Impaired Quality of Life and Need for Palliative Care in a German Cohort of Advanced Parkinson's Disease Patients.
Parkinson's disease (PD) is the second most frequent neurodegenerative disease of the elderly. Patients suffer from various motor and non-motor symptoms leading to reduced health-related quality of life (HRQOL) and an increased mortality. Their loss of autonomy due to dementia, psychosis, depression, motor impairments, falls, and swallowing deficits defines a phase when palliative care interventions might help to sustain or even improve quality of life. The aim of this study was to investigate the current status of palliative care implementation and quality of life in a local cohort of advanced PD patients in order to frame and improve future care. 76 geriatric patients with advanced idiopathic PD meeting the inclusion criteria for palliative care interventions were clinically evaluated by neurological examination using Movement Disorders Society Unified Parkinson's Disease Rating Scale, Barthel Index, Montreal Cognitive Assessment Test, and a structured interview concerning palliative care implementation. HRQOL is severely reduced in our cohort of geriatric advanced PD patients. We found motor deficits, impairment of activities of daily living, depression, and cognitive decline as most relevant factors determining decreased HRQOL. Only 2.6% of our patients reported present implementation of palliative care. By contrast, 72% of the patients indicated an unmet need for palliative care. Quality of life is dramatically affected in advanced PD patients. However, we found palliative care to be implemented extremely rare in their treatment concept. Therefore, geriatric patients suffering from advanced PD should be enrolled for palliative care to provide adequate and holistic treatment which may improve or sustain their quality of life.


Gene expression and single nucleotide polymorphism of ATP7B are associated with platinum-based chemotherapy response in non-small cell lung cancer patients.
Objectives: Platinum-based chemotherapy is first-line treatment for non-small cell lung cancer (NSCLC) patients. The efficacy is limited by drug resistance. Recent studies suggest that ATP7B, a copper efflux transporter, may be involved in platinum resistance. However, the clinical significance of ATP7B expression in NSCLC is controversial. Moreover, the effects of single nucleotide polymorphisms (SNPs) in ATP7B gene on the response to platinum-based chemotherapy are scarcely understood. The aim of our study is to evaluate the clinical value of ATP7B in NSCLC patients and explore the interrelationships between ATP7B SNPs and protein expression, and their association with chemotherapy response. Materials and Methods: A total of 247 NSCLC patients were recruited in this study. Among them, 158 patients who received platinum-based chemotherapy were used to explore the interrelationships between ATP7B SNPs, protein expression and chemotherapy response, while 89 patients who underwent surgical resection were used to further investigate the association between ATP7B SNPs and expression level. We genotyped 15 SNPs of ATP7B by Sequenom MassARRAY and determined ATP7B protein levels by immunohistochemistry. Results: Patients with ATP7B-negative tumors had improved chemotherapeutic response (p=0.025) and better overall survival (p=0.044) compared with the patients with ATP7B-positive tumors. The multivariate Cox regression analysis revealed that ATP7B expression was an independent prognostic factor (HR=0.639, 95%CI=0.424-0.962, p=0.032). Moreover, we found that the rs9526814 GG genotype was significantly associated with favorable response to platinum-based chemotherapy when compared with TT+TG genotypes (OR=0.362, 95CI%=0.140-0.935, p=0.036). Mechanistically, rs9526814 GG genotype showed a strong trend towards reduced expression level of ATP7B compared with the TT+TG genotypes (p= 0.048). Conclusion: Our findings indicate that ATP7B rs9526814 may contribute to platinum resistance by influencing ATP7B gene expression and can be used as a potential biomarker to predict the sensitivity of platinum-based chemotherapy in NSCLC patients.


Temperature- or guest-induced drastic single-crystal-to-single-crystal transformations of a nanoporous coordination polymer.
Aside from a temperature-induced structural transformation, a new nanoporous coordination polymer [Ag6Cl(atz)4].OH.6H2O (Hatz = 3-amino-1,2,4,-triazole) comprised of interpenetrated Ag3(atz)2 coordination nets exhibits a single-crystal-to-single-crystal transformation of a 5-fold to 6-fold net interpenetration change triggered by guest desorption/absorption.


Use of accelerometry to measure physical activity in older adults at risk for mobility disability.
The authors explored using the ActiGraph accelerometer to differentiate activity levels between participants in a physical activity (PA, n = 54) or "successful aging" (SA) program (n = 52). The relationship between a PA questionnaire for older adults (CHAMPS) and accelerometry variables was also determined. Individualized accelerometry-count thresholds (ThreshIND) measured during a 400-m walk were used to identify "meaningful activity." Participants then wore the ActiGraph for 7 days. Results indicated more activity bouts/day > or =10 min above ThreshIND in the PA group than in the SA group (1.1 +/- 2.0 vs 0.5 +/- 0.8, p = .05) and more activity counts/day above ThreshIND for the PA group (28,101 +/- 27,521) than for the SA group (17,234 +/- 15,620, p = .02). Correlations between activity counts/hr and CHAMPS ranged from .27 to .42, p < .01. The ActiGraph and ThreshIND might be useful for differentiating PA levels in older adults at risk for mobility disability.


[Sentinel node biopsy for breast cancer patients at the Bács-Kiskun County Teaching Hospital].
The optimal technique of sentinel node biopsy (SNB) is still debated. To compare two methods of SNB, describe the learning phase, the validation of the methods and the first results after implementing SNB as standard of care in selected breast cancer patients. SNB with peritumoral or intratumoral injection of Patent blue dye only was performed in 129 clinically T1-T2 and N0 breast cancers in 127 patients (Group A); it was later replaced by combined dye and radiocolloid-guided SNB preceded by lymphoscintigraphy in 72 breast cancer patients (Group B). All patients underwent completion axillary dissection. Group C, to date, comprises 50 patients, in whom axillary dissection was performed on the basis of the SNB. Intraoperative imprint cytology was performed, and whenever positive, the axillary dissection was completed in the same step, whereas in cases of negative cytology findings but positive final histology, the dissection was done as a second operation. Histopathological assessment of SNs involved step sectioning and immunohistochemistry. Means of 1.4 and 1.3 SNs were identified in Groups A and B, respectively. The mean number of non-SNs for the whole series was 14.7 (range 5-42). The first 53 cases of lymphatic mapping with patent blue dye comprised the institutional learning period, during which the identification rate of at least 1 SN in 30 consecutive attempts reached 90%. The identification rate for the subsequent 76 Group A patients was 92%. The accuracy of SNB for overall axillary nodal status prediction and the false-negative rate for Group A patients (after exclusion of the learning-phase cases) were 93% and 10%, respectively. All 72 Group B cases had at least 1 SN identified, and only 1 false-negative case occurred in this group, i.e. the accuracy and false-negative rate were 99% and 3%, respectively. The identification rate in Group C was 98%; axillary dissection could be avoided in 25 patients, it was performed at the same time as the SNB in 15 and as a second operation in 10. Till now, no axillary recurrence was detected in Group C patients, although the follow-up period is short for the moment. The dye only and the radioguided SNB methods are complementary, their combination improves the performance, and can be the basis of performing axillary dissection on the basis of SNB results. After the technique of SNB has been validated in a given institution, it can become standard of care in a well selected group of patients, but requires a close follow up.


Neurokinin Receptor 1 (NK1R) Antagonist Aprepitant Enhances Hematoma Clearance by Regulating Microglial Polarization via PKC/p38MAPK/NFκB Pathway After Experimental Intracerebral Hemorrhage in Mice.
Hematoma clearance is an important therapeutic target to improve outcome following intracerebral hemorrhage (ICH). Recent studies showed that Neurokinin receptor-1 (NK1R) inhibition exerts protective effects in various neurological disease models, but its role in ICH has not been explored. The objective of this study was to investigate the role of NK1R and its relation to hematoma clearance after ICH using an autologous blood injection mouse model. A total of 332 adult male CD1 mice were used. We found that the expression levels of NK1R and its endogenous ligand, substance P (SP), were significantly upregulated after ICH. Intraperitoneal administration of the NK1R selective antagonist, Aprepitant, significantly improved neurobehavior, reduced hematoma volume and hemoglobin levels after ICH, and promoted microglia polarization towards M2 phenotype. Aprepitant decreased phosphorylated PKC, p38MAPK, and NFκB p65, and downregulated M1 markers while upregulating M2 markers after ICH. Intracerebroventricular administration of the NK1R agonist, GR73632 or PKC agonist, phorbol 12-myristate 13-acetate (PMA) reversed the effects of Aprepitant. To demonstrate the upstream mediator of NK1R activation, we performed thrombin injection and found that it increased SP. Inhibiting thrombin suppressed SP and decreased M1 markers while increasing M2 microglia polarization. Thus, NK1R inhibition promoted hematoma clearance after ICH by increasing M2 microglial polarization via downregulating PKC/p38MAPK/NFκB signaling pathway, and thrombin may be a key upstream mediator of NK1R activation. Therapeutic interventions inhibiting NK1R signaling may be a new target for the treatment of ICH.


Amelioration of Cancer Employing Chitosan, Its Derivatives, and Chitosan-Based Nanoparticles: Recent Updates.
The limitations associated with the conventional treatment of cancer have necessitated the design and development of novel drug delivery systems based mainly on nanotechnology. These novel drug delivery systems include various kinds of nanoparticles, such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, hydrogels, and polymeric micelles. Among the various kinds of novel drug delivery systems, chitosan-based nanoparticles have attracted the attention of researchers to treat cancer. Chitosan is a polycationic polymer generated from chitin with various characteristics such as biocompatibility, biodegradability, non-toxicity, and mucoadhesiveness, making it an ideal polymer to fabricate drug delivery systems. However, chitosan is poorly soluble in water and soluble in acidic aqueous solutions. Furthermore, owing to the presence of reactive amino groups, chitosan can be chemically modified to improve its physiochemical properties. Chitosan and its modified derivatives can be employed to fabricate nanoparticles, which are used most frequently in the pharmaceutical sector due to their possession of various characteristics such as nanosize, appropriate pharmacokinetic and pharmacodynamic properties, non-immunogenicity, improved stability, and improved drug loading capacity. Furthermore, it is capable of delivering nucleic acids, chemotherapeutic medicines, and bioactives using modified chitosan. Chitosan and its modified derivative-based nanoparticles can be targeted to specific cancer sites via active and passive mechanisms. Based on chitosan drug delivery systems, many anticancer drugs now have better effectiveness, potency, cytotoxicity, or biocompatibility. The characteristics of chitosan and its chemically tailored derivatives, as well as their use in cancer therapy, will be examined in this review.


[Effects of urapidil on the cardiovascular response to intratracheal intubation].
The effects of urapidil on the haemodynamic response to endotracheal intubation were compared to that of placebo in two groups of 25 patients scheduled for general surgery. Normal saline solution or 0.4 mg.kg-1 urapidil were injected 3 min before induction of anaesthesia with 3 micrograms.kg-1 fentanyl, 0.3 mg.kg-1 etomidate and 0.1 mg.kg-1 vecuronium. Blood pressure (Pasys, Padia, Pa) and heart rate were measured continuously by servoplethysmomanometry before giving the test drug (T0), at the time when the lowest blood pressure was recorded during the three minute period between giving the drug and induction (T1), at the time when the lowest blood pressure was recorded during the three minute period between induction and endotracheal intubation (T2), at the time when the highest blood pressure was recorded immediately after intubation (T3), three minutes after intubation (T4), five minutes after intubation (T5), and at the time when the lowest blood pressure was recorded after surgery had been started (T6). It was planned to give a 25 mg urapidil dose to any patient, from either group, who had a Pasys greater than 200 mmHg for more than 60 sec. Giving urapidil lowered Pasys (T1) by 16%, whilst heart rate increased by 12%. The blood pressure peak due to endotracheal intubation was lower in those patients who had been given urapidil than in the placebo group (T3; p less than 0.05). Six patients in the latter group required the 25 mg urapidil dose, versus 2 in the urapidil group. The preventive effects of urapidil seem to be similar to those obtained with other antihypertensive agents.(ABSTRACT TRUNCATED AT 250 WORDS)


Micromechanical Origin of Particle Size Segregation.
We computationally study the micromechanics of shear-induced size segregation and propose distinct migration mechanisms for individual large and small particles. While small particles percolate through voids without enduring contacts, large particles climb under shear through their crowded neighborhoods with anisotropic contact network. Particle rotation associated with shear is necessary for the upward migration of large particles. Segregation of large particles can be suppressed with inadequate friction, or with no rotation; increasing interparticle friction promotes the migration of large particles, but has little effect on the percolation of small particles.


The Collaborative Assessment and Management of Suicidality (CAMS) stabilization plan for working with patients with suicide risk.
The Collaborative Assessment and Management of Suicidality (CAMS) provides clinicians with an evidence-based suicide-focused therapeutic framework to help patients understand and manage suicidal thoughts and behaviors. A key component in CAMS suicide-focused treatment planning is the development and use of the CAMS Stabilization Plan (CSP). The CSP is used to ensure between-session safety and stability by helping patients learn to cope differently, enabling clinicians to care for suicidal patients on an outpatient basis, and thereby rendering suicidal-oriented coping obsolete. While implementing and maintaining the CSP, clinicians work to identify, target, and treat patient-identified suicidal drivers aimed at lowering the patient's suicide risk. The CSP employs a collaborative, flexible, and problem-focused approach creating a unique dynamic between clinician and patient as they work together to address the patient's suicidal struggle. CAMS allows clinicians to be flexible in their approach to treating suicidal behavior, utilizing techniques and tools they know, while providing them with a unique framework to engage their suicidal patients. Additionally, there is an overt and ongoing emphasis on encouraging patients to cultivate purpose and meaning in their lives with plans, goals, and hope for the future-ultimately leading patients to discover a life worth living, which is the final focus in CAMS-guided care. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


14-Deoxy-11,12-Didehydroandrographolide Ameliorates Glucose Intolerance Enhancing the LKB1/AMPK[Formula: see text]/TBC1D1/GLUT4 Signaling Pathway and Inducing GLUT4 Expression in Myotubes and Skeletal Muscle of Obese Mice.
14-Deoxy-11,12-didehydroandrographolide (deAND), a bioactive component of Andrographis paniculata, has antidiabetic activity. AMP-activated protein kinase (AMPK) regulates glucose transport and ameliorates insulin resistance. The aim of the present study was to investigate whether activation of AMPK is involved in the mechanism by which deAND ameliorates insulin resistance in muscles. deAND amounts up to 40 [Formula: see text]M dose-dependently activated phosphorylation of AMPK[Formula: see text] and TBC1D1 in C2C12 myotubes. In addition, deAND significantly activated phosphorylation of LKB1 at 6 h after treatment, and this activation was maintained up to 48 h. deAND increased glucose uptake at 18 h after treatment, and this increase was time dependent up to 72 h. Compound C, an inhibitor of AMPK, suppressed deAND-induced phosphorylation of AMPK[Formula: see text] and TBC1D1 and reversed the effect on glucose uptake. In addition, the expression of GLUT4 mRNA and protein in C2C12 myotubes was up-regulated by deAND in a time-dependent manner. Promotion of GLUT4 gene transcription was verified by a pGL3-GLUT4 (837 bp) reporter assay. deAND also increased the nuclear translocation of MEF-2A and PPAR[Formula: see text]. After 16 weeks of feeding, the high-fat diet (HFD) inhibited phosphorylation of AMPK[Formula: see text] and TBC1D1 in skeletal muscle of obese C57BL/6JNarl mice, and deactivation of AMPK[Formula: see text] and TBC1D1 by the HFD was abolished by deAND supplementation. Supplementation with deAND significantly promoted membrane translocation of GLUT4 compared with the HFD group. Supplementation also significantly increased GLUT4 mRNA and protein expression in skeletal muscle compared with the HFD group. The hypoglycemic effects of deAND are likely associated with activation of the LKB1/AMPK[Formula: see text]/TBC1D1/GLUT4 signaling pathway and stimulation of MEF-2A- and PPAR[Formula: see text]-dependent GLUT4 gene expression, which account for the glucose uptake into skeletal muscle and lower blood glucose levels.


Non-surgical management of rectal tears in two mares.
Two mares presented with life-threatening rectal tears were successfully treated with intensive medical management. Although surgery has been regarded as mandatory for grade 3 or 4 rectal tears in the past, recent reports have indicated the value of medical management alone. The case reports presented in this article detail the use of antibiotics, flunixin meglumine, laxative diets and faecal softeners in the medical management of two mares presented with grade 3 rectal tears.


Retaining newly Registered Nurses in the profession.
Newly qualified nurses (NQNs) are one group at risk of early exit from the workforce. There is a need to reinforce the 'flaky bridge' (Health Education England [HEE] 2018) and ease 'transition shock' to facilitate NQN retention. (1) establish the current state of the art in the UK for nurse retention and transition from student to Registered Nurse; (2) provide UK healthcare organisations, higher education institutions and individual nurses with an evidence-based approach to plan for successful transition; (3) develop an evidence-based toolkit that enables NQNs and their employers to identify, implement and evaluate an individualised approach to transition. A rapid evidence assessment (REA) of NQN transition and retention was undertaken followed by 40 interviews with final year nursing students, NQNs, clinical leaders and academics and 113 written reflections from final year nursing students captured qualitative data on transition. A 'transition toolkit' was developed and used with one group of students (n=75) and data on retention and employment captured to determine impact on the number of nurses retained at the end of 12 months. A variety of formal and informal approaches that enhance and support transition were identified by the REA including having a formal orientation period; the initial placement; satisfaction with the unit and clinical supervision; empowerment; pre-registration employment; and low stress levels having had previous experience in the unit. Preceptorship was found to significantly increase NQNs competence, though no firm conclusions could be reached regarding the impact on retention. Qualitative data suggested that NQNs still experience transition shock and support during the transition period was important. Quantitative data indicated that most NQNs were employed full-time and working in local NHS hospitals. Most had undertaken employment during their programme and when qualified had not changed employer or role and did not plan to change. In the post-intervention group, most had engaged with the STaR project material and had accessed their place of first employment through the project. There were no statistically significant differences between cohorts, and no statistically significant relationships among the data. A supportive framework incorporating supernumerary status, preceptorship or equivalent, peer and organisational culture of support can help to ensure a smooth, seamless and comfortable transition. The link between NQN support and retention remains poorly evidenced.


Optofluidic tunable mode-locked fiber laser using a long-period grating integrated microfluidic chip.
An optofluidic tunable mode-locked fiber laser using a microfluidic chip integrated with long-period grating (LPG) is presented. The microfluidic chip enables ultrafine adjustment of the liquid's refractive index and, thus, LPG's spectrum via tuning the mixing ratio of the microfluidic flows. With such an optofluidic spectrum-tunable filter, the central wavelength of the mode-locked laser can be tuned continuously, while the mode-locking state is steadily maintained. The mode-locked pulses are measured with a pulse duration of 0.9 ps and repetition rate of 12.14 MHz, respectively. Moreover, bound solitons with variable soliton separations are experimentally demonstrated.


Recurrent granular cell tumor: how to treat.
Granular cell tumor is an uncommon lesion usually located in the head and neck region (50%) with a female sex predominance. It is believed to be of primitive neuroectodermal origin. Typical clinical presentation is a small, uninflamed, slowly growing, yellowish mass approximately 2 cm in diameter. Granular cell tumor has a peculiar clinical behavior ranging from clearly benign, locally aggressive, or manifestly malignant. Treatment is surgical excision, but recurrences are possible. In this article, we present a case of recurrent benign granular cell tumor with the discussion of the treatment modalities. The patient was a 16-year-old girl with a 3-year history of a painless mass on the right side of her neck. The mass was excised two times at different centers and diagnosed as granular cell tumor after the pathologic examination. The time interval between the operations and recurrences was approximately 1 year. On physical examination, a yellowish, firm, nodular mass measuring approximately 2 x 1 cm was noted. Cervical lymph nodes were evaluated with ultrasonography preoperatively to exclude metastasis and no pathologic lymph nodes were noted. The lesion was excised under local anesthesia with a 1-cm safe margin and the resulting defect was closed primarily after undermining of the wound edges. Postoperatively, the wound began to heal with a hypertrophic scar and immediate precautions were taken. Topical steroid treatment and silicone blocks were applied. Now the patient is in the sixth postoperative month and followed up every month for signs of recurrence.


Structure of human myeloma IgG3 Kuc.
An electron microscopy study of human myeloma IgG3 Kuc has shown that the hinge region in an intact molecule is in a compact state. The subunits are not fixed rigidly and are very mobile. These data are supported by results of ultracentrifugation and microcalorimetry. Non-extremal denaturating effects (pH 4.0, 20 degrees C or pH 7.8, 65 degrees C) lead to 'unfolding' of the hinge region which has a rod-like shape in electron micrographs.


Genetic Ablation of Inositol 1,4,5-Trisphosphate Receptor Type 2 (IP3R2) Fails to Modify Disease Progression in a Mouse Model of Spinocerebellar Ataxia Type 3.
Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disease caused by an abnormal polyglutamine expansion within the ataxin-3 protein (ATXN3). This leads to neurodegeneration of specific brain and spinal cord regions, resulting in a progressive loss of motor function. Despite neuronal death, non-neuronal cells, including astrocytes, are also involved in SCA3 pathogenesis. Astrogliosis is a common pathological feature in SCA3 patients and animal models of the disease. However, the contribution of astrocytes to SCA3 is not clearly defined. Inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is the predominant IP3R in mediating astrocyte somatic calcium signals, and genetically ablation of IP3R2 has been widely used to study astrocyte function. Here, we aimed to investigate the relevance of IP3R2 in the onset and progression of SCA3. For this, we tested whether IP3R2 depletion and the consecutive suppression of global astrocytic calcium signalling would lead to marked changes in the behavioral phenotype of a SCA3 mouse model, the CMVMJD135 transgenic line. This was achieved by crossing IP3R2 null mice with the CMVMJD135 mouse model and performing a longitudinal behavioral characterization of these mice using well-established motor-related function tests. Our results demonstrate that IP3R2 deletion in astrocytes does not modify SCA3 progression.


Feasibility of Crosslinked Acrylic Shape Memory Polymer for a Thrombectomy Device.
To evaluate the feasibility of utilizing a system of SMP acrylates for a thrombectomy device by determining an optimal crosslink density that provides both adequate recovery stress for blood clot removal and sufficient strain capacity to enable catheter delivery. Four thermoset acrylic copolymers containing benzylmethacrylate (BzMA) and bisphenol A ethoxylate diacrylate (Mn~512, BPA) were designed with differing thermomechanical properties. Finite element analysis (FEA) was performed to ensure that the materials were able to undergo the strains imposed by crimping, and fabricated devices were subjected to force-monitored crimping, constrained recovery, and bench-top thrombectomy. Devices with 25 and 35 mole% BPA exhibited the highest recovery stress and the highest brittle response as they broke upon constrained recovery. On the contrary, the 15 mole % BPA devices endured all testing and their recovery stress (5 kPa) enabled successful bench-top thrombectomy in 2/3 times, compared to 0/3 for the devices with the lowest BPA content. While the 15 mole% BPA devices provided the best trade-off between device integrity and performance, other SMP systems that offer recovery stresses above 5 kPa without increasing brittleness to the point of causing device failure would be more suitable for this application.


Corrigendum.
Failla MJ, Logerstedt DS, Grindem H, et al. Does extended pre-operative rehabilitation influence outcomes 2 years after ACL reconstruction? A comparative effectiveness study between MOON and Delaware-Oslo ACL cohorts. Am J Sports Med. 2016;44(10):2608-2614. (Original DOI: 10.1177/0363546516652594 ).


[Healthcare-associated bacteraemia in intensive care units of Ibn Rochd University Hospital, Casablanca].
Objective: This study was designed to determine the incidence of healthcare-associated bacteraemia in intensive care units (ICU) of Ibn Rochd University Hospital, Casablanca, Morocco, the frequency of the bacterial strains isolated and their antibiotic resistance patterns. Methods: A prospective longitudinal study was conducted between May and July 2015 on patients admitted to the Ibn Rochd University Hospital ICU. The Comité technique des infections nosocomiales et des infections liées aux soins (CITNILS) definition of bacteraemia was used. Micro-organisms were isolated and identified according to standard bacteriology techniques. Antibiotic susceptibility testing was performed according to CLSI 2013 guidelines. Results: A total of 720 patients were hospitalised during the study period; 48 (6.7%) acquired healthcare-associated bacteraemia with an incidence ranging from 7.3/1,000 HD to 13.7/1,000 HD. Fifty-four bacteria were isolated: A. baumannii and K. pneumoniae each accounted for 18.5% of isolates. 66.7% of A. baumannii strains were resistant to imipenem and 20% of K. pneumoniae strains were ESBL+ Conclusion: Healthcare-associated bacteraemia raises treatment problems due to multidrug-resistant bacteria, which is why regular surveillance is necessary to evaluate the time-course of these strains and the efficacy of prevention measures.


Sleep Period Time Estimation Based on Electrodermal Activity.
We proposed and tested a method to estimate sleep period time (SPT) using electrodermal activity (EDA) signals. Eight healthy subjects and six obstructive sleep apnea patients participated in the experiments. Each subject's EDA signals were measured at the middle and ring fingers of the dominant hand during polysomnography (PSG). For nine of the 17 participants, wrist actigraphy was also measured for a quantitative comparison of EDA- and actigraphy-based methods. Based on the training data, we observed that sleep onset was accompanied by a gradual reduction of amplitude of the EDA signals, whereas sleep offset was accompanied by a rapid increase in amplitude of EDA signals. We developed a method based on these EDA fluctuations during sleep-wake transitions, and applied it to a test dataset. The performance of the method was assessed by comparing its results with those from a physician's sleep stage scores. The mean absolute errors in the obtained values for sleep onset, offset, and period time between the proposed method, and the results of the PSG were 4.1, 3.0, and 6.1 min, respectively. Furthermore, there were no significant differences in the corresponding values between the methods. We compared these results with those obtained by applying actigraphic methods, and found that our algorithm outperformed these in terms of each estimated parameter of interest in SPT estimation. Long awakening periods were also detected based on sympathetic responses reflected in the EDA signals. The proposed method can be applied to a daily sleep monitoring system.


An optimized agonist peptide of protease-activated receptor 4 and its use in a validated platelet-aggregation assay.
Protease-activated receptor 4 (PAR4) is a promising drug target to improve the efficacy/safety window of antiplatelet agents. The native peptide GYPGQV, and the more-potent peptide AYPGKF, are PAR4-specific activators. However, these PAR4 agonist peptides (APs) elicit an agonist response, for example, platelet aggregation, at concentrations of 50 to 1000 µM in platelet-function assays, thereby limiting their utility to monitor the pharmacodynamic effects of PAR4 antagonists over a wide concentration range. Improved pharmacodynamic assays are needed for clinical development of PAR4 antagonists. We attempted to identify potent PAR4 APs to aid development of robust assays for optimization of PAR4 antagonists. Using an AYPG-based biased phage-display peptide library approach followed by chemical peptide optimization, A-Phe(4-F)-PGWLVKNG was identified. This peptide demonstrated an EC50 value of 3.4 µM in a platelet-aggregation assay, which is 16-fold more potent than AYPGKF. Using this new PAR4 AP, a platelet-rich plasma-aggregation assay using light-transmission aggregometry was developed and validated in a series of precision and reproducibility tests. PAR4 antagonist responses to PAR4 AP A-Phe(4-F)-PGWLVKNG (12.5 µM to 100 µM) were subsequently evaluated in this assay in vitro and ex vivo in a human study using BMS-986120, a PAR4 antagonist that entered clinical studies.


Exposure to foreign gut microbiota can facilitate rapid dietary shifts.
Dietary niche is fundamental for determining species ecology; thus, a detailed understanding of what drives variation in dietary niche is vital for predicting ecological shifts and could have implications for species management. Gut microbiota can be important for determining an organism's dietary preference, and therefore which food resources they are likely to exploit. Evidence for whether the composition of the gut microbiota is plastic in response to changes in diet is mixed. Also, the extent to which dietary preference can be changed following colonisation by new gut microbiota from different species is unknown. Here, we use Drosophila spp. to show that: (1) the composition of an individual's gut microbiota can change in response to dietary changes, and (2) ingestion of foreign gut microbes can cause individuals to be attracted to food types they previously had a strong aversion to. Thus, we expose a mechanism for facilitating rapid shifts in dietary niche over short evolutionary timescales.


A leptin-regulated circuit controls glucose mobilization during noxious stimuli.
Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor-expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores.


Hyperkalemic recurrent bilateral lower extremity weakness in a patient on hemodialysis.
Hyperkalemia is a severe life-threatening electrolyte disorder that commonly affects the cardiac conductivity and contractility. Ascending paralysis affecting the extremities with focal neurological deficit as well as quadriparesis and a seizure associated with hyperkalemia has been reported in the literature. Here, we describe a case of isolated recurrent lower extremity paralysis and an episode of seizure in an 83-year-old patient with end-stage renal disease on hemodialysis.


Superior positioning of the ptotic umbilicus in abdominoplasties and TRAM flaps.
The author finds that higher positioning of the umbilicus in cases of abdominoplasty and other similar operations such as transverse rectus abdominis musculocutaneous flap breast reconstruction is a useful technique. The operation renders better aesthetic results and also increases the margin of safety in lower abdominal flap circulation because tension is transferred from the lower abdomen to the upper abdomen. Technically, the procedure is easy to do and teach. The umbilicus is fixed to a higher point in the abdominal wall and the new umbilicus is reconstructed in a reasonably higher position with a safe degree of tension at the upper abdominal flap while trying to decrease tension in the lower part of the abdominal flap.


Formation of high concentrations of BrO(2) in acidic bromate solutions.
A new procedure to produce the BrO(2) transient species allowed time-resolved UV-vis spectra that show a structured band (lambda(max) = 502 nm) in dichloromethane to be obtained. In water, because of the increase of the dielectric constant, the lambda(max) presents a blue shift to 474 nm and the species decomposes much faster. The time-resolved spectra show evidence for its equilibrium with a nonidentified colorless form. This route opens new possibilities to the study this species in solution.


Association of arg16gly and gln27glu, b2-adrenergic receptor gene polymorphism with asthma. A systematic review and meta-analysis of case control studies.
The study was planned to assimilate quantitatively the available evidences on association of Arg16Gly and Glu27Gln with asthma and to produce more precise results. All case-control studies conducted on adults were searched on Medline, Embase, PubMed, Wiley online library according to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. The strength of association was measured by odds ratios with 95% confidence interval. A total of 17 case-control studies were included in the meta-analysis and there was no significant association of asthma with Arg16Gly (odds ratio = 1.19; 95% confidence interval = 0.75-1.50, p=0.459) and Glu27Gln of ADRb2 polymorphism (odds ratio=0.87, 95% confidence interval =0.44-1.71, p=0.683). Moreover, neither Gly16 allele (odds ratio = 0.98; 95% confidence interval = 0.70-1.38, p=0.867) nor Glu27 allele (odds ratio = 0.67, 95% confidence interval = 0.38-1.19, p=0.169) contributed to asthma susceptibility. There was also no significant association between haplotypes of both single nucleotide polymorphisms and asthma (p>0.05). Data indicated that adrenergic receptor b2 did not contribute markedly to susceptibility to asthma (p>0.05).


Identification of an altered immunoglobulin heavy-chain gene rearrangement in the central nervous system in B-precursor acute lymphoblastic leukemia.
In B-precursor acute lymphoblastic leukemia (ALL), the nucleotide sequence of the complementarity determining region III (CDRIII) in the rearranged immunoglobulin heavy chain gene (IgH) has been used as a molecular fingerprint to identify the leukemic cells. In a child with B-precursor ALL without central nervous system (CNS) disease at diagnosis and a subsequent isolated CNS relapse, we examined the stability of the rearranged IgH by comparing the nucleotide sequences of the CDRIII in the leukemic cells from the marrow at diagnosis to the sequences in the leukemic cells from the cerebrospinal fluid at relapse. Whereas two of the three IgH sequences isolated from the leukemic cells at CNS relapse were identical to sequences originally isolated from the marrow lymphoblasts at diagnosis, the third CNS sequence was similar but not identical to the third marrow sequence. The third IgH sequence identified in the CNS differed from the marrow sequence only at the variable gene segment adjoining the CDRIII. Using a detection method based on the polymerase chain reaction, the altered IgH sequence identified in the leukemic cells from the cerebrospinal fluid was noted to be present in the CNS at a higher frequency than the related diagnostic sequence and was not detected in the marrow either at diagnosis or at CNS relapse. These findings indicate that the clonal pattern of leukemia in the CNS may differ from that in the marrow.


Biochemical transformation of mouse cells by a purified fragment of marmoset herpesvirus DNA.
Although the size of marmoset herpesvirus (MarHV) DNA, estimated by velocity sedimentation in sucrose gradients, was similar to that of herpes simplex virus type 1 (HSV-1) DNA, the restriction endonuclease sites of MarHV and HSV-1 DNAs were quite different. A specific BamHI restriction fragment (6.2 x 10(6) daltons) of MarHV DNA biochemically transformed LM(TK-) mouse fibroblasts to the thymidine kinase(TK)-positive phenotype. Rabbit antisera, prepared against MarHV TK, inhibited MarHV-induced TK, but not HSV-1, HSV-2, or cellular TKs. Disc PAGE analyses and enzyme neutralization experiments with the anti-MarHV TK sera demonstrated that the TK expressed in MarHV transformants was MarHV-specific.


Absolute Quantification of Tomato leaf curl New Delhi virus Spain strain, ToLCNDV-ES: Virus Accumulation in a Host-Specific Manner.
Tomato leaf curl New Delhi virus (ToLCNDV) (family Geminiviridae, genus Begomovirus) has recently been introduced in western Mediterranean countries. Isolates in Spain constitute a new strain, denominated ToLCNDV-ES, that is causing losses in commercial zucchini and melon crops; however, it is also, although less often, detected in commercial tomato crops. We developed a tissue-print hybridization test to detect the two genomic components of the virus and a TaqMan quantitative polymerase chain reaction (qPCR) test to estimate the number of genome copies in plants. qPCR was approximately 104 to 106 times more sensitive than tissue-print hybridization to detect viral genomic DNA-A and DNA-B, respectively. It also detected the virus in more experimentally and naturally ToLCNDV-ES-infected zucchini squash and tomato plants. ToLCNDV-ES DNA-A titers were significantly lower in tomato than in zucchini plants, often falling below the detection limits in the hybridization test. In addition, the DNA-B accumulation was impaired in tomato when compared with zucchini. According to the data obtained in this study, the differences in viral titers of both plant species contribute to explain the dissimilarities in symptom expression, capability of detection, and transmission of the virus.


Attention to people and toys during social and object mastery in children with Down syndrome.
Attention to people versus objects by children with Down syndrome was examined. Subjects were presented with situations in which the primary focus alternated between an object stimulus (a toy) and a social stimulus (a singing experimenter). The children with Down syndrome monitored their environment in the same manner as did MA-matched typically developing children during object mastery and had a more focused attention style during social mastery. Reasons for this difference in attention across the two situations were discussed.


Assessing classroom and laboratory spread of COVID-19 in a university after elimination of physical distancing.
The objective of this study was to assess COVID-19 classroom transmission in the university setting when physical distancing was eliminated. Data was collected in fall 2021 at a private university. Universal masking, robust contact tracing, vaccination requirement, and enforced testing were in place. Exposures were classified as classroom versus non-classroom. ANOVA and chi-squared tests were used to identify significant relationships between predictors and COVID-19 test result. Logistic regression was conducted to investigate the relationship between exposure type and test result. A total of 162 student cases were identified with 1,658 associated close contacts. One-third of contacts (31.1%, n = 516) only had a non-classroom exposure, 63.8% (n = 1,057) only had a classroom exposure, and 5.1% (n = 85) had both. Close contacts were significantly more likely to test positive if they had a non-classroom exposure (60 of 601; 10.0%) compared to a classroom exposure (1 of 1057; 0.1%) (OR 58.8, CI 18.5-333.3, p < 0.001). Removing physical distancing in classrooms that had universal masking did not result in high rates of COVID-19 transmission. This has policy implications because eliminating physical distancing does not greatly increase transmission risk when universal masking is in place.


MEG source estimation from mesio-basal temporal areas in a child with a porencephalic cyst.
A child whose left temporal lobe contained mesial, anterior and basal structures but lacked superio-lateral cortex had intractable epilepsy secondary to a porencephalic cyst. Magnetoencephalography (MEG) shows equivalent current dipoles (ECDs) as dipole modeling for temporal lobe epilepsy rather than in an exact location. We hypothesized that the magnetic fields generated by the epileptic discharges in mesio-basal temporal areas could be detected by MEG without interference from the superio-lateral temporal cortices. We analyzed MEG spikes using single dipole analysis and synthetic aperture magnetometry (SAM), and compared with EEG spike topography. Two MEG ECDs corresponding to T3 spikes localized to the anterior mesio-basal temporal region with vertical orientation. Sixteen MEG ECDs corresponding to T5 spikes localized to the middle to posterior mesio-basal temporal region with vertical orientation. SAM revealed maximum current density at hippocampus and anterior fusiform gyrus for T3 spikes, and at posterior hippocampus and fusiform gyrus for T5 spikes. Vertically oriented ECDs were obtained without superio-lateral temporal cortices because of temporo-parieto-occipital porencephalic cyst. The absence of superio-lateral temporal cortices, prominent temporal EEG spikes, less prominent MEG spikes, and mesio-basal SAM spikes indicated that the vertically oriented ECDs were projected directly from the mesio-basal temporal region.


A Population-Based Cohort Study of Emergency Appendectomy Performed in England and New York State.
To compare selected outcomes (30-day reoperation and total length of hospital stay) following emergency appendectomy between populations from New York State and England. This retrospective cohort study used demographic and in-hospital outcome data from Hospital Episode Statistics (HES) and the New York Statewide Planning and Research Cooperative System (SPARCS) administrative databases for all patients aged 18+ years undergoing appendectomy between April 2009 and March 2014. Univariate and adjusted multivariable logistic regression were used to test significant factors. A one-to-one propensity score matched dataset was created to compare odd ratios (OR) of reoperations between the two populations. A total of 188,418 patient records, 121,428 (64.4%) from England and 66,990 (35.6%) from NYS, were extracted. Appendectomy was completed laparoscopically in 77.7% of patients in New York State compared to 53.6% in England (P < 0.001). The median lengths of hospital stay for patients undergoing appendectomy were 3 (interquartile range, IQR 2-4) days versus 2 (IQR 1-3) days (P < 0.001) in England and New York State, respectively. All 30-day reoperation rates were higher in England compared to New York State (1.2 vs. 0.6%, P < 0.001), representing nearly a twofold higher risk of 30-day reoperation (OR 1.88, 95% CI 1.64-2.14, P < 0.001). As the proportion of appendectomy completed laparoscopically increased, there was a reduction in the reoperation rate in England (correlation coefficient -0.170, P = 0.036). Reoperations and total length of hospital stay is significantly higher following appendectomy in England compared to New York State. Increasing the numbers of appendectomy completed laparoscopically may decrease length of stay and reoperations.


The effects of nutrition on unconjugated plasma bilirubin concentrations in squirrel monkeys.
Bolivian squirrel monkeys (Saimiri sciureus) have fasting unconjugated hyperbilirubinemia (males: 2.0 +/- 0.14; females: 3.0 +/- 0.26 mg per dl) which resembles that of humans with Gilbert's syndrome. Closely related Brazilian squirrel monkeys have fasting levels (males: 0.29 +/- 0.045; females: 0.36 +/- 0.073 mg per dl) similar to normal people. The purpose of this study was to identify the underlying mechanisms and the nutritional factors involved. Both Bolivian and Brazilian squirrel monkeys had higher plasma bilirubin concentrations after an 18 hr fast than 4 hr after feeding. The development of fasting hyperbilirubinemia was progressive for at least 24 hr. Both populations that received a semipurified diet containing 5% fat had lower fasting and postprandial plasma bilirubin concentrations than did animals receiving 0.3% fat but much lower than those receiving 20% fat. The emulsified complete meal, or glucose, sucrose, casein, or lactalbumin alone when given by intragastric tube lowered the plasma bilirubin levels of Bolivian monkeys to less than one-half of fasting values within 1 to 4 hr. Water or butter did not have a significant effect. Glucose or fructose, when given intravenously, lowered the plasma bilirubin levels to less than half of fasting values; the fat emulsion, Intralipid, did not have a statistically significant effect. Subcutaneous epinephrine increased plasma glucose concentrations and reduced plasma bilirubin concentrations. When glucose or glucose plus butter were given by stomach tube to Bolivian squirrel monkeys for 48 hr, a very low plasma bilirubin concentration resulted whereas butter given alone resulted in high values.(ABSTRACT TRUNCATED AT 250 WORDS)


Antagonism of PPAR-γ signaling expands human hematopoietic stem and progenitor cells by enhancing glycolysis.
Hematopoietic stem cells (HSCs) quiescently reside in bone marrow niches and have the capacity to self-renew or differentiate to form all of the blood cells throughout the lifespan of an animal. Allogeneic HSC transplantation is a life-saving treatment for malignant and nonmalignant disorders. HSCs isolated from umbilical cord blood (CB) are used for hematopoietic cell transplantation (HCT), but due to the limited numbers of HSCs in single units of umbilical CB, a number of methods have been proposed for ex vivo expansion of human HSCs. We show here that antagonism of peroxisome proliferator-activated receptor (PPAR)-γ promotes ex vivo expansion of phenotypically and functionally defined subsets of human CB HSCs and hematopoietic progenitor cells (HSPCs). PPAR-γ antagonism in CB HSPCs strongly downregulated expression of several differentiation-associated genes, as well as fructose-bisphosphatase 1 (FBP1; which encodes a negative regulator of glycolysis), and enhanced glycolysis without compromising mitochondrial metabolism. The expansion of CB HSPCs by PPAR-γ antagonism was completely suppressed by removal of glucose or inhibition of glycolysis. Moreover, knockdown of FBP1 expression promoted glycolysis and ex vivo expansion of long-term repopulating CB HSPCs, whereas overexpression of FBP1 suppressed the expansion of CB HSPCs that was induced by PPAR-γ antagonism. Our study suggests the possibility for a new and simple means for metabolic reprogramming of CB HSPCs to improve the efficacy of HCT.


Liver resection for cancer.
Liver resection was performed for primary and secondary cancer in 46 patients. Left lobe resection was performed in 11 patients, right lobe resection in 22 and extended right lobe resection in 13. There was no post-operative mortality after left lobe resection, 9 after right lobe and 5 after extended right lobe resection. Ten patients have survived two years after the liver resection. This surgical procedure seems to be of benefit especially for patients with primary liver cancer and with metastases from cancer coli-recti.


Morphology-controlled 2D ordered microstructure arrays by surface modification of colloidal template.
In this paper, we describe a convenient approach for fabricating two-dimensional, ordered TiO2 bowl-like structure and inverted-bowl-like structure patterns consisting of submicrometer arrays on a self-assembled monolayer film, for the first time using a surface-modified polystyrene colloidal monolayer as the template. Typically, the well-ordered two-dimensional TiO2 bowl-like structures were obtained by liquid phase deposition within the interstitial voids in assemblies of polystyrene spheres followed by the dissolution of the polystyrene template with dichloromethane. Otherwise, through a simple wet treatment by immersing in the sulfuric acid at 50 degrees C, the surface characteristics of polystyrene were turned from hydrophobic to hydrophilic. The ordered inverted-bowl-like structures could be prepared on this treated surface. We believe that this method could be extendable to colloidal template with smaller dimensions, and to periodic arrays made of other materials.


Endurance Running Training Individually Guided by HRV in Untrained Women.
da Silva, DF, Ferraro, ZM, Adamo, KB, and Machado, FA. Endurance running training individually guided by HRV in untrained women. J Strength Cond Res 33(3): 736-746, 2019-The aim of this study was to analyze the effects of heart rate variability (HRV)-guided training compared with a standardized prescription on (a) time to complete 5-km running performance (t5km), (b) peak treadmill running speed (Vpeak) and its time limit (tlim at Vpeak), and (c) autonomic cardiac modulation (i.e., parasympathetic activity and recovery) in untrained women. Additionally, we correlated changes in t5km with changes in Vpeak, tlim at Vpeak and autonomic cardiac modulation. Thirty-six untrained women were divided into a HRV-guided training group (HRVG) and a control group (CG). The CG followed a predefined program, alternating moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). The determination of MICT or HIIT was based on the pretraining HRV for HRVG. MICT was performed if HRV was <mean - 1 SD of previous measures. Otherwise, HIIT was prescribed. The t5km, Vpeak, tlim at Vpeak, parasympathetic activity (i.e., rMSSD) and parasympathetic reactivation (i.e., HRR) were measured before and after the training period. The t5km decreased to a greater magnitude in the HRVG (-17.5 ± 5.6% vs. -14 ± 4.7%; Effect Size (ES) between-group difference = moderate). rMSSD and tlim at Vpeak only improved in HRVG (+23.3 ± 27.8% and +23.6 ± 31.9%, respectively). The HRVG experienced greater improvements in Vpeak and HRR (Vpeak: 10 ± 7.3% vs. 8.2 ± 4.7%; HRR: 19.1 ± 28.1% vs. 12.6 ± 12.9%; ES between-group difference = small). Although HRVG performed less MICT than CG, the volume of MICT was negatively related to changes in t5km. Vpeak changes were highly correlated with t5km changes. The greater improvements in HRVG for t5km and autonomic modulation reinforce the potential application of this tool.


[Visualization of neuronal fiber tracts in white matter based on diffusion tensor].
In this paper, the basic principal or rational of diffusion tensor imaging (DTI), which develops rapidly in the field of functional magnetic resonance imaging study, is introduced. And how to reconstruct the imaging of neuronal fiber tracts in white matter with the data of DTI is described. The technique of tractography, its advantages and disadvantages are analyzed. Finally, the limitations and further applications of neuronal fiber tracts visualization are discussed.


The ethics of ex utero research on spare 'non-viable' IVF human embryos.
In this paper, the focus is not on some particular developmental feature of the human embryo, but rather on the embryo's potential for development tout court. To this end, the moral relevance of the difference between human embryos that have the potential for continued human growth and development and human embryos that do not have this potential is explored and a distinction between viable and non-viable IVF human embryos is introduced. This is followed by a discussion of what is morally wrong with killing to show that none of the concerns associated with the act of killing apply to the destruction of non-viable IVF human embryos. On this basis, it is argued that scientifically and ethically sound research on spare non-viable IVF human embryos may proceed.


Pathologic complete response and disease-free survival are not surrogate endpoints for 5-year survival in rectal cancer: an analysis of 22 randomized trials.
We performed a literature-based analysis of randomized clinical trials to assess the pathologic complete response (pCR) (ypT0N0 after neoadjuvant therapy) and 3-year disease-free survival (DFS) as potential surrogate endpoints for 5-year overall survival (OS) in rectal cancer treated with neoadjuvant (chemo)radiotherapy (CT)RT. A systematic literature search of PubMed, EMBASE, the Web of Science, SCOPUS, CINAHL, and the Cochrane Library was performed. Treatment effects on 3-year DFS and 5-year OS were expressed as rates of patients alive (%), and those on pCR as differences in pCR rates (∆pCR%). A weighted regression analysis was performed at individual- and trial-level to test the association between treatment effects on surrogate (∆pCR% and ∆3yDFS) and the main clinical outcome (∆5yOS). Twenty-two trials involving 10,050 patients, were included in the analysis. The individual level surrogacy showed that the pCR% and 3-year DFS were poorly correlated with 5-year OS (R=0.52; 95% CI, 0.31-0.91; P=0.002; and R=0.60; 95% CI, 0.36-1; P=0.002). The trial-level surrogacy analysis confirmed that the two treatment effects on surrogates (∆pCR% and ∆3yDFS) are not strong surrogates for treatment effects on 5-year OS % (R=0.2; 95% CI, -0.29-0.78; P=0.5 and R=0.64; 95% CI, 0.29-1; P=0.06). These findings were confirmed in neoadjuvant CTRT studies but not in phase III trials were 3-year DFS could still represent a valid surrogate. This analysis does not support the use of pCR and 3-year DFS% as appropriate surrogate endpoints for 5-year OS% in patients with rectal cancer treated with neoadjuvant therapy.


Identification of reproducible radiomic features from on-board volumetric images: A multi-institutional phantom study.
Radiomics analysis using on-board volumetric images has attracted research attention as a method for predicting prognosis during treatment; however, the lack of standardization is still one of the main concerns. This study investigated the factors that influence the reproducibility of radiomic features extracted from on-board volumetric images using an anthropomorphic radiomics phantom. Furthermore, a phantom experiment was conducted with different treatment machines from multiple institutions as external validation to identify reproducible radiomic features. The phantom was designed to be 35 × 20 × 20 cm with eight types of heterogeneous spheres (⌀ = 1, 2, and 3 cm). On-board volumetric images were acquired using 15 treatment machines from eight institutions. Of these, kilovoltage cone-beam computed tomography (kV-CBCT) image data acquired from four treatment machines at one institution were used as an internal evaluation dataset to explore the reproducibility of radiomic features. The remaining image data, including kV-CBCT, megavoltage-CBCT (MV-CBCT), and megavoltage computed tomography (MV-CT) provided by seven different institutions (11 treatment machines), were used as an external validation dataset. A total of 1,302 radiomic features, including 18 first-order, 75 texture, 465 (i.e., 93 × 5) Laplacian of Gaussian (LoG) filter-based, and 744 (i.e., 93 × 8) wavelet filter-based features, were extracted within the spheres. The intraclass correlation coefficient (ICC) was calculated to explore feature repeatability and reproducibility using an internal evaluation dataset. Subsequently, the coefficient of variation (COV) was calculated to validate the feature variability of external institutions. An absolute ICC exceeding 0.85 or COV under 5% was considered indicative of a highly reproducible feature. For internal evaluation, ICC analysis showed that the median percentage of radiomic features with high repeatability was 95.2%. The ICC analysis indicated that the median percentages of highly reproducible features for inter-tube current, reconstruction algorithm, and treatment machine were decreased by 20.8%, 29.2%, and 33.3%, respectively. For external validation, the COV analysis showed that the median percentage of reproducible features was 31.5%. A total of 16 features, including nine LoG filter-based and seven wavelet filter-based features, were indicated as highly reproducible features. The gray-level run-length matrix (GLRLM) was classified as containing the most frequent features (N = 8), followed by the gray-level dependence matrix (N = 7) and gray-level co-occurrence matrix (N = 1) features. We developed the standard phantom for radiomics analysis of kV-CBCT, MV-CBCT, and MV-CT images. With this phantom, we revealed that the differences in the treatment machine and image reconstruction algorithm reduce the reproducibility of radiomic features from on-board volumetric images. Specifically, the most reproducible features for external validation were LoG or wavelet filter-based GLRLM features. However, the acceptability of the identified features should be examined in advance at each institution before applying the findings to prognosis prediction.


Airway and pulmonary tissue responses to platelet-activating factor in rats.
We studied airway and pulmonary tissue responses to platelet-activating factor (PAF) in rats by measuring alveolar pressure with the alveolar capsule technique. We calculated airway resistance (Raw), dynamic elastance (Edyn), and pulmonary tissue resistance (Rtis). PAF was administered intravenously in doses of 0.1, 1, 10, and 30 micrograms (1 dose per animal, 5 rats for each dose). Infusion of PAF resulted in a significant increase in Rtis and Edyn (p < .05). Maximal values of Edyn were observed with the infusion of 10 micrograms of PAF (p < .02). Rtis presented a significant increase after infusion of 1 microgram of PAF (p < .05). The observed increase in Raw was transient and did not reach statistical significance. After infusion of PAF lungs were fixed by a quick-freezing method. Morphometric analysis showed that PAF infusion resulted in significant increases in intraluminal secretion (p = .001) and peribronchiolar edema (p < .001) but did not result in significant airway contraction. We conclude that intravenous infusion of PAF results in significant effects on lung tissue mechanics. The effects of PAF on the mechanical properties of lung parenchyma reflect the inflammatory alterations induced by this agonist in distal airspaces.


Evidence that GnRH decreases with gonadal steroid feedback but increases with age in postmenopausal women.
Studies of the effects of gonadal steroid negative feedback and age on the hypothalamic-pituitary axis in postmenopausal women (PMW) have identified significant but inconsistent changes in gonadotropin dynamics. In the current study, we investigated the effect of gonadal steroid replacement and age on overall GnRH secretion estimated by using submaximal GnRH receptor blockade. Twenty-four healthy PMW, 45-55 yr (n = 13) and 70-80 yr (n = 11), were studied. Subjects were studied at baseline (BL) on no hormone replacement therapy, after 1 month of transdermal estrogen (50 microg/d; E) and again after a further month of E and 7 d of transvaginal progesterone (100 mg bid; E + P). At each admission, blood was sampled every 30 min for 4 (BL and E) or 8 h (E + P) before and 10 h after sc administration of a submaximal dose (5 microg/kg) of the NAL-GLU GnRH antagonist ([Ac-D2Nal(1), D4ClPhe(2), DPal(3), Arg(5), DGlu(AA)(6), DAla(10)] GnRH). Percent inhibition of LH was calculated by expressing the difference between the nadir following GnRH antagonist administration and the preantagonist baseline as a percent of the baseline. Physiologic E and P levels were achieved with the appropriate hormone replacement regimens. Mean LH levels decreased from baseline with E alone and decreased further with E + P (81.4 +/- 6.6, 68.2 +/- 8.1 and 48.0 +/- 4.3 IU/liter, respectively; P < 0.005). Percent inhibition of LH following submaximal GnRH receptor blockade decreased with age (57.6 +/- 1.8% in young PMW vs. 51.4 +/-2.2% in old PMW; P < 0.05) implying an increase in GnRH secretion with age. There was an increase in percent inhibition of LH in response to submaximal GnRH receptor blockade with E and a further increase with E + P (54.8 +/-1.5%, 58.8 +/- 1.9% and 69.9 +/- 2.8%, respectively; P < 0.05), indicating a progressive decrease in endogenous GnRH secretion with gonadal steroid feedback. Mean LH and FSH levels were lower at baseline in old compared with young PMW. However, the effect of gonadal steroid feedback on endogenous GnRH secretion was similar in young and old PMW. 1) The overall quantity of GnRH secretion increases with age as demonstrated by the progressive decrease in LH inhibition following submaximal GnRH antagonist administration with increasing age; 2) E negative feedback is associated with a decrease in GnRH secretion (as indicated by an increased percent inhibition of LH following submaximal GnRH receptor blockade); 3) E2 and P are associated with a further decease in overall amount of GnRH secreted; and 4) Age does not dampen the inhibition of hypothalamic GnRH secretion by E and P in PMW.


Segregation of odor identity and intensity during odor discrimination in Drosophila mushroom body.
Molecular and cellular studies have begun to unravel a neurobiological basis of olfactory processing, which appears conserved among vertebrate and invertebrate species. Studies have shown clearly that experience-dependent coding of odor identity occurs in "associative" olfactory centers (the piriform cortex in mammals and the mushroom body [MB] in insects). What remains unclear, however, is whether associative centers also mediate innate (spontaneous) odor discrimination and how ongoing experience modifies odor discrimination. Here we show in naïve flies that Galphaq-mediated signaling in MB modulates spontaneous discrimination of odor identity but not odor intensity (concentration). In contrast, experience-dependent modification (conditioning) of both odor identity and intensity occurs in MB exclusively via Galphas-mediated signaling. Our data suggest that spontaneous responses to odor identity and odor intensity discrimination are segregated at the MB level, and neural activity from MB further modulates olfactory processing by experience-independent Galphaq-dependent encoding of odor identity and by experience-induced Galphas-dependent encoding of odor intensity and identity.


Platelet-lowering therapy with anagrelide as an adjuvant therapy for treatment of primary pulmonary neoplasm-associated extreme thrombocytosis.
Thrombocytosis is a common paraneoplastic syndrome in patients with lung cancer. However, complications associated with malignancy-related thrombocytosis, including thrombosis and hemorrhage, have rarely been reported. In this case, we describe a 57-year-old man with unresectable adenocarcinoma of the lung who presented with a platelet count over 100 × 10(4)/mm(3). In addition, deep venous thrombosis of the left femoral vein was found during admission. The circumference of the left lower leg and platelet count progressed during the period without chemotherapy and anticoagulants; however, with the addition of anagrelide they improved. We provided an adjuvant therapy with platelet-lowering therapy to treat cancer-induced thrombocytosis during the period without chemotherapy.


The significance of abnormally high and low maternal serum alpha-fetoprotein levels between 14 and 25 weeks of gestation.
A total of 6,160 gravidas with gestational ages from 14 to 25 weeks were collected to quantify maternal serum alpha-fetoprotein (MSAFP) using an enzyme immunoassay kit. A level over 2.5 MoM (multiples of the median) was defined as high and a level below 0.4 MoM as low. Ninety-eight women (1.59%) had an initially high MSAFP and 88 (1.42%) a low MSAFP. In the low MSAFP group, 80% returned for a further checkup. Among them, 46% had an over-estimation of gestational age based on their last menstrual period (LMP), 28% had a normal MSAFP and 9% still had a low MSAFP level on a repeat test. Pathologic conditions in other pregnancies included a hydatidiform mole, miscarriage and pseudocyesis. One nonresponder had an ectopic pregnancy. After delivery, no major fetal abnormalities, including trisomy syndromes, were noted in pregnancies carried to term. In the high MSAFP group, 84% returned for check-up. Among them, 15% had an under-estimation of gestational age based on LMP, 16% had twin pregnancies, 46% had a normal MSAFP and 12% still had a high MSAFP on a repeat test. Pathologic conditions in the other pregnancies included one anencephaly, one hydrocephaly and 6 miscarriages. Wrong dating by LMP and false positivity were the most frequent causes of abnormal levels of MSAFP. Two gravidas had artificial abortions because of undue anxiety. MSAFP screening in Taiwan for open neural tube defects does not seem appropriate and using 0.4 MoM as a fixed low cut-off point is inadequate for trisomy syndrome screening. Maternal anxiety should be seriously considered and proper genetic counseling implemented in a screening procedure.


Distinguishing expected negative outcomes from preparatory control in the human orbitofrontal cortex.
The human orbitofrontal cortex (OFC) plays a critical role in adapting behavior according to the context provided by expected outcomes of actions. However, several aspects of this function are still poorly understood. In particular, it is unclear to what degree any subdivisions of the OFC are specifically engaged when negatively valenced outcomes are expected, and to what extent such areas might be involved in preparatory active control of behavior. We examined these issues in two complementary functional magnetic resonance imaging (fMRI) studies in which we simultaneously and independently manipulated monetary incentives for correct performance, and demands for active preparation of cognitive control. In both experiments, preparation for performance was associated with lateral PFC activity in response to high incentives, regardless of their valence, as well as in response to increased task demands. In contrast, areas of the OFC centered around the lateral orbital sulcus responded maximally to negatively perceived prospects, even when such prospects were associated with decreases in preparatory cognitive control. These results provide direct support for theoretical models which posit that the OFC contributes to behavioral regulation by representing the value of anticipated outcomes, but does not implement active control aimed at avoiding or pursuing outcomes. Furthermore, they provide additional converging evidence that the lateral OFC is involved in representing specifically the affective impact of anticipated negative outcomes.


Emergency Information Communication Structure by Using Multimodel Fusion and Artificial Intelligence Algorithm.
With the development of The Times, social events are increasing, and emergency management has gradually become the main helper to solve the crisis in the public domain. By observing the current situation of many countries and regions, we can find that various types of public crises often occur in many countries and regions in the world, which have severely affected people's daily life, lives, and property. Through long-term research and analysis, it can be known that the emergency management mechanism currently established in China has certain shortcomings. The communication problem of emergency information is likely to cause the emergency work to not proceed smoothly. In addition, problems in the communication channels of emergency information are likely to cause problems in the cooperation of various departments when people carry out emergency management work, and the efficiency of the government in dealing with problems will also be reduced in real scenarios. In order to improve the efficiency of emergency information management, this paper aims at the various problems existing and facing in the construction of emergency management system. On this basis, the integration of various relevant emergency information management plan models is analyzed and sorted out, and based on the research and integration of the development of artificial intelligence algorithms. The main research results of emergency information management at home and abroad are comprehensively studied and evaluated. Finally, a QG algorithm based on more model fusion is developed. In the process of analysis, this article uses artificial intelligence algorithms to build a prediction model of multiple modes and collects the data needed to build the model by random extraction. Through the analysis of different data sets, it is used as the basic training data for prediction. Through comprehensive analysis, the model constructed in this paper can promote the sharing of emergency information among departments to a certain extent.


Supplementation of Probiotics and Its Effects on Physically Active Individuals and Athletes: Systematic Review.
The aim of this study was to conduct a systematic review of the effects of probiotic supplementation on physically active individuals. The participants, interventions, comparisons, outcome and study design inclusion criteria were (a) studies involving healthy adults or older subjects of both sexes who did physical exercise (including athletes and physically active individuals), (b) interventions with probiotics, (c) inclusion of a control group, (d) outcomes not previously defined, and (e) clinical trials and randomized clinical trials, with no language or date restrictions. The search was conducted in the following scientific databases: MEDLINE, Embase, SciELO, Scopus, and Lilacs. Search terms were "Probiotics" OR "Prebiotics" OR "Microbiota" AND "Exercise" OR "Athletes." The articles were first screened by title and abstract by two independent reviewers and disagreements resolved by a third reviewer. Data were extracted independently by the same two reviewers; results were extracted in duplicate and then compared to avoid errors. A total of 544 articles were retrieved and 24 were included. A total of 1,680 patients were included, most of them being male (n = 1,134, 67.5%), with a mean age of 30.9 ± 6.1 years. Following probiotic supplementation, positive effects have been reported for several outcomes including respiratory tract infection, immunologic markers, and gastrointestinal symptoms in both athletes and nonathletes. However, published studies have distinct protocols and measured outcomes, and some of them have small sample size and failed to prove beneficial effect on probiotic supplementation, leading to inconclusive results for standardized supplementation protocols.


Ultrasonography: an alternative to x-ray-guided needle localization of nonpalpable breast masses.
Preoperative ultrasonography was used as an alternative to x-ray mammography to localize 92 breast lesions encountered in 82 patients. Recommendation for biopsy was made on the basis of the ultrasonographic finding of a nonpalpable mass or an area of architectural distortion, or in the presence of equivocal physical findings if sonomammography demonstrated a solid or an anechoic mass. Sonomammography was performed in the operating room, just before anticipated biopsy, with a hand-held high-resolution scanner. When the suspicious area was imaged and its precise location noted, the breast was then prepared and draped in the usual manner, and a biopsy was performed. If the suspicious area could not be easily localized after the incision was made and the breast explored, the transducer was "gowned" and used directly in the wound to help find the lesion. This technique has proven effective and accurate. In selected patients ultrasonography may be used as well as, or instead of, x-ray needle localization for the precise excision of nonpalpable breast lesions, excluding calcifications.


Toxicological Effect of Metal Oxide Nanoparticles on Soil and Aquatic Habitats.
Metal oxide nanoparticles (MO-NPs) with multifunctional properties are used extensively in various industries and released into the environment as industrial effluents and waste nano-products. These non-degradable, toxic MO-NPs are accumulating in the environment, debilitating the ecosystem and their biological communities. In this review article, a real-time scenario of MO-NP toxicity towards the soil and aquatic ecosystem and their mode of toxicity have been addressed in detail. The up-to-date information presented here suggests serious consideration of the consequences before random utilization of MO-NPs.


Vulvovaginal-gingival syndrome.
Vulvovaginal-gingival syndrome is a distinct variant of classic lichen planus frequently associated with mucocutaneous scarring and vaginal stricture formation, therefore early diagnosis and treatment through a multidisciplinary approach is essential. Management is challenging and is characterised by wide variation in treatments and lack of evidence-based therapeutic approaches. Literature review with particular regard to therapeutic approaches is performed with a view towards a cooperative treatment study.


Androgen receptor gene amplification and protein expression in recurrent prostate cancer.
The androgen receptor (AR) is highly expressed in androgen dependent and recurrent prostate cancer, suggesting that it has a role in tumor growth and progression after androgen deprivation. AR amplification may contribute to androgen receptor activation in relative androgen absence. Formalin fixed and frozen specimens of recurrent prostate cancer were obtained by transurethral resection from men with increasing serum level of prostate specific antigen in whom urinary retention developed. AR amplification and X-chromosome number were determined by 2-color fluorescence in situ hybridization, and AR protein expression was determined by automated image analysis. We compared clinical characteristics and survival of patients with recurrent prostate cancer whose tumors did or did not exhibit AR amplification and X-chromosome polysomy. Thirty-three percent of the 24 recurrent prostate cancer specimens 8 (33%) showed AR amplification. AR was more intensely immunostained in tumors with amplified (AMP) AR (mean optical density 0.36 +/- 0.07) than in tumors lacking amplification (NO AMP) (mean optical density 0.24 +/- 0.09). No differences were found between the 2 groups when comparing serum levels of prostate specific antigen (AMP 11.9, 14.8; NO AMP 26.0, 60.3), Gleason sum (AMP 9.0, 0.5; NO AMP 9.0, 1.0), clinical TNM stage (AMP 4 cases M0, M1 4; NO AMP 8 M0, 8 M1), race (AMP 6 white and 2 black men, NO AMP white and 7 black men) or survival in months (AMP 47.5, 28.5; NO AMP 33.5, 72.0). Three of the recurrent prostate cancer specimens (13%) demonstrated X-chromosome copy number 2 or greater and no differences were found when comparing clinical characteristics between these groups. AR amplification in recurrent prostate cancer results in higher levels of AR protein expression but does not affect survival.


Maternal medication use and the risk of brain tumors in the offspring: the SEARCH international case-control study.
N-nitroso compounds (NOC) have been associated with carcinogenesis in a wide range of species, including humans. There is strong experimental data showing that nitrosamides (R(1)NNO.COR(2)), a type of NOC, are potent neuro-carcinogens when administered transplacentally. Some medications are a concentrated source of amides or amines, which in the presence of nitrites under normal acidic conditions of the stomach can form NOC. Therefore, these compounds, when ingested by women during pregnancy, may be important risk factors for tumors of the central nervous system in the offspring. The aim of the present study was to test the association between maternal use of medications that contain nitrosatable amines or amides and risk of primary childhood brain tumors (CBT). A case-control study was conducted, which included 1,218 cases and 2,223 population controls, recruited from 9 centers across North America, Europe and Australia. Analysis was conducted for all participants combined, by tumor type (astroglial, primitive neuroectodermal tumors and other glioma), and by age at diagnosis (< or =5 years; >5 years). There were no significant associations between maternal intake of medication containing nitrosatable amines or amides and CBT, for all participants combined and after stratification by age at diagnosis and histological subtype. This is the largest case-control study of CBT and maternal medications to date. Our data provide little support for an association between maternal use of medications that may form NOC and subsequent development of CBT in the offspring.


Bacteriological quality of crops irrigated with wastewater in the Xochimilco plots, Mexico City, Mexico.
Xochimilco county plots (Mexico City), one of the most fertile agricultural areas in the Valley of Mexico, produce a large portion of the fresh vegetables consumed in the city. These plots are generally irrigated with domestic wastewater, and for this reason, it was deemed important to examine and evaluate the bacteriological quality of the water, soil, and vegetables from these plots that are harvested and marketed. The soils were also examined for the classical parameters such as nitrates, ammonia, etc., and organic matter and texture. The crops selected for this study were radishes, spinach, lettuce, parsley, and celery because they are usually consumed raw. The highest bacterial counts were encountered in leafy vegetables, i.e., spinach (8,700 for total coliform and 2,400 for fecal coliform) and lettuce (37,000 for total coliform and 3,600 for fecal coliform). Statistically significant differences in bacterial counts between rinsed and unrinsed edible portions of the crops were observed even in rinsed vegetables, and high densities of fecal coliform were detected, indicating that their consumption represents a potential health hazard. The total coliform values found in irrigation water ranged from 4 X 10(4) to 29 X 10(4), and for fecal coliform the values ranged from 5 X 10(2) to 30 X 10(2).


Bone marrow cell extract promotes the regeneration of irradiated bone.
Mandibular osteoradionecrosis is a severe side effect of radiotherapy after the treatment of squamous cell carcinomas of the upper aerodigestive tract. As an alternative to its treatment by micro-anastomosed free-flaps, preclinical tissular engineering studies have been developed. Total bone marrow (TBM) associated with biphasic calcium phosphate (BCP) significantly enhanced bone formation in irradiated bone. One mechanism, explaining how bone marrow cells can help regenerate tissues like this, is the paracrine effect. The bone marrow cell extract (BMCE) makes use of this paracrine mechanism by keeping only the soluble factors such as growth factors and cytokines. It has provided significant results in repairing various tissues, but has not yet been studied in irradiated bone reconstruction. The purpose of this study was to evaluate the effect of BMCE via an intraosseous or intravenous delivery, with a calcium phosphate scaffold, in irradiated bone reconstruction. Twenty rats were irradiated on their hind limbs with a single 80-Gy dose. Three weeks later, surgery was performed to create osseous defects. The intraosseous group (n = 12) studied the effect of BMCE in situ, with six combinations (empty defect, BCP, TBM, BCP-TBM, lysate only, BCP-lysate). After four different combinations of implantation (empty defect, BCP, TBM, BCP-TBM), the intravenous group (n = 8) received four intravenous injections of BMCE for 2 weeks. Five weeks after implantation, samples were explanted for histological and scanning electron microscopy analysis. Lysate immunogenicity was studied with various mixed lymphocyte reactions. Intravenous injections of BMCE led to a significant new bone formation compared to the intraosseous group. The BCP-TBM mixture remained the most effective in the intraosseous group. However, intravenous injections were more effective, with TBM placed in the defect, with or without biomaterials. Histologically, highly cellularized bone marrow was observed in the defects after intravenous injections, and not after an in situ use of the lysate. The mixed lymphocyte reactions did not show any proliferation after 3, 5, or 7 days of lysate incubation with lymphocytes from another species. This study evaluated the role of BMCE in irradiated bone reconstruction. There were significant results arguing in favor of BMCE intravenous injections. This could open new perspectives to irradiated bone reconstruction.


Genome Engineering Technology for Durable Disease Resistance: Recent Progress and Future Outlooks for Sustainable Agriculture.
Crop production worldwide is under pressure from multiple factors, including reductions in available arable land and sources of water, along with the emergence of new pathogens and development of resistance in pre-existing pathogens. In addition, the ever-growing world population has increased the demand for food, which is predicted to increase by more than 100% by 2050. To meet these needs, different techniques have been deployed to produce new cultivars with novel heritable mutations. Although traditional breeding continues to play a vital role in crop improvement, it typically involves long and laborious artificial planting over multiple generations. Recently, the application of innovative genome engineering techniques, particularly CRISPR-Cas9-based systems, has opened up new avenues that offer the prospects of sustainable farming in the modern agricultural industry. In addition, the emergence of novel editing systems has enabled the development of transgene-free non-genetically modified plants, which represent a suitable option for improving desired traits in a range of crop plants. To date, a number of disease-resistant crops have been produced using gene-editing tools, which can make a significant contribution to overcoming disease-related problems. Not only does this directly minimize yield losses but also reduces the reliance on pesticide application, thereby enhancing crop productivity that can meet the globally increasing demand for food. In this review, we describe recent progress in genome engineering techniques, particularly CRISPR-Cas9 systems, in development of disease-resistant crop plants. In addition, we describe the role of CRISPR-Cas9-mediated genome editing in sustainable agriculture.


Validity of children's reports of parental alcohol abuse.
Data from interviews with parents and 9-12 year old children from 303 families were used to test the validity of children's reports of parental alcoholism or problem drinking status. Children's responses to several single-item screening questions that had been used previously to identify children of alcoholics, as well as their responses to the Short Michigan Alcoholism Screening Test for each parent, were compared to parents' alcoholism diagnosis and screening test scores. In general, children's responses correctly identified only a small portion of alcoholic parents and, when all screening items were combined into a single screening tool to increase sensitivity, the false positive rate became unreasonable for most applications. The screening items were better at identifying active alcoholics than abstaining alcoholics but were also better at identifying problem drinking parents than alcoholic parents. None of the screening options tested had optimal characteristics for use in research or intervention applications.


Gene-engineered T cells as a superior adjuvant therapy for metastatic cancer.
The major limiting factor in the successful application of adjuvant therapy for metastatic disease is the lack of adjuvant specificity that leads to severe side effects. Reasoning that T cells of the immune system are highly specific, we generated tumor-specific T cells by genetic modification of mouse primary T cells with a chimeric receptor reactive with the human breast cancer-associated Ag erbB-2. These T cells killed breast cancer cells and secreted IFN-gamma in an Ag-specific manner in vitro. We investigated their use against metastatic breast cancer in mice in an adjuvant setting, and compared their effectiveness with the commonly applied adjuvants doxorubicin, 5-fluorouracil, and herceptin. Mice were inoculated orthotopically with the human erbB-2-expressing spontaneously metastatic mouse breast cancer 4T1.2 in mammary tissue, and the primary tumor was surgically removed 8 days later. Significant metastatic disease was demonstrated in lung and liver at the time of surgery on day 8 with increased tumor burden at later time points. T cell adjuvant treatment of day 8 metastatic disease resulted in dramatic increases in survival of mice, and this survival was significantly greater than that afforded by either doxorubicin, 5-fluorouracil, or herceptin.


Dexamethasone modulates Salmonella enterica serovar Typhimurium infection in vivo independently of the glucocorticoid-inducible protein annexin-A1.
Salmonella enterica serovar Typhimurium (S. Typhimurium) infection causes an inflammatory response through activation of Toll-like receptor 4 by lipopolysaccharide. Dexamethasone, a glucocorticoid analogue, suppresses inflammatory responses by many mechanisms including inhibition of the lipopolysaccharide-induced production of proinflammatory mediators. There is little information on the effect of glucocorticoids on murine salmonellosis. In this study, we treated susceptible BALB/c mice by subcutaneous implantation of slow-release dexamethasone pellets before infection with S. Typhimurium. Dexamethasone promotes bacterial growth early in infection and induces a dose-dependent increase in bacterial growth within mouse livers and spleens. The bacterial load in organs from infected placebo-treated mice was lower than that in dexamethasone-treated mice. Glucocorticoids inhibit lipopolysaccharide-induced inflammation partially through the steroid-inducible protein annexin-A1 (ANXA1). Infection of wild-type and ANXA1 knock-out mice with S. Typhimurium led to similar organ bacterial loads. ANXA1 also did not affect the bacterial load in organs from infected dexamethasone-treated mice. This suggests that glucocorticoids, independently of ANXA1, accelerate S. Typhimurium growth in vivo in susceptible BALB/c mice.


Altered omega-3 polyunsaturated fatty acid status in depressed post-myocardial infarction patients.
Lower levels of long-chain omega-3 polyunsaturated fatty acids (n-3 LCPUFAs) and increased inflammation have been associated with both depressive disorder and myocardial infarction (MI). The present study investigated whether patients who develop depression post-MI, have higher arachidonic acid/eicosapentanoic acid (AA/EPA) ratios than non-depressed post-MI patients and whether depressed post-MI patients have signs of increased inflammation as measured by C-reactive protein (CRP). Serum AA/EPA ratio and plasma CRP levels were quantified in 50 post-MI patients, of which 29 were depressed and 21 non-depressed. Compared with the non-depressed group, depressed post-MI patients had significantly higher AA/EPA ratios. No significant difference was observed in CRP levels. Depressed post-MI patients had lower levels of n-3 LCPUFAs as measured by mean AA/EPA ratio and no signs of increased inflammation as determined by CRP levels.


Human influence and classical biogeographic predictors of rare species occurrence.
Biogeographic theory predicts that rare species occur more often in larger, less-isolated habitat patches and suggests that patch size and connectivity are positive predictors of patch quality for conservation. However, in areas substantially modified by humans, rare species may be relegated to the most isolated patches. We used data from plant surveys of 81 meadow patches in the Georgia Basin of Canada and the United States to show that presence of threatened and endangered plants was positively predicted for patches that were isolated on small islands surrounded by ocean and for patches that were isolated by surrounding forest. Neither patch size nor connectivity were positive predictors of rare species occurrence. Thus, in our study area, human influence, presumably due to disturbance or introduction of competitive non-native species, appears to have overwhelmed classical predictors of rare species distribution, such that greater patch isolation appeared to favor presence of rare species. We suggest conservation planners consider the potential advantages of protecting geographically isolated patches in human-modified landscapes because such patches may represent the only habitats in which rare species are likely to persist.


The management of pressure sores.
The authors review their clinical experience in diagnosis and management of over 2,500 cases of pressure sores, of which more than half (1,351) required surgical operations. Pressure sores have been classified in 4 grades, a classification that the authors believe is helpful in planning treatment. Different conservative regimens of management are given. Surgical operations are tabulated. Pre- and postoperative management is especially stressed.


Effects of Dietary Crude Protein Levels and Cysteamine Supplementation on Protein Synthetic and Degradative Signaling in Skeletal Muscle of Finishing Pigs.
Dietary protein levels and cysteamine (CS) supplementation can affect growth performance and protein metabolism of pigs. However, the influence of dietary protein intake on the growth response of CS-treated pigs is unclear, and the mechanisms involved in protein metabolism remain unknown. Hence, we investigated the interactions between dietary protein levels and CS supplementation and the effects of dietary crude protein levels and CS supplementation on protein synthetic and degradative signaling in skeletal muscle of finishing pigs. One hundred twenty barrows (65.84 ± 0.61 kg) were allocated to a 2 × 2 factorial arrangement with five replicates of six pigs each. The primary variations were dietary crude protein (CP) levels (14% or 10%) and CS supplemental levels (0 or 700 mg/kg). The low-protein (LP) diets (10% CP) were supplemented with enough essential amino acids (EAA) to meet the NRC AA requirements of pigs and maintain the balanced supply of eight EAA including lysine, methionine, threonine, tryptophan, valine, phenylalanine, isoleucine, and leucine. After 41 days, 10 pigs per treatment were slaughtered. We found that LP diets supplemented with EAA resulted in decreased concentrations of plasma somatostatin (SS) (P<0.01) and plasma urea nitrogen (PUN) (P<0.001), while dietary protein levels did not affect other traits. However, CS supplementation increased the average daily gain (P<0.001) and lean percentage (P<0.05), and decreased the feed conversion ratio (P<0.05) and back fat (P<0.05). CS supplementation also increased the concentrations of plasma insulin-like growth factor 1 (IGF-1) (P<0.001), and reduced the concentrations of leptin, SS, and PUN (P<0.001). Increased mRNA abundance of Akt1 and IGF-1 signaling (P<0.001) and decreased mRNA abundance of Forkhead Box O (FOXO) 4 (P<0.01) and muscle atrophy F-box (P<0.001) were observed in pigs receiving CS. Additionally, CS supplementation increased the protein levels for the phosphorylated mammalian target of rapamycin (mTOR), eIF-4E binding protein 1, and ribosomal protein S6 kinase 1 (P<0.001). There were no interactions between dietary protein levels and CS supplementation for all traits. In conclusion, dietary protein levels and CS supplementation influenced growth and protein metabolism through independent mechanisms in pigs. In addition, LP diets supplemented with EAA did not affect growth performance and other traits except the concentrations of SS and PUN probably through maintenance of protein synthesis and degradation signaling. Moreover, CS supplementation improved growth performance by increasing plasma IGF-1 concentrations possibly through alterations of mTOR and Akt/FOXO signaling pathways in skeletal muscle of finishing pigs.


Solving the Controversy on the Wetting Transparency of Graphene.
Since its discovery, the wetting transparency of graphene, the transmission of the substrate wetting property over graphene coating, has gained significant attention due to its versatility for potential applications. Yet, there have been debates on the interpretation and validity of the wetting transparency. Here, we present a theory taking two previously disregarded factors into account and elucidate the origin of the partial wetting transparency. We show that the liquid bulk modulus is crucial to accurately calculate the van der Waals interactions between the liquid and the surface, and that various wetting states on rough surfaces must be considered to understand a wide range of contact angle measurements that cannot be fitted with a theory considering the flat surface. In addition, we reveal that the wetting characteristic of the substrate almost vanishes when covered by any coating as thick as graphene double layers. Our findings reveal a more complete picture of the wetting transparency of graphene as well as other atomically thin coatings, and can be applied to study various surface engineering problems requiring wettability-tuning.


Local public health agency capacity and its relationship to public health system performance.
he study described in this article identifies local public health agency capacity characteristics that are related to their local public health systems' performance scores on the CDC's National Public Health Performance Standards Program assessment instrument. Public health system performance scores from a test version of the National Public Health Performance Standards instrument (5b) from county and city/county jurisdictions in three states were matched to organizational capacity data from the 1997 National Association of County and City Health Officials profile of health departments, resulting in a sample of 152 jurisdictions. Twenty-eight capacity variables from the profile and all 10 scores on the Essential Public Health Services plus the total performance score were analyzed in 11 separate multivariate regression models. Public health agency capacities in the areas of funding, organizational leadership, and certain nonprovider partnerships were found to be significantly related to public health system performance. Further study is needed to determine if these relationships between agency capacities and system performance are found, with data from other states now using the nationally released performance assessment instruments and with capacity measures that are more specific for evaluating public health system performance.


Urodynamic findings in Susac syndrome: first reported filling cystometrogram.
Susac syndrome is a rare neurological disease, with only 300 cases reported in the literature. Lower urinary symptoms are not an uncommon feature of the disease, yet there is no information on specific dysfunction typical urodynamic findings associated with the disease. We present what we believe to be the first reported filling cystometrogram study of Susac syndrome for the evaluation of voiding dysfunction.