RAFT aqueous dispersion polymerization yields poly(ethylene glycol)-based diblock copolymer nano-objects with predictable single phase morphologies.
A poly(ethylene glycol) (PEG) macromolecular chain transfer agent (macro-CTA) is prepared in high yield (>95%) with 97% dithiobenzoate chain-end functionality in a three-step synthesis starting from a monohydroxy PEG113 precursor. This PEG113-dithiobenzoate is then used for the reversible addition-fragmentation chain transfer (RAFT) aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA). Polymerizations conducted under optimized conditions at 50 °C led to high conversions as judged by (1)H NMR spectroscopy and relatively low diblock copolymer polydispersities (M(w)/M(n) < 1.25) as judged by GPC. The latter technique also indicated good blocking efficiencies, since there was minimal PEG113 macro-CTA contamination. Systematic variation of the mean degree of polymerization of the core-forming PHPMA block allowed PEG113-PHPMA(x) diblock copolymer spheres, worms, or vesicles to be prepared at up to 17.5% w/w solids, as judged by dynamic light scattering and transmission electron microscopy studies. Small-angle X-ray scattering (SAXS) analysis revealed that more exotic oligolamellar vesicles were observed at 20% w/w solids when targeting highly asymmetric diblock compositions. Detailed analysis of SAXS curves indicated that the mean number of membranes per oligolamellar vesicle is approximately three. A PEG113-PHPMA(x) phase diagram was constructed to enable the reproducible targeting of pure phases, as opposed to mixed morphologies (e.g., spheres plus worms or worms plus vesicles). This new RAFT PISA formulation is expected to be important for the rational and efficient synthesis of a wide range of biocompatible, thermo-responsive PEGylated diblock copolymer nano-objects for various biomedical applications.


Color Fringe Correction by the Color Difference Prediction Using the Logistic Function.
This paper proposes a new color fringe correction method that preserves the object color well by the color difference prediction using the logistic function. We observe two characteristics between normal edge (NE) and degraded edge (DE) due to color fringe: 1) the DE has relatively smaller R-G and B-G correlations than the NE and 2) the color difference in the NE can be fitted by the logistic function. The proposed method adjusts the color difference of the DE to the logistic function by maximizing the R-G and B-G correlations in the corrected color fringe image. The generalized logistic function with four parameters requires a high computational load to select the optimal parameters. In experiments, a one-parameter optimization can correct color fringe gracefully with a reduced computational load. Experimental results show that the proposed method restores well the original object color in the DE, whereas existing methods give monochromatic or distorted color.


Accent Intelligibility Differences in Noise Across Native and Nonnative Accents: Effects of Talker-Listener Pairing at Acoustic-Phonetic and Lexical Levels.
Purpose The intelligibility of an accent strongly depends on the specific talker-listener pairing. To explore the causes of this phenomenon, we investigated the relationship between acoustic-phonetic similarity and accent intelligibility across native (1st language) and nonnative (2nd language) talker-listener pairings. We also used online measures to observe processing differences in quiet. Method English ( n = 16) and Spanish ( n = 16) listeners heard Standard Southern British English, Glaswegian English, and Spanish-accented English in a speech recognition task (in quiet and noise) and an electroencephalogram task (quiet only) designed to assess phonological and lexical processing. Stimuli were drawn from the nonnative speech recognition sentences ( Stringer & Iverson, 2019 ). The acoustic-phonetic similarity between listeners' accents and the 3 accents was calculated using the ACCDIST metric ( Huckvale, 2004 , 2007 ). Results Talker-listener pairing had a clear influence on accent intelligibility. This was linked to the phonetic similarity of the talkers and the listeners, but similarity could not account for all findings. The influence of talker-listener pairing on lexical processing was less clear; the N400 effect was mostly robust to accent mismatches, with some relationship to intelligibility. Conclusion These findings suggest that the influence of talker-listener pairing on intelligibility may be partly attributable to accent similarity in addition to accent familiarity. Online measures also show that differences in talker-listener accents can disrupt processing in quiet even where accents are highly intelligible.


Issues and controversies in the plain-film diagnosis of asbestos-related disorders in the chest.
This article reviews the chest radiographic manifestations of asbestos exposure. While the chest radiograph (CXR) is a highly valuable tool in the evaluation of asbestos-related disease, there are ongoing controversies regarding the sensitivity and specificity of the plain film in diagnosing asbestos-related disorders. Autopsy series indicate that at least 60% of pleural plaques may be overlooked. Conversely, such series indicate that up to 20% of plaques are falsely diagnosed. The significance of visceral pleural thickening and the definition and positive predictive value of diffuse pleural thickening as they relate to asbestos exposure are unresolved issues. Data suggest that the CXR may fail to reflect significant asbestosis in 10% to 20% of cases. On the other hand, the presence of overlying pleural abnormalities as well as technical factors may contribute to overreading of interstitial disease. Data on the rate of false positive readings for asbestosis are limited. Considered alone, the CXR can support but not specifically establish nor exclude the diagnosis of asbestosis. In practice, an ILO grade of less than 1/0 implies that the diagnosis is unlikely. A constellation of positive CXR findings may increase specificity, although the diagnosis rests on a combination of multiple clinical criteria.


To meet with a stroke: patients' experiences and aspects seen through a screen of crises.
The aim of this study was to elucidate the experiences of stroke victims during the course of disease and the first few months after discharge. Ten individuals, recently having suffered their first manifest stroke with lasting neurological symptoms, narrated their experiences and gave their views at two different appointments during the first few months after discharge. A deductive approach was applied, on the basis of the theory of developmental crises. The analyses of the interviews were performed using a phenomenological hermeneutic method inspired by the philosophy of Ricoeur. The analyses disclosed phenomena signifying developmental crises in all the cases, though the crises profiles were marked by the sequelae the individuals suffered after stroke and by the age-specific stages of which they were in the middle. The solution of the crises was from being reached within the period of data collection, as the interviews were performed relatively early after home-coming and the individuals were in the middle of grasping their new situation. The phenomenon "to meet with a stroke' seems to challenge the whole of the individual's being. The study calls attention to the need for awareness of this matter, which should be indicated to a much greater extent in nursing care and education than has been done until to date.


Unambiguous determination of gravitational waveforms from binary black hole mergers.
Gravitational radiation is properly defined only at future null infinity (J+), but in practice it is estimated from data calculated at a finite radius. We have used characteristic extraction to calculate gravitational radiation at J+ for the inspiral and merger of two equal-mass nonspinning black holes. Thus we have determined the first unambiguous merger waveforms for this problem. The implementation is general purpose and can be applied to calculate the gravitational radiation, at J+, given data at a finite radius calculated in another computation.


A pilot study on the early use of the vacuum erection device after radical retropubic prostatectomy.
To evaluate the effect of the early use of the vacuum erection device (VED) on erectile dysfunction (ED) and penile shortening after radical retropubic prostatectomy (RP), as these are important concerns for men choosing among treatment alternatives for localized prostate cancer. Twenty-eight men undergoing RP were randomized to early intervention (1 month after RP, group 1) or a control group (6 months after RP, group 2) using a traditional VED protocol. An International Index of Erectile Function (IIEF) score of >11 (no, mild or mild to moderate ED) was required as a baseline criterion for inclusion in the study. Only patients in whom unilateral or bilateral nerves were spared were subsequently randomized. Patients in group 1 followed a daily rehabilitation protocol consisting of 10 min/day using the VED with no constriction ring, for 5 months. Patients were evaluated with the IIEF-5 questionnaire and measurements of penile flaccid length, stretched length, prepubic fat pad, and midshaft circumference before and at 1, 3, 6, 9 and 12 months after RP; the mean (range) last follow-up visit was 9.5 (6-12) months after RP. The mean (sd) baseline IIEF scores were similar in groups 1 and 2, at 21.1 (4.6) and 22.3 (3.3), respectively (P = 0.54). The IIEF scores were significantly higher in group 1 than group 2 at 3 months, at 11.5 (9.4) vs 1.8 (1.4) (P = 0.008) and at 6 months, at 12.4 (8.7) vs 3.0 (1.9) (P = 0.012) after RP. There were no significant changes in penile flaccid length, prepubic fat pad, or mid-shaft circumference in either group. Stretched penile length was significantly decreased at both 3 and 6 months, by approximately 2 cm (P = 0.013) in group 2. By contrast, stretched penile length was preserved in group 1 at all sample times. At the last follow-up, the proportion of men with a mean loss of penile length of >/= 2 cm was significantly lower in group 1 than group 2 (two/17, 12%, vs five/11, P = 0.044). Initiating the use of a VED protocol at 1 month after RP improves early sexual function and helps to preserve penile length.


Thermodilution curves for diagnosis of ventricular septal defect in cattle.
An indicator dilution method developed for detection of intracardiac shunts and determination of cardiac output in man and domestic animals was evaluated in 4 calves and 1 cow with holosystolic cardiac murmurs. Thermodilution curves recorded from the pulmonary artery and the right ventricle confirmed a left-to-right intracardiac shunt and provided a means for its quantitation. Ventricular septal defect was confirmed in 2 cows, which were euthanatized. The data obtained by thermodilution were evaluated along with information obtained from other diagnostic procedures (auscultation, oximetry, echocardiography, measurement of intravascular pressures). It was concluded that the procedure is a simple and accurate method for diagnosis of ventricular septal defect in cattle.


A NICE game of Minecraft: philosophical flaws underpinning UK depression guideline nosology.
Categorising mental disorders for purposes of diagnosis, research and practice has historically been justified on philosophical terms as a pragmatic activity; categories which have been subject to wide-ranging philosophical critique have been defended on the grounds that they serve as heuristic devices providing loose representations of shared experiences, not labels for real structures. In acknowledgement of this, there has been increasing recognition that subclassifying multiple discrete forms of persistent depression moves too far away from the notion of a heuristic and that attempts to create more precise categories become less clinically useful. Hence the most recent Diagnostic and Statistical Manual of Mental Disorders (V.5) and International Classification of Diseases (V.11) both group persistent forms of depression together. However, the UK National Institute for Health and Care Excellence has delineated certain subclassifications of persistent depression in its new guideline, which grossly distorts the phenomenology of depression. This approach commits a fundamental philosophical error in conflating absence of knowledge with knowledge of absence. In this sense, the new guideline appears to be engaging in an activity akin to the digital game Minecraft, in which the craft of building structures from units of construction is largely divorced from the laws of physics. The risk of ignoring these philosophical errors and making false claims about scientific plausibility is that the guideline recommendations inevitably represent a highly distorted phenomenology of depression and will be of very little value to patients or practitioners looking for guidance on best possible treatment options.


The lingering question of menthol in cigarettes.
Tobacco use is the single most important preventable cause of cancer-related deaths in the USA and many parts of the world. There is growing evidence that menthol cigarettes are starter tobacco products for children, adolescents, and young adults. Accumulating research also suggests that smoking menthol cigarettes reinforces nicotine dependence, impedes cessation, and promotes relapse. However, menthol cigarettes are exempt from the US Food and Drug Administration ban on flavored cigarettes due, in part, to the lack of empirical evidence describing the health consequences of smoking menthol cigarettes relative to regular cigarettes. Determining the biological effects of menthol cigarette smoke relative to regular cigarette smoke can clarify the health risks associated with the use of respective products and assist regulatory agencies in making scientifically based decisions on the development and evaluation of regulations on tobacco products to protect public health and to reduce tobacco use by minors. We highlight the inherent shortcomings of the conventional epidemiologic, clinical, and laboratory research on menthol cigarettes that have contributed to the ongoing debate on the public health impact of menthol in cigarettes. In addition, we provide perspectives on how future investigations exploiting state-of-the-art biomarkers of exposure and disease states can help answer the lingering question of menthol in cigarettes.


Increased serum carcinoembryonic antigen levels as an early sign of medullary thyroid carcinoma.
To emphasize the potential association between increased levels of carcinoembryonic antigen (CEA) and the presence of medullary thyroid carcinoma (MTC). We present two case reports of this association, including long-term serial measurements of CEA in one patient. CEA is a tumor marker often associated with colon cancer. In recent years, increased CEA in plasma has been reported in patients with other cancers. Diagnoses of MTC in two patients were preceded by increased CEA levels (for 6 years in one patient). Because CEA levels returned to normal after thyroidectomy, MTC may have been the cause of the increases. In patients with increased plasma CEA levels, MTC should be considered in the differential diagnosis even if thyroid palpation is nonrevealing and thyroid function is normal.


Psychometric Properties of the Multi-Affect Indicator in a Chinese Worker Sample.
The Multi-Affect Indicator is a new measure that assesses the core affect at work with 16 items. The current study examined the scale's psychometric properties in terms of internal consistency and composite reliability, factorial validity, convergent validity, and discriminant validity with a Chinese sample of 370 full-time workers. The results demonstrated that Multi-Affect Indicator has high internal consistency and composite reliability and a correlated four-quadrant structure. Furthermore, three of its four subscales show adequate convergent validity. Thus, the Chinese version of the Multi-Affect Indicator behaves consistently with the original and can be used in future studies of core workplace affect in Chinese context.


Yeast chemotropism: A paradigm shift in chemical gradient sensing.
The ability of cells to direct their movement and growth in response to shallow chemical gradients is essential in the life cycles of all eukaryotic organisms. The signaling mechanisms underlying directional sensing in chemotactic cells have been well studied; however, relatively little is known about how chemotropic cells interpret chemical gradients. Recent studies of chemotropism in budding and fission yeast have revealed 2 quite different mechanisms-biased wandering of the polarity complex, and differential internalization of the receptor and G protein. Each of these mechanisms has been proposed to play a key role in decoding mating pheromone gradients. Here we explore how they may work together as 2 essential components of one gradient sensing machine.


Cancer care in times of conflict: Treatment of patients from Afghanistan, in Pakistan.
Afghanistan has been in a near-continuous armed conflict, which has degraded the country's health infrastructure. Due to this, Afghans have opted to seek cancer treatment in Pakistan. This manuscript aims to understand the complex cancer journey of patients from Afghanistan seeking care in the largest tertiary care cancer institutions in Pakistan. This retrospective study explores the demographics, epidemiology and outcomes of Afghan cancer patients treated at the Shaukat Khanum Memorial Cancer Hospital and Research Centres (SKMCH&RC) in Lahore and Peshawar, Pakistan, over the period from 1995 to June 2022. A total of 6,370 patients from Afghanistan have undergone cancer care since 1995. The mean age at presentation was 40.7 years, 57% were male, and 87% were adults >19 years. Close to 30% of these patients came from Kabul and Nangarhar districts. 56% of all patients presented with stage III or IV disease. 34% of adult patients achieved a complete response to treatment, but more than half of all patients have since been lost to follow-up. Children generally had better outcomes, with 43% showing a complete response to treatment. The cancer journey for these patients remains long and difficult and the inability to ensure follow-up in so many remains frustrating for both patients and providers. The lack of a cancer infrastructure in Afghanistan after decades of conflict, means that policymakers need to develop and support alternative systems and structures to provide post-conflict domestic and cross-border cancer care.


Identifying and acting on inappropriate metadata: a critique of the Grattan Institute Report on questionable care in Australian hospitals.
In an era of ever-increasing medical costs, the identification and prohibition of ineffective medical therapies is of considerable economic interest to healthcare funding bodies. Likewise, the avoidance of interventions with an unduly elevated clinical risk/benefit ratio would be similarly advantageous for patients. Regrettably, the identification of such therapies has proven problematic. A recent paper from the Grattan Institute in Australia (identifying five hospital procedures as having the potential for disinvestment on these grounds) serves as a timely illustration of the difficulties inherent in non-clinicians attempting to accurately recognize such interventions using non-clinical, indirect or poorly validated datasets. To evaluate the Grattan Institute report and associated publications, and determine the validity of their assertions regarding hyperbaric oxygen treatment (HBOT) utilisation in Australia. Critical analysis of the HBOT metadata included in the Grattan Institute study was undertaken and compared against other publicly available Australian Government and independent data sources. The consistency, accuracy and reproducibility of data definitions and terminology across the various publications were appraised and the authors' methodology was reviewed. Reference sources were examined for relevance and temporal eligibility. Review of the Grattan publications demonstrated multiple problems, including (but not limited to): confusing patient-treatments with total patient numbers; incorrect identification of 'appropriate' vs. 'inappropriate' indications for HBOT; reliance upon a compromised primary dataset; lack of appropriate clinical input, muddled methodology and use of inapplicable references. These errors resulted in a more than seventy-fold over-estimation of the number of patients potentially treated inappropriately with HBOT in Australia that year. Numerous methodological flaws and factual errors have been identified in this Grattan Institute study. Its conclusions are not valid and a formal retraction is required.


Visualization of water drying in porous materials by X-ray phase contrast imaging.
We present in this study results from X-ray tomographic microscopy with synchrotron radiation performed both in attenuation and phase contrast modes on a limestone sample during two stages of water drying. No contrast agent was used in order to increase the X-ray attenuation by water. We show that only by using the phase contrast mode it is possible to achieve enough water content change resolution to investigate the drying process at the pore-scale. We performed 3D image analysis of the time-differential phase contrast tomogram. We show by the results of such analysis that it is possible to obtain a reliable characterization of the spatial redistribution of water in the resolved pore system in agreement with what expected from the theory of drying in porous media and from measurements performed with other approaches. We thus show the potential of X-ray phase contrast imaging for pore-scale investigations of reactive water transport processes which cannot be imaged by adding a contrast agent for exploiting the standard attenuation contrast imaging mode.


Traveling front solutions to directed diffusion-limited aggregation, digital search trees, and the Lempel-Ziv data compression algorithm.
We use the traveling front approach to derive exact asymptotic results for the statistics of the number of particles in a class of directed diffusion-limited aggregation models on a Cayley tree. We point out that some aspects of these models are closely connected to two different problems in computer science, namely, the digital search tree problem in data structures and the Lempel-Ziv algorithm for data compression. The statistics of the number of particles studied here is related to the statistics of height in digital search trees which, in turn, is related to the statistics of the length of the longest word formed by the Lempel-Ziv algorithm. Implications of our results to these computer science problems are pointed out.


[Macroscopic study of cholangiocarcinoma].
Fourty three autopsy cases of cholangiocarcinoma and 18 cases of Thorotrast-related cholangiocarcinoma were macroscopically studied. They were classified into two types, according to the intrahepatic location of the tumors; middle-peripheral type and hilar type. Most Thorotrast-related cases (83%) were middle-peripheral type, while the non-Thorotrast-related cases were hilar type (68%). According to the gross characteristics of the tumor. They were classified into four gross types: infiltrative type (54%), nodular type (21%), periductal type (18%), and diffuse type (7%). Non-specific liver cirrhosis (mixed macro and micronodular type) was associated in 4 of non-Thorotrast related cases, and the association of biliary cirrhosis was found in 3 of the non-Thorotrast cases of the hilar type.


Long-term inhibition of ferritin2 synthesis in trophocytes and oenocytes by ferritin2 double-stranded RNA ingestion to investigate the mechanisms of magnetoreception in honey bees (Apis mellifera).
Behavioral studies indicate that honey bees (Apis mellifera) have a capacity for magnetoreception and superparamagnetic magnetite is suggested to be a magnetoreceptor. The long-term inhibition of magnetite formation can be employed to explore the bee's magnetoreception. A recent study shows that magnetite formation, ferritin2 messenger RNA (mRNA) expression, and the protein synthesis of ferritin2 in trophocytes and oenocytes were all inhibited by a single injection of ferritin2 double-stranded RNA (dsRNA) into the hemolymph of honey bees but how to maintain this knockdown of ferritin2 for the long-term is unknown. In this study, we injected ferritin2 dsRNA into the hemolymph of worker bees three times every six days to maintain long-term inhibition; however, multi-microinjections accelerated the death of the bees. To overcome this problem, we further reared newly emerged worker bees daily with ferritin2 dsRNA throughout their lives, demonstrating no impact on their lifespans. Follow-up assays showed that the mRNA expression and protein synthesis of ferritin2 were persistently inhibited. These findings verified that daily ferritin2 dsRNA ingestion not only displays the long-term inhibition of mRNA expression and protein synthesis of ferritin2, but also did not damage the bees. This method of long-term inhibition can be used in behavioral studies of magnetoreception in honey bees.


Hospitalizations due to unintentional transport injuries among Aboriginal population of British Columbia, Canada: Incidence, changes over time and ecological analysis of risk markers.
Worldwide, Indigenous people have disproportionately higher rates of transport injuries. We examined disparities in injury-related hospitalizations resulting from transport incidents for three population groups in British Columbia (BC): total population, Aboriginal off-reserve, and Aboriginal on-reserve populations. We also examined sociodemographic, geographic and ethnic risk markers for disparities. We identified Aboriginal people through BC's universal health care insurance plan insurance premium group and birth and death record notations. We calculated crude incidence rate and Standardized Relative Risk (SRR) of hospitalization for unintentional transport injury, standardized for age, gender and Health Service Delivery Area (HSDA), relative to the total population of BC. We tested hypothesized associations of geographic, socio-economic, and employment-related characteristics of Aboriginal communities with SRR of transport injury by multivariable linear regression. During the period 1991-2010, the SRR for the off-reserve Aboriginal population was 1.77 (95% CI: 1.71 to 1.83); and 2.00 (95% CI: 1.93 to 2.07) among those living on-reserve. Decline in crude rate and SRRs was observed over this period among both the Aboriginal and total populations of BC, but was proportionally greater among the Aboriginal population. The best-fitting multivariable risk marker model was an excellent fit (R2 = 0.912, p<0.001), predicted SRRs very close to observed values, and retained the following terms: urban residence, population per room, proportion of the population with a high school certificate, proportion of the population employed; and multiplicative interactions of Aboriginal ethnicity with population per room and proportion of the population employed. Disparities in risk of hospitalization due to unintentional transport injury have narrowed. Aboriginal ethnicity modifies the effects of socioeconomic risk factors. Continued improvement of socioeconomic conditions and implementation of culturally relevant injury prevention interventions are needed.


Inhibition of gonadotropin secretion in castrated male rhesus monkeys (Macaca mulatta) induced by dietary restriction: analogy with the prepubertal hiatus of gonadotropin release.
The purpose of this study was to examine further the notion that in higher primates, analogous neuroendocrine mechanisms may underlie the hiatus in LH and FSH secretion during prepubertal development and the suppression of gonadotropin release in adults during states of malnutrition. To this end, the metabolic sequelae and the gonadotropin response to restricted food intake (RFI) were determined in nine castrated male rhesus monkeys. The results obtained were then evaluated in light of current understanding of the neuroendocrine bases of the ontogeny of gonadotropin secretion in primates. A reduction in food intake from approximately 1150 Cal/day to approximately 200 Cal/day for 20-34 days resulted in declines in body weight and circulating LH and FSH concentrations. The reduction in body weight and the suppression of LH secretion were statistically significant (P less than 0.05). The decrease in gonadotropin secretion induced by RFI was fully restored by the chronic iv intermittent infusion of GnRH (0.1 microgram/min for 3 min every hour). These findings graphically demonstrate that RFI, or a sequelae of this nutritional perturbation, inhibits gonadotropin secretion, in the absence of feedback influences by gonadal hormones, by an action at a suprapituitary level that is mediated by interruption of intermittent hypothalamic GnRH discharge. The apparent arrest of the neural mechanism that governs the timing of intermittent GnRH discharge, the so-called GnRH pulse generator, was associated with decreases in plasma insulin (P = 0.078), T4 (P less than 0.05), and T3 (P less than 0.05) concentrations and with a significant (P less than 0.05) elevation in circulating cortisol levels. Although a general decrease in circulating amino acid levels was not observed during RFI, plasma glutamate concentrations were significantly (P less than 0.05) reduced by the nutritional perturbation. RFI resulted in unremarkable hypoglycemia. While the suppression of gonadotropin secretion in castrated male monkeys during RFI resembled, in certain aspects, the hiatus in gonadotropin secretion during prepubertal development, the endocrine and metabolic concomitants of these two physiological states exhibited important differences. Thus, the contemporary notion that the study of dietary restriction in adult primates may provide insights into the neuroendocrine mechanisms that govern the timing of the onset of puberty in these species should not be accepted without careful consideration.


[Treatment of ergotism].
Ergotism occurs in patients so disposed, particularly under ergotamine therapy for migraine. The principal signs are arterial spasms in the legs, or sometimes also the arms, which can lead to gangrene. Intravenous or intra-arterial infusion of sodium nitroprusside or nitroglycerine has proved the only reliably efficacious therapy. The best results have been obtained using nitroprusside: twelve cases are described here. By contrast, nonefficacious measures include, in particular, sympathetic blockade.


Effect of wheat bran on bowel function and fecal calcium in older adults.
Seven healthy older volunteers participated in a 33-day study consisting of three sample collection periods, a 10-day control, and two 10-day experimental periods. Subjects consumed their usual self-selected diets throughout and a daily wheat bran supplement (30 g) during the two experimental periods. Food intake was recorded daily by subjects and accuracy and completeness checked daily by personal interview. Apparent calcium absorption decreased significantly from 22.1 +/- 5.6% (mean +/- SD) during the control to 8.6 +/- 5.2% during the second bran period. The wheat bran supplement significantly increased wet and dry stool weights but had no effect on stool moisture or defecation frequency. Gastrointestinal transit time of a dose of chromium decreased significantly, from 75 +/- 33 to 54 +/- 19 hr; of a dose of polyethylene glycol insignificantly, from 98 +/- 59 to 69 +/- 46 hr. Mean recovery of 21 doses of chromium of 98.7 +/- 5.0% verified that stool collection was complete. The results suggest that the ability of wheat bran to regulate bowel function in the apparently healthy older adult may be accompanied by increased fecal calcium losses similar to what has been reported for younger adults.


Improved modeling of the solid-to-plasma transition of polystyrene ablator for laser direct-drive inertial confinement fusion hydrocodes.
The target performance of laser direct-drive inertial confinement fusion (ICF) can be limited by the development of hydrodynamic instabilities resulting from the nonhomegeneous laser absorption at the target surface, i.e., the laser imprint on the ablator. To understand and describe the formation of these instabilities, the early ablator evolution during the laser irradiation should be considered. In this work, an improved modeling of the solid-to-plasma transition of a polystyrene ablator for laser direct-drive ICF is proposed. This model is devoted to be implemented in hydrocodes dedicated to ICF which generally assume an initial plasma state. The present approach consists of the two-temperature model coupled to the electron, ion and neutral dynamics including the chemical fragmentation of polystyrene. The solid-to-plasma transition is shown to significantly influence the temporal evolution of both free electron density and temperatures, which can lead to different shock formation and propagation compared with an initial plasma state. The influence of the solid-to-plasma transition on the shock dynamics is evidenced by considering the scaling law of the pressure with respect to the laser intensity. The ablator transition is shown to modify the scaling law exponent compared with an initial plasma state.


Sodium Cationization Enables Exotic Deprotonation Sites on Gaseous Mononucleotides.
We report observation and photoelectron spectroscopic characterization of sodium cationization on four doubly deprotonated mononucleotide dianions Na+·[dNMP-2H]2- (N = A, G, C, or T) in the gas phase. Multiple tautomers with distinct deprotonated sites are identified, in which Na+ enables novel double deprotonation patterns and folds the resultant mononucleotide dianions. The most stable isomer for the whole family is derived from detaching one proton from the phosphate and the other from the nucleobase (amino group for N = A, G, and C, but nitrogen atom for T), whereas high-lying isomers with protons detached separately from the phosphate and the hydroxy group of sugar coexist. Particularly, an exotic deprotomer with both protons deprived from guanosine is populated as well. This work thus displays a remarkably diverse binding landscape enabled by sodium cationization, a potentially critical element in developing a general formulism to better model metal cation and nucleotide interactions.


Effect of chromium yeast supplementation on lipid profile of swine fat.
This study was conducted to evaluate the period of chromium yeast supplementation on lipid profile of backfat and Longissimus lumborum muscle of barrows. It was evaluated carcass samples from forty barrows, genetically similar. Pigs diets were supplemented with 0.4 mg kg-1 of chromium yeast in four periods (0, 38, 62 and 94 days before slaughter). The experimental design was completely randomized with four treatments, ten replicates, and each experimental unit consisting of one animal. Lipid profiles of backfat and Longissimus lumborum muscle were analyzed by gas chromatography. The increase in the period of chromium yeast use had a quadratic effect (P<0.05) for stearic and oleic fatty acids, and total saturated, monounsaturated and unsaturated fatty acids in backfat. DH-γ-linolenic and arachidonic fatty acids reduced when the period of chromium yeast use increased. In the meat, there was a quadratic effect (P<0.05) only in the γ-linoleic fatty acid. The use of chromium yeast for different periods influences the lipid profile of the backfat and the Longissimus lumborum muscle, with less effect in the meat.


Physical mapping of the Coxiella burnetii genome.
Coxiella burnetii isolates from different genomic groups contain restriction fragment polymorphisms that were easily distinguishable using pulsed field gradient electrophoresis (PFGE). Conversely, isolates that belong to the same genomic group yield identical patterns indicating that PFGE can be used to identify the genomic grouping of new C. burnetii isolates. Intact C. burnetii cells were embedded in agarose and lysed in situ. The genomic DNA was digested with low-frequency cutting restriction endonucleases, and subjected to PFGE analysis. NotI and SfiI cut C. burnetii DNA least often and produced the largest fragments. ApaI, MluI, SalI, XbaI or XhoI produced only small DNA fragments (+/- 50 kbp). When PFGE was used to analyse C. burnetii genomes for the presence of plasmid-related sequences, all the plasmid sequences in Nine Mile and Priscilla were associated with their 36 kbp or 39 kbp plasmid bands, respectively. If these isolates contained plasmid sequences which had integrated into their chromosomes those sequences would have been visible as additional bands. These same studies also showed that plasmid sequences in the plasmidless-Ko isolate were completely contained within two NotI fragments, indicating that the integrated plasmid is localized to a concise region of the C. burnetii genome. Since it is difficult to conduct genetic analyses of obligate intracellular parasites using standard techniques, a physical map is being developed using PFGE. In addition to providing a means for determining gene loci, the physical maps provide a means for comparing genetic organization among the different strains of C. burnetii.


Immobilized Multifunctional Polymersomes on Solid Surfaces: Infrared Light-Induced Selective Photochemical Reactions, pH Responsive Behavior, and Probing Mechanical Properties under Liquid Phase.
Fixing polymersomes onto surfaces is in high demand not only for the characterization with advanced microscopy techniques but also for designing specific compartments in microsystem devices in the scope of nanobiotechnology. For this purpose, this study reports the immobilization of multifunctional, responsive, and photo-cross-linked polymersomes on solid substrates by utilizing strong adamantane-β-cyclodextrin host-guest interactions. To reduce nonspecific binding and retain better spherical shape, the level of attractive forces acting on the immobilized polymersomes was tuned through poly(ethylene glycol) passivation as well as decreased β-cyclodextrin content on the corresponding substrates. One significant feature of this system is the pH responsivity of the polymersomes which has been demonstrated by swelling of the immobilized vesicles at acidic condition through in situ AFM measurements. Also, light responsivity has been provided by introducing nitroveratryloxycarbonyl (NVOC) protected amine molecules as photocleavable groups to the polymersome surface before immobilization. The subsequent low-energy femtosecond pulsed laser irradiation resulted in the cleavage of NVOC groups on immobilized polymersomes which in turn led to free amino groups as an additional functionality. The freed amines were further conjugated with a fluorescent dye having an activated ester that illustrates the concept of bio/chemo recognition for a potential binding of biological compounds. In addition to the responsive nature, the mechanical stability of the analyzed polymersomes was supported by computing Young's modulus and bending modulus of the membrane through force curves obtained by atomic force microscopy measurements. Overall, polymersomes with a robust and pH-swellable membrane combined with effective light responsive behavior are promising tools to design smart and stable compartments on surfaces for the development of microsystem devices such as chemo/biosensors.


No clear evidence of superiority regarding pulp medicaments in primary molars.
Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, the Web of Science, OpenGrey, the US National Institutes of Health Trials Register and the World Health Organization (WHO) Clinical Trials Registry Platform. Two reviewers independently selected studies. Randomised controlled trials comparing different pulp interventions combining a pulp treatment technique and a medicament in primary teeth were considered. Data abstraction and risk of bias assessment were carried out independently by two reviewers. The primary outcomes were clinical failure and radiological failure, as defined in trials, at six, 12 and 24 months. Pairwise meta-analysis using fixed-effect models was conducted with statistical heterogeneity being assessed using I2 coefficients. Forty-seven trials involving 3910 teeth were included. All were small single centre studies. The overall level of evidence was low with only one trial having a low risk of bias, 20 a high risk and 26 unclear risk of bias.The 47 trials examined 53 different comparisons: 25 for pulpotomy, 13 for pulpectomy, 13 for direct pulp capping and two comparisons between pulpotomy and pulpectomy.Regarding pulpotomy, 14 trials compared mineral trioxide aggregate (MTA) with formocresol (FC). MTA reduced both clinical and radiological failures at six, 12 and 24 months, although the difference was not statistically significant. MTA also showed favourable results for all secondary outcomes measured, although again, differences between MTA and FC were not statistically significant (with the exception of pathological root resorption at 24 months and dentine bridge formation at six months). MTA showed favourable results compared with calcium hydroxide (CH) (two trials) for all outcomes measured, but the differences were not statistically significant (with the exception of radiological failure at 12 months). When comparing MTA with ferric sulphate (FS) (three trials), MTA had statistically significantly fewer clinical, radiological and overall failures at 24 months. This difference was not shown at six or 12 months.FC was compared with CH in seven trials and with FS in seven trials. There was a statistically significant difference in favour of FC for clinical failure at six and 12 months, and radiological failure at six, 12 and 24 months. FC also showed favourable results for all secondary outcomes measured, although differences between FC and CH were not consistently statistically significant across time points. The comparisons between FC and FS showed no statistically significantly difference between the two medicaments for any outcome at any time point.For all other comparisons of medicaments used during pulpotomies, pulpectomies or direct pulp capping, the small numbers of studies and the inconsistency in results limits any interpretation. We found no evidence to identify one superior pulpotomy medicament and technique clearly. Two medicaments may be preferable: MTA or FS. The cost of MTA may preclude its clinical use and therefore FS could be used in such situations. Regarding other comparisons for pulpectomies or direct pulp capping, the small numbers of studies undertaking the same comparison limits any interpretation.


Regulation of glucose homeostasis in rat jejunum by despentapeptide-insulin in vitro.
The regulation of the absorption and metabolism of glucose in rat small intestine by insulin was studied by the perfusion of isolated loops of proximal jejunum in vitro. The addition of an active, monomeric form of insulin, despentapeptide-insulin, to the serosal side of the intestine from normal rats inhibited luminal glucose absorption (421 (11) to 285 (11) mumol/h/g dry wt, p less than 0.001) and lactate production (340 (28) to 192 (26) mumol/h/g dry wt, p less than 0.001), but had no effect on glucose utilisation (231 (11) and 210 (16) mumol/h/g dry wt). The production of acute insulin deficiency by the injection of anti-insulin serum in vivo caused a marked inhibition of luminal glucose absorption (421 (11) to 240 (13) mumol/h/g dry wt, p less than 0.001), glucose utilisation (231 (11) to 48 (2) mumol/h/g dry wt, p less than 0.001) and lactate production (340 (28) to 94 (2) mumol/h/g dry wt, p less than 0.001) in vitro. The effects of insulin deficiency were reversed by despentapeptide-insulin in vitro, so that the rates of absorption and metabolism for intestine from insulin deficient and normal rats were similar in the presence of the modified insulin. All the effects caused by insulin deficiency and despentapeptide-insulin were apparent within minutes and could not be attributed to hyperglycaemia. It is concluded that rat small intestine is subject to rapid and direct regulation by insulin.


Solution dynamics and molecular structure elucidation of novel aluminium derivatives containing diaminodimethylsilane ligands.
The interaction of dimethyldiaminosilane ligands of general formula SiMe2(NR2)(NR'2)(NR2, NR'2 = NiHPr, NHtBu, NC4H8, NHCH2CH2NMe2) with AlX3 (X = Cl, Me) has been investigated and the synthesis of novel aluminium derivatives is reported, namely AlMe3[SiMe2(NR2)(NR'2)], AlX2[SiMe2(NR)(NR'2)] and AlMe[SiMe2(NR)2], containing the silane ligand as neutral, monoanionic and dianionic species, respectively. Moreover, the solution molecular structures and dynamics have been elucidated via 1D/2D variable temperature NMR spectroscopy showing the influence of the N-substituents of the silane ligand and of the aluminium ancillary ligands.


Relative contribution of central and peripheral aberrations to overall high order corneal wavefront aberration.
To analyze the influence of specific combinations of corneal high order aberrations on the optical image quality of the cornea before and after photorefractive keratectomy (PRK) for low to high myopia and myopic astigmatism. Corneal topography was obtained for 80 eyes that underwent PRK using a scanning-spot excimer laser. The eyes were subdivided into three groups according to the preoperative refraction. The topographical data were imported into a custom software program that combined the Zernike high order terms having the same sign and angular frequency up to seventh order for 4-mm and 6-mm pupils, ie, coma and spherical aberrations, and midperipheral and peripheral high order aberrations. Photorefractive keratectomy induced a significant amount of the root-mean-square (RMS) values of the combinations of midperipheral and peripheral high order aberrations over the smaller pupil size for deeper myopic ablations (P<.05). Over the larger pupil, spherical myopic ablations showed a significant increase (P<.05) of the RMS values of coma and spherical aberrations. In the astigmatism group, the combination of terms having higher angular frequency increased significantly (P<.05) after surgery both over 4-mm and 6-mm pupils. After surface ablation, ablation depth and profile significantly influence the distribution and contribution of determined combinations of high order aberrations to the overall high order corneal wavefront aberration. Terms having high angular frequency were increased following large myopic correction and wide treatment zone. Quality of the whole corneal optics will be enhanced by designing future ablation profiles to compensate for peripheral high order optical aberrations.


Neonatal macrophages express elevated levels of interleukin-27 that oppose immune responses.
Microbial infections are a major cause of infant mortality worldwide because of impaired immune defences in this population. The nature of this work was to further understand the mechanistic limitations of the neonatal and infant immune response. Interleukin-27 (IL-27) is a heterodimeric cytokine of the IL-12 family that is produced primarily by antigen-presenting cells and is immunosuppressive toward a variety of immune cell types. We show that IL-27 gene expression is elevated in cord blood-derived macrophages relative to macrophages originating from healthy adults. We also evaluated the duration over which elevated IL-27 gene expression may impact immune responses in mice. Age-dependent analysis of IL-27 gene expression indicated that levels of IL-27 remained significantly elevated throughout infancy and then declined in adult mice. Flow cytometric analysis of intracellular cytokine-stained splenocytes further confirmed these results. Interleukin-27 may be induced during pregnancy to contribute to the immunosuppressive environment at the fetal-maternal interface because we demonstrate dose-responsive gene expression to progesterone in macrophages. Neutralization of IL-27 in neonatal macrophages improved the ability of these cells to limit bacterial replication. Moreover, neutralization of IL-27 during incubation with the Mycobacterium bovis bacillus Calmette-Guérin vaccine augmented the level of interferon-γ elicited from allogeneic CD4+ T lymphocytes. This suggests that blocking IL-27 during vaccination and infection may improve immune responses in newborn and infant populations. Furthermore, mice will be a suitable model system to further address these possibilities.


Levetiracetam Liver Injury: A Benign Antiepileptic Agent?
Levetiracetam is a commonly prescribed antiepileptic agent and has rarely been linked to hepatotoxicity. This case describes a patient with drug-induced autoimmune hepatitis secondary to levetiracetam.


[Histological study of different organs in clinically healthy Amazon parrots].
Histologic examination of organs of clinically healthy amazons was carried out. Only variations from the chicken are presented, among others: Occurrence of a complex of vessels and many Herbst' corpuscles in the nasal cavity; evidence of a thick muscular layer as well as many Herbst' corpuscles and nerve fibers as the cover of the syrinx; demonstration of muscular trabeculae in the parabronchia; detection of an artery accompanying the testes with muscular layers reaching into the adventitia and many nerve fibers; very small numbers of active lymph follicles within the white pulp of the spleen.


Room temperature deoxofluorination of aromatic aldehydes with XtalFluor-E under highly concentrated conditions.
The synthesis of difluoromethyl-containing compounds exploiting the deoxofluorination reaction of aromatic aldehydes using XtalFluor-E is described. This transformation occurs at room temperature under highly concentrated conditions, i.e., with no added solvent. A wide range of difluoromethyl-containing compounds was obtained in 21 to 87% isolated yields.


Insulin resistance and central obesity determine hepatic steatosis and explain cardiovascular risk in steatotic liver disease.
Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed to replace non-alcoholic fatty liver disease and focus on patients with progressive disease due to the presence of metabolic dysfunction. However, it is unclear whether the new definition actually identifies patients with hepatic steatosis at increased cardiovascular risk. A total of 4,286 asymptomatic subjects from the SAKKOPI study aged 45-80 years undergoing screening colonoscopy were analyzed. Steatosis was diagnosed by abdominal ultrasound. MASLD was diagnosed according to the recent expert consensus. Insulin resistance was assessed by homeostasis model assessment-insulin resistance score (HOMA-IR) (cutoff: ≥2.5), subclinical inflammation was estimated by ferritin/CRP/uric acid, and cardiovascular risk was assessed using SCORE2/ASCVD. Mean age was 59.4 ± 8.5 years, 51.6% were male; mean BMI was 27.0 ± 4.5 kg/m², 9.2% had type 2 diabetes mellitus. In total, 1,903 (44.4%) were diagnosed with hepatic steatosis and were characterized by more severe metabolic dysfunction including insulin resistance (47.1% vs. 12.2%, p < 0.001) and central obesity (waist circumference ≥102/88 cm, 71.8% vs. 37.1%, p < 0.001). This translated into higher (subclinical) inflammation (ferritin 153 vs. 95 mg/dL, p < 0.001, uric acid 6.3 mg/dL vs. 5.2 mg/dL, p < 0.001) and 10-year cardiovascular risk (SCORE2 7.8 points vs. 5.1 points, p < 0.001, ASCVD 17.9 points vs. 10.8 points, p < 0.001). 99.0% of subjects with steatosis met the MASLD definition, 95.4% met the MAFLD definition, and 53.6% met the definition of metabolic syndrome, while 95.4% of subjects without steatosis also met the MASLD criteria for metabolic dysfunction compared to 69.0% and 17.4% who met the MAFLD and metabolic syndrome criteria, respectively. Forward stepwise regression indicated that waist circumference, HOMA-IR, and triglycerides were most relevant in explaining the presence of hepatic steatosis across all subgroups of increasing metabolic dysfunction. At the same time, hepatic steatosis was not associated with cardiovascular risk in the overall cohort (SCORE2: B = 0.060, 95% CI: -0.193-0.314, and p = 0.642) and in patients with metabolic dysfunction after adjusting for age, sex, and these three metabolic dysfunction components. Although hepatic steatosis is associated with increased central obesity and insulin resistance, metabolic dysfunction per se rather than hepatic steatosis explains cardiovascular risk in these patients.


Proteomic Analysis of the Neurotrophic Effect of Gelidium amansii in Primary Cultured Neurons.
Gelidium amansii is an edible and economically important red alga consumed in South Eastern Asia. In previous studies, we reported that the ethanol extracts of G. amansii (GAE) has promising modulatory activity with respect to the morphological and functional maturation of hippocampal neurons in culture. In this study, we show that the chloroform (CHCl3) subfraction of GAE and the ethyl acetate (EtOAc) fraction dose-dependently promoted neurite outgrowth, and their effects were comparable with that of GAE. We further assessed in cultured cortical neurons, proteins differentially expressed in the presence/absence of the GAE, CHCl3 subfraction, and the EtOAc fraction by 2D-PAGE and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Proteomic data revealed that a number of proteins responsible for multiple cellular and biochemical functions vital for neuronal development and maturation were significantly upregulated in neurons treated with the GAE, CHCl3 subfraction, and the EtOAc fraction. Of the identified proteins, profilin 2a, septin 7, cdc42, protein phosphatase 2A, DA11, eukaryotic translation initiation factor 5A-1, and γ-enolase are known to play important roles in neuritogenesis and dendritic arborization. Immunofluorescence data demonstrate that GAE-treated hippocampal neurons showed greater intensity ratios in the expressions of the septin 7 and cdc42 compared to vehicle control, validating their proteomic profiles. Together these results suggest that the GAE/CHCl3 subfraction and EtOAc fraction promote neurite development by up or downregulating several key proteins.


Negative aftereffect arising from prolonged viewing of induced movement-in-depth.
Prolonged induced movement-in-depth in a static circle was elicited by a spiral stimulus. Afterwards an aftereffect was observed in the circle. The aftereffect was towards the subject after induced movement away from the subject, and away from the subject after induced movement towards the subject. Longer aftereffect was observed with a circle central to the inducing stimulus than with a circle peripheral to the inducing stimulus. In contrast to some other psychophysical effects, no clear-cut directional asymmetry was observed.


Molecular cloning, characterization and functional analysis of a 2C-methyl- D-erythritol 2, 4-cyclodiphosphate synthase gene from ginkgo biloba.
2C-methyl-D-erythritol 2, 4-cyclodiphosphate synthase (MECPS, EC: 126.96.36.199) is the fifth enzyme of the non-mevalonate terpenoid pathway for isopentenyl diphosphate biosynthesis and is involved in the methylerythritol phosphate (MEP) pathway for ginkgolide biosynthesis. The full-length mecps cDNA sequence (designated as Gbmecps) was cloned and characterized for the first time from gymnosperm plant species, Ginkgo biloba, using RACE (rapid amplification of cDNA ends) technique. The full-length cDNA of Gbmecps was 874 bp containing a 720 bp open reading frame (ORF) encoding a peptide of 239 amino acids with a calculated molecular mass of 26.03 kDa and an isoelectric point of 8.83. Comparative and bioinformatic analyses revealed that GbMECPS showed extensive homology with MECPSs from other species and contained conserved residues owned by the MECPS protein family. Phylogenetic analysis indicated that GbMECPS was more ancient than other plant MECPSs. Tissue expression pattern analysis indicated that GbMECPS expressed the highest in roots, followed by in leaves, and the lowest in seeds. The color complementation assay indicated that GbMECPS could accelerate the accumulation of beta-carotene. The cloning, characterization and functional analysis of GbMECPS will be helpful to understand more about the role of MECPS involved in the ginkgolides biosynthesis at the molecular level.


Laser micro/nano fabrication in glass with tunable-focus particle lens array.
Based on medium-tuned optical field enhancement effect around a self-assembled particle-lens array (PLA) irradiated with a femtosecond (fs) laser source, we demonstrated that high-precision periodical array of micro/nano-structures can be readily fabricated on glass surface or inside glass in large areas in parallel without any cracks or debris. The technique has potential for rapid fabrication of three-dimensional structures in multiple layers inside glass.


Polyphenol Composition, Anticholinesterase and Antioxidant Potential of the Extracts of Clinopodium vulgare L.
Clinopidium vulgare L. (wild basil, Lamiaceae) is a well-known medicinal plant used in the traditional medicine in many countries. Medicinal plants present potential sources of bioactive compounds. Many of them are rich in polyphenol compounds that show biological potential in terms of protecting biological molecules from oxidation and in inhibition of cholinesterase enzymes, which may be significant in the treatment of diseases related to oxidative stress. In this work, we examined the chemical composition of Clinopodium vulgare L. hot water and methanol extract using spectroscopic and HPLC/DAD techniques. Using DPPH and FRAP methods the antioxidant activity was analyzed. The ability to protect proteins and lipids from oxidation was also determined as well as the ability of extracts to inhibit cholinesterase enzymes using Ellman's method. Analyzed extracts were rich in polyphenol compounds. Among 16 identified and quantified phenolic compounds dominant were: rosmarinic (26.63 and 34.21 mg/g) and ellagic acid (23.11 and 29.31 mg/g) of hot water and methanol extract, respectively. They show good antioxidant activity and good potential in protecting lipids from oxidation. The ability of extracts to inhibit enzyme acetylcholinesterase was weak, while inhibition of the butyrylcholinesterase was missing. Extracts show prooxidant activity in terms of protecting proteins from oxidation.


Wegener's granulomatosis mimicking a parotid abscess.
We present the case of a previously healthy 59-year-old man who was under treatment for scleritis and episcleritis when he developed a parotid-gland swelling and pus-producing sinus. On surgical exploration, the features were those of a parotid abscess, but the lesion not only failed to heal post-operatively but increased in size very significantly. There was also severe necrotizing keratitis of the eyes. Due to clinical suspicion and a positive antineutrophil cytoplasmic antibodies test, Wegener's granulomatosis was diagnosed and the patient successfully treated with cyclophosphamide and steroids. Previously, a number of cases of Wegener's granulomatosis causing salivary-gland swelling have been reported in the literature; this is the first case in which the disease has masqueraded as a parotid abscess.


Yoga Practice Is Beneficial for Maintaining Healthy Lifestyle and Endurance Under Restrictions and Stress Imposed by Lockdown During COVID-19 Pandemic.
Uncertainty about Coronavirus disease 2019 (COVID-19) and resulting lockdown caused widespread panic, stress, and anxiety. Yoga is a known practice that reduces stress and anxiety and may enhance immunity. This study aimed to (1) investigate that including Yoga in daily routine is beneficial for physical and mental health, and (2) to evaluate lifestyle of Yoga practitioners that may be instrumental in coping with stress associated with lockdown. This is a pan-India cross-sectional survey study, which was conducted during the lockdown. A self-rated scale, COVID Health Assessment Scale (CHAS), was designed by 11 experts in 3 Delphi rounds (Content valid ratio = 0.85) to evaluate the physical health, mental health, lifestyle, and coping skills of the individuals. The survey was made available digitally using Google forms and collected 23,760 CHAS responses. There were 23,290 valid responses (98%). After the study's inclusion and exclusion criteria of yogic practices, the respondents were categorized into the Yoga (n = 9,840) and Non-Yoga (n = 3,377) groups, who actively practiced Yoga during the lockdown in India. The statistical analyses were performed running logistic and multinomial regression and calculating odds ratio estimation using R software version 4.0.0. The non-Yoga group was more likely to use substances and unhealthy food and less likely to have good quality sleep. Yoga practitioners reported good physical ability and endurance. Yoga group also showed less anxiety, stress, fear, and having better coping strategies than the non-Yoga group. The Yoga group displayed striking and superior ability to cope with stress and anxiety associated with lockdown and COVID-19. In the Yoga group, participants performing meditation reportedly had relatively better mental health. Yoga may lead to risk reduction of COVID-19 by decreasing stress and improving immunity if specific yoga protocols are implemented through a global public health initiative.


Optimization of the dosimetric leaf gap for use in planning VMAT treatments of spine SABR cases.
The dosimetric leaf gap (DLG) is a beam configuration parameter used in the Varian Eclipse treatment planning system, to model the effects of rounded MLC leaf ends. Measuring the DLG using the conventional sliding-slit technique has been shown to be produce questionable results for some volumetric modulated arc therapy (VMAT) treatments. This study therefore investigated the use of radiochromic film measurements to optimize the DLG specifically for the purpose of producing accurate VMAT plans using a flattening-filter-free (FFF) beam, for use in treating vertebral targets using a stereotactic (SABR, also known as SBRT) fractionation schedule. Four test treatments were planned using a VMAT technique, to deliver a prescription of 24 Gy in 3 fractions to four different spine SABR treatment sites. Measurements of the doses delivered by these treatments were acquired using an ionization chamber and radiographic film. These measurements were compared with the doses calculated by the treatment planning system using a range of DLG values, including a DLG identified using the conventional sliding-slit method (1.1 mm). An optimal DLG value was identified, as the value that produced the closest agreement between the planned and measured doses (1.9 mm). The accuracy of the dose calculations produced using the optimized DLG value was verified using additional radiochromic film measurements in a heterogeneous phantom. This study provided a specific initial DLG (1.9 mm) as well as a film-based optimization method, which may be used by radiotherapy centers when attempting to commission or improve an FFF VMAT-based SABR treatment programme.


A comparative study between fungal pellet- and spore-assisted microalgae harvesting methods for algae bioflocculation.
Fungi assisted microalgae bioflocculation is an emerging, efficient and cost-effective microalgal harvesting method, but no study has systematically evaluated and compared fungal spore-assisted (FSA) and fungal pellet-assisted (FPA) microalgal harvesting methods. In this study, harvesting Chlorella sp. cells by co-culture with Penicillium sp. spores or pellets was compared. Temperature, glucose concentration, pH and fungi:algae ratio were the critical parameters for harvesting efficiency. The highest flocculation efficiency (99%) of FSA method was achieved in 28 h at 40 °C, 160 rpm, 5 g glucose/L and 1.1 × 104 cells/mL (spore). FPA method can harvest 98.26% algae cells in 2.5 h at 34 °C, 160 rpm, pH 4.0 with the fungi:algae ratio of 1:2. The carbon input for FPA is only half of that for FSA. FPA takes less time and needs less glucose input compared with FSA and may be more promising to be further developed as an effective microalgae bioflocculation method.


Coerced Abortion - The Neglected Face of Reproductive Coercion.
Reproductive coercion encompasses a collection of pregnancy promoting and pregnancy avoiding behaviours. Coercion may vary in severity and be perpetrated by intimate partners or others. Research is complicated by the inclusion of behaviours that do not necessarily involve an intention to influence reproduction, such as contraceptive sabotage. These behaviours are the most common, but are not always included in survey instruments. This may explain why the prevalence of reproductive coercion varies widely. Prevalence also varies when coerced abortion is included in survey instruments. When it is, it seems roughly comparable in prevalence to coercion intended to impregnate. The extent and nature of coerced abortion can also be derived from studies that explore the reasons why women access abortion, the relationship between abortion and intimate partner violence, and online blogs and forums. This narrative review of reproductive coercion examines the evidence and attempts to comprehend why coerced abortion has been neglected.


Separation of two pregnancy-associated proteins with SP1 determinants and the conversion of SP1 beta to SP1 alpha.
The alpha and beta forms of the pregnancy-associated protein, SP1 which have been previously identified in late pregnancy serum were found to be also present in the placenta. The alpha form was somewhat more difficult to extract, requiring the use of detergents in the extracting buffer. The two variants can be separated by ion exchange chromatography or by gel filtration and distinguished by the different shapes of the precipitation rockets on immunoelectrophoresis. The alpha variant appears to be the larger molecule on gel filtration. When solutions of SP1 are acidified to pH 2.5 the beta form is rapidly converted to the alpha form and the latter is slowly destroyed. It is suggested that SP1 alpha represents the combination of SP1 beta with some other protein present in the placenta and in the serum.


Sequence analysis of the beta-N-acetylhexosaminidase gene of Vibrio vulnificus: evidence for a common evolutionary origin of hexosaminidases.
DNA cloned from the marine bacterium Vibrio vulnificus into Escherichia coli HB101 can hydrolyze chitin oligomer analogs in the recipient. The nucleotide sequence of the cloned DNA was determined and a single long open reading frame of 2541 base pairs (initiation codon through termination codon) was found. The nucleotide sequence predicts a gene product of 847 amino acids and a molecular mass of 94.3 kDa. In vitro transcription and translation analyses indicated a single protein of 94 kDa encoded by the cloned DNA. The gene product hydrolyzes methylumbelliferyl beta-D conjugates of chitotriose, chitobiose, N-acetylglucosamine, and N-acetylgalactosamine and has, therefore, been termed a beta-N-acetylhexosaminidase. The predicted protein shares a high degree of sequence similarity with the chitobiase of Vibrio harveyi and limited similarity with the alpha chain of human beta-hexosaminidase. Cluster analyses suggest a common evolutionary ancestor for all known hexosaminidase enzymes, with no detectable relationship to known chitinases.


Targeting focal adhesion kinase overcomes erlotinib resistance in smoke induced lung cancer by altering phosphorylation of epidermal growth factor receptor.
EGFR-based targeted therapies have shown limited success in smokers. Identification of alternate signaling mechanism(s) leading to TKI resistance in smokers is critically important. We observed increased resistance to erlotinib in H358 NSCLC (non-small cell lung carcinoma) cells chronically exposed to cigarette smoke (H358-S) compared to parental cells. SILAC-based mass-spectrometry approach was used to study altered signaling in H358-S cell line. Importantly, among the top phosphosites in H358-S cells we observed hyperphosphorylation of EGFR (Y1197) and non-receptor tyrosine kinase FAK (Y576/577). Supporting these observations, a transcriptomic-based pathway activation analysis of TCGA NSCLC datasets revealed that FAK and EGFR internalization pathways were significantly upregulated in smoking patients, compared to the never-smokers and were associated with elevated PI3K signaling and lower level of caspase cascade and E-cadherin pathways activation. We show that inhibition of FAK led to decreased cellular proliferation and invasive ability of the smoke-exposed cells, and restored their dependency on EGFR signaling. Our data suggests that activation of focal adhesion pathway significantly contributes to erlotinib resistance, and that FAK is a potential therapeutic target for management of erlotinib resistance in smoke-induced NSCLC.


A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury.
Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury. Neighboring Paneth cells responded to IL-33 by augmenting production of EGF, which promoted ISC recovery and epithelial regeneration. These findings reveal an unknown pathway of niche regulation and crypt regeneration whereby the niche responds dynamically upon injury and the stem cells orchestrate regeneration by regulating their niche. This regenerative circuit also highlights the breadth of IL-33 activity beyond immunomodulation and the therapeutic potential of EGF administration for treatment of intestinal injury.


Endogenous neuregulin restores radial glia in a (ferret) model of cortical dysplasia.
Radial glia are integral components of the developing neocortex. During corticogenesis, they form an important scaffold for neurons migrating into the cortical plate. Recent attention has focused on neuregulin (NRG1), acting through erbB receptors, in maintaining their morphology. We developed a model of developmental radial glial disruption by delivering an antimitotic [methylazoxy methanol (MAM)] to pregnant ferrets on embryonic day 24 (E24). We previously found that normal ferret cortex contains a soluble factor capable of realigning the disorganized radial glia back toward their normal morphology. Characterization of the reorganizing activity in normal cortex demonstrated that the probable factor mediating these responses was a 30-50 kDa protein. To test whether this endogenous soluble factor was NRG1, we used organotypic cultures of E24 MAM-treated ferret neocortex supplemented with the endogenous factor obtained from normal cortical implants, exogenous NRG1beta, antibodies that either blocked or stimulated erbB receptors, or a soluble erbB subtype that binds to available NRG1. We report that exogenous NRG1 or antibodies that stimulate erbB receptors dramatically improve the morphology of disrupted radial glia, whereas blockade of NRG1-erbB signaling prevents the radial glial repair. Our results suggest that NRG1 is an endogenous factor in ferret neocortex capable of repairing damaged radial glia and that it acts via one or more erbB receptors.


Treatment of symptomatic spondyloptosis in an adult previously treated with in situ fusion and instrumentation by L5 vertebrectomy and L4-S1 instrumented reduction.
One traditional treatment for spondylolisthesis is fusion. However, for high-grade spondylolisthesis and spondyloptosis, posterior fusion has had high rates of nonunion, progression, and persistent physical deformity. Thus, some surgeons have recommended reduction and instrumentation. One such technique (Gaines procedure) entails a two-stage procedure: L5 vertebrectomy anteriorly, followed by resection of the L5 posterior elements and instrumented reduction of L4 onto S1. However, to our knowledge, there is no report of reversing the fusion and deformity reduction in a symptomatic patient with previous solid fusion of the spondyloptosis at L5-S1. To present the first reported revision via the Gaines procedure for failed fusion secondary to spondyloptosis. Patient report. A 24-year-old woman, who had undergone multiple procedures for L5-S1 spondylolisthesis and a final fusion and instrumentation attempt, presented with continued urinary retention, leg and back pain, and inability to stand. She subsequently underwent posterior hardware removal, followed by anterior L5 vertebral body resection. In the second stage, she had posterior osteotomy of the previous L5-S1 fusion, resection of the posterior elements of L5, and reduction and instrumentation of L4 to S1. At the 2-year follow-up, she had full resolution of symptoms, full return of motor strength, and resolution of urinary retention. The Gaines procedure has been performed successfully in patients without previous fusions at the level of spondylolisthesis or spondyloptosis. Patients for whom the traditional posterior fusion fails still may be candidates for this procedure, albeit at increased risk of neurologic injury.


Ocular examination findings and selected ophthalmic diagnostic tests in African green monkeys (Chlorocebus aethiops sabaeus).
To document ocular lesions and establish ophthalmic diagnostic test reference values in a colony of African green monkeys (Chlorocebus aethiops sabaeus). Fifty one geriatric (GAGM, 19-30 years old), 10 adult (AAGM, 5-9 years old) and 10 juvenile (JAGM, <2 years old) African green monkeys housed in a single Caribbean research colony. Ocular biomicroscopy, indirect fundoscopy, Schirmer tear test (STT), rebound tonometry (TonoVet®) and corneal fluorescein staining were performed. Mixed ANCOVA tests were performed to compare STT and IOP between groups. Common ocular lesions in GAGM included vitreal degeneration (27/51, 51/102 eyes) and cataracts (21/51, 32/102 eyes). Vitreal degeneration was also common in AAGM (8/10, 16/20 eyes) and infrequent in JAGM (3/10, 6/20 eyes). Cataracts were not present in any JAGM or AAGM. All eyes in all three groups had perilimbal corneal pigmentation and faint lace-like anterior corneal stromal opacification. Median (range) STT values were 16.0 (18) mm/min in GAGM. Mean (SD) STT values were 14.2 (4.6) mm/min in AAGM, and 8.9 (3.4) mm/min in JAGM. Median (range) IOP values were 16.5 (27) mmHg in GAGM. Mean (SD) IOP values were 18.0 (2.8) mmHg in AAGM, and 14.1 (2.2) mmHg in JAGM. JAGM had significantly lower STT and IOP values compared to AAGM (p = .0449, .0057, respectively) and GAGM (p = .0002, .0130, respectively). Spontaneous ocular lesions were common in geriatric monkeys in this research colony. IOP and STT values were lower in juvenile African green monkeys relative to adult or geriatric animals.


Sequence determination of phosphorothioated oligonucleotides using MALDI-TOF mass spectrometry for controlling gene doping in equestrian sports.
In human and equestrian sporting events, one method of gene doping is the illegal use of therapeutic oligonucleotides to alter gene expression. In this study, we aimed to identify therapeutic oligonucleotides via sequencing using matrix-assisted laser desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF MS). As a model of therapeutic oligonucleotides, 22 bp-long phosphorothioated oligonucleotides (PSOs) were used. By using a Clarity OTX kit for extracting short-length oligonucleotides, a spectrum of singly charged PSO with a mean intensity of 6.08 × 104 (standard deviation: 4.34 × 103 ) was detected from 500 pmol PSO in 1 ml horse plasma using the linear negative mode of MALDI-TOF MS. In addition, a 17 bp sequence was determined using in-source decay (ISD) mode, indicating that 500 pmol of a PSO in 1 ml plasma is the detection limit for sequencing. Using the determined sequences (17 bp), a targeted gene for PSO was singly identified on the horse reference genome, EquCab2.0, via a GGGenome search. These procedures can be potentially used to identify therapeutic oligonucleotides, whose nucleotides are unknown, for gene doping control.


Binasal Visual Field Defects Due to Sickle Cell Maculopathy.
A 26-year-old African American man with sickle cell disease noticed blurry vision in both eyes after a recent complicated hospital admission for sickle cell crisis. Anterior and posterior segment examination of each eye was normal, but visual field testing revealed binasal scotomas. Optical coherence tomography of the macula demonstrated severe thinning of the temporal inner retina, suggesting previous bilateral occlusions of terminal retinal arterioles involving the temporal macula, an uncommon complication of sickle cell disease. This case is a reminder that retinal pathology should always be considered as a potential cause of unexplained visual field defects and highlights the role of macular OCT in evaluation of these patients.


Rehabilitation outcome of post-acute lower limb geriatric amputees.
To characterize the lower-limb elderly amputee patients admitted to a post-acute rehabilitation program, assess their 1-year survival rate, estimate rate of prosthetic fit and report rate and factors associated with 1-year post-discharge prosthetic use. A cohort study performed in a post-acute rehabilitation department. Patients were evaluated by the Functional Independence Measure (FIM), motor FIM (mFIM), rate of prosthesis fit, length of stay (LOS), 1-year survival rate and long-term prosthetic use. One-hundred and seventeen lower limb elderly amputee patients consecutively admitted from January 2004 to June 2010 were enrolled in the study. Mean age was 74.7 ± 8.1; 56 patients (47.9%) had transtibial amputation (TTA); 46 (39.3%) transfemoral amputation (TFA) and 15 (12.8%) bilateral amputation. The main cause for amputation was diabetic foot (60.7%). Fifty-four (46.2%) patients died during first year post-admission. Twenty-seven patients (23.1%) were fitted with a prosthesis. When the bilateral amputees were considered separately, the rate of prosthetic fit among unilateral amputees was 24.5% (25/102) whereas among bilateral amputees it was 20% (3/15). Patients with prosthesis rehabilitation had a higher rate of TTA (p = 0.027), better metabolic status (p < 0.001), higher functional and cognitive levels (p < 0.001), and longer LOS (p < 0.001) compared with patients who received wheelchair rehabilitation. Twenty patients were contacted 1 year later: eight (40.0%) reported continuous functional prosthesis use, eight - partial prosthesis use and four (20%) did not use the prosthesis at all. The patient group with 1-year post-discharge prosthesis use had a significantly higher rate of TTA (p = 0.032), lower rate of congestive heart failure (CHF) (p = 0.014) and higher score changes on the FIM and mFIM (p = 0.043). Rehabilitation efforts should best be targeted depending on need. Rehabilitation professionals should make an educated estimate of outcomes at the beginning of rehabilitation based on the characteristics of the patients (level of amputation and functional level on admission).


[The effect of Hongjingtian (Gadol) injection on cardiac hemodynamics and myocardial oxygen consumption of dogs].
To study the effect of Hongjingtian (Gadol) injection on cardiac hemodynamics and myocardial oxygen consumption for analyzing its underlying mechanism in the treatment of coronary heart disease. A total of 20 dogs anesthetized with pentobarbital sodium (30 mg x kg(-1), i.v.) were evenly randomized into control group, low-dose Gadol (LDG) group, high-dose Gadol (HDG) group and Herbesser Injection group. The blood flow volume (BFV) of the left coronary artery and cardiac output (CO), left ventricular pressure (LVP), maximum ascending rate (dp/dtmax) of LVP, mean arterial pressure (MAP) of the femoral artery, oxygen contents of the coronary artery and coronary vein (venous sinus), oxygen consumption index (OCI), cardiac index (CI), coronary artery resistance (CAR) and total peripheral resistance (TPR) as well as oxygen utilization rate (OUR) were detected respectively. After venous injection of Gadol, CAR, MAP, TPR, OCI, myocardial oxygen consumption and heart rate lowered significantly (P < 0.05-0.01), while BFV and blood oxygen content of the venous sinus increased considerably (P < 0.05-0.01) in comparison with pre-injection. No significant differences were found in LVP and myocardial contractivity between control group and LDG, and between control and HDG groups respectively. It showed dilation of the coronary artery and reduction of the cardiac afterload after injection of Gadol. Besides, CO and stroke volume increased considerably and the cardiac effective work was raised without any significant simultaneous increase of both myocardial contractility and LVP. A decrease in the myocardial oxygen consumption and reduction of OCI indicates an improvement of the oxygen supply of the myocardium, and a favorable regulation of the compliance of the cardiac vessels. As a result, the cardiovascular performance was ameliorated. The abovementioned improvement of these indexes may contribute to the therapeutic effect of Gadol in the treatment of coronary heart disease in clinic.


Time course study of blood pressure in term and preterm infants immediately after birth.
To describe temporal changes in systolic, diastolic, and mean blood pressure (SBP, DBP, and MBP, respectively) in term and preterm infants immediately after birth. Prospective observational two-center study. In term infants SBP, DBP, and MBP were assessed non-invasively every minute for the first 15 minutes, and in preterm infants every minute for the first 15 minutes, as well as at 20, 25, 30, 45, and 60 minutes after birth. Regression analyses were performed by gender and respiratory support in all neonates; and by mode of delivery, cord clamping time, and development of ultrasound-detected brain injury in preterm neonates. Term infants (n = 54) had a mean (SD) birth weight of 3298 (442) g and gestational age of 38 (1) weeks, and preterm infants (n = 94) weighed 1340 (672) g and were 30 (3) weeks gestation. Term infants' SBP, DBP and MBP within the first 15 minutes after birth were independent of gender or respiratory support. Linear mixed regression analysis showed that preterm infants, who were female, born vaginally, had delayed cord clamping and did not require positive pressure ventilation nor develop periventricular injury or ventriculomegaly, had significantly higher SBP, DBP, and MBP at some measurement points within the first hour after birth. We present novel reference ranges of BP immediately after birth in a cohort of term and preterm neonates. They may aid in optimization of cardiovascular support during early transition at all gestations.


Intralesional amphotericin B in a cat with cutaneous protothecosis.
A domestic cat was presented with nodular lesions on the nose/muzzle and pinnae. Protothecosis was diagnosed through cytological and histopathological examination, and culture. Molecular identification confirmed Prototheca wickerhamii infection. Intralesional application of amphotericin B in conjunction with oral terbinafine resulted in a significant reduction of the nasal lesion and complete resolution of the pinnal lesion, without adverse effects.


Altered Expression of Three EGFR Posttranslational Regulators MDGI, MIG6, and EIG121 in Invasive Breast Carcinomas.
Epidermal growth factor receptor (EGFR) signalling is a highly regulated process with a tight balance between receptor activation and inactivation in invasive breast carcinomas (IBCs) particularly in triple-negative carcinomas (TNC). Clinical trials using anti-EGFR therapies are actually performed although no activating alterations (mutations, amplifications, or rearrangements) of EGFR have been clearly recognized in order to identify new targeted modalities for IBCs. We explored mammary-derived growth inhibitor (MDGI), estrogen-induced gene-121 (EIG121), and mitogen-induced gene-6 (MIG6), three posttranslational EGFR trafficking molecules implicated in EGFR spatiotemporal regulatory pathway. We quantified MDGI, EIG121, and MIG6 at mRNA levels by using real-time quantitative RT-PCR in a series of 440 IBCs and at protein levels by using immunohistochemistry in a series of 88 IBCs. Results obtained by RT-PCR showed that in IBCs, MDGI, MIG6, and EIG121 mRNA were mainly underexpressed (25.7%, 45.0%, and 16.1%, respectively) particularly in the TNC subtype for EIG121 (60.3%). We also observed mRNA overexpression of MDGI and EIG121, respectively, in 12.7% and 22.3% of IBCs. These altered mRNA expressions were confirmed at the protein level. Some links were found between expression patterns of these three genes and several classical pathological and clinical parameters. Only EIG121 was found to have a prognostic significance (p = 0.0038). Altered expression of these three major EGFR posttranslational negative regulators could create an aberrant EGFR-mediated oncogenic signalling pathway in IBCs. MDGI, MIG6, and EIG121 expression status also may be potential useful biomarkers (sensitivity or resistance) in targeted EGFR therapy.


Retrieval of crystallographically-derived molecular geometry information.
The crystallographically determined bond length, valence angle, and torsion angle information in the Cambridge Structural Database (CSD) has many uses. However, accessing it by means of conventional substructure searching requires nontrivial user intervention. In consequence, these valuable data have been underutilized and have not been directly accessible to client applications. The situation has been remedied by development of a new program (Mogul) for automated retrieval of molecular geometry data from the CSD. The program uses a system of keys to encode the chemical environments of fragments (bonds, valence angles, and acyclic torsions) from CSD structures. Fragments with identical keys are deemed to be chemically identical and are grouped together, and the distribution of the appropriate geometrical parameter (bond length, valence angle, or torsion angle) is computed and stored. Use of a search tree indexed on key values, together with a novel similarity calculation, then enables the distribution matching any given query fragment (or the distributions most closely matching, if an adequate exact match is unavailable) to be found easily and with no user intervention. Validation experiments indicate that, with rare exceptions, search results afford precise and unbiased estimates of molecular geometrical preferences. Such estimates may be used, for example, to validate the geometries of libraries of modeled molecules or of newly determined crystal structures or to assist structure solution from low-resolution (e.g. powder diffraction) X-ray data.


Creating and testing carbon interfaces - integrating oligomeric phthalocyanines onto single walled carbon nanotubes.
Two oligomers, that is, para-phenylenevinylene with either pendant Pd(ii)Pc or Zn(ii)Pc units, have been synthesized and their interactions with SWCNTs and peapods - C60@SWCNT - have been probed by complementary spectroscopy and microscopy. Spectroscopy assisted mainly in shedding light onto electronic interactions in the ground and excited state, while microscopy enabled insights into the degree of individualizing SWCNTs/C60@SWCNTs and their stabilization.


Teaching and Learning Pharmacy Services: A Teaching Method for Developing Competencies for Patient-Centered Care Through Experiential Learning in a Real Workplace.
Considering the transformation process that has been occurring in pharmacy education and the urgent need to address social health needs, proposals of teaching methods for the development of competences and skills in patient-centered care have become an issue worth discussing. The study describes and discusses the method that has been used for developing of these competencies through experiential learning in a university pharmacy in Brazil. The Teaching and Learning of Pharmacy Services (TLPS) method encompasses 2 components: theoretical-reflexive one (developing protocols covering the patient care process) and practical-reflexive one (using the protocols with real patients). TLPS connects the 2 components in a way to enable students to acquire and apply theoretical knowledge for a comprehensive assessment of the patients' needs and understand how clinical reasoning and decision-making take place. The assessment process is performed, by the supervisor, which evaluates the behaviors necessary for good professional performance. The active learning methodologies have been effectively used in the classroom as a way to stimulate critical thinking, problem-solving, and clinical reasoning. However, experiential learning is considered a central point in the learning process and essential for knowledge building. Thus, the method herein described is shown as an innovative tool to promote self-learning, consolidation and interrelation of the acquired knowledge, easier identification of patients' needs, normalization of behaviors, and improvement in the quality of care.


Streptozotocin Induces Mild Cognitive Impairment at Appropriate Doses in Mice as Determined by Long-Term Potentiation and the Morris Water Maze.
Alzheimer's disease (AD) is a progressive neurodegenerative disease, and effective therapeutic drugs in the clinic are still lacking. Ideally, AD progression could be stopped at an early stage, such as at the mild cognitive impairment (MCI) stage. MCI refers to the clinical condition between normal aging and dementia. Patients with MCI experience memory loss but do not meet the criteria for the diagnosis of clinically probable AD. However, few MCI animal models have been established. Here, we used in vivo long-term potentiation (LTP) recording and the Morris water maze (MWM) to evaluate the effects of intracerebroventricular injection of streptozotocin (ICV-STZ) in mice. We found a relationship between cognitive behavior and LTP in vivo and determined the appropriate doses of STZ for a putative MCI animal model. Animals that received≥150μg of STZ exhibited cognitive impairment in the MWM test, and few changes in behavior tests were observed in animals receiving less than 150μg of STZ. In vivo LTP recordings revealed that the induction of LTP decreased significantly in STZ-treated animals, even at the lowest dose (25μg/mouse), in a dose-dependent manner. Pathology analysis revealed STZ-induced neuron loss in a dose-dependent manner, both in the cortex and in the hippocampus, as evidenced by a significantly decreased neuronal number in the cohort treated with 75μg of STZ/mouse. Our study indicated that a low dose (25μg/mouse) of STZ impaired neural plasticity; at a higher dose of 75μg/mouse STZ, further LTP deficits were noted along with induced neuronal loss in both the cortex and the hippocampus, which could be considered a possible MCI or pre-MCI animal model; and finally, at 150μg/mouse STZ, dementia was induced, feasibly indicating a state of AD.


Chaotic flow and efficient mixing in a microchannel with a polymer solution.
Microscopic flows are almost universally linear, laminar, and stationary because the Reynolds number, Re, is usually very small. That impedes mixing in microfluidic devices, which sometimes limits their performance. Here, we show that truly chaotic flow can be generated in a smooth microchannel of a uniform width at arbitrarily low Re, if a small amount of flexible polymers is added to the working liquid. The chaotic flow regime is characterized by randomly fluctuating three-dimensional velocity field and significant growth of the flow resistance. Although the size of the polymer molecules extended in the flow may become comparable to the microchannel width, the flow behavior is fully compatible with that in a macroscopic channel in the regime of elastic turbulence. The chaotic flow leads to quite efficient mixing, which is almost diffusion independent. For macromolecules, mixing time in this microscopic flow can be three to four orders of magnitude shorter than due to molecular diffusion.


Phosphorylation of Ser-80 of VP1 and Ser-254 of VP2 is essential for human BK virus propagation in tissue culture.
BK virus (BKV) infection may cause polyomavirus-associated nephropathy in patients with renal transplantation. Recently, the phosphorylated amino acids on the structural proteins VP1, VP2 and VP3 of BKV have been identified by liquid chromatography-tandem mass spectrometry in our laboratory. In this study, we further analysed the biological effects of these phosphorylation events. Phosphorylation of the BKV structural proteins was demonstrated by [(32)P]orthophosphate labelling in vivo. Site-directed mutagenesis was performed to replace all of the phosphorylated amino acids. The mutated BKV genomes were transfected into Vero cells for propagation analysis. The results showed that expression of the early protein LT and of the late protein VP1 by the mutants VP1-S80A, VP1-S80-133A, VP1-S80-327A, VP1-S80-133-327A and VP2-S254A was abolished. However, propagation of other mutants was similar to that of wild-type BKV. The results suggest that phosphorylation of Ser-80 of VP1 and Ser-254 of VP2 is crucial for BKV propagation.


Induction of abnormal respiratory sounds by capsaicin in rats previously infected with Bordetella pertussis.
Sprague Dawley rats, previously infected with Phase-I Bordetella pertussis, developed more severe abnormal respiratory sounds than normal animals, but not coughing, when exposed to aerosolized capsaicin, one of several cough-inducing agents tested. Stethoscope examination suggested that greater production of pulmonary mucus might be occurring after capsaicin challenge of the infected animals, compared to the uninfected controls. Rats of three other strains gave characteristically different responses from the Sprague Dawleys. The administration of capsaicin to B. pertussis-infected rats may provide useful insights into the pathophysiology of excess mucus secretion in human pertussis.


Pregnancy and malignant catatonia.
The occurrence of malignant catatonia in pregnancy is a psychiatric emergency. In this article, we present the case of a pregnant woman with a first psychotic episode with catatonic features, autonomic abnormalities and elevated creatinine phosphokinase levels in the context of a severe adverse reaction to antipsychotic pharmacotherapy who had good responses to electroconvulsive therapy and lorazepam.


Altered platelet phosphatidylinositol metabolism in essential hypertension.
The metabolism of phosphoinositides was investigated in platelet membranes from nine patients with essential hypertension (EHT) and from 10 age/sex-matched normotensive subjects. 32P-labelling or phosphatidic acid (PA), phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP) and phosphatidylinositol-4,5-bisphosphate (PIP2) was measured in lipid extracts prepared from resting 32P-prelabelled platelets. There were no differences in 32P-PA between subject groups. In platelets of hypertensive patients, 32P-incorporation into both PIP and PIP2 was greater (P at least less than 0.01). This increase apparently occurred at the expense of lower 32P-incorporation into PI (P less than 0.001). An alteration in the interconversion equilibrium between phosphoinositides which is directed towards polyphosphoinositide formation may lead to altered membrane ionic fluxes.


Balance of power in host-virus arms races.
The sensing of viral RNA by the host innate immune system is mediated by RIG-I and its partner PACT. In this issue of Cell Host & Microbe, Luthra et al. (2013) show that the Ebola virus VP35 protein counteracts the action of PACT at the cost of compromising its own function in viral replication.


Gastric sarcoidosis presenting with haematemesis.
Sarcoidosis is a very rare disease in Singapore. Sarcoid granuloma involving the stomach alone is even more rare, and only about 21 cases have been reported in the literature up to 1953 (Scott et alii, 1953). In a review of the literature, Wadina and Melamed (1966) found 34 cases of granulomatous involvement of the stomach, all purporting to be sarcoidosis. However, on closer examination of the evidence, many of these 34 cases of so-called sarcoidosis of the stomach were subject to doubt. Bleeding from gastric sarcoidosis is also rare, and only about eight cases have been reported in the literature up to 1970. The present report presents a further example of this rare cause of upper gastrointestinal bleeding and attempts to review the significance of sarcoid granulomas in the stomach.