Lateral prefrontal damage affects processing selection but not attention switching.
A challenge for cognitive neuroscience is to determine how the prefrontal cortex (PFC) contributes to the cognitive control operations that oversee thought and action. We studied the effects of damage to the lateral PFC in two types of attentional control. Subjects performed a choice reaction time task that required attention switching and processing selection. The performance of individuals with PFC or parietal cortex damage was compared with that of age-matched and young control subjects. Damage to the lateral PFC did not significantly impair the switch from attending to one color to attending to another. PFC damage did, however, significantly increase the effects of distractor stimuli, implicating the lateral PFC in processing selection. Individual subjects' performance suggested that the left inferior posterior PFC was the most critical for processing selection. Our data are consistent with the view that the lateral PFC contributes to the top-down control of the information flow along pathways from sensory input to motor output.


Relationships between leaf age and the food quality of cottonwood foliage for the gypsy moth, Lymantria dispar.
The cottonwood tree, Populus deltoides, continues to produce leaves late into the growing season, exposing midseason herbivores to leaves of a wide range of maturity. Gypsy moth larvae preferred and grew best on the oldest cottonwood leaves and suffered higher mortality and 85% less growth when fed young, expanding leaves. Concentration of phenolics in the youngest leaves was 3 times that in the oldest leaves and was negatively correlated with caterpillar growth rate. The active phenolics were not identified; tannin was present but its concentration changed more with season than leaf age.


Long-lasting capture of tactile attention by body shadows.
Four experiments addressed the role of cast shadows of the body in orienting tactile spatial attention to the body itself. We used a modified spatial-cueing paradigm to examine whether viewing of the cast shadow of a hand can elicit spatial shifts of tactile attention to that very same hand. Participants performed a speeded tactile-discrimination task (thumb versus index finger, regardless of touched hand), while viewing the shadow of either the touched or untouched hand cast in front of them by a lateral light-source. The hand casting the shadow changed either between blocks (expt 1) or unpredictably within each block (expts 2-4). In experiments 1 and 2 tactile targets were preceded by central non-informative visual cues delivered near the shadow of the index finger and thumb. Despite the fact that cast shadows were always task-irrelevant and non-predictive of which hand was stimulated, tactile discrimination was consistently faster at the hand casting the shadow than at the other hand. This effect was not modulated by the duration of cue-target asynchrony, nor did it depend on whether the visual cue was present or not (expt 3). In addition, it was still reliable when vision of the hands was precluded, whereas it became inconsistent when the cast shadow of the hand was replaced by the cast shadow of an object (expt 4). Our results suggest that body shadows can induce a long-lasting capture of tactile attention for stimuli at the body itself.


Sustaining cardiac claudin-5 levels prevents functional hallmarks of cardiomyopathy in a muscular dystrophy mouse model.
Identification of new molecular targets in heart failure could ultimately have a substantial positive impact on both the health and financial aspects of treating the large heart failure population. We originally identified reduced levels of the cell junction protein claudin-5 specifically in heart in the dystrophin/utrophin-deficient (Dmd(mdx);Utrn(-/-)) mouse model of muscular dystrophy and cardiomyopathy, which demonstrates physiological hallmarks of heart failure. We then showed that at least 60% of cardiac explant samples from patients with heart failure resulting from diverse etiologies also have reduced claudin-5 levels. These claudin-5 reductions were independent of changes in other cell junction proteins previously linked to heart failure. The goal of this study was to determine whether sustaining claudin-5 levels is sufficient to prevent the onset of histological and functional indicators of heart failure. Here, we show the proof-of-concept rescue experiment in the Dmd(mdx);Utrn(-/-) model, in which claudin-5 reductions were originally identified. Expression of claudin-5 4 weeks after a single administration of recombinant adeno-associated virus (rAAV) containing a claudin-5 expression cassette prevented the onset of physiological hallmarks of cardiomyopathy and improved histological signs of cardiac damage. This experiment demonstrates that claudin-5 may represent a novel treatment target for prevention of heart failure.


Androstenedione stimulates progesterone production in corpora lutea of pregnant rats: an effect not mediated by oestrogen.
To determine if androstenedione, an aromatizable androgen, has a direct effect on luteal progesterone secretion, collagenase-dispersed luteal cells or whole corpora lutea from pregnant rats were incubated in the presence of the androgen. Luteal cells from 15-day pregnant rats responded to androstenedione in a dose-dependent manner, with an increase in progesterone output at doses of 1 and 10 microM, but with no effect at minor doses of the androgen. Luteal cells obtained from animals on day 4, 9, 15 or 19 of pregnancy and incubated with 10 microM of androstenedione, increased progesterone production by 243, 39, 84 and 146%, respectively. Androgens (androstenedione, testosterone or dihydrotestosterone) but no oestrogens (oestradiol or diethylstilboestrol) at a dose of 10 microM, stimulated progesterone production in incubated luteal cells obtained from 15-day pregnant rats. The time-course pattern of androstenedione-induced progesterone production was studied by superfusion experiments using corpora lutea from rats on day 15 of pregnancy. A significant progesterone output was observed when androstenedione, but not oestradiol, was perfused through the luteal tissue. Intrabursal ovarian administration of androstenedione (10 microM) to 19-day pregnant rats induced a significative increase in serum progesterone levels 8 and 24 h after treatment. These in vivo results confirm the stimulatory effect of androstendione on progesterone production obtained in incubated luteal cells from pregnant rats. This study reports a direct luteotrophic effect of androstenedione in rat corpus luteum, not mediated by previous conversion to oestrogens.


The identification of Lynch syndrome in Congolese colorectal cancer patients.
We aimed to investigate the prevalence of Lynch syndrome as one of hereditary causes of colorectal cancer (CRC) among young Congolese individuals affected by the CRC, and to define methods for diagnosis in Congo Brazzaville. We conducted a transversal cohort study of 34 patients having a CRC with a family history for a period of eight years. They were selected among 89 CRCs of any type from the Bethesda guidelines criteria combined with pedigrees. Mismatch repair (MMR) genes alterations were researched by immunohistochemistry (IHC). We identified with the Bethesda criteria a total of 38.2% (34/89) patients having familial CRC with a confidence interval (CI) of 95%=[0.34-0.41]. Only 14.7% (5/34) 95% CI=[0.34-2.32] patients showed MMR immunodeficiency involving firstly MLH1 protein then MSH2 protein. These data account for 5.6% (5/89) 95% CI=[0.15-0.33] of patients affected by Lynch syndrome with an earlier median age of 35 years (range 20 to 47 years). The prevalence of Lynch syndrome found in Brazzaville is comparable to that is found in northern countries. The combined Bethesda guidelines, pedigree and IHC is an accessible and good alternative method for the positive diagnosis of Lynch syndrome in current practice in Congo.


Development and evaluation of the information and communication technology-based Loneliness Alleviation Program for community-dwelling older adults: A pilot study and randomized controlled trial.
This study aimed to develop an information and communication technology (ICT)-based Loneliness Alleviation Program (LAP) for community-dwelling older adults, which was developed according to the ADDIE model. The LAP is a complex non-face-to-face program for physical, psychological, and interpersonal loneliness alleviation. We conducted a randomized controlled trial to verify the effects of the program on loneliness, depression, and laughter index in older adults. Program sessions were conducted twice a week for 6 weeks (12 sessions). Data on 40 older adults aged 65 years and above were collected from January 2, 2023 to February 17, 2023 at a public health center in South Korea. The experimental group showed statistically significant effects of the program on loneliness, depression, and laughter index scores. The older adults were alleviated their loneliness by utilizing non-face-to-face programs, and the program is expected to increase continuity and inclusiveness of care.


Development and dissemination of a statewide system to minimize use of Potentially Inappropriate Medications (PIMs).
Drug safety and adverse drug reactions in the community are of concern in the geriatric population. To help decrease the number of adverse drug reactions, the New Mexico Prescription Improvement Coalition created a consensus panel, the Potentially Inappropriate Medications (PIMs) Advisory Board. To develop consensus guidelines that would promote decreasing the use of PIMs, as defined by the Beers' criteria, through the promotion of safer alternative therapies and strategies. A consensus panel of clinical pharmacists, geriatricians, nurses, managed care specialists, and consumers evaluated the Beers' criteria and created clinical guidelines addressing the use of PIMs in older adults and disease state alternative treatment recommendations and strategies. The guidelines were distributed and made available electronically to health care providers. In addition, educational sessions were provided to health care providers throughout the state. Since development of the guidelines in 2009, they have been distributed to over 7500 practitioners and 140 pharmacists throughout New Mexico. The PIMs clinical guidelines were endorsed by 27 state-level health care organizations and have been promoted through several managed care organizations. The Web-based version of the guidelines have been viewed an average of 163 times per month and the alternative treatment recommendations and strategies was viewed an average of 407 times per month. Use of a consensus process to develop and promote guidelines that include alternative treatment recommendations and strategies can increase awareness of the use of medications that require caution in the elderly and promote safer prescribing practices.


Improved treatment and survival for lung cancer patients in South-East Scotland.
Lung cancer survival in Scotland has historically been poor but many changes to the lung cancer services have been introduced and this study was conducted to investigate the impact of these changes on treatment and survival. Data obtained from the Scottish Cancer Registry, South-East Scotland Cancer Network audit and Edinburgh Cancer Centre database were used to conduct a comparison of the management and outcomes of lung cancer patients from South-East Scotland diagnosed in 1995 and in 2002. Data on 971 patients diagnosed in 2002 and 927 in 1995 were analyzed and demonstrated that though the use of treatment overall had not changed (62% in 2002 versus 63% in 1995) the use of potentially curative radiotherapy (15 versus 5% chi p < 0.001) and chemotherapy for non-small cell lung cancer (18 versus 7% chi p < 0.001) had increased, but not resection rates (11 versus 10%). The use of palliative radiotherapy declined (38% versus 31% chi p < 0.001). Patients diagnosed in 2002 had an adjusted hazard of death of 0.7 (95% confidence interval, 0.6-0.8) compared with 1995, with median survival from date of diagnosis of 5.2 versus 4.1 month and 2 year overall survival 15 versus 11% (log rank p = 0.004). Localized disease and younger age were also associated with a reduced hazard of death. Patients diagnosed with lung cancer in Scotland in 2002 had a reduced hazard of death and improved survival compared with 1995. It is hypothesized that this was due in part to improvements in service organization and increased use of treatments likely to increase survival.


Association of inflammation-related exposures and ovarian cancer survival in a multi-site cohort study of Black women.
An association was observed between an inflammation-related risk score (IRRS) and worse overall survival (OS) among a cohort of mostly White women with invasive epithelial ovarian cancer (EOC). Herein, we evaluated the association between the IRRS and OS among Black women with EOC, a population with higher frequencies of pro-inflammatory exposures and worse survival. The analysis included 592 Black women diagnosed with EOC from the African American Cancer Epidemiology Study (AACES). Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of the IRRS and OS, adjusting for relevant covariates. Additional inflammation-related exposures, including the energy-adjusted Dietary Inflammatory Index (E-DIITM), were evaluated. A dose-response trend was observed showing higher IRRS was associated with worse OS (per quartile HR: 1.11, 95% CI: 1.01-1.22). Adding the E-DII to the model attenuated the association of IRRS with OS, and increasing E-DII, indicating a more pro-inflammatory diet, was associated with shorter OS (per quartile HR: 1.12, 95% CI: 1.02-1.24). Scoring high on both indices was associated with shorter OS (HR: 1.54, 95% CI: 1.16-2.06). Higher levels of inflammation-related exposures were associated with decreased EOC OS among Black women.


Treatment of Miescher's cheilitis granulomatosa in Melkersson-Rosenthal syndrome.
Cheilitis granulomatosa is the most frequent dermatological sign in the Melkersson-Rosenthal syndrome. We reviewed 27 cases of this syndrome diagnosed and treated in the last 20 years. All the patients were surgically treated and received intralesional corticosteroids during surgery and tetracycline hydrochloride (500 mg, twice daily) after the operation to prevent recurrence.


[A retrospective study of the effectiveness of lamotrigine in monotherapy for the treatment of epileptic seizures. The ERELMO study].
The efficacy and tolerability of lamotrigine (LTG) in monotherapy and in combination therapy have been demonstrated in clinical trials. The aim of the ERELMO study was to retrospectively evaluate the effectiveness and safety of LTG, as monotherapy in the control of epileptic seizures in routine clinical practice in Spain. 446 clinical records were selected of patients with LTG treatment in the twelve months previously to the beginning of the study. The main endpoints retrospectively analyzed were effectiveness (percentage of patients with 50% or greater reduction in seizure frequency, improvement in seizure control, percentage of patients remaining-seizure free at 2, 6 and 12 months of LTG monotherapy), and safety (adverse event profile reported and treatment withdrawal). The mean age was 41 years old, 57.8% were women. LTG monotherapy treatment (mean maintenance dose was 217.2 mg/day) reduced mean seizure frequency as compared with the basal condition at different study time points (2, 6, 12 months; p < 0.0001). At the end of the study 77% of the patients were seizure free. Loss of treatment effectiveness was shown in 8.5% of patients. Adverse reactions were reported by 15% of patients, the most frequent being insomnia, somnolence, headache and rash. At the end of the study, 88.8% patients were still receiving LTG monotherapy. The present study supports the use of LTG monotherapy due to its effectiveness and good tolerability to promote treatment compliance in usual clinical conditions in patients with epilepsy.


Effect of pistachio shell as a carbon source to regulate C/N on simultaneous removal of nitrogen and phosphorus from wastewater.
Acid-pretreated pistachio shells were used as carbon sources to investigate the effects of carbon source dosage on simultaneous nitrogen and phosphorus removal under different carbon/nitrogen (C/N) ratios (7, 9, and 11). Results showed that C/N was positively correlated with mixed liquor suspended solids (MLSS) (R2 = 0.998, p < 0.01) and f value (R2 = 0.975, p < 0.05). Moreover, it was negatively correlated with the sludge volume index (SVI) (R2 = - 0.959, p < 0.05). C/N was also significantly negatively related to chemical oxygen demand removal rate (R2 = - 0.986, p < 0.05) and positively related to ammonia nitrogen (NH4+-N), total nitrogen (TN), and total phosphorus (TP) removal rate (p < 0.05), the correlation coefficients were 0.992, 0.990 and 0.994, respectively. In the reactor with C/N of 11, the MLSS concentration and f value were the highest, the SVI was the lowest, and the removal efficiencies of NH4+-N (85.49 % ± 1.96 %), TN (84.19 % ± 1.42 %) and TP (94.10 % ± 1.67 %) were the highest. Furthermore, the relative abundance of denitrifying bacteria was the highest in the reactor. The abundance of nitrifying bacteria and phosphorus-removal bacteria was also relatively high.


Measurement of rapid membrane permeation in cell suspensions by application of a generalized capillary method.
An improved version of the capillary technique for the determination of diffusion coefficients has been developed as a simple method of measuring membrane permeabilities of single cells suspended at relative densities between 0.70 and 0.97. A new, generalized theoretical formulation to describe the diffusion process of a solute in a composite system was derived using a series-parallel-pathway model with explicit consideration of the diffusion pathways inside and between the cells. This renders the technique insensitive to unstirred layer effects. Any single cell population of known size distribution may be investigated. High permeabilities (above 5.10(-3) cm/s) can be measured with the greatest precision, but lower permeabilities, down to a limit of about 5.10(-4) cm/s, may also be determined by the method. Measurements in erythrocyte suspensions have been made using non-electrolytes such as hexanol, water and ethylene glycol as test solutes. The permeabilities obtained agree with the values obtained by much more sophisticated equipment. Cell shape was shown to be without significant influence on the permeability data obtained. The procedure may become of particular interest for measurement of suspensions of membrane vesicles.


A 20-hydroxyecdysone-enriched fraction from Pfaffia glomerata (Spreng.) pedersen roots alleviates stress, anxiety, and depression in mice.
Pfaffia glomerata roots are widely used in Brazil to treat various pathological conditions, particularly psychological disorders. 20-hydroxyecdysone, a phytosteroid present in the plant, can promote greater body resistance against exogenous and endogenous stressors. The objective of this study was to evaluate the possible neuroprotective effect of a 20-hydroxyecdysone-enriched fraction (20E-EF), obtained from P. glomerata roots, in an acute murine stress model. The 20E-EF was obtained by partitioning the methanol extract from P. glomerata roots with dichloromethane. Mice were treated by gavage with three doses of 20E-EF (3, 10, and 30 mg/kg) and parameters of stress, anxiety, and depression were evaluated. Biomarkers of oxidative stress (enzymes, antioxidant profile, and oxidized molecules) were evaluated in the cortex, striatum (basal ganglia), and hippocampus of animals treated with 30 mg/kg of 20E-EF. Mass spectrometry revealed that 20E was the main compound in the dichloromethane fraction. At a dose of 30 mg/kg, 20E-EF reduced stress, anxiety, and depression, while stimulating antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase), promoting antioxidant activity (antioxidant capacity, sulfhydryl groups, and reduced glutathione), and reducing oxidative markers (lipid peroxidation). In addition, 20E increased the concentration of NO in the striatum, possibly improving memory function and antioxidant activity. A 30 mg/kg dose of 20E-EF was able to reduce stress, anxiety, and depression, in addition to maintaining antioxidant defenses of the cortex and striatum. These findings open new perspectives for understanding the therapeutic properties of P. glomerata and the underlying mechanism(s).


Design, production, and characterization of a single-chain variable fragment (ScFv) derived from the prostate specific membrane antigen (PSMA) monoclonal antibody J591.
A single chain variable fragment (J591 ScFv) that recognizes the extracellular glyco-protein prostate specific membrane antigen (PSMA) was designed, constructed, and expressed in Pichia pastoris. Construction of the J591 ScFv was based on the reported complementarity-determining region (CDR) of the PSMA specific J591 monoclonal antibody (mAb). The nucleotide sequence encoding the J591-derived ScFv was codon-optimized for expression in P. pastoris and a 6× his-tag was added to facilitate affinity purification. A down-scale 2L methanol-induced P. pastoris fermentation yielded 330mg of total protein following a 96h induction. Following Immobolized Metal Affinity Chromatography, functionality of the J591 ScFv was confirmed via Western blot, immunoblot, binding studies, and flow cytometry analysis. The J591 ScFv showed binding affinity and specificity to cell extracts containing PSMA and PSMA-expressing prostate cancer cells. Our results demonstrate that functional J591 ScFv can be produced in P. pastoris for use in diagnostic and targeted therapeutic applications.


From Motivation to Action: Action Cost Better Predicts Changes in Premovement Beta-Band Activity than Speed.
Although premovement beta-band event-related desynchronization (β-ERD; 13-30 Hz) from sensorimotor regions is modulated by movement speed, current evidence does not support a strict monotonic association between the two. Given that β-ERD is thought to increase information encoding capacity, we tested the hypothesis that it might be related to the expected neurocomputational cost of movement, here referred to as action cost. Critically, action cost is greater both for slow and fast movements compared with a medium or "preferred" speed. Thirty-one right-handed participants performed a speed-controlled reaching task while recording their EEG. Results revealed potent modulations of beta power as a function of speed, with β-ERD being significantly greater both for movements performed at high and low speeds compared with medium speed. Interestingly, medium-speed movements were more often chosen by participants than low-speed and high-speed movements, suggesting that they were evaluated as less costly. In line with this, modeling of action cost revealed a pattern of modulation across speed conditions that strikingly resembled the one found for β-ERD. Indeed, linear mixed models showed that estimated action cost predicted variations of β-ERD significantly better than speed. This relationship with action cost was specific to beta power, as it was not found when averaging activity in the mu band (8-12 Hz) and gamma band (31-49 Hz) bands. These results demonstrate that increasing β-ERD may not merely speed up movements, but instead facilitate the preparation of high-speed and low-speed movements through the allocation of additional neural resources, thereby enabling flexible motor control.SIGNIFICANCE STATEMENT Heightened beta activity has been associated with movement slowing in Parkinson's disease, and modulations of beta activity are commonly used to decode movement parameters in brain-computer interfaces. Here we show that premovement beta activity is better explained by the neurocomputational cost of the action rather than its speed. Instead of being interpreted as a mere reflection of changes in movement speed, premovement changes in beta activity might therefore be used to infer the amount of neural resources that are allocated for motor planning.


A central mesencephalic reticular formation projection to the Edinger-Westphal nuclei.
The central mesencephalic reticular formation, a region associated with horizontal gaze control, has recently been shown to project to the supraoculomotor area in primates. The Edinger-Westphal nucleus is found within the supraoculomotor area. It has two functionally and anatomically distinct divisions: (1) the preganglionic division, which contains motoneurons that control both the actions of the ciliary muscle, which focuses the lens, and the sphincter pupillae muscle, which constricts the iris, and (2) the centrally projecting division, which contains peptidergic neurons that play a role in food and fluid intake, and in stress responses. In this study, we used neuroanatomical tracers in conjunction with immunohistochemistry in Macaca fascicularis monkeys to examine whether either of these Edinger-Westphal divisions receives synaptic input from the central mesencephalic reticular formation. Anterogradely labeled reticular axons were observed making numerous boutonal associations with the cholinergic, preganglionic motoneurons of the Edinger-Westphal nucleus. These associations were confirmed to be synaptic contacts through the use of confocal and electron microscopic analysis. The latter indicated that these terminals generally contained pleomorphic vesicles and displayed symmetric, synaptic densities. Examination of urocortin-1-positive cells in the same cases revealed fewer examples of unambiguous synaptic relationships, suggesting the centrally projecting Edinger-Westphal nucleus is not the primary target of the projection from the central mesencephalic reticular formation. We conclude from these data that the central mesencephalic reticular formation must play a here-to-for unexpected role in control of the near triad (vergence, lens accommodation and pupillary constriction), which is used to examine objects in near space.


Solution structure of a novel α-conotoxin with a distinctive loop spacing pattern.
α-Pharmacological conotoxins are among the most selective ligands of nicotinic acetylcholine receptors with typical cysteine frameworks. They are characterized by the intercysteine loop and classified into various subfamilies, such as α3/5 and α4/7 conotoxins. A novel α-conotoxin, Pu14a (DCPPHPVPGMHKCVCLKTC), with a distinct loop spacing pattern between cysteines was reported recently. Pu14a belongs to the Cys framework 14 (-C-C-C-C) family containing four proline residues in the loop 1 region. Similar to another framework 14 conotoxin Lt14a (MCPPLCKPSCTNC-NH2), Pu14a has C1-C3/C2-C4 disulfide linkage, and can inhibit some subtypes of nicotinic acetylcholine receptors. In this study, the solution structure of Pu14a was investigated using 1H nuclear magnetic resonance spectroscopy to understand the structure-activity relationship of this conotoxin. 20 converged structures of this conopeptide, with RMSD value of 0.77 Å, were obtained based on distance constraints, dihedral angles and disulfide bond constraints. The three-dimensional structure of Pu14a showed remarkable difference from typical α-conotoxins because of a large intercysteine loop between C2 and C13, as well as a 3(10)-helix near the C-terminal. Furthermore, four proline residues in Pu14a adopted the trans conformation that may correlate with the large loop configuration and the biological activity of this conopeptide. The distinct structural characteristics of Pu14a will be very useful for studying the structure-activity relationship of α-conotoxins.


Signaling from endosomes: location makes a difference.
In all transmembrane receptor systems the kinetics of receptor trafficking upon ligand stimulation is maintained in a balance between degradative and recycling pathways in order to keep homeostasis and to strictly control receptor-mediated signaling. Endocytosis is commonly considered as an efficient mechanism of uptake and transport of membrane-associated signaling molecules leading to attenuation of ligand-induced responses. Accumulating evidence, however, shows that signaling from internalized receptors not only continues in endosomal compartments, but that there are also distinct signaling events that require endocytosis. Endocytic organelles form a dynamic network of subcellular compartments, which actively control the timing, amplitude, and specificity of signaling. In this review we provide examples in which signal transduction either requires an active endocytic machinery, or directly originates from various types of endosomes. Based on recent discoveries, we emphasize the close interdependence between signaling and endocytosis, and the physiological relevance of endocytic transport in health and disease.


The coevolution of culture and environment.
We propose a model of multi level (group) selection in the presence of climate variability, where environment and culture coevolve. The model describes a population subdivided into groups, each with access to a renewable resource. Individuals employ different harvesting strategies: Defectors harvest more resources than cooperators and punishers. In groups with many defectors, resource extraction may exceed the level of sustainable harvests, causing resource exhaustion. Weather shocks accelerate resource scarcity and eliminate groups with many defectors. The model is used to study conditions under which resource conservation evolves. Conservation is costly but enhances group's chances of survival. We study conditions under which environmental crises enhance the evolution of cooperation. We examine how between-group interactions such as resource-conflict and harvest-sharing affect the probability of resource exhaustion.


Cu(II)-disulfide complexes with superoxide dismutase- and catalase-like activities protect mitochondria and whole cells against oxidative stress.
Mitochondria are a major subcellular site of superoxide (O2(-)) formation. Conditions leading to an uncontrolled production, accumulation and/or conversion of O2(-) into hydrogen peroxide result in an increment in the intramitochondrial oxidative tone which, ultimately leads to the loss of cell viability. Recently, we reported on the ability of a series of Cu(II)-disulfide complexes to act simultaneously as SOD- and catalase-like molecules. In the present study, we addressed the potential of such compounds to protect mitochondria and cells against the oxidative stress and the cytolytic damage induced by diclofenac. Exposure of Caco-2 cells to diclofenac (250µM, 20min) led to a near 80% inhibition of mitochondrial complex I activity and almost doubled the rate of mitochondrial O2(-) production (assessed by Mitosox). A comparable increment was seen in whole cells when the oxidative tone was assessed through the largely hydrogen peroxide-dependent dichlorofluorescein (DCFH) oxidation. The increment in mitochondrial O2(-) production was totally and concentration-dependently prevented by the addition of the complexes formed between Cu(II) and the disulfides of glutathione, homocysteine, or a-dehydro-lipoic acid (20µM each); comparatively, the Cu(II)-cystine complex exerted a weaker protection. A comparable protection pattern was seen at the whole cell level, as these complexes were also effective in preventing the increment in DCFH oxidation. The mitochondrial and whole cell antioxidant protection also translated into a full protection against the cytolytic effects of diclofenac (45min). Results from the present study indicate that the here-tested Cu(II)-disulfides complexes are able to effectively protect cells against the oxidative and the lytic effects of O2(-)-overproducing mitochondria, suggesting a potential for these type of compounds to act as SOD- and catalase-like molecules under oxidative-stress conditions. Supported by FONDECYT #1110018.


Changes in the demographics and prescription of peritoneal dialysis during the last decade.
Changes in the demographics and prescription of peritoneal dialysis (PD) during the past decade are reviewed using data from the United States and Canada. The number of patients in North America undergoing PD has increased markedly over the past decade, but the percentage of total chronic dialysis patients using the modality has remained relatively stable or decreased slightly during recent years. The average age of the patients undergoing PD has increased, and the percentage with diabetes has also increased. Comorbidity has otherwise remained relatively stable and tends to be significantly less than that in patients undergoing chronic hemodialysis (HD). The proportion of PD patients undergoing automated PD (APD) has increased markedly over the past decade and now includes more than one third of the PD patients in North America. The issue of adequacy of clearance achieved on PD has received a lot of attention over the past decade, and this is now being translated into changes in prescription. Patients undergoing continuous ambulatory PD (CAPD) are being prescribed larger dwell volumes, and more than one quarter use 2.5-L dwells or greater. A small number in the United States are being prescribed more than four exchanges a day, but this practice is more common in Canada. With regard to APD, the proportion of patients doing day dwells is now more than two thirds, and the average cycler dwell volumes have also increased. There are no baseline clearance data from a decade ago for comparative purposes, but it appears that clearances have increased in recent years. In general, more than 70% of the patients are achieving recommended clearance targets at the initiation of PD but, among prevalent US patients, the percentage achieving targets is in the range of 40% to 45%, reflecting a loss of residual renal function. In Canada, 60% to 70% of prevalent patients are achieving these targets. PD is a rapidly changing therapy at present. There have been dramatic and impressive improvements in prescription practices, but they need to change further if a higher proportion of patients is to achieve recommended clearance targets.


Measures of infection prevention and incidence of SARS-CoV-2 infections in cancer patients undergoing radiotherapy in Germany, Austria and Switzerland.
COVID-19 infection has manifested as a major threat to both patients and healthcare providers around the world. Radiation oncology institutions (ROI) deliver a major component of cancer treatment, with protocols that might span over several weeks, with the result of increasing susceptibility to COVID-19 infection and presenting with a more severe clinical course when compared with the general population. The aim of this manuscript is to investigate the impact of ROI protocols and performance on daily practice in the high-risk cancer patients during this pandemic. We addressed the incidence of positive COVID-19 cases in both patients and health care workers (HCW), in addition to the protective measures adopted in ROIs in Germany, Austria and Switzerland using a specific questionnaire. The results of the questionnaire showed that a noteworthy number of ROIs were able to complete treatment in SARS-CoV‑2 positive cancer patients, with only a short interruption. The ROIs reported a significant decrease in patient volume that was not impacted by the circumambient disease incidence, the type of ROI or the occurrence of positive cases. Of the ROIs 16.5% also reported infected HCWs. About half of the ROIs (50.5%) adopted a screening program for patients whereas only 23.3% also screened their HCWs. The range of protective measures included the creation of working groups, instituting home office work and protection with face masks. Regarding the therapeutic options offered, curative procedures were performed with either unchanged or moderately decreased schedules, whereas palliative or benign radiotherapy procedures were more often shortened. Most ROIs postponed or cancelled radiation treatment for benign indications (88.1%). The occurrence of SARS-CoV‑2 infections did not affect the treatment options for curative procedures. Non-university-based ROIs seemed to be more willing to change their treatment options for curative and palliative cases than university-based ROIs. Most ROIs reported a deep impact of SARS-CoV‑2 infections on their work routine. Modification and prioritization of treatment regimens and the application of protective measures preserved a well-functioning radiation oncology service and patient care.


Do Sleep Disturbances have a Dual Effect on Alzheimer's Disease?
Sleep disturbances and Alzheimer's disease have deleterious effects on various physiological and cognitive functions including synaptic plasticity, oxidative stress, neuroinflammation, and memory. In addition, clock genes expression is significantly altered following sleep disturbances, which may be involved in the pathogenesis of Alzheimer's disease. In this review article, we aimed to discuss the role of sleep disturbances and Alzheimer's disease in the regulation of synaptic plasticity, oxidative stress, neuroinflammation, and clock genes expression. Also, we aimed to find significant relationships between sleep disturbances and Alzheimer's disease in the modulation of these mechanisms. We referred to the controversial effects of sleep disturbances (particularly those related to the duration of sleep deprivation) on the modulation of synaptic function and neuroinflammation. We aimed to know that, do sleep disturbances have a dual effect on the progression of Alzheimer's disease? Although numerous studies have discussed the association between sleep disturbances and Alzheimer's disease, the new point of this study was to focus on the controversial effects of sleep disturbances on different biological functions, and to evaluate the potential dualistic role of sleep disturbances in the pathogenesis of Alzheimer's disease.


Adenocarcinoma of the cervix.
The current study examines 1) the sensitivity of detection of invasive adenocarcinoma of the cervix in a routine cervical screening service, and 2) the frequency in smears of cytologic criteria previously found to be useful in diagnosis. Data on women with diagnoses of adenocarcinoma of the cervix accessioned at the Western Australian Cervical Cytology Registry during the period 1993-1998 were examined, where smears had been reported by Western Diagnostic Pathology within three years of the biopsy diagnosis. Smears and biopsy material were reviewed. Thirty-six smears from 24 women were reviewed. Of those, 58.3% had been reported as a possible or definite high grade epithelial abnormality (HGEA). On review it was thought that this could be improved to 77.8%. The screening or diagnostic error was thus 19.4% and the sampling error 22.2%. The likelihood of an individual woman receiving a report of a possible or definite HGEA in the three years before biopsy was 83.3%. In retrospect this could have been improved to 91.7%. Heavy bloodstaining with abundant abnormal glandular epithelium (14 smears) and small three-dimensional or papillary clusters (16 smears) were the most frequent clues to invasion. Tumor necrosis/diathesis was present in eight smears, but easily seen in only four, while marked nuclear pleomorphism and macronucleoli were seen in three and one smears respectively. In cases with a discrepancy between the initial and the review findings, very small amounts of abnormal material (three smears), a resemblance to endometrial cells (one smear), and an unusual appearance of folded monolayered sheets (three smears) contributed to the difficulty of diagnosis. There were significant sampling and screening/diagnostic errors (22.2% and 19.4%, respectively). Screening and diagnostic errors could perhaps be reduced by a greater awareness of the range of cytologic changes, but these may be subtle. Heavy bloodstaining with abundant abnormal glandular material may be a useful clue to invasive, rather than in situ, adenocarcinoma, even in the absence of tumor diathesis or fully malignant nuclear criteria.


Inhibitory Effects of Prolonged Focal Muscle Vibration on Maximal Grip Strength and Muscle Activity of Wrist and Extrinsic Finger Flexor Muscles.
The objective of this study was to identify effective stimulus time by quantifying the inhibitory effects of focal muscle vibration (FMV) on maximal grip strength and muscle activities of the wrist and extrinsic finger flexors. A randomized repeated-measures design was used in this study. A total of 22 healthy volunteers (mean age, 20.9 years) participated. An FMV of 86 Hz was applied to the anterior surface of the distal forearm under the following 3 conditions: no FMV (control), 5-minute FMV, and 10-minute FMV. Maximal grip strength was measured before and after FMV. The muscle activities of the flexor digitorum superficialis, flexor digitorum profundus (FDP), and flexor carpi ulnaris were simultaneously recorded using surface electromyography. Discomfort and complications following FMV were also assessed. Compared with the control group, a significant decrease in muscle activity was observed in both the flexor digitorum superficialis and flexor carpi ulnaris after 5 and 10 minutes of FMV. In contrast, there was no significant decrease in the maximal grip strength or FDP muscle activity after either FMV condition. The discomfort was significantly higher immediately after both FMV conditions than in the control group, but it decreased 15 minutes after FMV, indicating no significant difference among the 3 conditions. Redness and/or swelling were observed in 13.6% and 36.3% of the participants after 5 and 10 minutes of FMV, respectively. Five-minute FMV to the distal forearm could be a useful therapeutic method with few complications. However, the FMV in this area alone was not sufficient to suppress the muscle activity of the FDP located in the deep layer.


Orexins stimulate glucocorticoid secretion from cultured rat and human adrenocortical cells, exclusively acting via the OX1 receptor.
Orexins A and B are hypothalamic peptides, that act via two subtypes of receptors, named OX1-R and OX2-R. Rat and human adrenal cortexes are provided with both OX1-R and OX2-R, and we have previously shown that orexin-A, but not orexin-B, enhances glucocorticoid secretion from dispersed adrenocortical cells. Since OX1-Rs preferentially bind orexin-A and OX2-Rs are non-selective for both orexins, the hypothesis has been advanced that the secretagogue effect of orexin-A is exclusively mediated by the OX1-R. Here, we aimed to verify this contention and to gain insight into the signaling mechanism(s) underlying the secretagogue effect of orexins using primary cultures of rat and human adrenocortical cells. Reverse transcription-polymerase chain reaction showed that cultured cells, as freshly dispersed cells, expressed both OX1-R and OX2-R mRNAs. Orexin-A, but not orexin-B, concentration-dependently increased corticosterone and cortisol secretion from cultured rat and human adrenocortical cells, respectively. The blockade of OX1-Rs by selective antibodies abrogated the secretagogue effect of orexin-A, while the immuno-blockade of OX2-Rs was ineffective. The glucocorticoid response of cultured cells to orexin-A was annulled by the adenylate cyclase and protein kinase (PK) A inhibitors SQ-22536 and H-89, and unaffected by the phospholipase C and PKC inhibitors U-73122 and calphostin-C. Orexin-A, but not orexin-B, enhanced cyclic-AMP production from cultured cells, and did not alter inositol-3-phosphate release. Collectively, our present results allow us to conclude that orexins stimulate glucocorticoid secretion from rat and human adrenocortical cells, exclusively acting through OX1-Rs coupled to the adenylate cyclase/PKA-dependent signaling cascade.


Isokinetic dynamometry in elderly women undergoing total knee arthroplasty: a comparative study.
The present study assessed the reliability and validity of isokinetic dynamometry in the qualitative determination of the evolution of total knee arthroplasty. 20 patients whose mean age was 71.35 years, undergoing knee arthroplasty, and 25 controls whose mean age was 71.36 years. Computerized isokinetic assessment of flexor and extensor muscles using a CYBEX 6000 dynamometer. The total flexor/extensor effort ratio for the treated side of patients vs the nondominant side of controls was not significantly different. The flexion/extension ratio concerning maximum torque for the treated side of patients vs the nondominant side of controls was significantly different. By detecting deficiencies in the balance of flexor and extensor muscles (a balance that is required for uniform gait), it will be possible to select specific rehabilitation exercises according to the individual needs of each patient undergoing surgery.


The effects of thoracic epidurally administered drugs on urethral sphincter function in women: a pooled analysis.
Thoracic epidural analgesia (TEA) has been shown to inhibit detrusor activity in patients undergoing open renal surgery, resulting in clinically relevant post-void residuals. However, the impact of different epidural drug mixtures on urethral sphincter function is not completely elucidated. Pooled analysis of an open observational study and a double-blind randomized trial. Single tertiary centre. Twenty-eight women without lower urinary tract symptoms and post-void residual <100 mL, who underwent open renal surgery with TEA. Pooling results in three groups with different epidural regimens (7 with bupivacaine 0.125%, 8 with bupivacaine 0.125% and fentanyl 2 μg/mL, and 13 with bupivacaine 0.1% plus fentanyl 2 μg/mL and epinephrine 2 μg/mL). All women underwent urethral pressure measurements before TEA and during TEA 2-3 days postoperatively. All patients received a TEA placed at the insertion site interspace T 8-9. Maximum urethral closure pressure at rest decreased significantly during TEA with bupivacaine alone (median 70 cm H2 O [interquartile range 66-76] to 43 [43-65], P = 0.031) and with bupivacaine/fentanyl/epinephrine (75 cm H2 O [68-78] to 56 [52-75], P = 0.028), whereas with bupivacaine/fentanyl, no significant change could be detected (74 [51-88] vs 67 [46-70], P = 0.156). In all groups, functional profile length at rest was not influenced during TEA. TEA with bupivacaine and the addition of fentanyl and epinephrine appears to decrease maximum urethral closure pressure at rest in women. The addition of fentanyl alone to bupivacaine may reduce this effect. Thus, the TEA effect on urethral sphincter function seems to depend on the drug mixture administered.


The genome of New Zealand trevally (Carangidae: Pseudocaranx georgianus) uncovers a XY sex determination locus.
The genetic control of sex determination in teleost species is poorly understood. This is partly because of the diversity of mechanisms that determine sex in this large group of vertebrates, including constitutive genes linked to sex chromosomes, polygenic constitutive mechanisms, environmental factors, hermaphroditism, and unisexuality. Here we use a de novo genome assembly of New Zealand silver trevally (Pseudocaranx georgianus) together with sex-specific whole genome sequencing data to detect sexually divergent genomic regions, identify candidate genes and develop molecular makers. The de novo assembly of an unsexed trevally (Trevally_v1) resulted in a final assembly of 579.4 Mb in length, with a N50 of 25.2 Mb. Of the assembled scaffolds, 24 were of chromosome scale, ranging from 11 to 31 Mb in length. A total of 28,416 genes were annotated after 12.8 % of the assembly was masked with repetitive elements. Whole genome re-sequencing of 13 wild sexed trevally (seven males and six females) identified two sexually divergent regions located on two scaffolds, including a 6 kb region at the proximal end of chromosome 21. Blast analyses revealed similarity between one region and the aromatase genes cyp19 (a1a/b) (E-value < 1.00E-25, identity > 78.8 %). Males contained higher numbers of heterozygous variants in both regions, while females showed regions of very low read-depth, indicative of male-specificity of this genomic region. Molecular markers were developed and subsequently tested on 96 histologically-sexed fish (42 males and 54 females). Three markers amplified in absolute correspondence with sex (positive in males, negative in females). The higher number of heterozygous variants in males combined with the absence of these regions in females support a XY sex-determination model, indicating that the trevally_v1 genome assembly was developed from a male specimen. This sex system contrasts with the ZW sex-determination model documented in closely related carangid species. Our results indicate a sex-determining function of a cyp19a1a-like gene, suggesting the molecular pathway of sex determination is somewhat conserved in this family. The genomic resources developed here will facilitate future comparative work, and enable improved insights into the varied sex determination pathways in teleosts. The sex marker developed in this study will be a valuable resource for aquaculture selective breeding programmes, and for determining sex ratios in wild populations.


Carbohydrate transport in bacteria under environmental conditions, a black box?
A typical eubacterium carries a battery of substrate transport systems which are the ultimate pacemakers for growth. These systems reflect a billion year old selection for coping with rapidly changing conditions in the environment and each of them is optimised for specific growth conditions. Metabolic pathways in combination with transport systems can be interpreted as transient sensory systems, where a transport system corresponds to a sensor for external stimuli. Characteristics is a tightly linked common control between a carbohydrate metabolic pathway and the corresponding transport system. Many of the observed growth phenomena are a direct result of adaptation and regulation of transport capacity to rapid changes in environmental conditions. Some of the better understood examples are discusses. Nevertheless, knowledge on bacterial carbohydrate transport under environmental conditions as documented in the literature is still scarce.


Robot-assisted stereoelectroencephalography in young children: technical challenges and considerations.
Robot-assisted stereoelectroencephalography (sEEG) is frequently employed to localize epileptogenic zones in patients with medically refractory epilepsy (MRE). Its methodology is well described in adults, but less so in children. Given the limited information available on pediatric applications, the objective is to describe the unique technical challenges and considerations of sEEG in the pediatric population. In this report, we describe our institutional experience with the technical aspects of robot-assisted sEEG in an exclusively pediatric epilepsy surgery unit, focusing on pre-, intra-, and post-operative nuances that are particular to the pediatric population. The pediatric population presents several unique challenges in sEEG, including reduced skull thickness relative to adults, incomplete neurologic development, and often special behavioral considerations. Pre-operative selection of putative epileptogenic zones requires careful multidisciplinary decision-making. Intraoperative attention to nuances in positioning, clamp selection, registration, and electrode placement are necessary. Activity considerations and electrode migration and removal are key post-operative considerations. Robot-assisted sEEG is a valuable tool in the armamentarium of techniques to characterize MRE. However, special considerations must be given to the pediatric population to optimize safety and efficacy.


Impact of protein-energy malnutrition on outcomes of patients with diffuse large B cell lymphoma admitted for inpatient chemotherapy.
Protein-energy malnutrition (PEM) is a major factor contributing to morbidity and mortality in cancer patients. Empiric data are limited on the effect of PEM on the outcomes of patients receiving chemotherapy in diffuse large B cell lymphoma (DLBCL). A retrospective cohort study was designed using data from the National Inpatient Sample for 2016 to 2019. Adult patients admitted for chemotherapy with DLBCL were stratified based on the presence of PEM. Primary outcomes assessed were mortality, length of stay, and total hospital charges. PEM was associated with an increased odds of mortality, 2.21% vs 0.25% (adjusted odds ratio 8.20, P < 0.001, 95% confidence interval [CI] 4.92-13.69). There was also an increased length of stay in patients with PEM, 7.89 vs 4.85 days (adjusted difference of 3.01 days, P < 0.001, 95% CI 2.37-3.66), as well as an increase in total charges, $137,940 vs $69,744 (adjusted difference of $65,427, P < 0.001, 95% CI $38,075-$92,778). Similarly, the presence of PEM was associated with increased odds of several secondary outcomes measured, including neutropenia, Candida sepsis, septic shock, acute respiratory failure, and acute kidney injury compared to the other cohort. This study demonstrated an eightfold increased odds of mortality and concomitant prolonged length of stay with a 50% total charge increment in malnourished individuals with DLBCL compared to those without PEM. Prospective trials to evaluate PEM as an independent prognostic marker of chemotherapy tolerance and adequate nutritional support can improve clinical outcomes.


Comparisons of the toxicity of CdCl2 and Cd-metallothionein in isolated rat hepatocytes.
In the intact animal, inorganic Cd distributes mainly to the liver and produces hepatotoxicity, while Cd-metallothionein (CdMT) distributes primarily to the kidney and produces nephrotoxicity. CdMT has also been demonstrated to be more toxic than Cd in cultured kidney cells, but it is not known if CdMT is more toxic to all cultured cells or if there is a good correlation between in vitro and in vivo toxicity. Therefore, hepatocytes, which were isolated and grown in monolayer culture for 24 h, were incubated with CdCl2 (1-100 microM) or CdMT (3-100 microM Cd). The intracellular K+ content was quantitated 24 h later as an index of toxicity. The K+ concentration of the hepatocytes was decreased 50% by 4 microM CdCl2, whereas 25 microM CdMT was required to produce similar injury. In the intact animal, zinc induces the synthesis of MT and decreases the hepatotoxicity of Cd. ZnCl2 added to the media (100 microM) for 24 h before exposure to Cd or CdMT increased the intracellular MT concentration 700%. This elevation in MT reduced the toxicity of CdCl2 approximately 80% but did not alter the toxicity of CdMT. In summary, CdCl2 is more toxic to cultured hepatocytes than Cd-MT, and MT induction decreases the toxicity of CdCl2 in hepatocytes, as has been observed in the intact animal. This indicates that cultured hepatocytes appear to be an excellent model for examining the hepatotoxicity of Cd.


A new device and method for rapid emergency pacing: clinical use in 10 patients.
A new multipurpose transthoracic pacing device is described that will simultaneously enable transthoracic electrode insertion, intracardiac drug infection, and blood sample removal for blood gas determination, all via a single myocardial needle insertion. The device proved efficacious and safe in trials in an animal model. In clinical use in 10 emergency room patients with brady-asystolic cardiac arrest, pacing was achieved in all 10 with one short-term survivor. Median insertion time was 30 seconds. Median threshold in 6 patients was 2.5 mA (1 to 6). This new device enables reliable and rapid emergency treatment of brady-asystolic cardiac arrest.


Determination of COVID-19 PCR positivity and mutation status in coronaVac vaccinated individuals in Turkey.
CoronaVac is an inactivated virus-based COVID-19 vaccine used in Turkey and approved for emergency use by the World Health Organization (WHO). In this study, it was aimed to retrospectively evaluate the mutation status and clinical status in individuals who received two doses of CoronaVac vaccine and were infected with COVID-19 at least two weeks after the second dose. 164 people were included in the study and COVID-19 diagnosis and mutation analyses were determined by RT-PCR using the Bioseepdy SARS CoV-2 Double Gene RT-qPCR Kit and the Biospeedy SARS-CoV-2 Variant Plus kit in accordance with the protocol determined by the manufacturer. 116 (70.7%) UK (Alpha, B.1.1.7) mutation and 3 (1.8%) South Africa (Beta, B.1.351), Brazil (Gamma, P.1) mutations were determined in 164 double doses CoronaVac vaccinated patients; 45 (27.5%) patients were mutation negative. Nine patients (5.5%) developed pneumonia. Eight patients (4.9%) had CT findings compatible with corona virus infection. Seven (4.3%) of the patients received treatment in the intensive care unit, and 5 (3%) of the patients were intubated. In conclusion, people who receive two doses of CoronaVac vaccine can be reinfected with mutant viruses, vaccine significantly reduces the need for hospitalization, CT findings and intensive care.


Therapy for Chronic Myelomonocytic Leukemia in a New Era.
Chronic myelomonocytic leukemia (CMML) is a myeloid malignancy which shares clinical and morphologic features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs) and is classified by the WHO as an MDS/MPN. The defining feature of CMML is clonal hematopoiesis that results in peripheral monocytosis. The benefit of early treatment is currently unclear, and treatment may be held until the disease exhibits accelerated blast counts or the patient becomes symptomatic. Optimal treatments for CMML are not well defined. Conventional treatments include hydroxyurea, cytarabine, and hypomethylating agents. However, all treatment options are limited and, with the exception of allogeneic stem cell transplantation, are considered palliative. As we continue to learn about the genomics of CMML and about arising therapeutic targets and those under active clinical investigation, the future therapy of CMML will likely improve considerably. Here, we review the data available for conventional therapies and highlight emerging therapeutic strategies.


Recombinant vaccinia virus expressing IL-2 generates effective anti-tumor responses in an orthotopic murine model of head and neck carcinoma.
We evaluated the efficacy of a replication-competent, attenuated recombinant vaccinia virus (rvv) expressing IL-2 as a tumor vaccine in an immunocompetent murine model of head and neck squamous cell carcinoma. We implanted oral tumors by injection of tumor cells (SCC VII/SF) into the floor of the mouth of the syngeneic C3H/HeJ mice. Previous studies with this model suggested the presence of tumor-induced immune suppression. To circumvent the immune suppression we subcutaneously (s.c.) immunized the mice with irradiated, rvv-infected tumor cells prior to or along with intratumoral (i.t.) vaccination. A single s.c. vaccination invoked tumor-specific T cell proliferation and cytotoxicity. Mice treated by this protocol survived longer compared to those treated with i.t. vaccination alone. Tumor growth was significantly inhibited (P < 0.0002) and tumor regression was observed in all mice. The numbers of CD4(+) and CD8(+) lymphocytes as well as macrophages in the tumor beds and in tumor-draining lymph nodes were significantly increased in the mice treated by s.c. plus i.t. vaccination compared to s.c. or i.t. vaccination alone. These results suggested that s.c. vaccination along with i.t. vaccination increased antitumoral immunity and that CD4(+), CD8(+) lymphocytes as well as macrophages may play an important role in this antitumoral immunity.


Growth performance, carcass criteria, and serum biochemical parameters of broiler chickens supplemented with either synbiotic or prebiotic under hot climatic conditions.
1. Two separate experiments were conducted to evaluate the efficacy of either prebiotic or synbiotic on growth performance, carcass yield, organ weights, and serum metabolic profile of broilers under hot climatic conditions. 2. In experiment 1, 150 1-d-old Ross 308 male broiler chickens were fed dietary synbiotic (Biomin® IMBO, 0, 1 or 1.5 g kg-1 of the starter diets and 0, 0.5 or 0.75 g kg-1 of the grower diets) for 6 weeks. In experiment 2, 150 1-d-old Ross 308 male broiler chickens were fed dietary prebiotic (Mannan oligosaccharide 0, 0.5 or 1 g kg-1 of the starter diets and 0, 0.25 or 0.5 g kg-1 of the grower diets) for 6 weeks. Each treatment had 10 replicates containing 5 broiler chickens each. 3. Supplementation of synbiotic at 1 or 1.5 g kg-1 feed to broiler diets during 1-21 d and 0.5 or 0.75 g kg-1 feed, respectively, during 22-42 d improved (P < 0.01) body weight gain, feed conversion ratio (FCR), and decreased (P < 0.01) abdominal fat, serum total cholesterol, and low-density lipoprotein (LDL) cholesterol levels in experiment 1. 4. Similarly, supplementation of the prebiotic at 0.5 or 1 g kg-1 in broiler diets during 1-21 d and 0.25 or 0.50 g kg-1 feed, respectively, during 22-42 d improved (P < 0.01) body weight gain, FCR, and decreased (P < 0.01) abdominal fat, serum cholesterol, and LDL-cholesterol levels in experiment 2.


Attempts to transfer Elaphostrongylus alces from moose (Alces alces) to sheep and goats.
Six 1 year old female and 6 four months old male goats were inoculated different numbers of E. alces third-stage larvae. Protostrongylid larvae were not detected in the faeces of these animals during the experiment. At the end of the experimental period the animals were euthanized and autopsied. Neither parasites nor pathological lesions related to larval or adult stages of E. alces could be demonstrated.


Association of deployment with maintenance of healthy weight among active duty service members in the Millennium Cohort Study.
Understanding body size in relation to deployment readiness can inform Department of Defense fitness policies. This study examined longitudinal associations between deployment and changes in body mass index (BMI) among active duty service members. Service branch-specific changes in BMI post-deployment were examined using logistic regression models among active duty Millennium Cohort Study participants without obesity at baseline (n = 22,995). BMI was categorized using self-reported height and weight as healthy weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (≥30 kg/m2). Number of deployments between baseline and follow-up and initial deployment lengths (in months, using service branch-specific deployment times) were examined. Among the pooled population and specifically Army and Marine Corps service members without obesity, those with longer deployments were significantly less likely to maintain a non-obese BMI than those deploying for shorter lengths. Each additional deployment increased the likelihood of maintaining a non-obese BMI post-deployment for personnel in the Army, Marine Corps, and within the pooled population. Multiple deployments may support healthy weight maintenance; longer deployments may adversely impact weight maintenance. Future research should determine modifiable behaviors related to weight gain post-deployment to inform fitness policies designed to optimize service member readiness and deployability.


Expectancy of alcoholism in a midwestern population.
The morbidity risk of alcoholism among men in a Midwestern population varied between 5.4 and 7.2%, depending on the criteria used. Among women the morbidity risk was about 0.4%.


Comparison of the Ct-values for genomic and subgenomic SARS-CoV-2 RNA reveals limited predictive value for the presence of replication competent virus.
SARS-CoV-2 is the causative agent of the acute respiratory disease COVID-19. In addition to the full length positive-sensed, single-stranded genomic RNA (gRNA), viral subgenomic RNAs (sgRNAs) that are required for expression of the 3' region of the genome are synthesized in virus-infected cells. However, whether these sgRNA-species might be used as a measure of active virus replication and to predict infectivity is still under debate. The commonly used methods to monitor and quantitate SARS-CoV-2 infections are based on RT-qPCR analysis and the detection of gRNA. The infectivity of a sample obtained from nasopharyngeal or throat swabs is associated with the viral load and inversely correlates with Ct-values, however, a cut-off value predicting the infectivity highly depends on the performance of the assay. Furthermore, gRNA derived Ct-values result from nucleic acid detection and do not necessarily correspond to active replicating virus. We established a multiplex RT-qPCR assay on the cobas 6800 omni utility channel concomitantly detecting SARS-CoV-2 gRNAOrf1a/b, sgRNAE,7a,N, and human RNaseP-mRNA used as human input control. We compared the target specific Ct-values with the viral culture frequency and performed ROC curve analysis to determine the assay sensitivity and specificity. We found no advantage in the prediction of viral culture when using sgRNA detection compared to gRNA only, since Ct-values for gRNA and sgRNA were highly correlated and gRNA offered a slightly more reliable predictive value. Single Ct-values alone only provide a very limited prediction for the presence of replication competent virus. Hence, careful consideration of the medical history including symptom onset has to be considered for risk stratification.


The removal of heavy metal pollution from wastewaters using thermophilic B. cereus SO-16 bacteria.
In this study, bioaccumulation, remediation, tolerance, and effects of manganese ions (Mn(II)) and copper ions (Cu(II)) on antioxidant enzymes of thermophilic Bacillus cereus (B. cereus) SO-16 were investigated in detail. The findings of the study showed that Mn(II) was less toxic than Cu(II) to B. cereus SO-16. Moreover, B. cereus SO-16 was exhibited less tolerance to Mn(II) and Cu(II) ions in the liquid medium compared to the solid medium. The growth of bacteria was expressively effective for Mn(II) and Cu(II) concentrations of 2.5 mg/L at 24th h. The highest Mn(II) and Cu(II) bioaccumulation values after 48 h incubation of thermophilic B. cereus SO-16 were measured as 102.04 (24th h) and 87.96 (36th h) metal/dry bacteria weight. The change in morphology and functionality of B. cereus SO-16 after interaction with Mn(II) and Cu(II) was tested using various methods. The results indicated that B. cereus SO-16, a thermophilic bacterium, can be utilized in industrial wastewaters to recover and remediation of toxic metals.


Side-by-side Comparative Study of the Immunogenicity of the Intramuscular and Intradermal Rabies Post-exposure Prophylaxis Regimens in a Cohort of Suspected Rabies Virus Exposed Individuals.
All World Health Organization (WHO) pre-qualified rabies vaccines for humans are inactivated tissue culture rabies virus formulations produced for intramuscular (IM) administration. Due to costs and vaccine shortage, dose-saving intradermal (ID) administration of rabies post-exposure prophylaxis (PEP) is encouraged by WHO. This study compared the immunogenicity of the ID 2-site, 3-visit Institut Pasteur Cambodge (IPC) PEP regimen to the IM 1-site, 4-visit 4-dose Essen regimen using Verorab vaccine (Sanofi). The development of neutralizing antibodies (nAbs) and T cell response was assessed in 210 patients with a category II or III animal exposure in a rabies-endemic country. At day 28, all participants developed nAbs (≥0.5 IU/mL), irrespective of PEP scheme, age, or administration of rabies immunoglobulin. T cell response and nAb titers were similar for both PEP schemes. This study demonstrated that the 1-week ID IPC regimen is as effective as the 2-week IM 4-dose Essen regimen in inducing an anti-rabies immune response under real-life PEP.


[Adhesion of urologists to the recommendations of the French Urological Association Cancer Committee (CCAFU) in the imaging work-up of localized prostate cancer].
The literature review shows a low adhesion of urologists to the recommendations of learned societies in the imaging work-up of localized prostate cancer (CaP), especially for low and intermediate risks of the D'Amico classification. We analyzed the adhesion of urologists in the Hérault region (France) to the CCAFU 2016/2018, 2018/2020 recommendations. From the Hérault Onco Urology Registry (RHESOU) database, we identified localized CaP diagnosed between 01/01/2017 and 31/12/2019, and then classified them into 3 distinct risk groups according to the D'Amico classification. We compared the imaging workup performed by each patient to the CCAFU 2016/2018, 2018/2020 recommendations, according to the risk group. Of the 2,049 localized CaPs included in our study, 591 belonged to the low-risk group, 1059 to the intermediate-risk group, and 399 to the high-risk group. In the low-risk group 45.2% of the cases did not follow the CCAFU 2016/2018, 2018/2020 recommendations in the imaging workup, 77.3% in the intermediate-risk group and 80.9% in the high-risk group. For our entire study, 1,408 patients (68.7%) had an imaging workup that did not follow the CCAFU recommendations. Our results show a low adhesion of urologists to the CCAFU recommendations in the imaging assessment of localized CaP. The causes of this non-adhesion are multifactorial and difficult to analyze.


[Patient education].
Patient education is considered to be a major feature of medical rehabilitation in chronic disorders. The rehabilitation sciences research programme funded by the German Pension Insurance scheme and the Federal Ministry of Education and Research comprises a considerable number of evaluation studies carried out with methodological rigor. Over two funding periods, patient education programmes were developed and evaluated with respect to their medical, psychosocial, occupational and economic effects. In this article, a conceptual definition of patient education is presented. Then, the aims and results of ten patient education studies of the funding programme as well as of several implementation projects are described. When integrating these results into previous research taking both a national and international perspective, it can be concluded that patient education programmes are effective regarding medical psychosocial and socio-economic outcomes, although effects sizes may vary. However, in some disorders the state of the research is still unsatisfactory and results are either scarce or heterogeneous. In particular, it is unclear whether such programmes are widely used in medical rehabilitation on a routine basis. Several education programmes provide train-the-trainer opportunities, others are still in the process of development or evaluation. Implementation projects such as those described in the article are aimed at closing these gaps and disseminating research results into the practice of rehabilitation.


[Changes in the systemic and regional circulation responses to immobilization stress in the rat after pharmacological sympathectomy].
A preliminary pharmacological desympathization (pirroxan, obzidan, ornid) decreased blood pressure, heart rate, cardiac output, and increased total vascular resistance in immobilized rats. The fraction of cardiac output decreased in lung (bronchial blood flow), liver and myocardium and increased in other organs and tissues. Relative blood supply increased in expansive regions of the skin, muscles and splanchnic organs but decreased in the liver. Opposite changes of transcapillary permeability were found in vascular regions of the skin and skeletal muscles as well as in splanchnic organs.


Trace elements in atmospheric wet precipitation in Detroit metropolitan area: Levels and possible sources.
Rain and snow samples were collected in the Detroit metropolitan area and analyzed by inductively coupled plasma-mass spectrometry (ICP-MS). Twenty-two elements were detected in a concentration range from ∼0.03 to ∼1.8 × 103 μg/kg. An enrichment factor (EF), defined as, EF=(X/Al)sample(X/Al)crust , was estimated for each element (X) detected, and used to determine possible origins of the element. Based on the hypothesis that crustal material is the only source of aluminum (Al) found in the atmospheric environment, an EF value near unity for an element suggests that crustal material is a major source of this element. If EF>10, an element is enriched in the atmosphere relative to its concentration in the earth's crust, implying a source other than the crust. Alkali, alkaline earth and lanthanide metals detected in the samples exhibit low EF values, indicating mainly a crustal source. Six elements (As, Cd, Cu, P, Pb and Zn) were significantly enriched in the samples as their EF values were greater than 10, thus originated likely from anthropogenic emissions. The relative order of the significantly enriched elements is estimated as follows: Cd > Pb > Zn > As > Cu > P. A high enrichment (EF∼100) for phosphorus was observed and caused plausibly by extensive usage of phosphorus-containing fertilizers and pesticides.


Welfare reform, time limits, and infant health.
This paper offers evidence that welfare time limits contributed to a deterioration of infant health. We use the fact that the dates at which TANF recipients were first subject to timing out varied by state. We show that by 2000 there was a marked difference in TANF duration spells depending on whether the state employed the 60-month Federally imposed time limit, or a shorter limit, differences that were not present under AFDC. There were significant increases in infant mortality when time limits became binding in a state. These increases occurred primarily among mothers who could have plausibly timed-out of TANF: poorly educated and unmarried women with at least one previous live-birth. There is some evidence that the population of mothers affected by time limits were less likely to seek prenatal care in the first trimester, suggesting a possible role for reduced medical care in explaining the deterioration in infant health.


Smoking as a risk factor for cystoid macular edema complicating intermediate uveitis.
To describe risk factors for the presence of cystoid macular edema (CME) among patients presenting with intermediate uveitis. Cross-sectional study. Single-center, academic practice. Two hundred and eight patients with intermediate uveitis evaluated from July 1, 1984 through September 30, 2006. Clinical and demographic data were entered retrospectively into a database and analyzed. Presence of CME at presentation to our clinic; risk factors for presenting with CME. Of the 208 patients, 74% had bilateral intermediate uveitis, yielding 363 affected eyes. Eighty-nine patients (43%) had CME in at least one eye at the time of presentation to our clinic. After controlling for potentially confounding variables including demographics, duration of disease, active intraocular inflammation, history of diabetes mellitus or hypertension, and presence of epiretinal membrane, actively smoking at presentation was associated with a four-fold increased risk of CME at presentation vs never smoking (odds ratio (OR), 3.90; 95% confidence interval (CI), 1.43, 10.66; P = .008). Former smoking also appeared to increase the risk of CME at presentation in the multivariate analysis, but the result was of borderline statistical significance (OR, 1.97; 95% CI, 0.99, 3.94; P = .055). After adjusting for confounding, there was a 4% increased risk of CME at presentation for each cigarette smoked per day (OR, 1.04; 95% CI, 1.01, 1.7; P = .005). CME was a common structural ocular complication observed in our cohort. Current smoking was associated with a dose-dependent increased risk of having CME at the time of presentation to our clinic.


Electrophoretical and histochemical characterization of Schistosoma mansoni phenol oxidases.
The phenol oxidase system, which is thought to play a central role in eggshell formation, was analyzed by means of electrophoretic and histochemical techniques. In contrast to current beliefs, our data show that males also express the phenol oxidase activity. The analysis of the electrophoretic pattern from males and females shows differences: adult males present a major band and a faint band, migrating slightly below. Adult females express a more complex pattern composed of four bands. Histochemical studies revealed that female phenol oxidase is concentrated in the vitelline cells, is inhibited by DDC, and this inhibition is correlated with disruption of female egg production. The present studies, in agreement with other reports, reveal that female phenol oxidase may be involved in sclerotization of the S. mansoni eggshell.


Decision for surgery.
Based on the clinical impression and the current knowledge of the clinical variables (rectal examination, abdominal distention, abdominal fluid, intractable pain) most likely to differentiate between medical and surgical cases, three decision trees are provided as a guide to making the management decision in a horse with abdominal pain. Prior elimination of horses with limited life expectancy because of age or function or where financial constraints are present is understood. It must be emphasized that most of the information presently available originates from referral centers where the prevalence of surgical candidates is much higher than in general practice. This would influence the accuracy of the clinician in identifying horses with a surgical lesion or estimating survival (positive predictive value).


Paliurus spina-christi Mill fruit extracts improve glucose uptake and activate the insulin signaling pathways in HepG2 insulin-resistant cells.
Paliurus spina-christi Mill. (PSC) fruit is frequently used in the treatment of diabetes mellitus in Mediterranean regions. Here, we investigated the effects of various PSC fruit extracts (PSC-FEs) on glucose consumption and some key mediators of insulin signaling pathways in high glucose and high insulin-induced insulin-resistant HepG2 cells. The effects of methanolic, chloroform and total extracts on cell proliferation were assessed by the MTT assay. The potential of non-toxic extracts on glucose utilization in insulin-resistant HepG2 cells was checked using a glucose oxidase assay. AKT and AMP-activated protein kinase (AMPK) pathway activation and mRNA expression levels of insulin receptor (INSR), glucose transporter 1 (GLUT1), and glucose transporters 4 (GLUT4) were determined by western blotting and real-time PCR, respectively. We found that high concentrations of methanolic and both low and high concentrations of total extracts were able to enhance glucose uptake in an insulin-resistant cell line model. Moreover, AKT and AMPK phosphorylation were significantly increased by the high strength of methanolic extract, while total extract raised AMPK activation at low and high concentrations. Also, GLUT 1, GLUT 4, and INSR were elevated by both methanolic and total extracts. Ultimately, our results shed new light on methanolic and total PSC-FEs as sources of potential anti-diabetic medications, restoring glucose consumption and uptake in insulin-resistant HepG2 cells. These could be at least in part due to re-activating AKT and AMPK signaling pathways and also increased expression of INSR, GLUT1, and GLUT4. Overall, active constituents present in methanolic and total extracts of PCS are appropriate anti-diabetic agents and explain the use of these PSC fruits in traditional medicine for the treatment of diabetes.


An efficient synthesis of gougerotin and related analogues using solid- and solution-phase methodology.
The first solid-phase synthesis of the natural product gougerotin has been accomplished. The synthetic route is versatile and allows for diversification at position C-4 of the heterocycle, C-6' of the sugar ring, and both residues of the peptidic moiety at N-4' in a parallel fashion. [structure: see text]


The estimation of mean nuclear volume in the diagnosis of breast carcinoma.
Sixty-two cases of breast pathology were randomly selected from the files of the Dunedin Public Hospital for evaluation of mean epithelial nuclear volume. The cases were comprised of both benign and malignant ductal epithelial disease, diagnosed in cytological smears or in histological sections. Nuclear volume in histological preparations was estimated by the stereological technique of point-line intercept measurements to derive volume-weighted mean volumes (vV). An index of the nuclear volume (Vi) of cytology smears was calculated from measurements of nuclear areas by either image analysis Vi(e) or point-line intercepts Vi(p). By all methods of analysis a clear distinction of nuclear volume was found between the benign [means for the cytology were 148 microns 3 (Vi(e)) or 246 microns 3 (Vi(p)), and 203 microns 3 (Vv) for the histology specimens] and malignant diseased cases [means for cytology: 524 microns 3 (Vi(e)) or 886 microns 3 (Vi(p)), and 587 microns 3 (vV) for the histology specimens].


Asymmetric periflexural exanthem of childhood and viral examinations.
We report on an asymmetric maculopapular exanthem of early childhood. One hundred eighty seven patients (111 girls, 76 boys) were examined over a four-year period, mainly in winter and spring. The first skin lesions appeared on the trunk or in the large flexures of the limbs. They spread centrifugally, often to the contralateral side, over two to four weeks, and disappeared with slight itching and moderate desquamation within another two to four weeks. Virologic studies were carried out in 34 cases; parainfluenzavirus 2, parainfluenzavirus 3, and adenoviral infection were diagnosed in two patients each. The chances of a causal relation between the viral infection and the skin symptoms were slight; only an incidental connection is likely to exist between the skin disorders and the viral infection.


Quantitative estimation of the effects of capsaicin on the mouse primary sensory neurons.
Studies were made on the quantitative effects of capsaicin on the L4 dorsal roots and their ganglia (DRG) in mice. Capsaicin at a dose of 50 mg/kg was injected s.c. 1-3 times into neonatal mice, while other mice received only vehicle as controls. After capsaicin treatment unmyelinated fibers decreased by 41.3-75.3% compared to controls. After 2 or 3 capsaicin injections there was a greater decrease in unmyelinated fibers than after a single treatment. Capsaicin had most effect on Schwann cell subunit size of more than 13 axons. Reduction of myelinated fibers ranged from 6.1 to 11.6% (mean: 7.9) in 4 mice. A beta and A delta fibers of 4-5 microns diameter were significantly reduced, whereas A delta fibers of less than 2.0 microns diameter were slightly increased. Small DRG neurons (50-500 microns 2 area) decreased by 50.6-77.4% (mean: 69.6) compared to controls. In addition, capsaicin caused a decrease of 14.2-51.6% (mean: 35.2, n = 4) in large-sized neurons (500-1950 microns 2 area). Thus, capsaicin widely affects small and certain types of large neurons as well as unmyelinated and certain myelinated fibers.


Impaired categorical perception of lexical tones in Mandarin-speaking congenital amusics.
The degree to which cognitive resources are shared in the processing of musical pitch and lexical tones remains uncertain. Testing Mandarin amusics on their categorical perception of Mandarin lexical tones may provide insight into this issue. In the present study, a group of 15 amusic Mandarin speakers identified and discriminated Mandarin tones presented as continua in separate blocks. The tonal continua employed were from a high-level tone to a mid-rising tone and from a high-level tone to a high-falling tone. The two tonal continua were made in the contexts of natural speech and of nonlinguistic analogues. In contrast to the controls, the participants with amusia showed no improvement for discrimination pairs that crossed the classification boundary for either speech or nonlinguistic analogues, indicating a lack of categorical perception. The lack of categorical perception of Mandarin tones in the amusic group shows that the pitch deficits in amusics may be domain-general, and this suggests that the processing of musical pitch and lexical tones may share certain cognitive resources and/or processes (Patel 2003, 2008, 2012).


Seasonal changes in components of male and female reproductive success in Raphanus sativus L. (Brassicaceae).
To document seasonal changes in the reproductive behavior of the perfect-flowered, self-incompatible mustard, Raphanus sativus L., we monitored individual survival, flower and fruit production among 58 individuals in a California population over six census dates (cohorts). Population size declined dramatically and mean individual levels of fruit set changed significantly between cohorts. The frequency distribution of flower and fruit production became increasingly skewed over the first four cohorts. The phenotypic maleness of individuals, a standardized measure of phenotypic gender, oscillated during the reproductive season, peaking in the third and fourth cohorts. We calculated a simple estimate of expected male reproductive success of each plant (the number of fruits sired on conspecifics); this estimate was a function of an individual's flower production and the fruit production of its potential mates in our sampled population. Mean expected male success did not differ significantly among cohorts; expected male success per flower did, however, change significantly among cohorts. Among individuals within each cohort, maternal fruit production and expected male success were both positively correlated with flower production throughout the season. Spearman rank correlation coefficients indicate that the strength of these associations, however, changed during the season. Linear regressions of transformed variables indicated that the shape of several fitness functions also changed over time. In addition, the amount of variation in maternal or expected paternal success explained by flower production declined over the first four cohorts. If typical of wild populations, these temporal changes in these functions suggest that measurements of the intensity of phenotypic selection on flower production will depend on when and how fitness is measured in natural populations.


Expression and activation of STAT family proteins in cerebral arteriovenous malformations.
Cerebral arteriovenous malformations (AVMs) do not seem to be static congenital vascular malformations but rather are dynamically changing pathologies. In this work, we investigated the expression and possible activation of different signal transducers and activators of transcription (STAT) family members in AVM nidus. Immunohistochemical analysis was conducted on 25 AVM specimens from 24 patients using antibodies against STATs 1, 3, 5, and 6 as well as their phosphorylated forms. Analysis was also undertaken to determine if there is any correlation between STAT activation and different clinical parameters of AVM patients. Our studies revealed that both STATs 1 and 3 were highly expressed in cerebral AVM, mainly in the endothelium of AVM blood vessels and perivascular infiltrating inflammatory cells within the nidus. STAT3 showed the most intense level of expression within the endothelium and perivascular infiltrating inflammatory cells. It was intensely expressed in the endothelium of 25 (100%) specimens and in the infiltrating inflammatory cells of 24 (96%) specimens. The expression of the phospho-STATs 1 and 3 was also high in the endothelium and perivascular infiltrating inflammatory cells indicating activation of STATs 1 and 3 in AVM. We could not find any significant effect of hemorrhage or preoperative embolization, or other clinical parameters, on the activation of STATs 1 and 3 in cerebral AVMs. We obtained evidence for significant overexpression and activation of both STATs 1 and 3 in cerebral AVM, thus suggesting an important role for these proteins in mediating the pathophysiology of cerebral AVM.


Patterns of alcohol use and psychiatric inpatient admissions.
The role of alcohol problems in psychiatric inpatient hospital admissions is not fully reflected in diagnostic statistics. A model is presented to guide the design and aid the interpretation of epidemiological research into the relationships between alcohol use and psychiatric disorder. The difficulties encountered in evaluating the role of alcohol in hospitalizations are discussed. Our preliminary research suggests that not enough attention has been paid to self-imposed abstinence from alcohol as a precipitant of symptoms and a precursor to hospitalization.


Laser Doppler flow for the hemodynamic differentiation of tachycardia.
Implantable cardioverter defibrillators (ICDs) offer effective therapy for the prevention of sudden cardiac death (SCD) due to ventricular arrhythmias. However, inappropriate shocks have detrimental effects on survival and quality of life. The addition of hemodynamic monitoring may be useful in discriminating clinically important ventricular arrhythmias. In this study, we assess the ability of laser Doppler flowmetry to assess the hemodynamic effect of paced atrial and ventricular arrhythmias using mean arterial blood pressure as the reference. In this acute human study in patients undergoing an elective electrophysiological study, laser Doppler flowmetry, arterial blood pressure, and surface ECG were acquired during high-rate atrial and ventricular pacing to simulate supraventricular and ventricular tachycardias. Arterial blood pressure and laser Doppler flow signals correlated well during atrial and ventricular pacing (rho = 0.694, p < .001). The hemodynamic impairment detected by both methods was greater during ventricular pacing than atrial pacing (-1.0% vs. 19.0%, p < .001). Laser Doppler flowmetry performed better than rate alone to identify hemodynamic impairments. In this acute study, laser Doppler flowmetry tissue perfusion served as a good surrogate measure for arterial pressure, which could be incorporated into future ICDs.


A microcomputer-based quantitative morphometric analysis system for computing areas of amorphous patches.
A method for analysis of irregular areas has been developed for use with histological sections. The analysis is performed utilizing a digitizing tablet and a microcomputer. The advantages of this system are a specialized form of output suited to the analysis of mosaic tissues, disk storage of all data, plotter output for verification, and an inexpensive hardware environment. The program results of determinations of liver patch size in a novel chimeric rat system are described.


Distinct changes in adult lymphopoiesis in Rag2-/- mice fully reconstituted by alpha4-deficient adult bone marrow cells.
alpha4 Integrins are major players in lymphoid cell trafficking and immune responses. However, their importance in lymphoid reconstitution and function, studied by antibody blockade or in genetic models of chimeric animals with alpha4(KO) embryonic stem (ES) cells, competitive repopulation experiments with fetal liver(KO) cells, or in beta1/beta7 doubly-deficient mice has yielded disparate conclusions. To study the role of alpha4 integrin (alpha4beta1, alpha4beta7) during adult life, we transplanted lethally irradiated Rag2(-/-) mice with alpha4(Delta/Delta) or alpha4(f/f) adult bone marrow (BM) cells and evaluated recipients at several points after transplantation. Lymphomyeloid repopulation (8 months later) was entirely donor-derived in all recipients, and novel insights regarding lymphoid reconstitution and function were revealed. Thymic repopulation was impaired in all alpha4(Delta/Delta) recipients, likely because of homing defects of BM-derived progenitors, although a role of alpha4 integrin in intrathymic expansion/maturation of T cells cannot be excluded; reconstitution of gut lymphoid tissue was also greatly diminished because of homing defects of alpha4(Delta/Delta) cells; impaired immunoglobulin (Ig) M and IgE, but normal IgG responses were seen, suggesting compromised initial B-/T-cell interactions, whereas interferon-gamma production from ovalbumin-stimulated cells was increased, possibly reflecting a bias against Th2 stimulation. These data complement previous observations by defending the role of alpha4 integrin in thymic and gut lymphoid tissue homing, and by strengthening evidence of attenuated B-cell responses in alpha4-deficient mice.


A Mouse Model That Reproduces the Developmental Pathways and Site Specificity of the Cancers Associated With the Human BRCA1 Mutation Carrier State.
Predisposition to breast and extrauterine Müllerian carcinomas in BRCA1 mutation carriers is due to a combination of cell-autonomous consequences of BRCA1 inactivation on cell cycle homeostasis superimposed on cell-nonautonomous hormonal factors magnified by the effects of BRCA1 mutations on hormonal changes associated with the menstrual cycle. We used the Müllerian inhibiting substance type 2 receptor (Mis2r) promoter and a truncated form of the Follicle stimulating hormone receptor (Fshr) promoter to introduce conditional knockouts of Brca1 and p53 not only in mouse mammary and Müllerian epithelia, but also in organs that control the estrous cycle. Sixty percent of the double mutant mice developed invasive Müllerian and mammary carcinomas. Mice carrying heterozygous mutations in Brca1 and p53 also developed invasive tumors, albeit at a lesser (30%) rate, in which the wild type alleles were no longer present due to loss of heterozygosity. While mice carrying heterozygous mutations in both genes developed mammary tumors, none of the mice carrying only a heterozygous p53 mutation developed such tumors (P < 0.0001), attesting to a role for Brca1 mutations in tumor development. This mouse model is attractive to investigate cell-nonautonomous mechanisms associated with cancer predisposition in BRCA1 mutation carriers and to investigate the merit of chemo-preventive drugs targeting such mechanisms.


Prevalence Estimate of Cerebral Palsy in Northern Alberta: Births, 2008-2010.
The objectives of this study were to determine prevalence estimates of cerebral palsy (CP) among 5-year-old children in northern Alberta; to provide congenital, gestational age- and birth weight-specific, and postneonatal CP rates; and to describe motor subtypes and function. This population-based prevalence estimate study, part of the Canadian Cerebral Palsy Registry, reports confirmed CP diagnoses at age 5 years made by pediatric rehabilitation and child neurology specialists. Prevalence rates with 95% confidence intervals (CIs) used Alberta government denominators of same-age children and live births. The Northern Alberta CP rate (birth years, 2008-2010) for 173 5-year-old children is 2.22 (95% CI 2.12, 2.32) per 1000 5-year-old children. The congenital CP rate is 1.99 (95% CI, 1.89-2.09) per 1000 live births; unilateral congenital CP, 1.0 (95% CI, 0.64-1.36) per 1000 live births; and postneonatal CP, 0.12 (95% CI, 0.1-0.14) per 1000 live births. Gestational age-specific rates are similar: age <28 weeks, 27.2 (95% CI, 23.05-31.35) and 28 to 31 weeks, 29.5 (95% CI, 25.78-33.22). Motor subtypes for 169 children (data missing, 4; male, 97; postnatal, 9) are: spastic, 148 (87.6%) including 31 (20.9%) with diplegia, 10 (6.8%) triplegia, 33 (22.2%) quadriplegia, 74 (50%) hemiplegia/monoplegia); and dyskinetic, 18 (10.6%) and ataxic, 3 (1.8%). A total of 107 (63.3%) ambulate without assistive devices and 111(65.7%) handle most objects with their hands independently. This is the fourth Canadian CP prevalence study; one from Quebec used a similar case ascertainment approach and two 1980s studies from Alberta and British Columbia used administrative databases. Northern Alberta CP rates are comparable with other developed countries. The hemiplegic subtype is the most common. Rates among preterm children have declined but are similar for the <28 and 28 to 31 gestation-week groups.


Effects of COVID-19 lockdown on the dietary habits and lifestyle in a population in southern Spain: a cross-sectional questionnaire.
Few studies have assessed the effect of lockdown on physical activity and eating behaviours in a population from the Autonomous Community of Andalusia in southern Spain. The aim of our study was to describe the effect of COVID-19 pandemic home lockdown on eating habits and lifestyle in the Andalusian population. A cross-sectional observational study was carried out on a population from southern Spain, Andalusian population. An online questionnaire was shared through social networks and snowball sampling. A total of 1140 people filled in the questionnaire. The questionnaire consisted of 34 items classified into three sections: sociodemographic data, work and leisure activities and questions on food consumption. Each item offered pre- and post-lockdown information. The participants were classified into three age groups: 18-35, 36-65 and over 65. Statistically significant differences were found between the three groups, with the younger age group undergoing greater changes, increasing their physical activity and consumption of fresh food, and decreasing both their consumption of fast food at home and alcohol intake. These findings suggest that, in the current social and health crisis, the citizens of southern Spain have become aware of the importance of maintaining an appropriate lifestyle to remain healthy, particularly the younger population with less well-consolidated habits.