Creation of recognition sites for organophosphate esters based on charge transfer and ligand exchange imprinting methods.
This manuscript describes a method for the selective binding behavior of paraoxan and parathion compounds on surface imprinted polymers which were prepared using both charge transfer (CT) (methacryloyl-antipyrine, MAAP) and ligand-exchange (LE) (methacryloyl-antipyrine-gadalonium, MAAP-Gd) monomers. These polymers were prepared in the presence of azobisisobutyronitrile (AIBN) as an initiator and crosslinking EDMA and were imprinted with organophosphate esters. Influence of CT and LE imprinting on the creation of recognition sites toward paraoxan and parathion was determined applying adsorption isotherms. The effect of initial concentration of paraoxan and parathion, adsorption time and imprinting efficiency on adsorption selectivity for MIP-CT and MIP-LE was investigated. Association constant (K(ass)), number of accessible sites (Q(max)), relative selectivity coefficient (k') and binding ability were also evaluated.


Inhibition of CN (protein phosphatase-2B) suppresses Ca2+-mediated acid secretion in rats.
It has been suggested that CN (calcineurin, protein phosphatase-2B) regulates signal transduction, particularly in various secretory cells. In this study, we examined whether CN plays a role in stimulus-secretion coupling of gastric parietal cells. Localization of CN in gastric epithelial cells was examined immunohistochemically. The role of CN in the acid secretion pathway of gastric parietal cells was assessed by evaluating the effect of FK506, a specific inhibitor of CN, on gastric acid secretion in pylorus-ligated rats. In addition, the effect of FK506 on secretagogue (carbachol, tetragastrin and histamine)-stimulated acid secretion was investigated in lumen-perfused rats. CN was specifically expressed in gastric parietal cells and chief cells of the gastric mucosal epithelium immunohistochemically. FK506 dose-dependently inhibited gastric acid secretion in pylorus-ligated rats. In lumen-perfused rats, FK506 completely inhibited acid secretion prestimulated by carbachol and tetragastrin, agonists known to increase cytosolic Ca2+, but did not affect acid secretion prestimulated by histamine. Our findings demonstrate that FK506 has a potent antisecretory effect in parietal cells through inhibition of only Ca2+-mediated acid secretion pathways. As FK506 is known to specifically inhibit CN, which plays an important role in signal transduction in various secretory cells, protein dephosphorylation signalling might also be crucial for gastrin and M3 muscarine receptor-mediated stimulation of proton pump.


Increases in newly acquired HIV infections in Victoria, Australia: epidemiological evidence of successful prevention?
Rates of newly acquired HIV notifications provide useful data for monitoring transmission trends. We describe 10-year (2001-10) trends in newly acquired HIV notifications in Victoria, Australia. We also examine recent trends in HIV testing and incidence and risk behaviours among gay and other men who have sex with men (MSM) attending four high MSM caseload clinics. Between 2001 and 2010 there was a significant increasing linear trend in newly acquired HIV that was driven primarily by increases between 2009-2010. MSM accounted for 85% of newly acquired HIV notifications. Between 2007-10, the total number of HIV tests per year at the high caseload clinics increased 41% among MSM and HIV incidence declined by 52%; reported risk behaviours remained relatively stable among these MSM. More newly acquired HIV notifications may reflect recent increased testing among MSM; continued scrutiny of surveillance data will assess the sustained effectiveness of testing as prevention, health promotion and the contribution of risk and testing behaviours to HIV surveillance outcomes.


Orrin hatch and the dietary supplement health and education act: Pandora's Box revisited.
Products of unknown safety and efficacy were once referred to as "quackery," and the US Food and Drug Administration (FDA) was empowered to protect public health by preventing their sale and forcing them from the market. However, in 1994, the Dietary Supplement Health and Education Act legitimized their sale as "dietary supplements." Sales increased dramatically, and many Americans now use herbals, homeopathics, and other so-called supplements. The Food and Drug Administration cannot act against them until patients have already been harmed, a dangerous situation. Furthermore, no governmental agency has the authority to force the manufacturers to furnish proof of efficacy. It is vital for physicians to warn their patients that they should use these unproven products only with great caution, and must never discontinue legitimate medical therapy in lieu of unproven products.


Evaluation of Left to Right Shunts by the Pediatrician: How to Follow, When to Refer for Intervention?
Left to right shunts are the most common congenital heart defects which may cause increased pulmonary blood flow leading to dilatation of cardiac chambers, congestive heart failure, pulmonary artery hypertension and eventually Eisenmenger's syndrome. Many children are, however, referred late for correction making them either high risk for intervention or inoperable. The device closure of atrial septal defect, ventricular septal defect and patent ductus arteriosus can literally cure the patient for life, without a scar on the chest. Hence, it is important for every pediatrician to know how to follow and when to refer the patients with left to right shunts for either device closure or surgical intervention, so that the patient can lead a near normal life.


Management of dyslipidemia as a cardiovascular risk factor in individuals with nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the United States and is associated with an increased risk of cardiovascular disease (CVD) and cardiovascular (CV) mortality, independent of traditional cardiovascular risk factors. CVD is one of the most common causes of death among individuals with NAFLD and management of NAFLD must extend beyond liver disease to include CVD risk modification. Clinicians should assess CVD risk with the Framingham Risk Score and screen for CVD risk factors including dyslipidemia, diabetes mellitus, hypertension, tobacco use, and the metabolic syndrome. CVD risk factors, particularly dyslipidemia, require aggressive medical management to reduce the high risk of CVD events and death in individuals with NAFLD.


PCDD/Fs characteristics in flue gas and surrounding environment of iron and steel smelting industry.
Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) concentrations and distributions, emission factors and amounts, and ambient air and soil potential sources were investigated by collecting flue gas, ambient air, and soil samples from ten sintering furnaces and two electric arc furnaces of eight iron and steel smelting industries (ISSI) in China. In flue gas, the concentrations of PCDD/Fs ranged from 0.05 to 2.93 ng I-TEQ Nm-3 (mass, from 0.38 to 30.67 ng Nm-3), with an average of 0.42 ng I-TEQ Nm-3 (mass, 4.99 ng Nm-3), respectively. In ambient air, the concentrations ranged from 0.05 to 0.35 pg I-TEQ m-3 (mass, from 0.66 to 5.66 pg m-3), with an average of 0.20 pg I-TEQ m-3 (mass, 2.96 pg m-3), respectively. In surface soil, the concentrations ranged from 1.80 to 21.02 ng I-TEQ kg-1 (mass, from 34.29 to 836.00 ng kg-1), with an average of 5.82 ng I-TEQ kg-1 (mass, 252.10 ng kg-1), respectively. In deep soil, the concentrations ranged from 1.17 to 12.00 ng I-TEQ kg-1 (mass, from 56.83 to 1488.00 ng kg-1), with an average of 7.76 ng I-TEQ kg-1 (mass, 433.20 ng kg-1), respectively. Compared with emission limits for PCDD/Fs, the compliance was 78.9% in flue gas, 100% in ambient air, and 77.3% in soil. In congener profiles, the contributions of PCDFs were much higher than those of PCDDs in flue gas and ambient air, but the opposite was observed in soil. In ten sintering furnaces, the emission factors ranged from 22.11 to 901.22 ng I-TEQ t-1, with an average of 373.80 ng I-TEQ t-1, respectively. In two electric arc furnaces, the emission factors were 1667.52 and 894.96 ng I-TEQ t-1, with an average of 1281.24 ng I-TEQ t-1. According to both principal component analysis and hierarchical cluster analysis, all ambient air samples were affected by the emissions of PCDD/Fs from ISSIs, but to different degrees. However, the concentrations of PCDD/Fs in most soil samples were not influenced by the ISSI emissions.


Plasma alpha amino-n-butyric acid: leucine ratio. Normal values in alcoholics.
A gas--liquid chromatographic method was developed and employed to determine the plasma ratio of alpha-amino-n-butyric acid to leucine in 40 alcoholic patients and 9 healthy controls. The findings did not support the hypothesis that the ratio may be an empirical marker for alcoholism.


A coin as a tracheal foreign body for 30 years.
A rare case of long-standing tracheal foreign body, a coin retained in the trachea for over 30 years, is presented. A 35-year-old female patient came to the hospital complaining of recurring cough and sensation of a lump in the throat since childhood. A round radiopaque shadow between the clavicles was found in routine chest X-ray film. She recalled swallowing a coin at about the age of five. Reviewing an old film taken for her cough problem at another hospital 11 years previously, we noted the same shadow at the same level. A rusty coin was removed through a ventilating bronchoscope from the trachea, where a narrow sulcus and some granulation tissue were found. Her complaints disappeared thereafter.


Microglia-derived HIV Nef+ exosome impairment of the blood-brain barrier is treatable by nanomedicine-based delivery of Nef peptides.
The negative factor (Nef) of human immunodeficiency virus (HIV) is an accessory protein that is thought to be integral to HIV-associated immune- and neuroimmune pathogenesis. Here, we show that nef-transfected microglia-released Nef+ exosome (exNef) disrupts the apical blood-brain barrier (BBB) and that only nef-transfected microglia release Nef in exosomes. nef-gfp-transduced neurons and astrocytes release exosomes but did not release exNef in the extracellular space. Apical administration of exNef derived from nef-transfected 293T cells reduced transendothelial electrical resistance (TEER) and increased permeability of the BBB. Microglia-derived exNef applied to either the apical/basal BBB significantly reduced expression of the tight junction protein, ZO-1, suggesting a mechanism of exNef-mediated neuropathogenesis. Microglia exposed to exNef release elevated levels of Toll-like receptor-induced cytokines and chemokines IL-12, IL-8, IL-6, RANTES, and IL-17A. Magnetic nanoparticle delivery of Nef peptides containing the Nef myrisolation site across an in vitro BBB ultimately reduced nef-transfected microglia release of Nef exosomes and prevented the loss of BBB integrity and permeability as measured by TEER and dextran-FITC transport studies, respectively. Overall, we show that exNef is released from nef-gfp-transfected microglia; exNef disrupts integrity and permeability, and tight junctions of the BBB, and induces microglial cytokine/chemokine secretion. These exNef-mediated effects were significantly restricted by Nef peptides. Taken together, this study provides preliminary evidence of the role of exNef in HIV neuroimmune pathogenesis and the feasibility of a nanomedicine-based therapeutics targeting exNef to treat HIV-associated neuropathogenesis.


Hormonal environment in the induction of breast cancer in castrated rats using dimethylbenzanthracene: influence of the presence or absence of ovarian activity and of treatment with estradiol, tibolone, and raloxifene.
The influence of hormone therapy on the induction or the promotion of breast cancer has yet to be determined. Recent studies establish a cause-effect relation between hormones and cancer, although epidemiological data and studies of tumor behavior give rise to doubts. The aim of the study was to observe and evaluate the influence of different hormonal environments on the induction of breast cancer in a well-established experimental model. In this experimental animal study, breast cancer was induced by using a single intragastric dose of 20 mg of dimethylbenzanthracene in prepubertal Sprague-Dawley rats randomized into five groups: group 1 (control); group 2 (castrated prepubertal animals); and groups 3, 4, and 5 (castration of prepubertal animals followed by hormonal treatment starting at puberty [11 weeks] with tibolone, raloxifene, and estradiol, respectively). Follicle-stimulating hormone and estradiol levels were measured at 6, 11, 16, and 31 weeks. Absence of ovarian activity was observed in groups 2, 3, 4, and 5, as well as the expected variations in hormone levels in all groups. Breast cancers were obtained in 100% of the animals in the control group, with an average of four (two to seven) tumors per animal in this group. Only one cancer appeared in groups 2, 3, and 4, and none appeared in group 5. In this experimental model and using the hormone treatments chosen, neither the treatments nor the absence of ovarian activity induced breast cancer.


Statistical mechanics of supercoils and the torsional stiffness of the DNA double helix.
The distribution of closed unknotted polymer chains over the writhing number is calculated by the Monte-Carlo method. For circular duplex DNA the variance of the distribution equals approximately half the observed variance of equilibrium distribution over the linking number. The balance which arises from fluctuations in DNA twisting makes it possible to estimate the torsional stiffness of the double helix.


Pharmacologic Heterogeneity and Risk of Severe Hypoglycemia with Concomitant Use of Sulfonylureas and DPP-4 Inhibitors: Population-Based Cohort Study.
Dipeptidyl peptidase-4 inhibitors (DPP-4i) interact with sulfonylureas to increase their risk of hypoglycemia. Our population-based study assessed whether intraclass pharmacologic heterogeneity among sulfonylureas (long- vs. short-acting) and DPP-4i (peptidomimetic vs. non-peptidomimetic) modifies this interaction. We conducted a cohort study using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data. We assembled a cohort of patients initiating sulfonylureas (2007-2020). Using a time-varying exposure definition, we assessed the risk of severe hypoglycemia (hospitalization with or death due to hypoglycemia) associated with (i) concomitant use of long-acting sulfonylureas (glimepiride and glibenclamide) with DPP-4i compared with concomitant use of short-acting sulfonylureas (gliclazide and glipizide) with DPP-4i; and (ii) concomitant use of sulfonylureas with peptidomimetic DPP-4i (saxagliptin and vildagliptin) compared with concomitant use of sulfonylureas with non-peptidomimetic DPP-4i (sitagliptin, linagliptin, and alogliptin). Time-dependent Cox models estimated confounder-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Our cohort included 196,138 sulfonylurea initiators. During a median follow-up of 6 years, 8,576 events of severe hypoglycemia occurred. Compared with concomitant use of short-acting sulfonylureas with DPP-4i, concomitant use of long-acting sulfonylureas with DPP-4i was not associated with the risk of severe hypoglycemia (adjusted HR: 0.87, 95% CI: 0.65-1.16). Compared with concomitant use of sulfonylureas with non-peptidomimetic DPP-4i, concomitant use of sulfonylureas with peptidomimetic DPP-4i was also not associated with the risk of severe hypoglycemia (HR: 0.96, 95% CI: 0.76-1.22). Intra-class pharmacologic heterogeneity did not modify the association between concomitant use of sulfonylureas (short- vs. long-acting) and DPP-4i (peptidomimetic vs. non-peptidomimetic) and the risk of severe hypoglycemia.


The Hayek oscillator. Nomograms for tidal volume and minute ventilation using external high frequency oscillation.
The Hayek Oscillator is a recent development in external high frequency ventilation and is a useful mode of ventilatory support during anaesthesia, in chronic respiratory failure and weaning in intensive care. The Hayek Oscillator is new and its application is growing, as are the number of patients who have benefited from its use. However, there are no clear guidelines on how best to adjust the oscillator to achieve optimum ventilation. A simple method of predicting changes in tidal volume and minute ventilation following adjustment would make the oscillator more useful. We present nomograms for tidal volume, minute ventilation and effective alveolar ventilation when the three variables, oscillator frequency, mean chamber pressure and peak-to-trough pressure span were adjusted. The frequency-tidal volume relationship was unaffected by a mean chamber pressure of 0, -5, -10 cmH2O, but altered with changes in peak-to-trough pressure span. We have also determined the effect of increasing negative extrathoracic pressure on functional residual capacity. The relationship between tidal volume and frequency was non-linear and related to the peak-to-trough pressure span. Mean functional residual capacity significantly increased from 2.25 l (SEM 0.10) without the cuirass at rest to 2.61 l (SEM 0.14) at -10 cmH2O (p < 0.05; n = 5) and 2.47 (SEM 0.12) at -20 cmH2O of mean chamber pressure. Vital capacity was unchanged by increasing extrathoracic pressure as was total lung capacity.


Centrally and peripherally administered bombesin decreases food intake in turkeys.
The effects of intracerebroventricular (ICV) and intravenous injections of bombesin (BBS) on food intake were investigated in turkeys. Adult turkey hens were injected ICV with 50 to 1000 ng of BBS. In addition, the effect of pretreatment with the BBS antagonist [d-Arg1, D-Phe5, D-Trp7,9, Leu11]-substance P was investigated. To determine if BBS also had a peripheral site of action, 0.5 to 8 micrograms/kg body weight of BBS was injected IV into turkey poults. The ICV and IV injections of BBS decreased food and water intake in a dose-dependent manner. The most efficacious doses when injected ICV for decreasing food and water intake were 1000 and 500 ng, respectively, whereas 8 micrograms/kg was most efficacious in decreasing food intake when administered IV. The satiating effect of ICV-injected BBS could be attenuated with pretreatment with the BBS antagonist. The results of these studies suggest that BBS acts to decrease food and water intake in both the periphery and the central nervous systems of turkeys.


Post-poliomyelitis syndrome as a possible viral disease.
This review summarizes current concepts on post-polio syndrome (PPS), a condition that may arise in polio survivors after partial or complete functional recovery followed by a prolonged interval of stable neurological function. PPS affects 15-20 million people worldwide. Epidemiological data are reported, together with the pathogenic pathways that possibly lead to the progressive degeneration and loss of neuromuscular motor units. As a consequence of PPS, polio survivors experience new weakness, generalized fatigue, atrophy of previously unaffected muscles, and a physical decline that may culminate in the loss of independent life. Emphasis is given to the possible pathogenic role of persistent poliovirus infection and chronic inflammation. These factors could contribute to the neurological and physical decline in polio survivors. A perspective is then given on novel anti-poliovirus compounds and monoclonal antibodies that have been developed to contribute to the final phases of polio eradication. These agents could also be useful for the treatment or prevention of PPS. Some of these compounds/antibodies are in early clinical development. Finally, current clinical trials for PPS are reported. In this area, the intravenous infusion of normal human immunoglobulins appears both feasible and promising.


The nursing home comprehensive eye examination.
There is significant need for optometric care in long-term care facilities which can be expected to increase in the next decade. The previous ophthalmic and medical literature was reviewed and the practical aspects of providing eye care in a nursing home were analyzed. Comprehensive nursing home care requires the integration of portable ophthalmic equipment, a modification of standard testing procedures, clear and concise documentation, and close communication with other health care providers on the nursing home clinical staff. Optometrists must consider the incorporation of nursing home care into their clinical practice, while recognizing the unique aspects of providing eye care within a long-term care facility.


Does high field MRI allow an earlier diagnosis of multiple sclerosis?
High field magnetic resonance imaging (MRI) provides higher lesion load measurements in patients presenting with clinically isolated syndromes (CIS) suggestive of demyelination and has impact upon the classification of these syndromes and potentially, the diagnosis of multiple sclerosis (MS). To investigate whether high field MRI can provide an earlier diagnosis of definite MS within the International Panel (IP) and Swanton criteria. Forty patients presenting with CIS suggestive of MS were included. All patients received multi-sequence MRI at 1.5 Tesla (T) and 3T as well as a neurological assessment at baseline. Follow-up visits including MRI at both field strengths and neurological examinations were scheduled 3-4 and 6-7 months after the first clinical event. Based on MRI and clinical findings, fulfilled IP criteria as well as Swanton criteria were analysed. At baseline, the higher detection rate of inflammatory lesions using high field MRI leads to higher classifications according to the Swanton criteria in 15 % of the patients. One additional patient was diagnosed with dissemination in space according to Swanton and IP criteria. During follow-up, an earlier diagnosis of definite MS could not be accomplished, neither according to the IP nor to the Swanton criteria. Although high field MRI shows a higher detection rate of inflammatory brain lesion in CIS and MS patients with an influence according to MRI criteria, this influence does not lead to an earlier diagnosis of lesion dissemination in time and therefore definite MS.


Projections from upper cervical inspiratory neurons to thoracic and lumbar expiratory motor nuclei in the cat.
Previous studies have demonstrated the existence of axonal projections from propriospinal respiratory neurons in the rostral cervical cord of the cat (upper cervical inspiratory neurons) to the vicinity of the phrenic and rostral thoracic inspiratory (external) intercostal motoneurons. However, no synaptic targets of the upper cervical inspiratory neurons have been identified. This study investigated the axonal projections to the caudal thoracic and upper lumbar cord and the possible existence of inhibitory connections to the expiratory intercostal and abdominal motoneurons. The connections from upper cervical inspiratory neurons to expiratory motoneurons in the lower thoracic cord were examined using the methods of antidromic mapping and the spike-triggered averaging of intracellular potentials. Of the 70 upper cervical inspiratory neurons examined, only four (5.7%) could not be antidromically activated from the T9 segment of the spinal cord. The axons of 66 upper cervical inspiratory antidromic activation at less than 5 microV, and the presence of collaterals was confirmed by antidromic mapping in 30 cases (49.2%). Of 21 axons tested for lumbar projections, 13 (61.9%) projected as far as T12, seven (33.3%) as far as L1, three (14.3%) as far as L2, and one (4.8%) was antidromically activated from L3. Spike-triggered averaging of the synaptic potentials recorded intracellularly from expiratory intercostal motoneurons in T9 and T10 spinal segments was done for 27 upper cervical inspiratory neurons, 17 of these with 4 or more motoneurons, for a total of 111 expiratory motoneurons. In 16 cases the motoneurons were injected with Cl- to reverse IPSPs and the spike-triggered averaging was repeated. No monosynaptic or disynaptic post-synaptic potentials were seen in any of the spike-triggered averages. We concluded that the upper cervical inspiratory neurons may provide inspiratory inhibition to expiratory motoneurons via a di- or oligosynaptic pathway involving segmental inhibitory interneurons and that either the spike-triggered averaging technique was not sensitive enough to detect the ipsilateral connections or the interneuron pathway was to the contralateral side of the spinal cord.


Enzyme-Linked Immunosorbent Assay (ELISA).
Food allergy is a public health concern especially after recognizing its constantly increased prevalence and severity. Despite careful reading of food ingredient statements, food allergic individuals may experience reactions caused by "hidden", "masked", or "contaminated" proteins that are known major allergens. Many techniques have been developed to detect even small traces of food allergens, for clinical or laboratory purposes. Enzyme-linked immunosorbent assay (ELISA) is one of the best validated and most routinely used immunoassay in allergy research, in allergy diagnosis in allergy-related quality control in various industries. Although as a technique it has been implemented for the last 45 years, the evolution in biochemistry allowed the development of ultrasensitive ELISA variations that are capable of measuring quantities in the scale of picograms, rendering ELISA attractive, robust, and very famous.


Why Are Rates of Reported Chlamydia Changing in the United States? Insights From the National Job Training Program.
In 2010 to 2017, rates of reported chlamydia decreased among young Black women but increased for White women and all men. Because chlamydia case rates can be influenced by changes in prevalence, screening, and other factors, we compared chlamydia prevalence trends in a sentinel population with national case rate trends to understand potential drivers of case rate trends. Chlamydia prevalence was calculated annually among 16- to 24-year-old entrants to the National Job Training Program (NJTP) in 2010 to 2017. An expectation-maximization-based maximum likelihood approach was used to adjust for misclassification due to imperfect test sensitivity and specificity. Models were stratified by sex, age, and race/ethnicity. A statistically significant trend in prevalence was defined as nonoverlapping 95% confidence intervals comparing 2010 and 2017. Trends in chlamydia prevalence were compared with trends in case rates using percentage change over time; relative changes ≥10% were considered meaningful. Among NJTP entrants in 2010 to 2017, chlamydia prevalence was stable for all Black women, whereas case rates decreased for adolescents (-12%) and were stable for 20- to 24-year-olds (-4%). Among adolescent White women, prevalence was stable, whereas case rates increased (+30%). For White women aged 20 to 24 years, prevalence increased +62% and case rates increased +43%. Trends in prevalence differed from trends in case rates for all subgroups of men. Prevalence trends in this sentinel population differed from national case rate trends for Black women, White women, and men, suggesting potential decreased screening among Black women aged 16 to 19 years, increased prevalence among White women aged 20 to 24 years, and increased screening among men.


Streptococcus gordonii soluble inorganic pyrophosphatase: an important role for the interdomain region in enzyme activity.
Streptococcus gordonii DL1(Challis) soluble inorganic pyrophosphatase was shown to be a homo dimer with a subunit molecular mass of 33407. In solution, in the presence of Mn(2+), the protein is ellipsoidal with an axial ratio of 3.37 and molecular mass of 67000. In the absence of the divalent cation, the molecular mass is unchanged but the axial ratio increases to 3.94. The enzyme, in the presence of 5 mM Mg(2+), at 25 degrees Celsius and pH 9.0, has K(m) and k(cat) values of 62 microM and 6290 s(-1), respectively. The free N- and C-terminal domains of Streptococcus gordonii PPase did not interact productively when mixed together. Replacing the interdomain region with that from Bacillus subtilis decreased the catalytic efficiency of the enzyme whereas inserting the same region from the Archaeglobus fulgidus thermophilic enzyme yielded an inactive protein. Substitution, deletion and insertion of amino acid residues in the interdomain region were found to affect the monomer dimer equilibrium in the absence of Mn(2+) ions. In the presence of these ions however the variant proteins were dimers. Proteins with altered interdomain regions also displayed a 2- to 625-fold decrease in catalytic efficiency. These data together with that of computer analysis show that the interdomain region has characteristics of a mechanical hinge. Modelling mutant proteins onto the wild type shows that the active site regions are not significantly perturbed. These results show that, although distant from the active site, the interdomain region plays a role in enzyme activity and both its length and composition are important. This supports the hypothesis that catalytic activity requires the N- and C terminal domains of the enzyme to open and close using the interdomain region as a hinge.


Cross-sectional survey of antenatal education attendance among nulliparous pregnant women in Sydney, Australia.
Antenatal education aims to provide expectant parents with strategies for dealing with pregnancy, childbirth and parenthood and may have the potential to reduce obstetric intervention and fear of childbirth. We aimed to investigate antenatal education attendance, reasons for and barriers to attending, and techniques taught and used to manage labour. Antenatal and postnatal surveys were conducted among nulliparous women with a singleton pregnancy at two maternity hospitals in Sydney, Australia in 2018. Classes were classified into psychoprophylaxis, birth and parenting, other, or no classes. Reasons for and barriers to attendance, demographic characteristics, and techniques taught and used in labour were compared by class type, using Pearson's Chi Squared tests of independence. 724 women were surveyed antenatally. The main reasons for attending classes were to better manage the birth (86 %), feel more secure in baby care (71 %) and as a parent (60 %); although this differed by class type. Reasons for not attending classes included being too busy (33 %) and cost (27 %). Epidural, breathing techniques, massage and nitrous oxide were the most common techniques taught. Women who attended psychoprophylaxis classes used a wider range of pain relief techniques in labour. Women found antenatal classes useful preparation for birth (94 %) and parenting (74 %). Women surveyed postnatally wanted more information on baby care/sleeping and breastfeeding. The majority of women found antenatal education useful and utilised techniques taught. Education providers should ensure breastfeeding and infant care information is provided, and barriers to attendance such as times and cost should be addressed.


Depression, anxiety, and quality of life in siblings of children with intractable epilepsy.
Thirty-seven siblings (aged 6-18) of children with intractable epilepsy were surveyed regarding their anxiety, depression, and quality of life, by both self-report (Revised Children's Manifest Anxiety Scale, RCMAS; Children's Depression Inventory, CDI; and Peds QL) and parental report (Child Behavior Checklist, CBCL). Completed forms were returned by 37 of 58 (64%) eligible families. No sibling had a score in the clinical range on the CDI, and only 2 of 37 (6%) scored in the clinical range on the RCMAS, a proportion similar to the normative population. In contrast, 25% were rated by their parents to have elevated Internalizing Behaviors scores on the CBCL. There was a trend for PedsQL scores to be lower than the normative mean. Comorbid behavior and attention problems in the child with epilepsy and sibling CDI and RCMAS scores correlated significantly with self-reported quality of life. However, other epilepsy, child, and family variables (income, parental education, family function, maternal depression) did not correlate. We conclude that siblings of children with intractable epilepsy are functioning well overall and have a good quality of life.


Health care contacts before and after attempted suicide among adolescent and young adult versus older suicide attempters.
The pattern of all health care contacts among young people before and after attempted suicide is not well documented. Neither is it known if the health care contacts of young suicide attempters differ from those of older suicide attempters. This study investigated the age-related clinical characteristics of suicide attempters and the pattern of their contacts with health care before and after attempted suicide in different age groups, particularly adolescence and young adulthood. All consecutive 1198 suicide attempters treated in hospital emergency rooms in Helsinki between January 1997 and January 1998 were identified and divided into three age groups (15-24 years, 25-39 years, 40 years and over). Data were gathered on all health care contacts 1 year before and after the index attempt. Although adolescent and young adult suicide attempters suffered from severe mental disorders, a remarkable proportion of them were left without psychiatric consultation and aftercare recommendation following the attempt. Two-thirds of 15-19-year-old male suicide attempters had no treatment contact during the month before the attempt, while a quarter of them were referred to psychiatric consultation and a half had no healthcare contact in the month following the attempt. These findings indicate considerable scope for improvement in the assessment of young suicide attempters and their referral to aftercare.


Investigation of the mechanism of casein protein to enhance 3D printing accuracy of cassava starch gel.
This work evaluated the potential mechanism of casein protein (CP) in enhancing the 3D printing performance of cassava starch (CS) gel in terms of the multi-scale structure of starch and gel properties. The addition of CP could increase the average molecular weight (-Rh) of starch after thermal processing, which reduced the line width and increased the centre height of the 3D-printed product, despite the reduction of the structural recovery of the gel system. In addition, the increase in CS content caused a decrease in the short-range ordered structure of starch, resulting in a decline in relaxation time and an increase in free water content (A23), which in turn provided the gel system with a greater elastic modulus and ultimately increased the printing precision of 3D printed products. This study presented meaningful information for the application of 3D printing to starch-protein complex foods.


Strategies to Support Sustained Breastfeeding of Late Preterm Multiple Birth Infants.
Strategies to support sustained breastfeeding in late preterm multiple birth infants include developing a family-centered feeding plan in collaboration with the medical team, assessing and supporting breastfeeding sessions, promoting lactogenesis with pumping or manual expression, and activating a support system for families.


F-M 100-Hue total error scores have discrete values.
A proof is presented which shows that the total error scores derived from the Farnsworth-Munsell 100-Hue test are an integer multiple of 4. The one proviso for this relates to the way in which the first and last caps in a box are handled.


How Charles Huggins made his Nobel prize winning discovery--in his own words: an historic audio recording. Interviewed by Willard Goodwin and Elmer Bell.
On February 12, 1962, 4 years before he was awarded the Nobel Prize, Charles Huggins gave an informal interview to Dr. Willard Goodwin and co-workers at UCLA on how he made one of the greatest discoveries in our field-hormonal therapy for prostate cancer. In this fascinating story, he tells how he transformed the investigation of what causes a hydrocele into a Nobel Prize winning discovery.


Control of mitochondrial permeability by Bcl-2 family members.
Programmed cell death (apoptosis) is regulated by the Bcl-2 family of proteins. Although it remains unclear how these family members control apoptosis, they clearly have the capacity to regulate the permeability of intracellular membranes to ions and proteins. Proapoptotic members of the Bcl-2 family, especially Bax and Bid, have been extensively analyzed for the ability to form channels in membranes and to regulate preexisting channels. Anti-apoptotic members of the family tend to have the opposing effects on membrane channel formation. The molecular mechanisms of the different models for the permeabilization of membranes by the Bcl-2 family members and the regulation of Bcl-2 family member subcellular localizations are discussed.


Dual disassembly and biological evaluation of enzyme/oxidation-responsive polyester-based nanoparticulates for tumor-targeting delivery.
Polyester-based nanoparticulates (NPs) are ideal nanocarriers for intracellular delivery of anticancer drugs because of their biocompatibility. However, an on-going challenge is the controlled and enhanced release of encapsulated therapeutics in response to unique changes that occur within cancer cells. Herein, we report the versatility of dual responses to enzymatic and oxidative reactions found in cancer cells toward the development of polyester-NPs as effective tumor-targeting intracellular nanocarriers. A facile nanoprecipitation method allows for the preparation of hydrophobic cores composed of novel polyester designed with esterase-responsive ester groups and oxidation-responsive sulfide linkages on their backbones, physically stabilized with poly(ethylene glycol)-based polymeric shells. The formed core/shell-type NPs with a diameter of 120 nm exhibit excellent colloidal stability in physiological conditions and in the presence of serum proteins. When exposed to esterase and hydrogen peroxide, NP integrity is disrupted, leading to the enhanced release of encapsulated doxorubicin, confirmed by dynamic light scattering and spectroscopic analysis. Combined results from epifluorescence microscopy, confocal laser scanning microscopy, flow cytometry, and cell viability demonstrate that doxorubicin-loaded NPs reveal rapid penetration and enhanced intracellular release of doxorubicin, thus inhibiting tumor progression. Importantly, the cellular uptake of doxorubicin-loaded core/shell NPs primarily via caveolae-dependent mechanism promotes their use in targeting a broad spectrum of cancers.


In-situ graft-crosslinked gold nanoparticles with high-density surface defects and coated with a polytaurine membrane for the voltammetric determination of dopamine.
Well-dispersed and graft-crosslinked gold nanoparticles (AuNPs) were synthesized by the reduction of tetrachloroaurate with hydrazine at room temperature. The AuNPs possess a high density of surface defects which is due to grafting of n-octanoic acid to polyvinylpyrrolidone. The physical and chemical properties of the resulting AuNPs were characterized by UV-vis, XRD, TEM/HRTEM, SAED, and XPS, respectively. The modified AuNPs were placed on a glassy carbon electrode (GCE) in an electropolymerized taurine layer to obtain a sensitive, selective, stable and rapid electrochemical dopamine sensor. The peak current, typically measured at 0.17 V (vs. SCE), increases linearly in the 1.0 to 120 μM dopamine concentration range, and the limit of detection (at S/N = 3) is 0.16 μM with a sensitivity of 2.94 μA·μM-1·cm-2. The sensor was successfully applied to the determination of dopamine in injections and spiked serum samples. The recoveries from spiked serum samples range from 97.5 to 102.4%, with RSDs ranging between 2.8 and 3.4%. Graphical abstract Schematic representation of a glassy carbon electrode modified with in-situ graft-crosslinked gold nanoparticles combined with an electropolymerized polytaurine membrane. The sensor exhibits excellent features towards dopamine determination.


Gate-tunable Veselago interference in a bipolar graphene microcavity.
The relativistic charge carriers in monolayer graphene can be manipulated in manners akin to conventional optics. Klein tunneling and Veselago lensing have been previously demonstrated in ballistic graphene pn-junction devices, but collimation and focusing efficiency remains relatively low, preventing realization of advanced quantum devices and controlled quantum interference. Here, we present a graphene microcavity defined by carefully-engineered local strain and electrostatic fields. Electrons are manipulated to form an interference path inside the cavity at zero magnetic field via consecutive Veselago refractions. The observation of unique Veselago interference peaks via transport measurement and their magnetic field dependence agrees with the theoretical expectation. We further utilize Veselago interference to demonstrate localization of uncollimated electrons and thus improvement in collimation efficiency. Our work sheds new light on relativistic single-particle physics and provide a new device concept toward next-generation quantum devices based on manipulation of ballistic electron trajectory.


Study of fragmentation pathways of metastable negative ions in aliphatic dipeptides using the statistical theory.
Dipeptide molecules are good model systems for investigation of resonant reactions of low-energy electrons with proteins. The present work is devoted to the study of the processes of formation and fragmentation of negative ions in aliphatic dipeptides glycyl-glycine and glycyl-alanine. The metastable decays of negative ions were detected in these objects, and have been investigated with the aim of clarification of the mechanisms of fragmentation. The effective yield curves for negative ions as functions of electron energy were obtained using a magnetic sector mass spectrometer rebuilt for generation and detection of negative ions. For analysis of the observed metastable decays statistical and thermochemical approaches have been used. The ions structures, the enthalpies of formation of neutral and charged particles, and the rate constants of dissociative reactions have been found. Comparison of the experimental results with theoretical data leads to the conclusion that metastable ion decay proceeds with minimal structural changes avoiding complicated rearrangements and isomerization processes.


Evaluation of Potential Food Effects and Drug Interactions With Lansoprazole in Healthy Adult Volunteers Receiving Futibatinib.
Futibatinib, an oral, irreversible fibroblast growth factor receptor (FGFR) 1-4 inhibitor, is being evaluated for FGFR-aberrant tumors. Two open-label phase 1 studies evaluated the effects of high-fat, high-calorie food and concomitant proton pump inhibitors (PPIs; lansoprazole) on single-dose futibatinib (20 mg) pharmacokinetics and safety in healthy adults. In the food effect study (N = 17), subjects received futibatinib under fed and fasted conditions, separated by a 7-day washout. In the PPI study (N = 20), subjects received futibatinib alone, underwent a 2-day washout, and then received lansoprazole 60 mg once daily for 5 days, with futibatinib also administered on day 5. Under fed versus fasted conditions, futibatinib bioavailability was 11.2% lower (area under the plasma concentration-time curve from time 0 to infinity geometric mean ratio 88.8%; 90% confidence interval, 79.8%-98.9%), and median time to maximum plasma concentration was significantly delayed (4.0 vs 1.5 hours; P < .0001). There were no significant differences in futibatinib exposure between futibatinib plus lansoprazole and futibatinib alone. No serious adverse events occurred in either study. These findings suggest that food and PPIs are unlikely to have clinically meaningful impacts on futibatinib bioavailability. Thus, futibatinib may be used with or without food and concomitantly with acid-reducing agents.


Relationship between nuchal translucency at 11-14 weeks and nuchal fold at 20-24 weeks of gestation.
To examine the relationship between the measurement of nuchal translucency in the first trimester and nuchal fold in the second trimester in normal pregnancy. This was a prospective study of 592 singleton pregnancies. Fetal nuchal translucency was measured at 11-14 weeks of gestation and nuchal fold at 20-24 weeks of gestation. Linear regression models were used to assess the relationship between nuchal translucency and nuchal fold after adjustment for gestational age. There was no significant association between nuchal translucency and nuchal fold thickness. It is possible that measurement of nuchal translucency and nuchal fold may provide an independent contribution in screening for trisomy 21.


Gut microbiome and Parkinson's disease: Perspective on pathogenesis and treatment.
Parkinson's disease (PD) is a disease of ⍺-synuclein aggregation-mediated dopaminergic neuronal loss in the substantia nigra pars compacta, which leads to motor and non-motor symptoms. Through the last two decades of research, there has been growing consensus that inflammation-mediated oxidative stress, mitochondrial dysfunction, and cytokine-induced toxicity are mainly involved in neuronal damage and loss associated with PD. However, it remains unclear how these mechanisms relate to sporadic PD, a more common form of PD. Both enteric and central nervous systems have been implicated in the pathogenesis of sporadic PD, thus highlighting the crosstalk between the gut and brain. of Review: In this review, we summarize how alterations in the gut microbiome can affect PD pathogenesis. We highlight various mechanisms increasing/decreasing the risk of PD development. Based on the previous supporting evidence, we suggest how early interventions could protect against PD development and how controlling specific factors, including our diet, could modify our perspective on disease mechanisms and therapeutics. We explain the strong relationship between the gut microbiota and the brain in PD subjects, by delineating the multiple mechanisms involved inneuroinflammation and oxidative stress. We conclude that the neurodetrimental effects of western diet (WD) and the neuroprotective effects of Mediterranean diets should be further exploredin humans through clinical trials. Key Scientific Concepts of Review: Alterations in the gut microbiome and associated metabolites may contribute to pathogenesis in PD. In some studies, probiotics have been shown to exert anti-oxidative effects in PD via improved mitochondrial dynamics and homeostasis, thus reducing PD-related consequences. However, there is a significant unmet need for randomized clinical trials to investigate the effectiveness of microbial products, probiotic-based supplementation, and dietary intervention in reversing gut microbial dysbiosis in PD.


Clinical and physiological basis for a new method underlying rehabilitation of the damaged visual nerve function by direct electric stimulation.
A new method of rehabilitation of damaged visual nerves has been tested during clinical physiological investigations in 45 patients with pathological opticochiasmal brain tumor, inflammation and trauma. The essence of the new method was in implanting the electrode into the nerve when the patient was operated on for the pathological formation and in directly stimulating the nerves for 2 or 3 postoperational weeks. Effectiveness of electrical stimulation was increased by direct recording of the electroneurogram as well as by the results of ophthalmological observations. Considerable improvement of vision was observed in 75%, and in 25% of these cases the vision was found to actually normalize. Even in cases of total blindness, vision was partially rehabilitated in 8 of 10 cases. Direct electrophysiological investigation of the visual nerve potentials enabled us to objectively estimate their functional state, predict the probability of visual rehabilitation as well as increase the efficiency of therapy. Neurophysiological mechanisms of visual rehabilitation under the influence of electrical stimulation of the visual nerves are discussed.


Four-Way Crossover Phase 1 Thorough QT Study to Assess Cardiac Safety of Domperidone and Consideration for Design and Conduct of QT/QTc Study in China.
This study aimed to evaluate the QT prolongation potential of domperidone in healthy Chinese participants and explore the possibility of a thorough QT (TQT) study in China with a smaller sample size using concentration-QT (C-QT) modeling. Part 1 was a randomized, placebo- and positive-controlled, multiple-dose, 4-way crossover TQT study in healthy Chinese participants; 44 participants were randomized to either domperidone 10/20 mg or placebo 3 times daily, on days 1 to 3, followed by a single dose of either 10/20 mg domperidone/domperidone-placebo/domperidone-placebo plus 400 mg of moxifloxacin, on day 4. Twelve-lead electrocardiograms were recorded in triplicate at predefined time points with pharmacokinetic sampling. The results were that change from baseline in QT interval corrected for heart rate (QTc) using the Fridericia formula (QTcF) between domperidone and placebo was 1.3 milliseconds and 2.7 milliseconds for 10 and 20 mg 3 times daily, and upper limits of 2-sided 90%CI for all time points were below regulatory threshold of 10 milliseconds. In part 2, resampling analysis using C-QT modeling for moxifloxacin showed false-negative rates of <5% with sample sizes ≥6. We could conclude that no clinically relevant effect on corrected QT interval or new safety signals was observed with domperidone. A dedicated TQT study with C-QT modeling could assess drug effects on QT/corrected QT intervals for novel drug development in China.


Invasion and lysis of HeLa cell monolayers by Salmonella typhi: the role of lipopolysaccharide.
Adhesion to and penetration of HeLa cell monolayers by Salmonella typhi Ty2 requires the presence of a complete lipopolysaccharide as demonstrated by the inability of polysaccharide-defective mutants to invade the monolayer. Lysis of HeLa cell monolayers by Salmonella typhi Ty2 is associated with intracellular bacterial multiplication and no detectable production of extracellular toxins. The ability of Salmonella typhi to invade and lyse monolayers could provide a novel system for the study of its ability to invade the bloodstream from the intestine.


SOCS-1 inhibits TNF-alpha-induced cardiomyocyte apoptosis via ERK1/2 pathway activation.
Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine involved in mitogen-activated protein kinase (MAPK) signaling pathways, contributes to the pathogenesis of cardiovascular diseases. Recently, suppressor of cytokine signaling-1 (SOCS-1) has been shown to modulate responses to TNF-alpha. However, whether SOCS-1 suppresses TNF-alpha-dependent apoptotic processes in cardiomyocytes and whether MAPK pathways mediate this effect have not been clearly elucidated. This study was carried out to define the role of SOCS-1 on TNF-alpha-induced apoptosis in neonatal rat cardiomyocytes and to investigate the signal pathways involved. Exposure to TNF-alpha (10 ng/ml for 24 h) significantly increased the number of apoptotic cells, the activity of caspase-8 and caspase-3, and the Bax/Bcl-xl ratio. In contrast, adenovirus-mediated gene transfer of SOCS-1 reversed the pro-apoptotic effect of TNF-alpha. Additionally, preincubation of cardiomyocytes with the extracellular signal-regulated kinase-1 and -2 (ERK1/2) inhibitor PD98059 attenuated the protective effect of SOCS-1, but the p38-MAPK inhibitor SB203580 and the c-Jun amino-terminal kinase (JNK) inhibitor SP600125 had no effect. Furthermore, the TNF-alpha-induced decrease in the phosphorylation of ERK1/2 was abolished by overexpression of SOCS-1. These findings suggest that SOCS-1 prevents TNF-alpha-induced apoptosis in cardiac myocytes via ERK1/2 pathway activation.


Lambert-Eaton myasthenic syndrome: I. Early morphological effects of IgG on the presynaptic membrane active zones.
In the freeze-fractured presynaptic membrane of the motor end-plate, the active zones consist of two parallel arrays and each array contains 10- to 12-nm particles arranged in two rows. In the Lambert-Eaton myasthenic syndrome (LEMS) and in mice treated with 10 mg/day of LEMS IgG, administered intraperitoneally for several weeks, there was a paucity and disorganization of the active zones, and clusters of 10- to 12-nm particles appeared. To further define the changes in the active zones, mice were studied that had been treated over 2 days with 104 to 180 mg of IgG. Treatment transferred the physiological defect of LEMS. Control mice received normal human IgG or no IgG. The spacing and density (number/unit area) of active-zone particles were evaluated in presynaptic membrane P-faces using computer-assisted stereometry. In the normal active zone, the distance between particles in a given row and between adjacent rows of an array was less than, but the distance between the two arrays was greater than, the distance between the two antigen-binding sites on human IgG. In mice treated with LEMS IgG, the initial alteration in the active zone was a decrease in the distance between particles in a given row and between adjacent rows of an array; the distance between the two arrays remained unaltered. In more affected active zones, the parallel orientation of the rows was disturbed and the arrays became clusters. There was a significantly reduced density of active zones and of large-membrane particles associated with all active zones and clusters.(ABSTRACT TRUNCATED AT 250 WORDS)


Small molecule c-MET inhibitor PHA665752: effect on cell growth and motility in papillary thyroid carcinoma.
c-Met is upregulated in papillary thyroid carcinoma (PTC) and can be an attractive therapeutic target. We tested the effects of the small molecule c-met inhibitor PHA665752 in blocking c-met-dependent phenotypic effects in PTC cell lines. PTC patient tissues and cell lines were evaluated for c-met expression. The effect of PHA665752 on c-met phosphorylation, downstream signaling, hepatocyte growth factor (HGF)-dependent cell growth, and induction of apoptosis was studied. The IC(50) of PHA665752 in c-met-expressing PTC cells was determined, and growth curves at 0.1x, 1x, and 10x IC(50) concentrations were obtained. Poly(ADP-ribose) polymerase (PARP) and caspase-9-processing post-PHA665752 treatment were studied as markers of apoptosis, and assays analyzing HGF-dependent cell invasion and migration in the presence and absence of PHA665752 were done. c-Met was upregulated in most of the patient tissues with PTC and in many PTC cell lines. PHA665752 specifically inhibited c-met phosphorylation, c-met-dependent cell growth, signal transduction, cell survival, cell invasion, and migration in PTC cells with high c-met. PHA665752 is an effective and specific inhibitor of c-met in PTC cells with high levels of c-met expression.


Arterial vascularization of the pineal gland.
The arterial vascularization of the pineal gland (PG) remains a debatable subject. This study aims to provide detailed information about the arterial vascularization of the PG. Thirty adult human brains were obtained from routine autopsies. Cerebral arteries were separately cannulated and injected with colored latex. The dissections were carried out using a surgical microscope. The diameters of the branches supplying the PG at their origin and vascularization areas of the branches of the arteries were investigated. The main artery of the PG was the lateral pineal artery, and it originated from the posterior circulation. The other arteries included the medial pineal artery from the posterior circulation and the rostral pineal artery mainly from the anterior circulation. Posteromedial choroidal artery was an important artery that branched to the PG. The arterial supply to the PG was studied comprehensively considering the debate and inadequacy of previously published studies on this issue available in the literature. This anatomical knowledge may be helpful for surgical treatment of pathologies of the PG, especially in children who develop more pathology in this region than adults.


Effects of competition, herbivory and substrate disturbance on growth and size structure in pin cherry (Prunus pensylvanica L.) seedlings.
We examined separate and interactive effects of intraspecific competition, vertebrate browsing and substrate disturbance on the growth and size structure of pin cherry (Prunus pensylvanica L.) in the first two seasons of growth after clearcutting, in a hardwoods forest in New Hampshire, United States. Over the 15-month study period, 97.5% of 1801 individuals survived, and mean plant height increased from 4-fold at high density to 5-fold at low density. Relative height growth was significantly lower at higher plant densities in two of the three growth periods examined. Vertebrate browsers (moose and deer) significantly preferred taller plants. Browsed plants had higher relative height growth following browsing than unbrowsed plants (compensatory growth) at low and intermediate densities. The degree of compensation declined with density and compensation was not significant at the highest density level. At low and intermediate densities, plants browsed early in life regained height dominance through compensatory growth; they failed to regain dominance at high density. Because compensatory growth tended to offset the effects of size-selective browsing, there was no difference in the degree of size inequality between browsed and unbrowsed plots. However, size inequality increased with plant density. Substrate disturbance caused by logging had no significant effects on either relative height growth or size inequality. The slope of the relationship between relative height growth and initial height increased significantly with density and time, and was higher in unbrowsed than in browsed plots, suggesting that competition among plants was size-asymmetric. Despite the preference of browsers for large plants, there was a clear net growth advantage for plants of large initial size, when the effects of competition, browsing and compensatory growth were combined. The interactive effects of density and browsing demonstrate the importance of a multifactorial approach to the analysis of individual plant performance and population structure.


Imaging the lymphatic system: possibilities and clinical applications.
The lymphatic system is anatomically complex and difficult to image. Lymph ducts are responsible for the drainage of part of the body's interstitial fluid. Lymph nodes account for the enrichment of lymph fluid, and can be involved in a large variety of diseases, especially cancer. For a long time, lymphatic imaging was limited to the sole use of conventional lymphography involving invasive procedures and patient discomfort. New contrast agents and techniques in ultrasound, nuclear medicine, and MR imaging are now available for imaging of both the lymphatic vessels and the lymph nodes. The objective of this review is to discuss the different imaging modalities of the lymphatic system, with a special focus on the new possibilities of lymphatic imaging including enhanced MR lymphography, sentinel node and positron emission tomography imaging, and contrast-enhanced ultrasound.


Parallel EPI artifact correction (PEAC) for N/2 ghost suppression in neuroimaging applications.
Echo Planar Imaging (EPI) is a neuroimaging tool for clinical practice and research investigation. Due to odd-even echo phase inconsistencies, however, EPI suffers from Nyquist N/2 ghost artifacts. In standard neuroimaging protocols, EPI artifacts are suppressed using phase correction techniques that require reference data collected from a reference scan. Because reference-scan based techniques are sensitive to subject motion, EPI performance is sub-optimal in neuroimaging applications. In this technical note, we present a novel EPI data processing technique which we call Parallel EPI Artifact Correction (PEAC). By introducing an implicit data constraint associated with multi-coil sensitivity in parallel imaging, PEAC converts phase correction into a constrained problem that can be resolved using an iterative algorithm. This enables "reference-less" EPI that can improve neuroimaging performance. In the presented work, PEAC is investigated using a standard functional magnetic resonance imaging (fMRI) protocol with multi-slice 2D EPI. It is demonstrated that PEAC can suppress ghost artifacts as effectively as the standard reference-scan based phase correction technique used on a clinical MRI system. We also found that PEAC can achieve dynamic phase correction when motion occurs.


Evaluation of the Stratus CS Acute Care D-dimer assay (DDMR) using the Stratus CS STAT Fluorometric Analyzer: a prospective multisite study for exclusion of pulmonary embolism and deep vein thrombosis.
D-dimer testing is an integral part of the diagnostic algorithm in excluding patients with venous thromboembolism. In this study, we prospectively evaluated the Stratus DDMR D-dimer test in patients suspected of pulmonary embolism (PE) and deep vein thrombosis (DVT). Patients suspected of venous thromboembolism were prospectively enrolled at four different clinical sites, with sodium citrate and lithium heparin plasma was tested using the DDMR D-dimer test on the Stratus CS analyzer. 1,012 patients were enrolled for analysis, with 85/603 (14.1%) patients with PE and 80/443 (18.1%) with DVT, and four of the patients (0.4%) with PE and DVT. For the samples collected in 3.2% sodium citrate, the DDMR method had a sensitivity, specificity, and negative predictive value for VTE of 98.0%, 38.1%, and 99.1%, respectively. For the samples collected in lithium heparin, the DDMR method had a sensitivity, specificity, and negative predictive value (NPV) for VTE of 98.9%, 28.8%, and 99.4%, respectively. In PE, DDMR testing on citrate plasma had a sensitivity, specificity, and NPV of 98.8%, 39.5%, and 99.6%, respectively, while heparin samples had a sensitivity, specificity, and NPV for PE of 98.0%, 28.4%, and 99.1%, respectively. In DVT, citrate plasma had a sensitivity, specificity, and NPV for DVT of 97.5%, 32.0%, and 98.3%, respectively, while heparin samples had a sensitivity, specificity, and NPV for DVT of 100%, 27.8%, and 100%, respectively. The Stratus CS DDMR D-dimer can be used in those patients with non-high clinical pre-test probability for the exclusion of PE.


Multivessel Giant Coronary Artery Aneurysms Incidentally Demonstrated During Angiography for Acute Myocardial Infarction.
Giant coronary artery aneurysms are a rare manifestation of coronary artery disease and are defined by an aneurysmal diameter of >20 mm. Multimodal invasive and noninvasive imaging is required for accurate assessment We describe a case of multivessel giant coronary artery aneurysms noted during angiography for myocardial infarction. (Level of Difficulty: Intermediate.).


Software for the quantitative evaluation of in vitro monoclonal antibody production from ELISA data.
Software has been developed which permits the quantitation of monoclonal antibodies secreted by B cell hybridomas. This program does not require the user to enter a large number of complex parameters and can be easily used without any previous computer experience. It fits all the experimental and standard curves by determining overlapping linear domains using the linear least-squares method. The program is based on logarithmic interpolations for determining Ig concentrations comparing experimental samples to Ig concentrations in standards. It provides a complete print-out of the data with editing options and is written in BASIC EDEX 4.0 Commodore computer language. It permits the accurate quantification of minute amounts of monoclonal antibodies and can be used to detect the inhibitory or enhancing effects of lymphokines or cytokines on Ig secretion by hybridoma B cells.


Cannabinoid addiction: behavioral models and neural correlates.
The use of cannabis sativa preparations as recreational drugs can be traced back to the earliest civilizations. However, animal models of cannabinoid addiction allowing the exploration of neural correlates of cannabinoid abuse have been developed only recently. We review these models and the role of the CB1 cannabinoid receptor, the main target of natural cannabinoids, and its interaction with opioid and dopamine transmission in reward circuits. Extensive reviews on the molecular basis of cannabinoid action are available elsewhere (Piomelli et al., 2000; Schlicker and Kathmann, 2001).


Complex electrograms within the coronary sinus: time- and frequency-domain characteristics, effects of antral pulmonary vein isolation, and relationship to clinical outcome in patients with paroxysmal and persistent atrial fibrillation.
The mechanistic and clinical significance of complex fractionated atrial electrograms (CFAE) in the coronary sinus (CS) has been unclear. Antral pulmonary vein isolation (APVI) was performed in 77 patients with paroxysmal (32) or persistent AF (45). CS electrograms recorded for 60 seconds before and after APVI were analyzed in the time- and frequency-domains. Dominant frequency (DF), complexity index (CI: change in polarity of depolarization), and fractionation index (FI: change in direction of depolarization slope) were determined. Before APVI, there was no difference in DF, CI, or FI between paroxysmal and persistent AF. APVI resulted in a significant decrease in DF, CI, and FI in all patients. Baseline CI (43 +/- 13/s vs 54 +/- 14/s, P = 0.03) and FI (64 +/- 23/s vs 87 +/- 30/s, P = 0.02) were lower in patients with paroxysmal AF who had AF terminated by ablation than who did not. At 10 +/- 2 months, 69% of patients with paroxysmal AF and 49% of patients with persistent AF were free from AF after single ablation. Baseline CI was higher among patients with paroxysmal AF who had AF after APVI (56 +/- 20/s vs 44 +/- 10/s, P = 0.03). In patients with persistent AF, there was a larger decrease in DF after APVI among patients who remained free from AF (13 +/- 11% vs 7 +/- 9%, P < 0.05). Complexity of CS electrograms may reflect drivers of AF that perpetuate paroxysmal AF after APVI. In persistent AF, the extent to which APVI decreases DF in the CS correlates with efficacy, suggesting that DF identifies patients who may require additional ablation beyond APVI.


Methodology for estimating soil carbon for the forest carbon budget model of the United States, 2001.
The largest carbon (C) pool in United States forests is the soil C pool. We present methodology and soil C pool estimates used in the FORCARB model, which estimates and projects forest carbon budgets for the United States. The methodology balances knowledge, uncertainties, and ease of use. The estimates are calculated using the USDA Natural Resources Conservation Service STATSGO database, with soil dynamics following assumptions based on results of site-specific studies, and area estimates from the USDA Forest Service. Forest Inventory and Analysis data and national-level land cover data sets. Harvesting is assumed to have no effect on soil C. Land use change and forest type transitions affect soil C. We apply the methodology to the southeastern region of the United States as a case study.


Deep Neuromuscular Block Improves Surgical Conditions during Bariatric Surgery and Reduces Postoperative Pain: A Randomized Double Blind Controlled Trial.
It remains unknown whether the administration of a deep neuromuscular block (NMB) during bariatric surgery improves surgical conditions and patient outcome. The authors studied the effect of deep versus moderate NMB in laparoscopic bariatric surgery on surgical conditions and postoperative pain. One hundred patients scheduled to undergo elective bariatric surgery were randomized to a deep NMB (post-tetanic-count 2-3) or a moderate NMB (train-of-four 1-2). The quality of the surgical field was scored using the Leiden-Surgical Rating Scale (L-SRS), a 5-point scale ranging from 1 (extremely poor conditions) to 5 (optimal conditions). Three surgeons scored the L-SRS at 10-min intervals during surgery; postoperative pain scores were obtained in the postanesthesia-care-unit (PACU) and on the ward. Mean (95% confidence interval) L-SRS scores in moderate NMB 4.2 (4.0-4.4) versus 4.8 (4.7-4.9) in deep NMB (p < 0.001). Moderate NMB resulted in 17% of scores at L-SRS scores of 1-3, while deep NMB resulted in 100% scores at the high end of the L-SRS (4-5). Deep NMB led to improved pain scores in the PACU (4.6 (4.2-4.9) versus 3.9 (3.6-4.4), p = 0.03) and reduced shoulder pain on the ward (1.8 (1.5-2.1) versus 1.3 (1.1-1.5), p = 0.03). A composite score of pain and opioid use in the PACU favoured deep NMB (p = 0.001). In bariatric surgery, deep relaxation has advantages for surgeon and patient. Compared to moderate NMB, deep NMB produced stable and improved surgical conditions with less postoperative pain.


Malformations of cortical development: New surgical advances.
Epilepsy related to malformations of cortical development is frequently drug resistant or requires heavy medication, therefore surgery is key in their management. The role of stereotactic surgery has recently changed the diagnosis and treatment of focal cortical dysplasias (FCD), hypothalamic hamartomas (HH) and periventricular nodular heterotopias (PNH). In HH, radiosurgery using Gammaknife® leads to 60 % of seizure control and is associated with excellent neuropsychological results without significant endocrine function impairment. The seizure control rate is even higher (more than 80 %) with monopolar multiple stereotactic thermocoagulations and Laser interstitial Thermal Therapy (LiTT). While the first technique is associated with a 2 % complications rate (but with excellent neuropsychological outcomes), the latest has up to 22 % side effects in some series. All three of these techniques have encouraging results, but controlled studies are still lacking to provide evidence-based new therapeutic algorithms. With regard to the PNH, surgical management has long been limited by the depth of the lesions and their close anatomical relations with the functional brain connectome. Stereotactic approaches required to perform a SEEG, to locate the part of the PNH responsible for the seizure onset, are later followed by a stereotactic lesioning procedure, therefore doubling the bleeding risk. That is why SEEG-guided radiofrequency-thermocoagulation (SEEG guided-RF-TC), which makes it possible to perform these two steps in a single procedure, was considered as a promising option. A recent meta-analysis confirmed this intuition and reported 38 % of seizure-free patients and 81 % of responders with only 0.3 % of complications, making this approach the first treatment line, followed by LiTT. Among the multiple advances in the FCD identification by non-invasive investigations, a new modality of per-operative diagnostic procedure, the three-dimensional electrocorticography may lead to simplify the preoperative investigation and enhance the accuracy of FCD delineation. Evidence is nevertheless still insufficient to validate this promising concept. Conventional surgical resection has also been concerned by significant conceptual advances during the past few years, in particular with the development of the hodotopic approach, initially in oncologic surgery. Associated with a better understanding of neuroplasticity in epilepsy and the setting up of functional mapping during SEEG or during awake surgery, the possibility of surgical resections grew up. A short-term perspective in this field, when surgical resection remains impossible, would be to target crucial nodes of the epileptic network, distinct from the core functional connectome.


Metabolic modulation of acute myocardial infarction. The ECLA (Estudios Cardiológicos Latinoamérica) Collaborative Group.
Several trials have been performed in the past using glucose, insulin, and potassium infusion (GIK) for the treatment of acute myocardial infarction (AMI). Because of continuing uncertainty about the potential role of this therapeutic intervention, we conducted a randomized trial to evaluate the impact of a GIK solution during the first hours of AMI. Four hundred seven patients with suspected AMI admitted within 24 hours of symptoms onset were enrolled. In a ratio of 2:1, 268 patients were allocated to receive GIK (high- or low-dose) and 139 to receive control. Phlebitis and serum changes in the plasma concentration of glucose or potassium were observed more often with GIK. A trend toward a nonsignificant reduction in major and minor in-hospital events was observed in patients allocated to GIK. In 252 patients (61.9%) treated with reperfusion strategies, a statistically significant reduction in mortality (relative risk [RR] 0.34; 95% CI: 0.15 to 0.78; 2P=0.008) and a consistent trend toward fewer in-hospital events in the GIK group were observed. Our results confirm that a metabolic modulation strategy in the first hours of an AMI is feasible, applicable worldwide, and has mild side effects. The statistically significant mortality reduction in patients who underwent a reperfusion strategy might have important implications for the management of AMI patients. It is now essential to perform a large-scale trial to reliably determine the magnitude of benefit.


Development of a Novel Amorphous Agomelatine Formulation With Improved Storage Stability and Enhanced Bioavailability.
The present work describes the development of a novel formulation of amorphous agomelatine (AGM) that exhibits enhanced in vitro dissolution rate and bioavailability, as well as improved storage stability. AGM was loaded on a mixture of microcrystalline cellulose with a high specific surface area excipient, namely colloidal silicon dioxide, employing a wet granulation method, and the resultant AGM granules were subsequently formulated into immediate release film-coated tablets. Modulated temperature differential scanning calorimetry, hot-state light microscopy, powder X-ray diffraction, attenuated total reflectance FTIR, and micro-Raman spectroscopy revealed that the active pharmaceutical ingredient existed primarily in the amorphous state within the prepared formulations, with some crystals of polymorph I also present. Accelerated stability studies for up to 6 months in alu-alu blisters showed good physicochemical stability during storage. Finally, in vitro dissolution studies and clinical trials in healthy human volunteers showed a remarkable increase in the in vitro dissolution rate and a ∼1.5-fold increase in bioavailability, respectively, compared to the marketed product.


Immunohistological indication for arthroscopic synovectomy in rheumatoid knees: analysis of synovial samples obtained by needle arthroscopy.
To determine the histological indication for arthroscopic synovectomy in rheumatoid knees, 23 patients underwent lavage and biopsy by needle arthroscopy. Eighty-one patients were treated with arthroscopic knee synovectomy after needle arthroscopy, and 51 of these patients underwent only arthroscopic synovectomy. Thirty patients who showed no improvement following arthroscopic synovectomy underwent open surgical synovectomy. Intra-articular lavage of knee joints by needle arthroscopy did not result in any clinical improvements. In the patients who underwent only arthroscopic synovectomy, two groups (only macrophages, no macrophages or B cells) showed clinical improvement (symptoms of the knee, ESR, RF). Patients in whom open surgical synovectomy was performed because of the failure of arthroscopic synovectomy showed clinical improvement. However, there was a significant loss of movement in the knee joint and more severe radiological deterioration in patients who underwent open surgical synovectomy than in those who underwent only arthroscopic synovectomy. Arthroscopic synovectomy should be used for rheumatoid patients with synovial tissue containing only macrophages or none of these two cells.


Microbial fingerprints of methanation in a hybrid electric-biological anaerobic digestion.
Biomethane as a sustainable, alternative, and carbon-neutral renewable energy source to fossil fuels is highly needed to alleviate the global energy crisis and climate change. The conventional anaerobic digestion (AD) process for biomethane production from waste(water) streams has been widely employed while struggling with a low production rate, low biogas qualities, and frequent instability. The electric-biologically hybrid microbial electrochemical anaerobic digestion system (MEC-AD) prospects more stable and robust biomethane generation, which facilitates complex organic substrates degradation and mediates functional microbial populations by giving a small input power (commonly voltages < 1.0 V), mainly enhancing the communication between electroactive microorganisms and (electro)methanogens. Despite numerous bioreactor tests and studies that have been conducted, based on the MEC-AD systems, the integrated microbial fingerprints, and cooperation, accelerating substrate degradation, and biomethane production, have not been fully summarized. Herein, we present a comprehensive review of this novel developing biotechnology, beginning with the principles of MEC-AD. First, we examine the fundamentals, configurations, classifications, and influential factors of the whole system's performances (reactor types, applied voltages, temperatures, conductive materials, etc.,). Second, extracellular electron transfer either between diverse microbes or between microbes and electrodes for enhanced biomethane production are analyzed. Third, we further conclude (electro)methanogenesis, and microbial interactions, and construct ecological networks of microbial consortia in MEC-AD. Finally, future development and perspectives on MEC-AD for biomethane production are proposed.


Multiple-dose cimetidine administration does not influence the single-dose pharmacokinetics of quinapril and its active metabolite (CI-928).
The potential effect of cimetidine on the pharmacokinetic profiles of quinapril and its active metabolite CI-928 was evaluated in eight healthy volunteers. Each subject received a single 40-mg quinapril dose on days 1 and 12 and cimetidine 300 mg four times daily on days 8 through 13. Serial blood and urine samples were collected for assay of quinapril and CI-928 concentrations. No statistically significant differences were observed in quinapril or CI-928 Cmax, tmax, AUC(0-infinity), beta, or percent of dose excreted in urine values for quinapril administered alone and in combination with cimetidine. Therefore, multiple-dose cimetidine administration does not influence the single-dose pharmacokinetics of quinapril and its active metabolite, CI-928, in healthy volunteers.


Polypharmacy with common diseases in hospitalized elderly patients.
Elderly persons are exposed to polypharmacy because of multiple chronic conditions. Many risk factors for polypharmacy have been identified including age, race/ethnicity, sex, educational achievement level, health status, and number of chronic diseases. However, drugs prescribed for individual diseases have not been analyzed. The objective of this study was to analyze each common disease in the elderly with respect to prescribed drugs and polypharmacy. A 1-year (January through December 2009) cross-sectional study was performed in which all drugs given to hospitalized elderly patients (age, >65 years) were investigated. Common diseases of the elderly were separated into disease groups including hypertension, hyperlipidemia, gastric ulcer, previous stroke, reflux esophagitis, diabetes mellitus, malignancy, osteoporosis, angina pectoris, congestive heart failure, chronic obstructive pulmonary disease, dementia, and depression. Among 1768 elderly patients, the mean (range) age of study patients was 78 (65 to 100) years. The mean (SD) number of diseases was 7.7 (3.4), and the number of drugs overall was 4.9 (3.6). The number of drugs and prevalence of polypharmacy were hypertension, 5.2 (3.9 [51%]); hyperlipidemia, 5.6 (3.8 [58%]); gastric ulcer, 5.4 (3.8 [53%]); previous stroke, 5.8 (3.2 [61%]); reflux esophagitis, 5.6 (3.8 [40%]), diabetes mellitus, 5.6 (3.1 [54%]); malignancy, 4.1 (3.1 [37%]); osteoporosis, 5.4 (3.4 [45%]); angina pectoris, 5.7 (3.6 [42%]); congestive heart failure, 6.1 (4.0 [60%]); chronic obstructive pulmonary disease, 5.0 (3.5 [53%]); dementia, 5.1 (3.2 [52%]); and depression, 7.0 (4.2 [73%]). When assessing the risk of polypharmacy, physicians should carefully consider the type of any chronic disease. Elderly patients with multiple diseases may be subjected to further polypharmacy.


Interactions amongst species in a guild of subtidal benthic herbivores.
The subtidal coralline flats of northeastern New Zealand support a characteristic guild of grazing herbivores. The most important members of this guild are an echinometrid echinoid, patellid, turbinid and trochid gastropods. Densities of these herbivores fluctuate through time. Interactions within and among the different species of echinoids and gastropods were investigated experimentally. Different combinations of species were caged at densities up to 5 times that of ambient for a 24 week period in an experiment designed to differentiate between intra- and interspecific competition.The echinoidEvechinus chloroticus and the turbinid gastropodCookia sulcata exhibited reduced mean dry weight with increasing intraspecific densities. There was little evidence of density-related mortality in these species. The limpetCellana stellifera showed comparatively large losses of weight and enhanced mortalities in intraspecific experimental treatments but this was not related to density.Investigation of interspecific interactions amongstEvechinus andCookia revealed no evidence of a negative influence of one species on the other. In terms of dry weight,Cookia was indifferent to the presence ofEvechinus, andEvechinus benefited in the reciprocal interaction.Cookia also enjoyed an enhanced mean dry weight when in the presence ofCellana compared to the equivalent intraspecific treatments. There were no coherent trends in proportional mortality in any treatments with enhanced interspecific densities. Cellana, in the presence ofCookia, exhibited a dramatic decrease in mortality rate and increase in mean dry weight. The presence of the turbinid gastropod was clearly beneficial to the limpet when compared to the intraspecific treatments with enhanced intraspecific densities and the control cages containingCellana at ambient density. We suggest that subtidal areas constitute poor habitats for limpets in the absence of agents such asCookia which may provide or maintain suitable sites for attachment and grazing.For the combinations of densities and species investigated there was a consistent trend towards positive interspecific interactions. It seems unlikely that at the sites investigated interspecific competition could act to restrict distributions, or limit abundances of species.


Circulating progesterone concentrations and ovarian functional anatomy in the African elephant (Loxodonta africana).
Mean plasma progesterone concentrations measured in pregnant and non-pregnant elephants did not differ significantly from each other because of considerable variation, particularly for stage of pregnancy. Maximum progesterone values were recorded during pregnancy (5-8 months) and declined towards term (22 months). The numbers of corpora lutea or total luteal tissue volume were not critical in maintaining progesterone secretion. An increase in plasma progesterone concentrations with the luteal phase of the ovarian cycle was evident. A possible role of the placenta in the second half of gestation is indicated by an increase in fetal progesterone concentrations towards term.


Electrophysiological properties of the mitochondrial permeability transition pores: Channel diversity and disease implication.
The mitochondrial permeability transition pore (mPTP) is a channel that, when open, is responsible for a dramatic increase in the permeability of the mitochondrial inner membrane, a process known as the mitochondrial permeability transition (mPT). mPTP activation during Ca2+ dyshomeostasis and oxidative stress disrupts normal mitochondrial function and induces cell death. mPTP opening has been implicated as a critical event in many diseases, including hypoxic injuries, neurodegeneration, and diabetes. Discoveries of recent years indicate that mPTP demonstrates very complicated behavior and regulation, and depending on specific induction or stress conditions, it can function as a high-conductance pore, a small channel, or a non-specific membrane leak. The focus of this review is to summarize the literature on the electrophysiological properties of the mPTP and to evaluate the evidence that it has multiple molecular identities. This review also provides perspective on how an electrophysiological approach can be used to quantitatively investigate the biophysical properties of the mPTP under physiological, pharmacological, pathophysiological, and disease conditions.


Online resources for the molecular contextualization of disease.
Searching online resources can provide medical researchers with an efficient means of gathering existing knowledge on the molecular causes of disease. The researcher may choose to explore the following areas, e.g., genetic mutations associated with the disease, function and cellular sub-localization of the associated protein(s) and their protein interaction partners. Using a small case study, examining the disease retinoblastoma, this chapter guides the reader through the relevant information contained within relevant databases. It is shown that the integration of online biological knowledge with genomic and proteomic experimental data provides insights into the understanding of diseases in their molecular context.


[Information and education interventions on hygiene levels of a population in which trachoma exists in a hyperendemic and serious form].
The aim of this work is to develop information and education methods in order to obtain better hygienic conditions in Tissint Zaouia (Moroccan province of Ouarzazate). 41% of the population is affected by trachoma with a rate of 18% of active trachoma, 1.6% of the population has a blindness of corneal origin. Topical treatment and surgery of trichiasis must be associated to a better hygiene of the community. Until now mothers and families have not fully perceived the connection between flies and insufficiency of narsing and trachoma transmission. Our specific goals are the following: A--information of target population, B--better understanding of hygiene by mothers and families, C--incitation to face-washing of children, D--perfect identification of trachoma signs by health workers, E--official integration of this program by local authority, F--evaluation of trachoma incidence.


Impairment of mitochondrial metabolism differentially affects striatal neuronal subtypes.
Electrophysiological and microfluorometric measurements were combined to analyse the responses of rat striatal medium spiny (MS) and large aspiny (LA) interneurons to the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylidrazone (FCCP). FCCP produced a membrane depolarisation coupled to an irreversible increase in intracellular calcium [Ca2+]i in MS. Conversely, LA interneurons hyperpolarised and a moderate [Ca2+]i rise was observed. Cyclosporin A, inhibitor of the mitochondrial membrane transition pore, prevented the FCCP-induced changes in LA interneurons, whereas only a partial reduction was observed in MS cells. The present results indicate that mitochondrial Ca2+ released into the cytosol may contribute to the selective vulnerability to metabolic impairment in striatal neuronal subtypes.


Crayfish stretch receptor: an investigation with voltage-clamp and ion-sensitive electrodes.
1. The membrane characteristics of the slowly adapting stretch receptor from the crayfish, Astacus fluviatilis, were examined with electrophysiological techniques consisting of membrane potential recording, voltage clamp and ion-sensitive microelectrodes. 2. The passive membrane current (Ip) following step changes of the membrane potential to levels above 0 mV required more than a minute to decay to a steady-state level. 3. The stretch-induced current (SIC, where SIC = Itotal--Ipassive) was not fully developed until the Ip had decayed to a steady state. 4. With Ip at the steady state and the stretch-induced current at the O-current potential, a slow stretch-induced inward current was isolated. The latter reaches a maximum after 1 sec of stretch and declines even more slowly after stretch. The I-V relation of the slow current had a negative slope and reversed sign near the resting potential. It is suggested that this current is due to a Cl- conductance change. 5. The stretch-induced current, consisting of a rapid transient phase and a steady component can be isolated from the slow stretch-induced current at a holding potential corresponding to the resting potential. 6. The SIC-Em relation is non-linear and reverses sign at about +15 mV. 7. In a given cell, the reversal potential of the stretch-induced potential change obtained with current clamp coincided with the 0-current potential of the stretch-induced current obtained by voltage clamp. The average value from twenty-six cells was +13 +/- 6.5 mV; cell to cell variability seemed to be correlated with dendrite length. 8. Tris (mol. wt. 121) or arginine (mol. wt. 174) susbstituted for Na+ reduces but does not abolish the stretch-induced current. 9. The permeability ratios of Tris:Na and arginine:Na were estimated from changes in the 0-current potential as these cations replaced Na+ in the external medium. The PTris:PNa was somewhat higher (0.31) than the Parginine:PNa ratio (0.25). 10. Changes in the external Ca2+ concentration had no effect on the 0-current potential in Na or Tris saline. However, reducing Ca2+ did augment the stretch-induced current in either saline. A tenfold reduction of Ca2+ increased the conductance (at the 0-current level) about twofold. 11. Intracellular K+ and Cl- activities were obtained with ion sensitive electrodes. The average values from six cells were aiK = 133 +/- 34 mM and aiCl = 15.2 +/- 1.8 mM S.D.). EK was about 20 mV more negative than Em and ECl was about 10 mV more positive than Em. 12. aik and resting Em undergo large changes in K+-free solutions. After 60 min, ak was reduced eightfold and Em was reduced from -67 to -40 mV. Reduced Ca2+ in K+-free augments the rate of these changes. Receptor potential amplitude was also reduced in K+-free solution but could be restored upon polarizing the membrane to the pre-existing resting level.


Discriminatory Ability of Gas Chromatography-Ion Mobility Spectrometry to Identify Patients Hospitalized With COVID-19 and Predict Prognosis.
Rapid diagnostic and prognostic tests for coronavirus disease (COVID-19) are urgently required. We aimed to evaluate the diagnostic and prognostic ability of breath analysis using gas chromatography-ion mobility spectrometry (GC-IMS) in hospitalized patients with COVID-19. Between February and May 2021, we took 1 breath sample for analysis using GC-IMS from participants who were admitted to the hospital for COVID-19, participants who were admitted to the hospital for other respiratory infections, and symptom-free controls, at the University Hospitals of Leicester NHS Trust, United Kingdom. Demographic, clinical, and radiological data, including requirement for continuous positive airway pressure (CPAP) ventilation as a marker for severe disease in the COVID-19 group, were collected. A total of 113 participants were recruited into the study. Seventy-two (64%) were diagnosed with COVID-19, 20 (18%) were diagnosed with another respiratory infection, and 21 (19%) were healthy controls. Differentiation between participants with COVID-19 and those with other respiratory tract infections with GC-IMS was highly accurate (sensitivity/specificity, 0.80/0.88; area under the receiver operating characteristics curve [AUROC], 0.85; 95% CI, 0.74-0.96). GC-IMS was also moderately accurate at identifying those who subsequently required CPAP (sensitivity/specificity, 0.62/0.80; AUROC, 0.70; 95% CI, 0.53-0.87). GC-IMS shows promise as both a diagnostic tool and a predictor of prognosis in hospitalized patients with COVID-19 and should be assessed further in larger studies.


Circadian variation of acute myocardial infarction in young people.
The aim was to investigate the circadian and weekly variation in Chinese young patients with acute myocardial infarction (AMI). This was a 10-year retrospective cohort study. We studied patients (>18 to <45 years of age) with a first attack of AMI from the emergency departments of 3 university teaching hospitals in Taiwan from January 1, 2001, to December 31, 2010. We analyzed patients in the standard circadian fashion using 6-hour intervals (00:01-06:00, 06:01-12:00, 12:01-18:00, and 18:01-24:00). We also did an analysis by day of week. The database had 505 patients with AMI with complete data. The percentage of total AMIs that occurred in the 6-hour intervals were as follows: 00:01 to 06:00, 30.9%; 06:01 to 12:00, 23.4%; 12:01 to 18:00, 25.9%; and 18:01 to 24:00, 19.8%. The percentage of AMIs between 00:01 and 06:00 was significant higher compared with that in the other three 6-hour intervals (df = 3, χ(2) = 91.7, P < .001). However, there was no significant weekly variation for these patients in the present study. There was a significant circadian variation with a peak from 00:01 to 06:00 in Chinese young patients with AMI. However, there was no significant weekly variation in these patients. The circadian periodicity may create new possibilities for disease prevention and medication prescription.


Degradation Mechanism Detection in Photovoltaic Backsheets by Fully Convolutional Neural Network.
Materials and devices age with time. Material aging and degradation has important implications for lifetime performance of materials and systems. While consensus exists that materials should be studied and designed for degradation, materials inspection during operation is typically performed manually by technicians. The manual inspection makes studies prone to errors and uncertainties due to human subjectivity. In this work, we focus on automating the process of degradation mechanism detection through the use of a fully convolutional deep neural network architecture (F-CNN). We demonstrate that F-CNN architecture allows for automated inspection of cracks in polymer backsheets from photovoltaic (PV) modules. The developed F-CNN architecture enabled an end-to-end semantic inspection of the PV module backsheets by applying a contracting path of convolutional blocks (encoders) followed by an expansive path of decoding blocks (decoders). First, the hierarchy of contextual features is learned from the input images by encoders. Next, these features are reconstructed to the pixel-level prediction of the input by decoders. The structure of the encoder and the decoder networks are thoroughly investigated for the multi-class pixel-level degradation type prediction for PV module backsheets. The developed F-CNN framework is validated by reporting degradation type prediction accuracy for the pixel level prediction at the level of 92.8%.


Change of glycosaminoglycan in pus of patients with purulent pleurisy.
The glycosaminoglycan content in pus from patients with purulent pleurisy was studied. The uronic acid content rose in the first 4 hospital days, continued at a high level during hospital days 5-8, and then fell to a low level after 9 hospital days. Four glycosaminoglycans were isolated from the preparation; they were identified as hyaluronic acid, chondroitin 4-sulfate, chondroitin 6-sulfate, and dermatan sulfate. Hyaluronic acid was the main component and its relative proportion increased with increasing hospital days. The relative proportions of chondroitin 4-sulfate and chondroitin 6-sulfate were low during the first 4 day and during Days 10-21, whereas they were high during Days 5-9. The proportion of dermatan sulfate was high during the early hospital days, and thereafter decreased with increasing hospital days.


Twist drill craniostomy for traumatic acute subdural hematoma in the elderly: case series and literature review.
A large craniotomy is usually the first choice for removal of traumatic acute subdural hematoma (TASDH). To date, few studies have reported that TASDH could be successfully treated by twist drill craniostomy (TDC) alone or combined with instillation of urokinase. We aimed to define the TDC for the elderly with TASDH and performed literature review. A total of 7 TASDH patients, who were presented and treated by TDC in this retrospective study between January 2009 and May 2017, consisted of 5 men and 2 women, ranging in age from 65 to 89 (average, 78.9) years. The patients' baseline characteristics, including age, sex, medical history, received ventriculoperitoneal shunt for hydrocephalus or not, reason for avoiding or refusing large craniotomy, preoperative Glasgow Coma Scale (GCS), suffered from cerebral herniation or not, the location of TASDH, imaging characteristics of TASDH in CT scan, injury/surgery time interval, midline shift, preoperative neurologic deficit, operation time, and infusions of urokinase or not, were collected. The postoperative GCS, postoperative neurologic deficit, rebleeding or not, intracranial infection, and modified Rankin Scale (mRS) at 6 months after surgery were analyzed to access the safety and efficacy of evacuation with TDC. The results showed that the mean time interval from injury to TDC was 68.6 min (30-120 min). The mean distance of midline shift was 14.6 mm (10-20 mm). The preoperative GCS in all patients ranged from 4 to 13(median, 9). The mean duration of the operation was 14.4 min (6-19 min). Postoperative CT scan showed that hematoma evacuation rate was more than 70% in all cases. There were no cases of acute rebleeding and intracranial infection after TDC. No cases presented with chronic SDH at the ipsilateral side within 6 months after being treated by TDC alone or combined with instillation of urokinase. Favorable outcomes were shown in all cases (mRS scores 0-2) at 6 months after surgery. TASDH in the elderly could be safely and effectively treated by TDC alone or combined with instillation of urokinase, which was a possible alternative for the elderly.