Introducing BITTSy: The Behavioral Infant & Toddler Testing System.

This manuscript introduces BITTSy, the Behavioral Infant & Toddler Testing System. This software system is capable of running the headturn preference procedure, preferential looking, conditioned headturn, and visual fixation/habituation procedures. It uses only commercial-off-theshelf (COTS) hardware to implement the procedures in an affordable and space-efficient setup. The software package, example protocols and data sets, and manual are freely available and downloadable from go.umd.edu/BITTSy, making this entire set of procedures available to resource-limited labs. Researchers can easily use BITTSy at multiple sites in a uniform manner, resulting in a standardized, powerful research tool that can enhance cross-site research collaborations.

Electrochemical microdevices for rapid and on-site determination of the minimum inhibitory concentration of antibiotics.

A tool for rapid selection of appropriate antibiotics may be useful to maximize the benefits of their effectiveness against severe infectious diseases. In this study, we propose a microdevice that works with surface tension-driven sample introduction and impedance measurements for on-site, rapid estimation of suitable antibiotics.

Earlier biomarkers in fish evidencing stress responses to metal and organic pollution along the Doce River Basin.

The Doce River Basin (DRB) represents a well-described watershed in terms of contamination by metals, especially after a major environmental disaster of a mining tailing dam failure. Despite the massive mortality of the ichthyofauna, very few studies addressed the risks to the health of wild fish exposed to complex mixtures of pollutants from multiple sources. The present study proposed to investigate earlier responses of fish for assessing the impacts of multiple sources of pollution, considering: different niches of fish and target organs; and the influence of seasonality, associated with their probable sources of pollution. To achieve that, fish were collected along the DRB, and biomarkers responses were assessed in target organs and correlated with the levels of inorganic and organic contaminants. As one of the most prominent responses, fishes from the Upper DRB showed the highest expression of the metallothionein and oxidative stress parameters which were related to the higher levels of metals in this region due to the proximity of mining activities. On the other hand, higher levels of DNA damage and increased AChE activity from fish sampled in the Mid and Lower DRB were more associated with organic contaminants, from other sources of pollution than mining residues. The integrated biomarker responses also revealed seasonal variations, with higher values in fishes from the dry season, and pelagic fish showing greater variation within the seasons. The multivariate analysis integrating suitable biomarkers with chemical data represented an adequate strategy for assessing the ecological risks in the DRB, allowing the identification of distinct spatio-temporal impacts from multiple sources of contaminants. The continued exposure of the ichthyofauna representing future risks reinforces the need for ecological restoration and the protection of the fauna from the Doce River.

Complex genetic nature of sex-independent transmission ratio distortion in Asian rice species: the involvement of unlinked modifiers and sex-specific mechanisms.

Transmission ratio distortion (TRD), in which one allele is transmitted more frequently than the opposite allele, is presumed to act as a driving force in the emergence of a reproductive barrier. TRD acting in a sex-specific manner has been frequently observed in interspecific and intraspecific hybrids across a broad range of organisms. In contrast, sex-independent TRD (siTRD), which results from preferential transmission of one of the two alleles in the heterozygote through both sexes, has been detected in only a few plant species. We previously reported an S(6) locus-mediated siTRD, in which the S(6) allele from an Asian wild rice strain (Oryza rufipogon) was transmitted more frequently than the S(6)(a) allele from an Asian cultivated rice strain (O. sativa) through both male and female gametes in heterozygous plants. Here, we report on the effect of a difference in genetic background on S(6) locus-mediated siTRD, based on the analysis using near-isogenic lines and the original wild strain as a parental strain for crossing. We found that the degree of TRD through the male gametes varied depending on the genetic background of the female (pistil) plants. Despite the occurrence of TRD through both male and female gametes, abnormality was detected in ovules, but not in pollen grains, in the heterozygote. These results suggest the involvement of unlinked modifiers and developmentally distinct, sex-specific genetic mechanisms in S(6) locus-mediated siTRD, raising the possibility that siTRD driven by a single locus may be affected by multiple genetic factors harbored in natural populations.

Atomic-resolution imaging in liquid by frequency modulation atomic force microscopy using small cantilevers with megahertz-order resonance frequencies.

In this study, we have investigated the performance of liquid-environment FM-AFM with various cantilevers having different dimensions from theoretical and experimental aspects. The results show that reduction of the cantilever dimensions provides improvement in the minimum detectable force as long as the tip height is sufficiently long compared with the width of the cantilever. However, we also found two important issues to be overcome to achieve this theoretically expected performance. The stable photothermal excitation of a small cantilever requires much higher pointing stability of the exciting laser beam than that for a long cantilever. We present a way to satisfy this stringent requirement using a temperature controlled laser diode module and a polarization-maintaining optical fiber. Another issue is associated with the tip. While a small carbon tip formed by electron beam deposition (EBD) is desirable for small cantilevers, we found that an EBD tip is not suitable for atomic-scale applications due to the weak tip-sample interaction. Here we show that the tip-sample interaction can be greatly enhanced by coating the tip with Si. With these improvements, we demonstrate atomic-resolution imaging of mica in liquid using a small cantilever with a megahertz-order resonance frequency. In addition, we experimentally demonstrate the improvement in the minimum detectable force obtained by the small cantilever in measurements of oscillatory hydration forces.

Reliability and validity of Japanese version of the McGill Quality of Life Questionnaire assessed by application in palliative care wards.

The McGill Quality of Life Questionnaire (MQOL), which consists of 16 items constructing physical, psychological, existential and support subscales and one item of overall quality of life (QOL), has been developed to assess QOL of terminal cancer patients. To examine if MQOL Japanese version (MQOL-J) is applicable, it was administered to 83 terminal cancer patients in palliative care wards several days after admission and then 7 to 10 days after the first interview. Cronbach's alpha coefficient for four subscales was 0.584-0.860. Sixteen items were classified into four factors by factor analysis, similar to the original English version. The results indicated that psychological and existential domains of the MQOL-J significantly related to overall QOL. Existential and support domains as well as overall QOL were significantly improved between the first and second interviews, although performance status assessed by Eastern Cooperative Oncology Group worsened. It is suggested that MQOL-J can reflect perceived health status of terminal cancer patients.

Hypertrophy of the extra-articular tendon of the long head of biceps correlates with the location and size of a rotator cuff tear.

AIMS: The aim of this study was to assess hypertrophy of the extra-articular tendon of the long head of biceps (LHB) in patients with a rotator cuff tear. PATIENTS AND METHODS: The study involved 638 shoulders in 334 patients (175 men, 159 women, mean age 62.6 years; 25 to 81) with unilateral symptomatic rotator cuff tears. The cross-sectional area (CSA) of the LHB tendon in the bicipital groove was measured pre-operatively in both shoulders using ultrasound. There were 154 asymptomatic rotator cuff tears in the contralateral shoulder. Comparisons were made between those with a symptomatic tear, an asymptomatic tear and those with no rotator cuff tear. In the affected shoulders, the CSAs were compared in relation to the location and size of the rotator cuff tear. RESULTS: The mean CSA was 21.0 mm2 (4 to 71) in those with a symptomatic rotator cuff tear, 19.9 mm2 (4 to 75) in those with an asymptomatic rotator cuff tear and 14.1 mm2 (5 to 43) in those with no rotator cuff tear. The mean CSA in patients with both symptomatic and asymptomatic rotator cuff tears was significantly larger than in those with no rotator cuff tear (p < 0.001). In the affected shoulders, there were significant differences between patients with more than a medium sized posterosuperior cuff tear and those with an antero-superior cuff tear. CONCLUSION: Regardless of the symptoms, there was significant hypertrophy of the extra-articular LHB tendon in patients with a rotator cuff tear. The values were significantly related to the size of the tear. Cite this article: Bone Joint J 2017;99-B:806-11.

Effect of Gender Differences on Transplant Kidney Function.

BACKGROUND: Transplant kidney function is thought to be affected by sex differences, such as physical conditions including muscle volume, sex hormones, immune responses, and so forth. We examined the effect of sex differences on transplant kidney function. METHODS: The subjects were selected from kidney transplant recipients, who received kidney transplantation on our hospital between January 2000 and August 2015. Cadaveric donors and parent-child pairs with an age difference were excluded, then we included 47 recipients whose sex was different from the sex of the donor. We compared transplant kidney function between male donors and female recipients group (M→F, n = 20) and female donors and male recipients group (F→M, n = 27). RESULTS: Nadir creatinine value was higher in the F→M group than in the M→F group (1.09 mg/dL vs 0.76 mg/dL, P < .0001). The estimated glomerular filtration rate (eGFR) was significantly higher in the M→F group than in the F→M group (66.6 mL/min/1.73 m2 vs 50.1 mL/min/1.73 m2, P = .002), and eGFR ratio (recipient to donor) was significantly higher in the M→F group than in the F→M group (1.13 vs 0.57, P < .0001). Multiple linear regression analysis showed that the only the sex of the recipient was significant prognostic factor of eGFR after renal transplantation (P = .037). CONCLUSIONS: The short-term kidney function of the graft from male to female was better than that of the graft from female to male.

Upregulation of functional beta(3)-adrenergic receptor in the failing canine myocardium.

Altered expression and functional responses to cardiac beta(3)-adrenergic receptors (ARs) may contribute to progressive cardiac dysfunction in heart failure (CHF). We compared myocyte beta(3)-AR mRNA and protein levels and myocyte contractile, [Ca(2+)](i) transient, and Ca(2+) current (I(Ca,L)) responses to BRL-37344 (BRL, 10(-8) mol/L), a selective beta(3)-AR agonist, in 9 instrumented dogs before and after pacing-induced CHF. Myocytes were isolated from left ventricular myocardium biopsy tissues. Using reverse transcription-polymerase chain reaction, we detected beta(3)-AR mRNA from myocyte total RNA in each animal. Using a cloned canine beta(3)-AR cDNA probe and myocyte poly A(+) RNA, we detected a single band about 3.4 kb in normal and CHF myocytes. beta(3)-AR protein was detected by Western blot. beta(3)-AR mRNA and protein levels were significantly greater in CHF myocytes than in normal myocytes. Importantly, these changes were associated with enhanced beta(3)-AR-mediated negative modulation on myocyte contractile response and [Ca(2+)](i) regulation. Compared with normal myocytes, CHF myocytes had much greater decreases in the velocity of shortening and relengthening with BRL accompanied by larger reductions in the peak systolic [Ca(2+)](i) transient and I(Ca,L). These responses were not modified by pretreating myocytes with metoprolol (a beta(1)-AR antagonist) or nadolol (a beta(1)- and beta(2)-AR antagonist), but were nearly prevented by bupranolol or L-748,337 (beta(3)-AR antagonists). We conclude that in dogs with pacing-induced CHF, beta(3)-AR gene expression and protein levels are upregulated, and the functional response to beta(3)-AR stimulation is increased. This may contribute to progression of cardiac dysfunction in CHF.

Functional effects of endogenous bradykinin in congestive heart failure.

OBJECTIVES: The purpose of this study was to determine the level and functional effects of endogenous bradykinin in congestive heart failure (CHF). BACKGROUND: There is experimental evidence that bradykinin is increased in several cardiac disease states. However, it is unknown whether plasma levels of bradykinin are elevated in CHF. Further, the cardiac and vascular responses to bradykinin in CHF are unclear. METHODS: The circulating levels of bradykinin and the effects of endogenous bradykinin were assessed in eight instrumented, conscious dogs both before and after pacing-induced CHF. RESULTS: Before CHF, the plasma bradykinin level was 53.1 +/- 12.4 pg/ml. Blocking endogenous bradykinin with HOE-140 (0.3 mg/kg), a specific bradykinin B2-receptor antagonist, produced no significant alterations in heart rate, left ventricular (LV) end-systolic pressure (Pes), total systemic resistance (TSR), the time constant of LV relaxation (tau) or the maximal rate of LV filling (dV/dt(max)). However, coronary blood flow was significantly reduced (p < 0.05). LV contractile performance measured by the slopes of pressure-volume relations was unaffected. After induction of CHF, the plasma bradykinin level increased to 234.2 +/- 19.4 pg/ml (p < 0.05). Blocking endogenous bradykinin with HOE-140 reduced coronary blood flow and produced significant increases in Pes and TSR, prolonged tau, decreased dV/dt(max) and elevated minimal LV pressure and mean left atrial pressure. Furthermore, the slopes of pressure-volume relations (p < 0.05) were decreased, indicating depressed contractility with HOE-140 after CHF. CONCLUSIONS: Before CHF, endogenous bradykinin results in coronary dilation but has no effect on systemic arterial vasodilation or cardiac performance. After CHF, endogenous bradykinin is significantly increased and, acting through B2-receptors, produces coronary and arterial vasodilation and improves LV relaxation and contractile performance. Thus, endogenous bradykinin may play an important role in preserving cardiovascular function in CHF.

Blood pressure and its regulation in spontaneously hypertensive rats bred on the lowest sodium diet for normal growth.

To investigate the effects of dietary sodium restriction from conception to adulthood on blood pressure and its regulatory mechanisms, male offspring were derived from inbreeding in spontaneously hypertensive rats fed a diet containing sodium of 175 mumol/g food (control) or 22 mumol/g (low sodium), which is the least sodium content for normal growth. While urinary sodium excretion was markedly less, the low sodium diet did not inhibit body growth and failed to blunt the development of hypertension. Neither plasma catecholamine concentration nor depressor response to hexamethonium was different between the two groups at any age examined (8, 12, and 20 weeks). Plasma renin concentration was not elevated, whereas urinary excretion of aldosterone was increased at any age in the low sodium group compared with that in the control group. Other sets of rats were fed a diet containing sodium of 175 mumol/g plus mefruside (a diuretic) of 0.001% in the same manner as in the other two groups. Urinary sodium excretion per creatinine was higher than in the other groups. The diuretic treatment inhibited body growth and suppressed adult blood pressure. While the sympathetic function was not affected, both plasma renin concentration and urinary excretion of aldosterone were elevated. These results indicate that dietary sodium restriction with the least sodium for normal growth from conception cannot blunt either the sympathetic nervous function or the development of hypertension in spontaneously hypertensive rats. Aldosterone appears to play an important role in maintaining sodium homeostasis under the dietary sodium restriction.

An aspect of sentence processing in Alzheimer's disease: quantifier-noun agreement.

We assessed sentence processing in Alzheimer's disease (AD) with measures of sentence-picture matching, grammaticality judgments of sentences, and sentence completion. The results demonstrated significant and consistent difficulty with a grammatical feature of sentences on all three experiments. This impairment could not be explained by factors such as sentence length, dementia severity, or a short-term memory deficit and was independent of difficulty interpreting the meanings of words. We hypothesize that AD patients are impaired at appreciating the conceptual relations that underlie certain grammatical features of sentences.

Phonologic processing deficits in Alzheimer's disease.

We investigated phonologic production in patients with mild to moderate Alzheimer's disease (AD) on a repetition task. AD patients produced significantly more speech errors than age-matched controls. AD patients' errors, unlike those of controls, resulted in the transformation of real words into pseudowords, occurred disproportionately in word-initial positions, and were not influenced by the phonologic environment. This pattern of errors suggests a lexical phonologic retrieval deficit in AD.

Language comprehension and regional cerebral defects in frontotemporal degeneration and Alzheimer's disease.

We related profiles of language comprehension difficulty to patterns of reduced cerebral functioning obtained with high-resolution single photon emission computed tomography (SPECT) in patients with neurodegenerative conditions. We found different patterns of reduced relative cerebral perfusion in patients with frontotemporal degeneration (FD) and patients with Alzheimer's disease (AD). Cognitive assessments also showed different patterns of impaired comprehension in patients with FD and patients with AD. Grammatical comprehension difficulty in FD correlated with relative cerebral perfusion in left frontal and anterior temporal brain regions; impaired semantic processing in AD correlated with relative cerebral perfusion in inferior parietal and superior temporal regions of the left hemisphere. These findings are consistent with the hypothesis that a neural network distributed throughout the left hemisphere subserving different aspects of language comprehension, rather than a single brain region, is responsible for understanding language.

Language comprehension profiles in Alzheimer's disease, multi-infarct dementia, and frontotemporal degeneration.

We assessed language functioning in 116 age-, education-, and severity-matched patients with the clinical diagnosis of Alzheimer's disease (AD), multi-infarct dementia (MID) due to small-vessel ischemic disease, or a frontotemporal form of degeneration (FD). Assessments of comprehension revealed that patients with AD are significantly impaired in their judgments of single word and picture meaning, whereas patients with FD had sentence comprehension difficulty due to impaired processing of grammatical phrase structure. Patients with MID did not differ from control subjects in their comprehension performance. Traditional aphasiologic measures did not distinguish between AD, MID, and FD. Selective patterns of comprehension difficulty in patients with different forms of dementia emphasize that language deficits cannot be explained entirely by the compromised memory associated with a progressive neurodegenerative illness.

Serial position and temporal cue effects in multiple sclerosis: two subtypes of defective memory mechanisms.

Neurocognitive studies of multiple sclerosis (MS) have identified a robust long-term memory deficit. We hypothesized that this is due in part to the limited representation and use of serial order information. MS patients and controls were studied with a supraspan list learning procedure with post-encoding retrieval and recognition trials. MS patients demonstrated post-encoding negative recency with normal recognition, and word order recall was impaired. These findings appear to be in part to difficulty using temporal order cues in long-term memory. Two dissociable memory deficits were identified, suggesting that there are at least two neurocognitive mechanisms underlying memory impairment in MS.

Effects of therapeutic doses of human atrial natriuretic peptide on load and myocardial performance in patients with congestive heart failure.

The benefits of atrial natriuretic peptide (ANP) in patients with congestive heart failure (CHF) have been demonstrated. However, the myocardial actions of ANP remain unclear. Using relatively load-insensitive left ventricular pressure-volume analysis, the myocardial and load-altering actions of ANP in patients with moderate CHF were studied. After obtaining steady-state data using micromanometers and conductance catheters, ANP was infused in 9 patients with CHF at 0.01 and 0.1 microg/kg/min for 30 minutes, respectively. Hemodynamic variables, plasma ANP, and cyclic guanosine monophosphate (cGMP) levels were determined before and 30 minutes after each ANP infusion. ANP at 0.01 microg/kg/min increased plasma ANP and cGMP levels from 73 +/- 34 to 139 +/- 34 pg/ml and from 4 +/- 1 to 8 +/- 2 pmol/ml, respectively. ANP infusion caused a significant decrease in end-systolic pressure without any changes in heart rate. End-diastolic pressure was significantly decreased but there was no significant change in left ventricular end-diastolic volume. The time constant for isovolumetric relaxation was decreased. ANP infusion at 0.1microg/kg/min caused further decreases in end-systolic pressure, end-diastolic pressure and volume, and the time constant for isovolumetric relaxation (p <0.05) without any changes in heart rate. The slope of the end-systolic pressure-volume relation was increased from 1.3 +/- 0.2 to 1.6 +/- 0.3 mm Hg/ml (p <0.05), indicating increased contractility. Plasma ANP and cGMP levels were increased to 422 +/- 44 pg/ml and 16 +/- 3 pmol/ml, respectively. Thus, ANP infusion increased cGMP generation, decreased afterload and preload, and improved left ventricular systolic and diastolic function.

SMRT as a T3SF-binding protein.

p53-binding consensus-like sequence (T3SF) is located in the murine promoter region of tissue inhibitor of metalloproteinase 3 gene. To identify the genes that encode proteins that bind to T3SF DNA sequence, we screened a cDNA library using the Southwestern technique. The SMRT gene was cloned as one of the candidates. Addition of antibody against SMRT reduced the intensity of a band that is supposed to contain SMRT in electrophoresis mobility shift assay, although antibody against p53 had no effect. Ultraviolet (UV)-irradiation reduced the intensity of the SMRT complex whereas p53 complex was stabilized by UV-irradiation. These results suggest that SMRT may bind to T3SF sequence in p53-independent manner and dissociate from the sequence by UV irradiation.

Changes in calcium transient and left ventricular function during positive inotropic stimulation and myocardial ischemia in indo-1-loaded beating guinea pig heart.

To elucidate the issues such as excitation-contraction coupling and myocardial ischemia, it is necessary to measure intracellular free Ca2+ concentration and mechanical function of hearts perfused via the normal arterial circulation. For this purpose, we simultaneously measured Ca(2+)-dependent indo-1 fluorescence and left ventricular (LV) pressure on a beat-to-beat basis in Langendorff guinea-pig hearts, and investigated the changes in Ca2+ transient and LV function during inotropic stimulation and myocardial ischemia. The indo-1 fluoresence ratio and LV developed pressure increased the perfusate [Ca2+] increased from 1.6 to 3.2 mmol/L, and there was a good correlation between Ca2+ transient and LV contractility. Digoxin (10(-6) mol/L) and milrinone (10(-5) mol/L) increased LV contractility with a concomitant increase in Ca2+ transient, and the relative increase of Ca2+ transient produced by milrinone was much more than that by digoxin. The reduction of coronary perfusion pressure from 80 to 40 mm Hg decreased LV contractility with an increase in indo-1 fluorescence ratio. These results suggest that Ca2+ responsiveness of contractile apparatus declines during inotropic stimulation by milrinone and during myocardial ischemia. Thus, this experimental technique is useful to investigate the interrelation of Ca2- regulation and LV function during a variety of pharmacological and physiologic perturbations.

Circadian rhythm of blood pressure is transformed from a dipper to a non-dipper pattern in shift workers with hypertension.

Shift workers make great use of health care services because they are associated with increased cardiovascular morbidity and mortality. Whether the circadian rhythm of blood pressure rapidly adapts to shift work is controversial. It is unknown if shift work has adverse effects on blood pressure in patients with hypertension. To evaluate the effects of shift work, we examined 12 male shift workers with untreated hypertension aged 53.6 +/- 2.5 years. Twenty-four hour ambulatory blood pressure monitoring was performed three times as follows: the last day of a 4-day period of day shifts (09.00 to 21.00), the first day of a 4-day period of night shifts (21.00 to 09.00), and the fourth day of night shifts (21.00 to 09.00). Blood pressure at night-time dropped significantly in the day-shift workers, showing a dipper pattern. Average differences in blood pressure in the sleep-wake cycle were decreased by 8.5% at the beginning of night shift work showing a non-dipper pattern. After 4 days the pattern was completely reversed to a dipper pattern. The results indicate that the circadian blood pressure pattern is changed from a dipper to a non-dipper pattern on the first day of the night shift and reverses to a dipper pattern within a few days. We suggest that night shift work may have unfavourable effects on blood pressure in patients with hypertension.