchgrass cultivar for biomass production in Yangling with dry matter (DM) yields of 44.22t/ha; Illinois USA and Cave-in-Rock grown at Guyuan had DM yield of 10.59t/ha and 9.36t/ha, respectively. Similarly, Cave-in-Rock in Dingbian performed better than others except the lowland cultivars (Alamo and Kanlow), which could not overcome cold stress at Guyuan and Dingbian. Moreover, Cave-in-Rock and Nebraska 28 has the highest photosynthesis rate which reflects its high productivity. Nebraska 28 and Pathfinder shown strong drought tolerance due to their higher WUE. It appears that the upland cultivars with high ploidy (e.g. 8n) would have better establishment than lowland varieties there. Optimal mown management seems to enhance the growth and productivity of switchgrass. Morphological characteristics were further studied using light-and scanning electron microscopy (SEM). Silica particles, vacuole size and other traits in switchgrass tissues (stem, leaf and root), as well as trichomes (leaf) showed that Cave-in-Rock and Pathfinder had larger stoma area, up to 824.4μm(2) and 770.1μm(2), respectively. Silica particle length was the longest in Pathfinder and shortest in Cave-in-Rock. There was a highest density of silica particles in cv. Forestberg, and lowest in Cave-in-Rock and Pathfinder. The morphological characters seemed to be associated with their ploidy levels and the arid habitat from which they were selected. Therefore, if switchgrass is to be introduced and extended on the Loess Plateau of China, Cave-in-Rock and other upland cultivars with a high chromosome ploidy might be optimal choices for biomass plants.


Application of solid-phase microextraction for determination of pyrethroids in groundwater using liquid chromatography with post-column photochemically induced fluorimetry derivatization and fluorescence detection.
Solid-phase microextraction (SPME) is a rapid and simple analytical technique which uses coated fused-silica fibers to extract analytes from aqueous samples. This study develops a method of SPME analysis for seven pyrethroids, including fenpropathrin, lambda-cyhalothrin, deltamethrin, fenvalerate, permethrin, tau-fluvalinate and bifenthrin in groundwater samples using high performance liquid chromatography combined with post-column photochemically induced fluorimetry derivatization and fluorescence detection (SPME-LC-PIF-FD). To perform the SPME, a 60 microm polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber was used for the extraction of the pesticides from groundwater samples. The main factors affecting the SPME process, such as extraction time, stirring rate, extraction temperature, pH and the desorption process were studied. The use of photochemically induced fluorescence for detection improved sensitivity and selectivity. The limits of quantification (LOQs) obtained in the matrix, with respect to EURACHEM Guidance, varied between 0.03 and 0.075 microgL(-1). Relative recoveries ranged from 92 to 109% and relative standard deviations values ranged from 2 to 9%.


Three-Dimensional Arterial Distribution Over the Midline of the Nasal Bone.
A comprehensive understanding of arterial variations around the midline of the nose is of great importance for the safety of filler injection. The aim of the study was to clearly define the 3-dimensional location of the arteries along the midline of the nasal bone. The arterial structures overlapping the nasal bone along the midline were observed in 79 cadavers. The present study found that 0 to 3 named arteries per nose segment could be identified. All the arterial structures were located in or above the superficial musculoaponeurotic system layer overlapping the nasal bone. The probability of encountering named arteries at 5 defined points, P1 to P5, was 5/79 (6.3%), 4/79 (5.1%), 1/79 (1.3%), 6/79 (7.6%), and 9/79 (11.4%), respectively. The depth of the main arterial trunk was 1.2 ± 0.4 mm, 1.6 ± 0.6 mm, 1.8 ± 0 mm, 1.0 ± 0.4 mm, and 0.9 ± 0.5 mm below the skin at P1 to P5, respectively. The authors confirmed that sub-superficial musculoaponeurotic system injection along the midline through a needle is anatomically reliable and that a technique with 1 entry point through the rhinion via a cannula can easily keep the needle sufficiently deep for safe nasal filler injection.


Treatment of ganglia by a thread technique.
Seventy ganglia of the wrist have been treated by a new method whereby two sutures are passed through the ganglion, at right angles to each other, and each is tied in a loop. At intervals thereafter, the contents of the ganglion are expelled by massage. Only three recurrences occurred in 62 patients followed-up. This compares well with the results of surgical excision and avoids the complications of operation and anaesthetic.


Natural History of Nonoperative Management of Grade II Blunt Thoracic Aortic Injury.
The morbidity and mortality of thoracic blunt aortic injury (BAI) has been both diminished and revolutionized by the advent of endovascular repair. Nevertheless, the question remains as to what severity of injury requires endovascular repair. We therefore conducted a retrospective analysis of our experience with nonoperative grade II BAI of the thoracic aorta. The records of patients with BAI from 2007 to 2017 at a Level I trauma center were retrospectively reviewed. Images were reviewed and graded by a radiologist according to the Society of Vascular Surgery Guidelines (grade I-IV). Demographics, injury severity, and outcomes were recorded. We identified 111 patients with BAI. Of these, 15 were deemed grade II injuries and were managed nonoperatively. Mean patient age was 45 ± 21 years; 60% of patients were male. The mean injury severity scale was 36 ± 13. No patients had progression of BAI to a more severe grade requiring intervention. Until now, the survival rate is 86.7% with a mean follow-up of 69 months (range 7-138). Within the grade II BAI cohort, injury progression did not occur, nor were any operative interventions performed. We conclude that grade II BAI can be managed nonoperatively. However, given that progression of the BAI is possible, follow-up aortic imaging is encouraged as well as appropriate blood pressure control and exercise restriction.


The role of climate on the geographic variability of asthma, allergic rhinitis and respiratory symptoms: results from the Italian study of asthma in young adults.
Variations in the prevalence of respiratory symptoms according to geo-climatic factors could provide important clues to the knowledge of the aetiology of asthma. Geo-climatic variations in the prevalence of current asthma, allergic rhinitis and chronic cough, and phlegm were assessed on a random sample of 18 873 subjects (response rate = 72.7%) from different climatic regions of Italy. An ecological analysis, supported by robust statistical methods, was employed to investigate potential trends. The prevalence of all symptoms was significantly heterogeneous throughout the peninsula. Only asthma-like symptoms showed a north-south trend: the prevalence increased at a decreasing latitude [odds ratio (OR) varies from 0.92 to 0.96, P < 0.05], at a decreasing distance from the sea (OR: 0.90-0.93 for 30 km distance, P < 0.05), at higher annual mean temperatures (OR: 1.11-1.14, P < 0.05) and at smaller annual temperature ranges (OR: 0.94-0.95, P < 0.05). Of the geo-climatic variables considered, temperature range had the greatest influence on most asthma-like symptoms. No association was found between geo-climatic variables and allergic rhinitis or chronic cough and phlegm. Asthma prevalence seems to be significantly affected by climate as asthma-like symptoms were more common in central-southern Italy, with a Mediterranean climate, than in areas with a continental climate (northern Italy).


Multi-agent neoadjuvant chemotherapy improves response and survival in patients with resectable pancreatic cancer.
We sought to examine the impact of neoadjuvant chemotherapy (NCT), single agent (SA) or multi-agent (MA) chemotherapy, and chemoradiation (NCRT) on response and survival in pancreatic cancer. Utilizing the National Cancer Database, we identified patients who underwent resection of the pancreatic head for adenocarcinoma [2006-2013]. Overall survival (OS) analysis was performed using the Kaplan-Meier method. Multivariable cox proportional hazard models (MVA) and propensity score matching (PSM) were developed to identify predictors of survival. For upfront surgery (UFS), OS was limited to receipt of adjuvant treatment. We identified 26,563 patients who underwent pancreatic head resection: UFS =23,877, NCRT =1,482, and NCT =1,204. MA-NCT was utilized in 77% and after PSM, 52%. There was improved R0 resections and 30-day mortality associated with neoadjuvant therapy compared to UFS. Overall response rate to neoadjuvant therapy was 24%. The highest response rate seen with MA-NCRT. Response rates for SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT were 11.5%, 18.1%, 27.5%, and 33.1% (P=0.01). However, OS was improved with neoadjuvant therapy regardless of response compared to UFS (P=0.03). After PSM, the median OS for UFS, SA-NCT, MA-NCT, SA-NCRT, and MA-NCRT was 21.9, 21.5, 29.8, 25.3, and 25.8 months in all patients (P=0.001). MVA after PSM demonstrated that only MA-NCT was associated with decreased mortality while increasing age, higher Charlson-Deyo index, N1, higher grade, tumor size, and positive margins were associated with higher mortality. There was improved OS associated with MA-NCT in pancreatic cancer patients compared to UFS with adjuvant therapy. OS was improved regardless of response to therapy.


Co-production of hydrogen and methane from potato waste using a two-stage anaerobic digestion process.
Hydrogen and methane co-production from potato waste was examined using a two-stage process of anaerobic digestion. The hydrogen stage was operated in continuous flow under a pH of 5.5 and a HRT of 6h. The methane stage was operated in both continuous and semi-continuous flows under HRTs of 30 h and 90 h, respectively, with pH controlled at 7. A maximum gas production rate of 270 ml/h and an average of 119 ml/h were obtained from the hydrogen stage during the operation over 110 days. The hydrogen concentration contained in the gas was 45% (v/v), on average. The maximum and average gas production rates observed from methane reactor during the 74 days of semi-continuous flow operation were 187 and 141 ml/h, respectively, with an average methane concentration of 76%. Overall, 70% of VS, 64% of total COD in the feedstock were removed. The hydrogen and methane yields from the potato waste were 30 l/kg TS (with a maximum of 68 l/kg) and 183 l/kg TS (with a maximum of 225 l/kg), respectively. The total energy yield obtained was 2.14 kW h/kg TS, with a maximum of 2.74 kW h/kg TS.


AMg2+ -dependent class of thick filaments and correlated nuclear chromatin condensation in catfish photoreceptors.
Photoreceptor cells of excised catfish retinae show morphological differences when incubated in Ringer's solutions of varying ionic composition. Two striking changes were observed in photoreceptor cells incubated in a high Mg2+ (25 mM) Ringer's: (1) Thick filaments appeared in the cytoplasm of receptor terminals and myoids; (2) A pronounced condensation of nuclear chromatin occurred in certain nuclei in the outer nuclear layer. The filaments occurred in lattices or bundles. The bundles had a diameter of approximately 0.05--0.2 micrometer and had either tapered or frayed ends. They were observed with somewhat higher incidence in tissue incubated in a 25 mM Mg2+ Ringer's with EGTA added to chelate Ca2+. A common basis for the cytoplasmic and nuclear changes may lie in a redistribution of fibrous protiens brought about by the increased Mg2+ concentration.


Superficialization of hemodialysis access using a video-assisted procedure.
Brachiocephalic fistula is one of the main options to gain blood access for hemodialysis. Although the fistula is easy to establish, puncture becomes increasingly difficult because the cephalic vein runs deep and fibrous tissue is being continually deposited over the cephalic vein. Although superficialization-i.e., the removal of fibrous tissue along the basilic vein-has been performed with conventional surgery, the long incision along the cephalic vein induces the buildup of hard fibrous tissue so that puncture may remain difficult even after the operation. To avoid this problem, we tried superficialization of hemodialysis access using a video-assisted procedure and obtained a good result.


Systemic availability of acetylsalicylic acid in normal men and women and its effect on in vitro platelet aggregability.
The systemic availability of acetylsalicylic acid (ASA) after oral ingestion of 1 g in an effervescent formulation was 16.3 +/- 2.0% and 16.9 +/- 3.2% of the ingested dose in normal women and men, respectively. The average plasma half-life of ASA in each sex was also identical at 18.5 +/- 1.4 and 18.1 +/- 1.2 min, respectively. The inhibitory effect of ASA on collagen-induced platelet aggregation in vitro on blood from both sexes was studied. The IC50 was 23.9 +/- 2.9 micrograms/ml in females and 22.5 +/- 2.7 micrograms/ml in males, which did not differ significantly. The inhibition by salicylic acid (SA) of the antiaggregatory effect of ASA was similar in both sexes with increases in IC50 to 33.5 +/- 5.1 micrograms/ml in females (p less than 0.02) and to 29.5 +/- 3.8 micrograms/ml in males (p less than 0.05). It is concluded that the observed sex-difference in the antithrombotic effect of ASA cannot be explained neither by differences between females and males in the pharmacokinetic properties of ASA after oral ingestion, nor by differences in the in vitro effect of ASA on the platelet aggregation induced by collagen.


Thermodynamic assessment of the stability of thrombin receptor antagonistic peptides in hydrophobic environments.
In this paper, a general procedure is described to determine thermodynamic parameters associated with the interaction of thrombin receptor antagonistic peptides (TRAPs) with immobilized nonpolar ligands. The results show that these interactions were associated with nonlinear van't Hoff dependencies over a wide temperature range. Moreover, changes in relevant thermodynamic parameters, namely the changes in Gibbs free energy of interaction, DeltaG(0)assoc, enthalpy of interaction, DeltaH(0)assoc, entropy of interaction, DeltaS(0)assoc, and heat capacity, DeltaC(0)p, have been related to the structural properties of these TRAP analogs. The implications of these investigations for the design of thrombin receptor agonists/antagonists with structures stabilized by intramolecular hydrophobic interactions are discussed.


A Suite of Tools for Biologists That Improve Accessibility and Visualization of Large Systems Genetics Datasets: Applications to the Hybrid Mouse Diversity Panel.
In this chapter we address the recent explosion in large multilevel population studies such as the METSIM study in humans as well as large panels of animal models such as the Hybrid Mouse Diversity Panel or the BXD set of recombinant inbred strains. These studies have harnessed the increasing affordability of large-scale high-throughput profiling to gather massive quantities of data. These datasets, spread across different -omics levels (genome, transcriptome, etc.), different tissues (e.g. heart, plasma, bone) and different environmental factors (e.g. diet, drugs) each individually have led to a number of novel findings relevant to a variety of complex diseases and other phenotypes. The analysis of these results, however, is often limited to individuals with a comprehensive understanding of database languages such as SQL. In this chapter, we describe the development of a GUI-based database analysis suite, using the Hybrid Mouse Diversity Panel as an example to lay out a series of methods for visualization and integration of large systems genetics datasets. The database is based on the Shiny suite of tools in R, and is transferrable to other SQL-based datasets.


Comparative morphology of early stages of two Mediterranean Sarcophaga Meigen, 1826 (Diptera; Sarcophagidae) and a review of the feeding habits of Palaearctic species.
The third instar larva of Sarcophaga hirticrus Pandellé, 1896 and Sarcophaga javita (Peris, González-Mora and Mingo, 1998) are described and figured for the first. The use of scanning electron microscopy (SEM) has been demonstrated as an effective tool for determining differences at the specific level, and is here applied. The two species are distinguished from other Sarcophaga spp. and the principal diagnostic character states are illustrated and discussed. Comparative information on immature stages morphology of the described Palaearctic Sarcophaga species and its feeding habits are compiled and provided in a tabulated form.


Lipid extraction from microalgae cell using persulfate-based oxidation.
In this study, persulfate, a solid-type oxidant, was adopted as a substitute for hydrogen peroxide in extracting lipid from microalgae biomass. Microalgae cells were concentrated at pH 3 and with 200mg/L of ferric chloride, conditions which can activate oxidants such as hydrogen peroxide and persulfate. At a persulfate concentration of 2mM and a reaction temperature of 90°C, exceedingly high extraction efficiency over 95% was obtained, which was higher than with 0.5% hydrogen peroxide at the same temperature. This result showed that persulfate is sufficiently powerful and incomparably cheap enough to replace the potent yet expensive oxidant. It appears that combining iron-based coagulation and persulfate-based lipid extraction is indeed a competitive approach that can possibly lighten the process burden for the microalgae-derived biodiesel production.


Parental Preferences for Mental Health Screening of Youths From a Multinational Survey.
Screening youths for mental disorders may assist in prevention, promote early identification, and be associated with reduced related lifetime impairment and distress. To assess parents' and caregivers' comfort with and preferences for pediatric mental health screening and factors associated with these preferences. This survey study used an online survey available from July 11 to 14, 2021, through Prolific Academic. Analyses were conducted from November 2021 to November 2022. The survey was administered to English-speaking parents and caregivers in the US, UK, Canada, and 16 other countries who were aged 21 years or older and had at least 1 child aged 5 to 21 years living at home. The main outcomes were parental preferences regarding content, implementation, and review of the findings of pediatric mental health screening. Parental comfort with screening topics was reported on a 6-point Likert scale with 6 indicating highest comfort. Mixed-effects logistic regression models were used to evaluate factors associated with parental comfort levels. Of 1200 survey responses requested, data were collected from 1136 participants (94.7%). The final sample meeting the inclusion criteria comprised 972 parents and caregivers aged 21 to 65 years (mean [SD] age, 39.4 [6.9] years; 606 [62.3%] female). A total of 631 participants (64.9%) supported annual mental health screening for their child, and 872 (89.7%) preferred reviewing the screening results with professional staff (eg, physicians). Participants reported significantly decreased comfort with child self-report compared with parent-report screening assessments (b = -0.278; SE = 0.009; P < .001), although they were generally comfortable with both options. Despite slight variations based on country of residence, screening topic, and child's age, participants were generally comfortable discussing all 21 screening topics on the survey. The greatest comfort was with sleep problems (mean [SE] score, 5.30 [0.03]); the least comfort was with firearms (mean [SE] score, 4.71 [0.05]), gender identity (mean [SE] score, 4.68 [0.05]), suicidality (mean [SE] score, 4.62 [0.05]), and substance use or abuse (mean [SE] score, 4.78 [0.05]). In this survey study of parents and caregivers, parent-reported and child self-reported mental health screening in primary care settings was supported by the majority of the sample, although comfort levels differed according to various factors (eg, screening topic). Participants preferred to discuss screening results with professional health care staff. In addition to parental need for expert guidance, the study findings highlight the growing awareness of child mental health needs and the importance of addressing mental health concerns early via regular mental health screenings.


Circulating endothelial progenitor cells during normal pregnancy and pre-eclampsia.
Endothelial progenitor cell (EPC), which mediates neovascularization of uterine endometrium may be involved in the neovascularization in the utero-placental circulation. We evaluated whether EPC proliferation in pre-eclampsia (PE) differed from that in normal pregnancy. EPC number in peripheral blood (20 non-pregnancy, 36 normal pregnancy, 10 PE) was measured using flow cytometry. Peripheral blood mononuclear cell was cultured for 7 days and EPC proliferation was assessed based on detection of the uptake of acetylated low-density lipoprotein and lectin. Furthermore, the proliferative activity induced by angiotensin II (Ang II) and tumor necrosis factor-alpha (TNF-alpha) was measured by BrdU assay. EPC number in peripheral blood did not differ significantly between PE and normal pregnancy; however, EPC proliferation was significantly increased in PE. Furthermore, Ang II and TNF-alpha induced the proliferation of EPC derived from patients with PE. In PE, some factors including Ang II and TNF-alpha stimulated EPC proliferation; however, the impairment of EPC mobilization into systemic circulation by serum factors may contribute to insufficient regeneration of EC in disturbed utero-placental circulation of PE.