Regular budding modes in a zooxanthellate dendrophylliid Turbinaria peltata (Scleractinia) revealed by X-ray CT imaging and three-dimensional reconstruction.
The zooxanthellate dendrophylliid coral, Turbinaria peltata (Scleractinia), exhibit various growth forms that increase the photoreception area through the development of coenosteum skeletons. Because it is difficult to make detailed observations of the internal structures, we visualized inner skeletal structures using nondestructive microfocus X-ray computed tomography (CT) imaging. After removal of the coenosteum skeletons from the X-ray CT images, three-dimensional 3D-models were reconstructed for individual corallites. Regular budding was observed from the 3D-model and cross-sectional images as follows: 1) lateral corallites occurred only near the two primary septa on one side, apart from a directive primary septum with distinct polarity; 2) the budding occurred upward at acute angles; and 3) these regular structures and polarity were repeated throughout growth with every generation. Even in zooxanthellate dendrophylliids, the same budding modes as observed in azooxanthellate equivalents control the colonial growth. These characteristics provide clues for understanding the mechanisms that regulate the shapes of modular marine organisms.


Gender Related Survival Differences in ST-Elevation Myocardial Infarction Patients Treated with Primary PCI.
Data about gender as an independent risk factor for death in ST-elevation myocardial infarction (STEMI) patients is still contrasting. Aim was to assess how gender influences in-hospital and long-term all-cause mortality in STEMI patients with primary percutaneous coronary intervention (PCI) in our region. We analysed data from 2069 STEMI patients undergoing primary PCI in our institution from January 2009-December 2014, of whom 28.9% were women. In-hospital and long-term mortality were observed in women and men. The effect of gender on in-hospital mortality was assessed by binary logistic regression modelling and by Cox regression analysis for long-term mortality. Women were older (68.3±61.8 vs 61.8±12.0 years; p<0.0001), with a higher prevalence of diabetes (13.7% vs 9.9%; p=0.013) and tend to be more frequently admitted in cardiogenic shock (8.4% vs 6.3%; p =0.085). They were less frequently treated with bivalirudin (15.9% vs 20.3%; p=0.022). In-hospital mortality was higher among women (14.2% vs 7.8%; p<0.0001). After adjustment, age (adjusted OR: 1.05; 95% CI: 1.03 to 1.08; p < 0.001) and cardiogenic shock at admission (adjusted OR: 24.56; 95% CI: 11.98 to 50.35; p < 0.001), but not sex (adjusted OR: 1.47; 95% CI: 0.80 to 2.71) were identified as prognostic factors of in-hospital mortality. During the median follow-up of 27 months (25th, 75th percentile: 9, 48) the mortality rate (23.6% vs 15.1%; p<0.0001) was significantly higher in women. The multivariate adjusted Cox regression model identified age (HR 1.05; 95% CI 1.04-1.07; p<0.0001), cardiogenic shock at admission (HR 6.09; 95% CI 3.78-9.81; p<0.0001), hypertension (HR 1.49; 95% CI 1.02-2.18; p<0.046), but not sex (HR 1.04; 95% CI 0.74-1.47) as independent prognostic factors of follow-up mortality. Older age and worse clinical presentation rather than gender may explain the higher mortality rate in women with STEMI undergoing primary PCI.


Iliac vein compression syndrome: an unusual cause of varicocele.
Iliac vein compression syndrome is the phenomenon of nonthrombotic iliac vein obstruction caused by compression of left iliac vein between the right iliac artery and fifth lumbar vertebra. Affected patients usually present with unilateral leg edema. The condition is most often seen in women, in whom it may also be a cause of vulvar varicosities. Presented here is a case of idiopathic iliac vein obstruction associated with an ipsilateral varicocele in a young man. This varicocele was caused by multiple collateral venous channels and was resistant to surgical high ligation. This case illustrates an unusual cause of varicocele formation and an anatomic reason for failure of standard surgical therapy.


The parathyroid glands in the skeletal development of the ovine foetus.
The ionized plasma calcium concentration in foetal lambs during the last third of gestation is greater than that in the ewe. Since foetal plasma immunoreactive parathyroid hormone is less than that in the ewe the role of the foetal parathyroid glands is not clear. The effects of foetal parathyroidectomy (PTX) on the foetal:maternal gradient and on skeletal development are examined. The histomorphometry and ash content of six PTX lambs was compared with that of 11 intact animals. A reversal of the plasma ionized calcium gradient took place within 3 days without significant change in the foetal plasma inorganic phosphate or 1,25-dihydroxycholecalciferol content. Skeletal changes consistent with rickets were observed and increased in severity with the time after PTX. It is concluded that the foetal parathyroid glands play an important role in placental calcium transfer and skeletal calcification. However, the agent may be a hypercalcaemic substance other than parathyroid hormone.


Impact of pulmonary vein anatomy and left atrial size on postoperative atrial fibrillation after esophagectomy for esophageal cancer.
This study aimed to investigate the relationship between postoperative atrial fibrillation (POAF) after esophagectomy and pre-existing cardiac substrate. We retrospectively analyzed 212 consecutive patients from between July 2010 and December 2022 who were scheduled to undergo esophagectomy for esophageal cancer without previous history of atrial fibrillation. All the patients underwent both echocardiography and contrast-enhanced multi-detector computed tomography (MDCT). POAF occurred in 49 patients (23.1%). Multivariable logistic analysis demonstrated that independent predictors for POAF were age [OR; 1.06 (1.01-1.10), P < 0.01), three-field lymph node dissection [OR; 2.55 (1.25-5.23), P < 0.01), left atrial dilatation (> 35 mm) assessment by echocardiography [OR; 3.05 (1.49-6.25), P < 0.01) and common left pulmonary vein [OR; 3.03 (1.44-6.39), P < 0.01). The correlation coefficient was high for left atrial dimensions assessed by echocardiography and MDCT (r = 0.91, P < 0.01). Combination of left atrial dilatation by echocardiography and common left pulmonary vein had high odds ratio [OR; 8.10 (2.62-25.96), P < 0.01). Instead of echocardiographic assessment, combination of left atrial enlargement (> 35 mm) assessed by MDCT and common left pulmonary vein also showed high odds ratio for POAF [OR; 11.23 [2.19-57.63], P < 0.01). Incidence of POAF after esophagectomy was related to both left atrial enlargement and common left pulmonary vein assessed by preoperative MDCT. Additional analysis of atrial size and pulmonary vein variation would facilitate preoperative assessment of the risk of POAF, but future studies must ascertain therapeutic strategy.


Simulation of lipid-lowering therapy (LLT) intensification in very high-risk patients with atherosclerotic cardiovascular disease.
We aim to estimate the number and proportion of very-high risk patients with atherosclerotic cardiovascular disease (ASCVD) who would be able to achieve low-density lipoprotein cholesterol (LDL-C) <70 mg/dL with various lipid-lowering therapies (LLTs), including statins, ezetimibe, bempedoic acid, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, and evinacumab, using a Monte Carlo simulation model described previously. With current treatment options for LDL-C lowering, including statin, ezetimibe, bempedoic acid, and PCSK9 inhibitors, it was estimated that most very-high risk patients with ASCVD (99.1%) were able to achieve the LDL-C goal of <70 mg/dL. Nevertheless, approximately 88,715 patients in the USA were estimated to not be able to achieve the LDL-C goal after current available LLTs, thus remaining at elevated risk for recurrent cardiovascular events. Evinacumab may be useful to address such unmet needs effectively, as the majority of those not at goal after PCSK9 inhibitors could achieve the goal of <70 mg/dL after taking evinacumab.


A modular framework for the automatic classification of chromosomes in Q-band images.
The manual analysis of the karyogram is a complex and time-consuming operation, as it requires meticulous attention to details and well-trained personnel. Routine Q-band laboratory images show chromosomes that are randomly rotated, blurred or corrupted by overlapping and dye stains. We address here the problem of robust automatic classification, which is still an open issue. The proposed method starts with an improved estimation of the chromosome medial axis, along which an established set of features is then extracted. The following novel polarization stage estimates the chromosome orientation and makes this feature set independent on the reading direction along the axis. Feature rescaling and normalizing techniques take full advantage of the results of the polarization step, reducing the intra-class and increasing the inter-class variances. After a standard neural network based classification, a novel class reassignment algorithm is employed to maximize the probability of correct classification, by exploiting the constrained composition of the human karyotype. An average 94% of correct classification was achieved by the proposed method on 5474 chromosomes, whose images were acquired during laboratory routine and comprise karyotypes belonging to slightly different prometaphase stages. In order to provide the scientific community with a public dataset, all the data we used are publicly available for download.


Changes in the treatment outcome of node-positive breast cancer stratified by menopausal status: comparison of patients treated in 1965-75 versus those treated in 1976-86.
The objective of this study was to examine whether and to what extent the outcome of treatment for lymph-node positive breast cancer patients improved between the periods 1965-75 and 1976-86. The subjects were 1595 patients with breast cancer positive for lymph node metastasis who were treated at the National Cancer Center Hospital between 1965 and 1986. In order to analyze background factors and treatment outcome, we classified the patients into four groups stratified by the time of initial surgery (1965-75/1976-86) and menopausal status (premenopause/postmenopause). With respect to the clinicopathological background factors, significant changes between the periods 1965-75 and 1976-86 were more frequent use of modified radical mastectomy and postoperative adjuvant chemoendocrine therapy and less frequent use of postoperative radiotherapy in both pre- and postmenopausal patients. The 10-year disease-free and overall survival rates improved by approximately 15-20% between 1965-75 and 1976-86 in this group of patients, regardless of menopausal status. The patients with node-positive disease treated at our hospital showed an increase in both disease-free and overall survival from 1965 to 1986.


Novel carbohydrate blend enhances chemical and sensory properties of lobster (Homarus americanus) after one-year frozen storage.
It has previously been shown that a novel blend of carbohydrates could preserve lobster meat after 6 months of frozen storage. Increased year-round demand for high-quality lobster may make selling to the frozen seafood market an unintended option for some fishermen. Yet, the chemical and sensory changes that occur in lobster meat after one-year frozen storage in this cryoprotectant blend is not known. The objective of this study was to determine the chemical and sensory characteristics of lobster frozen in five different solutions: solution-1 (water); solution-2 (water + NaCl + STPP, sodium tripolyphosphate, 0.5%); solution-3 (water + NaCl + carbohydrate blend); solution-4 (water + NaCl + STPP, 0.25% + carbohydrate blend), and solution-5 (water + NaCl + STPP, 0.5% + carbohydrate blend). No difference (P > 0.05) existed among the treatments with regard to Malondialdehyde levels as a measure of lipid oxidation. Lobster frozen in the cryoprotectant showed increased tenderness, compared to the control which was frozen in water. The lobster meat treated with a combination of the carbohydrate blend and STPP had lower (P < 0.05) moisture content than the control. In addition, consumers preferred (P < 0.05) lobster frozen in the novel cryoprotectant blend and STPP with respect to flavour, texture, and overall acceptability compared to the control. Penalty analysis revealed that overall liking scores were positively associated with the attributes moist and sweet. In conclusion, the combination of the novel carbohydrate blend and STPP enhanced the sensory quality and the chemical properties of frozen lobster, which in turn extended the shelf-life of these products. These findings may have wide implications for the long-term preservation of frozen lobster meat.


P-glycoprotein regulates Staphylococcus aureus enterotoxin B-stimulated interleukin-5 and thymic stromal lymphopoietin secretion in organotypic mucosal explants.
T-helper 2 (Th2) inflammation is a hallmark of chronic rhinosinusitis with nasal polyps (CRSwNP) although the pathogenesis is poorly understood. P-glycoprotein (permeability glycoprotein, P-gp) is an efflux pump that is capable of regulating cytokine transport and is expressed within sinonasal mucosa. The purpose of this study was to examine if the oversecretion of interleukin 5 (IL-5) and thymic stromal lymphopoietin (TSLP) in CRSwNP could be explained through P-gp-mediated secretory pathways. Fifteen ethmoid mucosal explants were harvested from patients with CRS (n = 10) and CRSwNP (n = 10) and stimulated with Staphylococcus aureus enterotoxin B (SEB). P-gp was inhibited using zosuquidar trihydrochloride (herein Zosuquidar). P-gp expression was measured using real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). IL-5, IL-8, and TSLP secretion were quantified using ELISA. P-gp protein was overexpressed in CRSwNP (28.32 ± 25.94 ng/mL per mg explant) as compared to CRS (10.74 ± 8.61; p = 0.01, 2-tailed Mann-Whitney U test). There was no difference in messenger RNA (mRNA) expression. SEB induced a significant increase in IL-5 and TSLP but not IL-8 secretion relative to control in the CRSwNP explants only. Subsequent P-gp inhibition significantly reduced IL-5 and TSLP secretion (p = 0.04 for both, 2-tailed Student t test) to control levels. The concentration of IL-5 and TSLP secretion were strongly and significantly correlated to the concentration of P-gp within the same explant (IL-5: r = 0.791, p = 0.001; TSLP: r = 0.687, p = 0.003; 2-tailed Spearman's rank-order correlation). P-gp protein is expressed at higher concentrations in CRSwNP as compared to CRS. This overexpression directly contributes to the relative hypersecretion of IL-5 and TSLP. These findings suggest a novel mechanism for Th2 skewing in CRSwNP.


Injectable microenvironment-responsive hydrogels with redox-activatable supramolecular prodrugs mediate ferroptosis-immunotherapy for postoperative tumor treatment.
Immunotherapy is an emerging antitumor modality with high specificity and persistence, but its application for resected tumor treatment is impeded by the low availability of tumor-specific antigens and strong immunosuppression in the wound margin. Here a nanoengineered hydrogel is developed for eliciting robust cooperative ferroptosis-immunotherapeutic effect on resected tumors. Specifically, β-cyclodextrin (β-CD) is first grafted onto oxidized sodium alginate (OSA) through Schiff base ligation, which could trap cRGD-modified redox-responsive Withaferin prodrugs (WA-cRGD) to obtain the hydrogel building blocks (Gel@WA-cRGD). Under Ca2+-mediated crosslinking, Gel@WA-cRGD rapidly forms physiologically stable hydrogels, of which the porous network is used to deliver programmed cell death ligand 1 antibodies (aPD-L1). After injection into the post-surgical wound cavity, the β-CD-entrapped WA-cRGD is detached by the local acidity and specifically internalized by residual tumor cells to trigger ferroptosis, thus releasing abundant damage-associated molecular patterns (DAMPs) and tumor-derived antigens for activating the antigen-presenting cell-mediated cross-presentation and downstream cytotoxic T cell (CTL)-mediated antitumor responses. Furthermore, aPD-L1 could block PD-1/PD-L1 interaction and enhance the effector function of CTLs to overcome tumor cell-mediated immunosuppression. This cooperative hydrogel-based antitumor strategy for ferroptosis-immunotherapy may serve as a generally-applicable approach for postoperative tumor management. STATEMENT OF SIGNIFICANCE: To overcome the immunosuppressive microenvironment in resected solid tumors for enhanced patient survival, here we report a nanoengineered hydrogel incorporated supramolecular redox-activatable Withaferin prodrug and PD-L1 antibody, which could elicit robust cooperative ferroptosis-immunotherapeutic effect against residual tumor cells in the surgical bed to prevent tumor relapse, thus offering a generally-applicable approach for postoperative tumor management.


High-level generation of polyclonal antibodies by genetic immunization.
Antibodies are important tools for investigating the proteome, but current methods for producing them have become a rate-limiting step. A primary obstacle in most methods for generating antibodies or antibody-like molecules is the requirement for at least microgram quantities of purified protein. We have developed a technology for producing antibodies using genetic immunization. Genetic immunization-based antibody production offers several advantages, including high throughput and high specificity. Moreover, antibodies produced from genetically immunized animals are more likely to recognize the native protein. Here we show that a genetic immunization-based system can be used to efficiently raise useful antibodies to a wide range of antigens. We accomplished this by linking the antigen gene to various elements that enhance antigenicity and by codelivering plasmids encoding genetic adjuvants. Our system, which was tested by immunizing mice with >130 antigens, has shown a final success rate of 84%.


Serious Gastrointestinal Complications After Cardiac Surgery and Associated Mortality.
Severe gastrointestinal (GI) complications (GICs) after cardiac surgery are associated with poor outcomes. Herein, we characterize the severe forms of GICs and associated risk factors of mortality. We retrospectively analyzed the clinically significant postoperative GICs after cardiac surgical procedures performed at our institution from January 2010 to April 2017. Multivariable analysis was used to identify predictors for in-hospital mortality. Of 29,909 cardiac surgical procedures, GICs occurred in 1037 patients (3.5% incidence), with overall in-hospital mortality of 14% compared with 1.6% in those without GICs. GICs were encountered in older patients with multiple comorbidities who underwent complex prolonged procedures. The most lethal GICs were mesenteric ischemia (n = 104), hepatopancreatobiliary (HPB) dysfunction (n = 139), and GI bleeding (n = 259), with mortality rates of 45%, 27%, and 17%, respectively. In the mesenteric ischemia subset, coronary artery disease (odds ratio [OR], 4.57; P = .002], coronary bypass grafting (OR, 6.50; P = .005), reoperation for bleeding/tamponade (OR, 12.07; P = .01), and vasopressin use (OR, 11.27; P < .001) were predictors of in-hospital mortality. In the HPB complications subset, hepatic complications occurred in 101 patients (73%), pancreatitis in 38 (27%), and biliary disease in 31 (22%). GI bleeding occurred in 20 patients (31%) with HPB dysfunction. In the GI bleeding subset, HPB disease (OR, 10.99; P < .001) and bivalirudin therapy (OR, 12.84; P = .01) were predictors for in-hospital mortality. Although relatively uncommon, severe forms of GICs are associated with high mortality. Early recognition and aggressive treatment are mandatory to improve outcomes.


A method for simultaneous recording of eight behavioral parameters related to monoamine neurotransmission.
In response to the increasing demand for refined techniques to record drug induced changes in motor activity we have designed and evaluated against observations an automatic test box that quantifies eight defined components of behaviour in rats. Activity, corresponding to the recordings from the commonly used photocell activity boxes. Total, and forward locomotion, expressing the actual distance the rat walks. Corner count, and corner time, reflecting the position of the animal in the box. Hole count, and hole time, expressing the reaction of the rat to an environmental stimulus i.e. holes in the bottom of the test box. Gnawing, which is a direct counting of the number of gnaws made by the animal. The recording parameters relate to our interest in behaviour influenced by monoamine neurotransmission and the result shows that the selected parameters are recorded with high reliability.


Assessing cohesion and diversity in the collaboration network of the SALURBAL project.
The SALURBAL (Urban Health in Latin America) Project is an interdisciplinary multinational network aimed at generating and disseminating actionable evidence on the drivers of health in cities of Latin America. We conducted a temporal multilayer network analysis where we measured cohesion over time using network structural properties and assessed diversity within and between different project activities according to participant attributes. Between 2017 and 2020 the SALURBAL network comprised 395 participants across 26 countries, 23 disciplines, and 181 institutions. While the cohesion of the SALURBAL network fluctuated over time, overall, an increase was observed from the first to the last time point of our analysis (clustering coefficient increased [0.83-0.91] and shortest path decreased [1.70-1.68]). SALURBAL also exhibited balanced overall diversity within project activities (0.5-0.6) by designing activities for different purposes such as capacity building, team-building, research, and dissemination. The network's growth was facilitated by the creation of new diverse collaborations across a range of activities over time, while maintaining the diversity of existing collaborations (0.69-0.75 between activity diversity depending on the attribute). The SALURBAL experience can serve as an example for multinational research projects aiming to build cohesive networks while leveraging heterogeneity in countries, disciplines, career stage, and across sectors.


Laparoscopic exploration for the clinically undetected hernia in infancy and childhood.
Routine contralateral groin exploration in infants and children with a clinically detected inguinal hernia is the subject of much debate. The detection of a patent processus vaginalis by transinguinal laparoscopy has proven advantageous. However, controversy remains regarding the true incidence of a contralateral patent processus vaginalis as well as which of these will actually develop into a clinically apparent hernia. From January 1997 through December 1999, 358 infants and children (aged 1 to 157 months, mean 32) were treated in the three University of Oklahoma teaching hospitals in Tulsa, Oklahoma, for inguinal hernia. The findings at laparoscopic exploration of the contralateral side were recorded to determine the incidence of contralateral patency as it relates to a child's age, gender, and side of the initial clinical diagnosis. The overall incidence of a patent processus vaginalis on contralateral examination was 33% (117 of 358). All patent processus vaginalis were repaired. Bilateral inguinal hernia was significantly more common in younger patients (present in 50% if less than 1 year, 45% if less than 2 years, 37% if less than 5 years, and 15% if greater than 5 years of age; P <0.05). In boys, the incidence was 49%, 45%, and 32% in those under 1 year of age, under 2 years of age, and in total, respectively. In girls, the incidence was 59%, 50%, and 37% in those under 1 year of age, under 2 years of age, and in total, respectively. The side of the clinically detected hernia did not influence the laparoscopic findings of a contralateral hernia with 30% (50 of 169) positive findings on left inguinal exploration versus 31% (28 of 90) positive findings on right inguinal exploration. The high incidence of a contralateral patent processus vaginalis warrants routine laparoscopic exploration in infants and children undergoing unilateral inguinal hernia repair, especially those less than 5 years of age. The use of transinguinal laparoscopic explorations avoids unnecessary open exploration in 66% of infants and children undergoing inguinal hernia repair.


Identification, structure elucidation, and synthesis of volatile compounds in the exhaust gas of food factories.
Our investigations deal with the identification and synthesis of volatile, odoriferous compounds contained in the exhaust gas of food factories and on the biodegradation of alkylpyrazines. Collection of odour emissions samples was performed with a gas sampler equipped with filter tubes containing the styrene-polymer SuperQ. After elution with solvents of different polarity, the extracts were analysed by GC/MS and chemical microreactions. Proposed structures were verified by comparison of analytical data with those of synthetic reference samples. Major components in the exhaust gas of a fat finishing factory were found to be aliphatic aldehydes, strongly dominated by hexanal. The identification of 1,2,3,3-tetramethylcyclohexene shows that for structural proof of target compounds the use of authentic reference samples is indispensable. In the exhaust gas from a chocolate factory, several carbonyl compounds and alkylated pyrazines could be identified. Biodegradation of the latter starts with hydrogenation at the nucleus.


In vivo click reaction between Tc-99m-labeled azadibenzocyclooctyne-MAMA and 2-nitroimidazole-azide for tumor hypoxia targeting.
The bioactivity of nitroimidazole in Tc-99m-labeled 2-nitroimidazole, a traditional solid tumor hypoxia-imaging agent for single photon emission computed tomography (SPECT), is reduced by the presence of large ligand and metallic radionuclide, exhibiting lower tumor-to-nontumor ratios. In an effort to solve this general problem, a pretargeting strategy based on click chemistry (strain-promoted cyclooctyne-azide cycloaddition) was applied. The functional click synthons were synthesized as pretargeting components: an azide group linked to 2-nitroimidazole (2NIM-Az) serves for tumor hypoxia-targeting and azadibenzocyclooctyne conjugated with monoamine monoamide dithiol ligand (AM) functions as radiolabeling and binding group to azides in vivo. 2NIM-triazole-MAMA was obtained from in vitro click reaction with a reaction rate constant of 0.98M(-1)s(-1). AM and 2NIM-triazole-MAMA were radiolabeled with Tc-99m. The hypoxia-pretargeting biodistribution was studied in Kunming mice bearing S180 tumor; (99m)Tc-AM and (99m)Tc-triazole-2NIM were used as blank control and conventional control. Compared to the control groups, the pretargeting experiment exhibits the best radio-uptake and retention in tumor, with higher tumor-to-muscle and tumor-to-blood ratios (up to 8.55 and 1.44 at 8h post-(99m)Tc-complex-injection, respectively). To some extent, the pretargeting strategy protects the bioactivity of nitroimidazole and therefore provides an innovative approach for the development of tumor hypoxia-SPECT imaging agents.


Ancestry adjustment improves genome-wide estimates of regional intolerance.
Genomic regions subject to purifying selection are more likely to carry disease-causing mutations than regions not under selection. Cross species conservation is often used to identify such regions but with limited resolution to detect selection on short evolutionary timescales such as that occurring in only one species. In contrast, genetic intolerance looks for depletion of variation relative to expectation within a species, allowing species-specific features to be identified. When estimating the intolerance of noncoding sequence, methods strongly leverage variant frequency distributions. As the expected distributions depend on ancestry, if not properly controlled for, ancestral population source may obfuscate signals of selection. We demonstrate that properly incorporating ancestry in intolerance estimation greatly improved variant classification. We provide a genome-wide intolerance map that is conditional on ancestry and likely to be particularly valuable for variant prioritization.


[Clinical manifestations and diagnostic delay in Wolfram's syndrome].
Wolfram's syndrome (SW): diabetes mellitus (DM), diabetes insipidus (DI), blindness and deafness, is multiorganic, hereditary and uncommon. Mitochondrial dysfunction damages the oxidative pathway. To analyze the clinical characteristics, diagnostic delay in constituent diseases and early diagnostic impact over morbidity-mortality. Descriptive retrospective study of 23 Spanish patients with SW. Different clinical entities analysis, onset age, lapse of time before diagnosis, morbidity-mortality causes, prescribed therapy and consanguinity between parents. Components prevalence: DM and optic atrophy (AO), 100%; auditory impairment, 95.65%; DI, 82.6%; gonadal atrophy, 75% in men; menstrual disorders, 87.5% in women. Other diseases: urinary tract, neurologic and heart disorders. Most of the patients will develop almost all the complications. Juvenile DM in association with AO is its best diagnostic criteria. Early therapy should delay progression and control mortality causes.


Evaluation of variables in immunofluorescence procedures for the detection of antibodies against human herpesvirus 6 (HHV-6).
Ten human sera were used to study different parameters, namely, methods of smear preparation and fixation, and age of infected HSB-2 cells in order to optimize indirect immunofluorescence assay (IFA) and anticomplement immunofluorescence (ACIF) procedures to measure antibody levels against HHV-6. Results showed a greater sensitivity of rapid smear drying and methanol fixation over conventional acetone smear preparation. Cells harvested 6 days after infection and fixed with methanol exhibited a sharper and more intense fluorescence. IFA titers were higher than those obtained with ACIF, although the latter procedure enabled the distinction between three fluorescent sites. Reactivity pattern of individual sera against infected cells was variable and indicated that the human immune response to HHV-6 is directed against different antigens. An easier interpretation and a better definition of the fluorescence of HSB-2 cell line infected with HHV-6 strain Dv is obtained with the following conditions: cells should be harvested at 5-8 days after infection (at the giant cell stage of infection), cell smears have to be dried quickly before fixation with methanol at -20 degrees C, and finally, they should be stained by IFA.


Hypoglycemic drugs increase liver plasma membrane microviscosity in vitro.
The effect of hypoglycemic drugs chlorpropamide and phenformin has been tested on isolated liver plasma membranes as to their microviscosity parameters. Results reported suggest that both drugs are able to increase in vitro plasma membrane microviscosity in a dose-dependent way.


Hidden-loop colostomy.
Records of 15 patients having hidden-loop colostomies were reviewed. All patients had metastatic colonic cancers with impending obstructions. Six colostomies were subsequently opened because of obstructions due to cancer. All colostomy openings were done using local anesthesia in the emergency room. This technique prevented six major celiotomies and provided additional time of living without a stoma. There were two postoperative stomal prolapses, one of which necessitated reoperation. A hidden-loop colostomy is easily constructed and readily opened. It should be considered at celiotomy for selected patients who have metastatic colonic cancer with impending obstruction.


Proposal open for discussion: defining agreed diagnostic procedures in experimental diabetes research.
Animal experimentation has a long tradition in diabetes research and has provided invaluable benefits with regard to insulin discovery and treatment assessment. The review focuses on chemical-induced diabetes in rats and surveys the protocols of diabetes induction, diabetes diagnosis, and glucose tolerance evaluation in a selection of recent research. This brief review of techniques in experimental diabetes highlights that there is no uniformity, whereas standardisation of procedures is desirable so that comparability will exist among experiments carried out in different settings. On this basis, questions are put and standards are proposed. It would be a platform to promote the exchange of ideas through expert consultation about practical issues related to animal research and a basis on which standards can be set according to user requirements and animal respect.


Combined evaluation of preoperative FDG uptake on PET, ground-glass opacity area on CT, and serum CEA level: identification of both low and high risk of recurrence in patients with resected T1 lung adenocarcinoma.
Patients with the same pathological stage of lung adenocarcinoma display marked variability in postoperative recurrence. The aim of this study was to predict the postoperative prognosis in patients with small-sized pulmonary adenocarcinoma on the basis of FDG uptake on PET, the extent of ground-glass opacity (GGO) on CT, and serum carcinoembryonic antigen (CEA) levels. We evaluated 87 patients (40 men, 47 women; mean age 64 years, age range 42-84 years) with lung adenocarcinoma of 3.0 cm or smaller. The level of FDG uptake (low or high), the extent of GGO (GGO or solid), and serum CEA levels (<20 ng/ml or > or =20 ng/ml) were correlated with the pathological findings of cell dedifferentiation, aggressiveness, N factor, and the incidence of relapse. The patients were divided into the following four groups: those with the GGO pattern (group I, 13 patients), those with solid pattern and low FDG uptake (group II, 35 patients), those with solid pattern, high FDG uptake, and CEA <20 ng/ml (group III, 32 patients), and those with solid pattern, high FDG uptake, and CEA > or =20 ng/ml (group IV, 7 patients). The incidence of cell dedifferentiation, aggressiveness, and lymph node metastasis were significantly different among the groups (p<0.0001); . The 5-year disease-free survival rates were 100% in group I, 80.1% in group II, 43.7% in group III, and 16.7% in group IV (p<0.0001). Combined evaluation of preoperative FDG uptake, GGO, and serum CEA level may enable patients with T1 lung adenocarcinoma at low risk and at high risk of postoperative recurrence to be identified.


Subcellular localization shapes the fate of RNA polymerase III.
RNA polymerase III (Pol III) plays a vital role in transcription and as a viral-DNA sensor, but how it is assembled and distributed within cells remains poorly understood. Here, we show that Pol III is assembled with chaperones in the cytoplasm and forms transcription-dependent protein clusters upon transport into the nucleus. The largest subunit (RPC1) depletion through an auxin-inducible degron leads to rapid degradation and disassembly of Pol III complex in the nucleus and cytoplasm, respectively. This generates a pool of partially assembled Pol III intermediates, which can be rapidly mobilized into the nucleus upon the restoration of RPC1. Our study highlights the critical role of subcellular localization in determining Pol III's fate and provides insight into the dynamic regulation of nuclear Pol III levels and the origin of cytoplasmic Pol III complexes involved in mediating viral immunity.


Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on cirrhosis rats.
Clinical studies suggest that splenectomy improves liver function in cirrhotic patients, but the influence of splenectomy on stem cell transplantation is poorly understood. This study investigated the effect of splenectomy on stem cell infusion and elucidated its mechanism. Rat adipose tissue-derived mesenchymal stem cells were infused into cirrhosis rats with or without splenectomy, followed by the assessment of the in vivo distribution of stem cells and pathological changes. Stromal cell-derived factor-1 and hepatocyte growth factor expression were also investigated in splenectomized cirrhosis patients and rats. Splenectomy, prior to cell infusion, improved liver function and suppressed fibrosis progression more efficiently than cell infusion alone in the experimental cirrhosis model. Stromal cell-derived factor-1 and hepatocyte growth factor levels after splenectomy were increased in patients and rats. These upregulated cytokines significantly facilitated stem cell motility, migration and proliferation in vitro. C-X-C chemokine receptor type 4 neutralization weakened the promotion of cell migration by these cytokines. The infused cells integrated into liver fibrosis septa and participated in regeneration more efficiently in splenectomized rats. Direct coculture with stem cells led to inhibition of hepatic stellate cell proliferation. In addition, hepatocyte growth factor induced hepatic stellate cell apoptosis via the c-jun N-terminal kinase-p53 pathway. Splenectomy prior to cell infusion enhanced the therapeutic effect of stem cells on cirrhosis, which involved upregulation of stromal cell-derived factor-1 and hepatocyte growth factor after splenectomy.


Zinc . protoporphyrin is a selective inhibitor of heme oxygenase activity in the neonatal rat.
The present study was undertaken to examine the liver, spleen and kidney heme oxygenase activity in the rat, and also to investigate the response of the enzyme to a variety of metalloporphyrin complexes. The enzyme activity in the liver and the kidney of 3--4 day-old rats was several-fold greater than the corresponding values in the adult animals; however, the splenic enzyme activity was markedly depressed in comparison to that of adult rats. During the first 2--3 weeks post-parturation period, the activity of heme oxygenase in the spleen progressively increased, and in 4 weeks approached the adult values. The treatment of the newborn animals with the metalloporphyrin complex. Zn . protoporphyrin-IX, inhibited heme oxygenase activity in the spleen, liver and the kidney. Sn . protoporphyrin treatment also inhibited the activity of the enzyme in the liver and the spleen. The mechanism of the inhibition appeared to be competitive in nature. In contrast, the treatment of the newborn animals with Co . protoporphyrin increased the activity of the enzyme in the tested organs. The treatment of newborn animals with Fe . protoporphyrin (heme) also increased heme oxygenase activity in the spleen and the kidney. In addition, Co . and Fe . protoporphyrin complexes inhibited the activity of delta-aminolevulinate synthetase in the spleen; Sn . protoporphyrin and Zn . protoporphyrin, however, did not alter the activity of this enzyme. The effects of Co . protoporphyrin and Zn. protoporphyrin on the microsomal contents of cytochromes P-450, b5, the total heme, and the microsomal drug metabolism activity in the liver were compared. Zn . protoporphyrin was ineffective in altering the indicated cellular variables. According to these findings Zn . protoporphyrin may be useful as an experimental tool for the selective suppression of heme degradation activity.


Primary Central Nervous System Lymphoma Presenting as Isolated Multiple Cranial Neuropathies: An Extremely Rare Case.
Primary central nervous system lymphoma (PCNSL) is an uncommon malignancy of B-cell origin that typically involves the brain, eyes, and spinal cord without systemic spread. PCNSL typically involves the cerebral hemispheres, basal ganglia, or periventricular region. Isolated leptomeningeal PCNSL without any evidence of parenchymal involvement is very rare. We present a very unusual case of PCNSL presenting as persistent bilateral Bell's palsy and trigeminal neuralgia with magnetic resonance imaging (MRI) brain showing significantly hypertrophied enhancing bilateral facial and trigeminal nerves.


Tissue-specific expression of the human neuropeptide Y gene in transgenic mice.
Neuropeptide Y (NPY) is the most abundant neuropeptide detected in the mammalian brain, and is found throughout the central and peripheral nervous system. This peptide is a proposed regulator of appetite, blood pressure, and pituitary hormone release. Previous experiments have demonstrated the ability of 5' sequences within the human NPY gene to promote transcription in cultured neuronal cells. To identify sequences in this gene that regulate tissue-specific expression, a NPY/CAT fusion gene, containing approximately 850 bp of NPY sequences, was microinjected into fertilized mouse ova. Five lines of transgenic mice were derived from these ova and several tissues from mice of each line were tested for transgene expression using the CAT assay. One line demonstrated X-chromosome-linked transmission of the transgene while the other lines demonstrated autosomally-linked transmission. Three lines demonstrated transgene expression with significant levels of CAT activity detectable only in tissues which have been shown to express endogenous NPY. One autosomally-linked line did not demonstrate significant levels of transgene activity because the transgene appeared to have undergone structural alteration during genomic integration. No transgene activity was detected in either male of female mice from the X-linked line, suggesting a positional regulation of the transgene locus other than X-inactivation in this line. The present research demonstrated the NPY regulatory sequences included in pCATNPY delta 796 sufficiently directed tissue-appropriate gene expression in transgenic mice.


Density differences between water masses preclude laminar flow in two-current choice flumes.
Two-current choice flumes are used to measure preference and avoidance behaviour in response to chemical cues in aquatic animals. If used correctly, they produce two parallel, non-overlapping, laminar water currents in which the animal can move freely and choose between the two currents. As climate change is affecting water temperature, and altered precipitation patterns are changing water salinity, two-current choice flumes are increasingly being used to test the choice between water currents of different temperatures and salinities. This inevitably means that water currents of different densities are being used simultaneously in the flume. Here, we investigated the tolerance range for density differences due to temperature and salinity in five common flume designs. Through dye tests and stepwise modifications of temperatures and salinities we determined the limits for laminar and non-overlapping flows. We also developed an automated method for quantifying the overlap precisely and objectively. The tolerance for density differences between the water currents where laminar and non-overlapping flows were maintained was surprisingly low, withstanding ± 0.5 °C temperature differences, and ± 0.1 PSU salinity differences, i.e. a maximum density difference of 0.28 gL-1. Above these very narrow limits we found a range where the flumes showed partly overlapping, stratified water currents that preclude easy determination of cue preference. We conclude that two-current choice flumes are not suitable for testing the behavioural choices of aquatic animals using water currents of anything other than minor differences in temperature and/or salinity.


Effects of intranasal cocaine on human learning, performance and physiology.
The behavioral and physiological effects of intranasally administered cocaine (placebo, 48, 96 mg/70 kg) were examined in eight recreational cocaine users under controlled laboratory conditions. The 48 and 96 mg doses of cocaine significantly improved subjects' performance on the Digit Symbol Substitution Test above levels observed either prior to drug administration or when placebo was administered. These effects were discernible for up to 120 min after cocaine administration. Cocaine had no statistically significant effects on learning and performance of ten-response sequences. The 48 and 96 mg doses increased heart rate and blood pressure for up to 180 min, and increased subject ratings of drug effects and decreased skin temperature for 60-90 min after drug administration. Cocaine produced no significant effects on the electrocardiogram. To our knowledge, this is the first experimental demonstration that acutely administered cocaine can improve behavioral performance in rested subjects. In addition, the duration of cardiac effects in this study was longer than previously reported with intranasal cocaine, perhaps due to the concurrent behavioral testing.


Covalent protein binding and tissue distribution of houttuynin in rats after intravenous administration of sodium houttuyfonate.
To investigate the potential of houttuynin to covalently bind to proteins in vitro and in vivo and to identify the adduct structures. Male Sprague-Dawley rats were intravenously injected with sodium houttuyfonate (10 mg/kg). The concentrations of houttuynin in blood, plasma and five tissues tested were determined using an LC/MS/MS method. The covalent binding values of houttuynin with hemoglobin, plasma and tissue proteins were measured in rats after intravenous injection of [1-(14)C]sodium houttuyfonate (10 mg/kg, 150 mCi/kg). Human serum albumin was used as model protein to identify the modification site(s) and structure(s) through enzymatic digestion and LC/MS(n) analysis. The drug was widely distributed 10 min after intravenous injection. The lungs were the preferred site for disposition, followed by the heart and kidneys with significantly higher concentrations than that in the plasma. The extent of covalent binding was correlated with the respective concentrations in the tissues, ranging from 1137 nmol/g protein in lung to 266 nmol/g protein in liver. Houttuynin reacted primarily with arginine residues in human serum albumin to form a pyrimidine adduct at 1:1 molar ratio. The same adduct was detected in rat lungs digested by pronase E. This study showed that the β-keto aldehyde moiety in houttuynin is strongly electrophilic and readily confers covalent binding to tissue proteins, especially lung proteins, by a Schiff's base mechanism. The findings explain partially the idiosyncratic reactions of houttuyniae injection in clinical use.


Biomechanical investigation of head impacts in football.
This study sought to measure the head accelerations induced from upper extremity to head and head to head impact during the game of football and relate this to the risk of mild traumatic brain injury using the Head Impact Power (HIP) index. Furthermore, measurement of upper neck forces and torques will indicate the potential for serious neck injury. More stringent rules or punitive sanctions may be warranted for intentional impact by the upper extremity or head during game play. Game video of 62 cases of head impact (38% caused by the upper extremity and 30% by the head of the opposing player) was provided by F-MARC. Video analysis revealed the typical impact configurations and representative impact speeds. Upper extremity impacts of elbow strike and lateral hand strike were re-enacted in the laboratory by five volunteer football players striking an instrumented Hybrid III pedestrian model crash test manikin. Head to head impacts were re-enacted using two instrumented test manikins. Elbow to head impacts (1.7-4.6 m/s) and lateral hand strikes (5.2-9.3 m/s) resulted in low risk of concussion (<5%) and severe neck injury (<5%). Head to head impacts (1.5-3.0 m/s) resulted in high concussion risk (up to 67%) but low risk of severe neck injury (<5%). The laboratory simulations suggest little risk of concussion based on head accelerations and maximum HIP. There is no biomechanical justification for harsher penalties in this regard. However, deliberate use of the head to impact another player's head poses a high risk of concussion, and justifies a harsher position by regulatory bodies. In either case the risk of serious neck injury is very low.


Efficient preparation of alkali-insoluble (1 → 3)-β-D-glucan.
The alkali-insoluble (1 → 3)-β-d-glucan was prepared by alkaline-acid method and followed deproteinization by alkaline method using yeast cell wall as the starting material. The deproteinized product was characterized by infrared (IR) spectroscopy, and the polysaccharide components were analysed by paper chromatography. It indicated that the alkaline-acid method was an ideal way for preparing (1 → 3)-β-d-glucan. The obtained glucan had high purity and good yield.


Do adenine derivatives have a special role in biological regulation?
The hypothesis is raised "that adenine by way of its many derivatives plays an important role in regulating a wide variety of biological functions". Evidence is cited for such a role in cell-to-cell communication, intracellular regulation and interorganism communication. It is predicted that many more key biological functions will be found to be modulated by adenine derivatives and that adenine compounds which have not yet been studied in great depth will become recognized as biological regulators. The hypothesis also predicts that some disease states may be caused by perturbations of the adenine derivative-receptor system.


The promoter of the wheat puroindoline-a gene (PinA) exhibits a more complex pattern of activity than that of the PinB gene and is induced by wounding and pathogen attack in rice.
Puroindolines form the molecular basis of wheat grain hardness. However, little is known about puroindoline gene regulation. We previously reported that the Triticum aestivum puroindoline-b gene (PinB) promoter directs beta-glucuronidase gene (uidA) seed-specific expression in transgenic rice. In this study, we isolated a puroindoline-a gene (PinA), analyzed PinA promoter activity by 5' deletions and compared PinA and PinB promoters in transgenic rice. Seeds of PinA-1214 and PinB-1063 transgenic plants strongly expressed uidA in endosperm, in the aleurone layer and in epidermis cells in a developmentally regulated manner. The GUS activity was also observed in PinA-1214 embryos. Whereas the PinB promoter is seed specific, the PinA promoter also directed, but to a lower level, uidA expression in roots of seedlings and in the vascular tissues of palea and pollen grains of dehiscent anthers during flower development. In addition, the PinA promoter was induced by wounding and by Magnaporthe grisea. By deletion analysis, we showed that the "390-bp" PinA promoter drives the same expression pattern as the "1214-bp" promoter. Moreover, the "214-bp" PinA promoter drives uidA expression solely in pollen grains of dehiscent anthers. The presence of putative cis-regulatory elements that may be related to PinA expression is discussed from an evolutionary point of view. By electrophoretic mobility shift assay, we showed that putative cis-elements (WUN-box, TCA motifs and as-1-like binding sites) whose presence in the PinA promoter may be related to wounding and/or the pathogen response form complexes with nuclear extracts isolated from wounded wheat leaves.


Cerebral imaging of post-stroke plasticity and tissue repair.
Six months after stroke onset, 50 % of patients are still disabled and dependent, while many brain mechanisms of recovery remain partially unknown or misunderstood. However, brain imaging and cerebral connectivity analytical techniques have provided invaluable insights into such mechanisms and identified two main patterns of brain reorganization depending on stroke severity. The contralesional primary motor cortex can take over motor function in severely impaired patients, whereas the ipsilesional motor cortex or hemisphere reorganize themselves in good recoverers. These patterns evolve with time after stroke, and highlight ipsilesional and contralesional primary and secondary areas that appear to take over lost functions. The crucial role of these areas has been confirmed by histological tracer studies. In addition, non-invasive techniques can stimulate post-stroke brain plasticity, although appropriate targets first need to be found. Imaging has proved useful for finding such appropriate targets and has also provided biomarkers of efficacy with various therapies. Moreover, it has provided some clues to the mechanisms of action of recovery-enhancing drugs. These imaging techniques have also identified patients who show atypical reorganization and recovery patterns. Thus, it may be necessary to design individualized and targeted therapies.


Bulk-modified modified screen-printing carbon electrodes with both lactate oxidase (LOD) and horseradish peroxide (HRP) for the determination of L-lactate in flow injection analysis mode.
A screen-printed carbon electrode modified with both HRP and LOD (SPCE-HRP/LOD) has been developed for the determination of L-lactate concentration in real samples. The resulting SPCE-HRP/LOD was prepared in a one-step procedure, and was then optimised as an amperometric biosensor operating at [0, -100]mV versus Ag/AgCl for L-lactate determination in flow injection mode. A significant improvement in the reproducibility (coefficient variation of about 10%) of the preparation of the biosensors was obtained when graphite powder was modified with LOD in the presence of HRP previously oxidised by periodate ion (IO4-). Optimisation studies were performed by examining the effects of LOD loading, periodation step and rate of the binder on analytical performances of SPCE-HRP/LOD. The sensitivity of the optimised SPCE-HRP/LOD to L-lactate was 0.84 nAL micromol(-1) in a detection range between 10 and 180 microMol. The possibility of using the developed biosensor to determine L-lactate concentrations in various dairy products was also evaluated.


'It feels smaller now': The impact of the COVID-19 lockdown on apartment residents and their living environment - A longitudinal study.
The COVID-19 pandemic and associated lockdown restrictions prolonged residents' exposure to their home environment. The impact of lockdowns could be heightened for apartment residents as they typically have smaller, less versatile homes, and share communal and circulation spaces. This study examined changes in apartment residents' perceptions and experiences of their dwelling before and after the Australian COVID-19 national lockdown. Participants consisted of 214 Australian adults who completed a survey on apartment living between 2017 and 2019 and a follow-up survey in 2020. Questions focused on residents' perceptions of their dwelling design, apartment living experiences, and personal life events/changes due to the pandemic. Differences between pre- and post-lockdown periods were assessed via paired sample t-tests. The lived experience of a subset of residents (n = 91) following lockdown was also assessed using qualitative content analysis of free-text responses to an open-ended survey item. Compared to the pre-pandemic period, after the lockdown residents reported less satisfaction with the amount/layout of their apartment space and private open space (e.g., balconies or courtyards). Increased noise annoyance from indoor and outdoor noise sources was also reported, however disputes with neighbours decreased. The qualitative content analysis highlighted a complex interplay of personal, social and environmental impacts of the pandemic on residents. Findings suggest an increased 'dose' of the apartment facilitated by stay-at-home orders negatively influenced residents' apartment perceptions. Design strategies that maximise spacious, flexible dwelling layouts with health-promoting elements (e.g., enhanced natural light/ventilation and private open space) are recommended to promote healthy and restorative living environments for apartment residents.


The outcome of twin-twin transfusion syndrome complicated with placental insufficiency.
The aim was to evaluate the incidence and perinatal outcomes of TTTS complicated with placental insufficiency (PI/TTTS). This was a retrospective study of all TTTS with PI. PI is defined as estimated fetal weight < 10% with elevated head circumference/abdominal circumference ratio and weight discordance > 20%. Fifty-two out of 270 (19%) pregnancies met criteria. Forty-nine (94.2%) donor twins were diagnosed with PI/TTTS. Fifteen were treated with amnioreduction, 26 with selective fetoscopic laser photocoagulation, 4 with donor intrafetal radiofrequency ablation (RFA), and 7 had expectant management. There was a high incidence of abnormal Dopplers and abnormal placental cord insertion in the donor twin (58% marginal, 35% membranous) with a mean estimated fetoscopic donor placental share of 26.1 +/- 14.3%. There was a significant decrease in the overall donor survival rate of 61% (4 RFA selected donors were excluded) as compared to overall recipient survival rate of 85%, respectively (P = .009). There was no significant difference in donor or recipient survival rate among the treatment groups (P = .058). Placental insufficiency impacts the survival of the affected twins in the setting of TTTS. Studies are needed for appropriate treatment in TTTS with placental insufficiency.


Role of liver fatty acid binding protein in hepatocellular injury: effect of CrPic treatment.
This study was designed to investigate the molecular mechanisms of chromium picolinate (CrPic, Fig. 1) hepatoprotective activity from alloxan-induced hepatic injury. Diabetes is induced by alloxan-treatment concurrently with the hepatic injury in mice. In this study, we investigate the protective effect of CrPic treatment in hepatic injury and the signal role of liver fatty acid binding protein in early hepatocellular injury diagnostics. In this study, alanine aminotransferase (ALT; EC 126.96.36.199) and aspartate aminotransferase (AST; EC 220.127.116.11) levels in the alloxan group were higher 71% and 50%, respectively, than those of the control group (ALT: 14.51±0.74; AST: 22.60±0.69). The AST and ALT levels in CrPic group were of minimal difference compared to the control groups. Here, CrPic exhibited amelioration alloxan induced oxidative stress in mouse livers. A significant increase in liver fatty acid-binding protein (L-FABP) was observed, which indicates increased fatty acid utilization in liver tissue [1]. In this study, the mRNA levels of L-FABP increased in both the control (1.1 fold) and CrPic (0.78 fold) groups compared the alloxan group. These findings suggest that hepatic injury may be prevented by CrPic, and is a potential target for use in the treatment of early hepatic injury.


The effect of structural changes on swelling kinetics of polybasic/hydrophobic pH-sensitive hydrogels.
The effect of pendent side-chain length and crosslinking agent concentration in methyl methacrylate/dimethylaminoethyl methacrylate as a polybasic/hydrophobic pH-sensitive hydrogel was studied. Increasing both side-chain length and crosslinking agent concentration decreased the sharpness of response to pH and water-uptake capacity of the polymer. A case-II water transport mechanism and a nonlinear swelling kinetic was observed for the homologues of this hydrogel.


Spontaneous mentalizing in neurotypicals scoring high versus low on symptomatology of autism spectrum disorder.
Spontaneous mentalizing ability has been linked to symptoms severity in individuals with autism spectrum disorder (ASD). Here we investigated whether in neurotypicals, higher levels of ASD symptomatology could also be linked to lower levels of spontaneous mentalizing, by comparing neurotypicals scoring high with those scoring low on the short Autism Spectrum Quotient. Participants watched movies during which they, and another agent, formed beliefs about the location of an object. These beliefs could influence reaction times (RT) to that object in the outcome phase. We expected participants with more ASD symptoms to show less spontaneous mentalizing, as reflected by a smaller effect of the other agent's beliefs on RT patterns (the ToM index). In contrast, the effect of own beliefs on RTs, reflecting an egocentric bias, was expected to be larger in the high-scoring group. Results showed that groups differed in the effect of the agent's beliefs; the ToM index was highly significant in the low-scoring group, while being absent in the high-scoring group. No difference in egocentric bias was observed. These findings suggest that the relationship between levels of ASD symptomatology and spontaneous mentalizing is not only present in individuals with ASD, but also in the neurotypical population.


Emodin inhibits NF-κB signaling pathway to protect obese asthmatic rats from pathological damage via Visfatin.
Emodin has a protective effect on asthma. Obesity is closely related to asthma. We further explored the role of Emodin in obese asthmatic rats. Ovalbumin (OVA) was used to induce asthma model, and high fat diet (HFD) was used to induce obese rat model. Body weight was measured before and after the modeling. Serum lipid levels were evaluated using commercial kits. Then, lung tissue and airway tissue of rat were separated forin vivo. Hematoxylin-eosin staining (HE) analyzed the extent of lung lesions. Quantitative reverse transcription PCR assessed the mRNA expression of Visfatin and Enzyme linked immunosorbent assay measured NF-κB protein expression in airway tissues. MTT, Brdu and Western blot detected cell viability, proliferation and NF-κB level of human bronchial epithelial cells 16HBE, respectively. Asthma and Emodin alone had no effect on the body weight of normal rats, while HFD promoted the body weight of rats and could be reversed by Emodin. Both asthma and obesity promoted the pathological damage of rat lungs, including emphysema, lipid accumulation, edema changes, lymphoid hypertrophy and airway smooth muscle hyperplasia as well as lipid accumulation in surum, and Emodin treatment could reduce the damage. In the airway tissues of asthma and obesity models, up-regulated Visfatin mRNA and NF-κB protein were observed. In 16HBE, Emodin reversed Visfatin's role in promoting cell viability, proliferation and activating NF-κB signaling pathway. Emodin inhibited NF-κB expression to relieve the pathological symptoms of obese asthmatic rats by Visfatin.


Presence and characterization of lymphocytotoxins in acute and chronic Plasmodium berghei malaria.
The role of lymphocytotoxic antibodies in elimination of lymphocytes and characterization of these antibodies during Plasmodium berghei infection was examined in BALB/c mice. When assayed at 15 degrees, an increase in lymphocytotoxic levels above base line values was detected in acute infection when parasitaemia exceeded 10%. There was an increase in lymphocytotoxins with increase in parasitaemia to a plateau beyond 25% parasitaemia. When assayed at 37 degrees, lymphocytotoxic activity during acute infection was lower than at 15 degrees but the increase detected was significant. During chronic infection there was a lower increase in the activity detected at 15 degrees and no significant increase in activity assayed at 37 degrees (P greater than 0.05). In addition, peripheral blood lymphocyte counts also dropped during acute infection while there was little change in lymphocyte numbers in the chronic infection group. The lymphocytotoxic antibodies present in sera of infected mice were predominantly of IgM class during acute infection and IgM or IgG class during chronic infection. The relevance of these observations to plasmodium infection is discussed.


Patient-reported Outcome Measurement and Reporting for Patients with Advanced Renal Cell Carcinoma: A Systematic Literature Review.
In the oncology setting, patient-reported outcome measures (PROMs) provide important data that help to ensure patient-relevant endpoints are captured and reported. Use of this information for treatment decision-making by clinicians and patients in real-world settings is facilitated by consistent and transparent reporting of trial methods. To identify and compare PROMs used in advanced renal cell carcinoma (RCC) trials in terms of the rationale for the choice of measure, endpoint hierarchy (primary, secondary, exploratory), assessment time points, statistical methods, and statistical metrics for interpretation. A systematic literature review via searches of four online databases (2016-2021) and recent conference abstracts (2019-2021) identified 2616 articles, of which 33 were included in the review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among the 33 clinical studies included, 19 different PROMs were identified: three kidney cancer-specific scales, two cancer-specific scales, two generic scales, and 12 symptom-specific scales. The endpoint hierarchy for patient reported outcome (PRO) assessment was reported in 42% of the studies; one study included PROs as a primary endpoint. Reporting of time points, minimal important differences, and statistical analyses was highly heterogeneous. A diverse range of PROMs have been included in clinical studies for patients with advanced/metastatic RCC. Prespecified analyses for PRO assessments were generally not stated, while analytical methods and reporting varied. An improvement in alignment across studies would better inform regulatory, market-access, reimbursement, and clinical decision-making to improve patient care. We reviewed how the impact of cancer therapies on health outcomes from the patient's point of view is being measured in clinical trials for kidney cancer. The techniques and reporting varied across trials. Standardisation of how these data are captured and reported may improve care and decision-making for patients with kidney cancer.


Comparative survival risks in patients undergoing abdominoperineal resection and sphincter-saving operation for rectal cancer: a 10-year cohort analysis using propensity score matching.
Abdominoperineal resection (APR) has been considered to have a higher risk of local recurrence and poorer survival outcome than sphincter-saving operation (SSO) in patients with rectal cancer. This study compared long-term oncologic outcomes and prognostic parameters in propensity score-matched patients who underwent APR and SSO. This study analyzed 958 consecutive patients with lower rectal cancer who underwent preoperative chemoradiotherapy followed by APR or SSO between 2005 and 2015. Propensity score matching analysis was performed to adjust baseline characteristics, including clinical stage, tumor distance from the anal verge, and tumor size. In the entire cohort, the APR group had larger and lower tumors and showed significantly shorter 5-year disease-free survival (DFS) than the SSO group (64.5% vs. 75.8%, p = 0.01). After propensity score matching, there were no significant between-group differences in local (9.5% vs. 8.0%, p = 0.59) and systemic (27.9% vs. 23.4%, p = 0.3) recurrence rates, and 5-year DFS (67.5% vs. 69.9%, p = 0.49) and overall survival (80.8% vs. 82.9%, p = 0.65) rates. A lower number of lymph nodes retrieved was independently associated with recurrence and survival outcomes in the APR group, whereas poorly differentiated histology was an independent associated parameter in the SSO group. Advanced stage and perineural invasion were identified as independent prognostic parameters in both groups. This study indicated that the long-term oncologic outcomes of APR were comparable to those of SSO. Because prognostic parameters associated with oncologic outcomes differed between the respective procedures, correctable parameters could be ameliorated through complete total mesorectal excision and personalized systemic treatment.


Association of glutathione S-transferase M1 and T1 null polymorphisms with the development of cervical lesions: a meta-analysis.
An accumulation of evidence suggests that gene-based self-susceptibility may contribute to the development of cancer. Some studies have found that particular polymorphisms of the glutathione S-transferase M1 and T1 genes are associated with increased risk of cervical lesions, but other studies have had contrary results. The present meta-analysis evaluated the association of glutathione S-transferase M1 and T1 null polymorphisms with the development of cervical lesions. In addition, stratified analyses were performed in an attempt to identify any race-specific effects. Twenty-one related studies were included in the meta-analysis, comprising glutathione S-transferase M1 data from 1423 patients with cervical lesions and 2415 healthy matched controls, and glutathione S-transferase T1 data from 2081 patients with cervical lesions and 2287 healthy matched controls. The fixed-effect model (Mantel-Haenszel method) and the random-effect (DerSimonian and Laird) model were used to examine the difference in frequency of glutathione S-transferase M1 and T1 null polymorphisms between pre- and invasive cervical lesions. Subgroup analyses were also conducted to evaluate any race-specific effect on the frequencies of glutathione S-transferase polymorphisms in cervical lesions. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Heterogeneity was assessed using the heterogeneity metric (I²) and Chi-squared test. The glutathione S-transferase M1 null polymorphism was associated with increased risk of low-grade intra-epithelial lesions (OR 1.37, 95% CI 1.05-1.77), but no increased risk of high-grade intra-epithelial lesions (OR 1.29, 95% CI 0.87-1.8) or invasive cervical cancer (OR 1.20, 95% CI 0.99-1.46). The association seemed to be confined to Southeast Asians (OR 1.97, 95% CI 1.44-2.71). No significant associations were found for the glutathione S-transferase T1 null polymorphism for any of the populations. The glutathione S-transferase M1 null polymorphism significantly increases susceptibility to early-stage cervical lesions in Southeast Asians. However, the glutathione S-transferase T1 null polymorphism does not appear to be a risk factor for cervical lesions in any population.


Sister chromatid exchanges in the peripheral blood of cigarette smokers and in lung cancer patients; and the effect of chemotherapy.
Peripheral blood sister chromatid exchange (SCE) rates in chronic cigarette smokers and in subjects with cancer do not differ from those in healthy nonsmokers. SCE patterns were normal in 69 chronic cigarette smokers, including 62 patients with untreated lung cancer. In three chronic smokers with lung cancer, high SCE levels were related to recent intravenous chemotherapy.


Long term outcome study of a salutogenic psychoeducational recovery oriented intervention (Inte.G.R.O.) in severe mental illness patients.
Inte.G.R.O. is a standardized Salutogenic-Psychoeducational intervention designed to help people with severe mental illness manage their life-stress and achieve personal recovery goals through the improvement of social functioning. The aim of this study is to evaluate the long-term outcome of this approach, characterized by health promotion rather than correction of dysfunctional strategies. 41 people underwent an observational study with a three time-point evaluation (t0, pre- treatment; t1, 12 months; t2, 36 months). At each time point, social functioning was assessed as primary outcome by the Personal and Social Functioning scale (PSP); furthermore, psychopathological status was assessed by Brief Psychiatric Rating Scale (BPRS), stress management was measured by means of Stress-Scale and cognitive flexibility variables were assessed by Modified Five-Point Test (M-FPT). Personal and Social Functioning increased at t1 and t2 vs t0; psychopathological status improved at t2 vs t0; stress management improved at t2 vs t1; cognitive flexibility improved at t2 vs t0. these results substantially confirm after a three-year follow-up the improvements in functioning, psychopathology, stress management and cognitive flexibility seen in previous studies. Furthermore, they show a complex time-dependent fashion. Overall, they confirm a remarkable and long-term impact of Inte.G.R.O. on key Recovery variables. Further studies are needed to address extent and duration of these improvements.


Inferior subluxation of humeral head after osteosynthesis for greater tuberosity fracture.
Inferior subluxation of the humeral head is frequently observed immediately after surgery for proximal humerus fractures; however, the incidence and risk factors of inferior subluxation after osteosynthesis for isolated greater tuberosity fractures remain unsolved. Additionally, the postoperative course of inferior subluxation has not been elucidated. The purpose of the present study is to identify the predictors for the occurrence of postoperative inferior subluxation by multivariate analysis and investigate the postoperative shift of inferior subluxation and its effect on surgical outcomes. We retrospectively identified 68 patients who underwent surgery for isolated greater tuberosity fractures. The dependent variable was the inferior subluxation at 1 week postoperatively. The explanatory variables were age, sex, affected side of the shoulder, body mass index, history of smoking, local osteoporosis, time period to surgery, axillary nerve injury, inferior subluxation before surgery, fracture dislocation, surgical approach, surgical method, operative time, amount of blood loss, and postoperative drainage. Baseline variables that were statistically significant in the univariate analyses were included in the logistic regression analysis. The patients were further categorized into two groups according to the presence of inferior shoulder subluxation exhibited 1 week postoperatively: patients with inferior subluxation (+ IS group) and patients without inferior subluxation (- IS group). We compared the incidence of postoperative complications between the two groups. Of 68 patients, 17 (25.0%) had inferior shoulder subluxation observed 1 week postoperatively. Multivariate analysis showed that long operative time was a risk factor for postoperative subluxation (odds ratio = 1.03; P = 0.030). In all cases, inferior subluxation disappeared within 3 months of surgery. No significant difference in complication rate was observed between the + IS and - IS groups. The present study provides novel information regarding postoperative inferior subluxation of fractures of the greater tuberosity. Inferior subluxation occurred in 25% of patients immediately after surgery. Long operative time contributes to the onset of postoperative inferior subluxation; however, this was temporary in all cases and had no significant effect on the surgical outcomes. Level III.


Proton therapy for newly diagnosed pediatric diffuse intrinsic pontine glioma.
Diffuse intrinsic pontine glioma (DIPG) is a type of brain malignancy with a very poor prognosis. Although various radiation and chemotherapy protocols have been attempted, only conventional radiotherapy has yielded improvements in survival. In this study, we aimed to compare proton therapy versus conventional photon radiotherapy in terms of the outcomes of pediatric patients with DIPG. This retrospective review included 12 pediatric patients with newly diagnosed DIPG who received a total proton therapy dose of 54 Gy (relative biological effectiveness) in 30 fractions at the University of Tsukuba Hospital between 2011 and 2017 (proton group). We additionally reviewed the medical records of 10 patients with DIPG who previously underwent conventional photon radiotherapy at our institute (historical cohort). The median progression-free survival (PFS) duration was 5 months (range 1-11 months), and the 6-, 12-, and 18-month PFS rates were 50%, 33%, and 25%, respectively. The median overall survival (OS) duration was 9 months (range 4-48 months), and the 6-, 12-, 18-, and 24-month OS rates were 66.8%, 50%, 41%, and 20%, respectively. There were no significant differences in survival between the proton and historical groups (PFS, p = 0.169 and OS, p = 0.16). Proton therapy was well tolerated by the majority of patients. No severe adverse events, including radiation necrosis, were recorded. Proton therapy did not yield superior survival outcomes vs. conventional photon radiotherapy in patients with DIPG at our institution. Further research is needed to identify the factors associated with better survival in this population.


The mesosternum of the Regourdou 1 Neandertal revisited.
Fossil hominin mesosterna, while scarce, can provide useful morphological data in addition to rib remains regarding aspects of thoracic size and shape. These data, in turn, can address hypotheses related to respiratory dynamics, climatic adaptation, and ecogeographical patterning. In this study, we re-evaluate the anatomical representation of the mesosternum of the Regourdou 1 Neandertal individual that alters key aspects of the original description of the fossil remains. We compare this specimen together with the mesosterna of the Kebara 2 Neandertal male individual and the Tabun C1 Neandertal female individual to a large extant modern sample. Our study shows that the current evidence available for Neandertals indicates longer mesosterna, reflecting larger thorax sizes among Neandertals, in comparison with extant humans. Additionally, while this study weakens previous suggestions of ecogeographically mediated differences in the size and shape of upper thorax between Neandertals from the Mediterranean Levant and those deriving from Western Europe, we cannot unambiguously disprove the notion of such clinal differences.


Compliance with enhanced recovery after surgery criteria and preoperative and postoperative counselling reduces length of hospital stay in colorectal surgery: results of a randomized controlled trial.
The aim of this randomized clinical trial was to compare patients treated using a multimodal approach [enhanced recovery after surgery (ERAS)], with a special focus on counselling, to patients treated in a standard conventional care pathway, who underwent elective colorectal resection. In a single-centre trial, adult patients eligible for open or laparoscopic colorectal resection were randomized to an ERAS programme or standard care. The primary end-point was postoperative total hospital stay. Identical discharge criteria were defined for both treatment groups. Secondary end-points included postoperative complications, postoperative C-reactive protein levels, postoperative hospital stay, readmission rate and mortality. All parameters were recorded before operation, on the day of surgery and daily thereafter until discharge. Total hospital stay was significantly shorter among patients randomized to ERAS than among the standard group [median 5 days (range 2-50 days) vs median 8 days (range 2-48 days); P = 0.001]. The two treatment groups exhibited similar outcomes regarding overall major and minor morbidity, reoperation rate, readmission rate and 30-day mortality. There were also no differences in tolerance of enteral nutrition or in the inflammatory response, as reflected by postoperative C-reactive protein levels. ERAS care was associated with a significantly shorter length of hospital stay. Without any difference in surgical or general complications, tolerance of enteral nutrition or postoperative C-reactive protein levels, peri-operative information and guidance for ensuring that patients comply with the ERAS approach appear to be important factors to reduce the length of hospital stay.


HLA, GM, KM, and Diego blood group typing of Chippewa Indians.
This is the first report characterizing HLA antigen distribution in North American Indians of the Chippewa tribe. One hundred seventy-four Chippewa from Minnesota underwent HLA-A,B,C,DR, and DQ typing in a search for a single unrelated bone marrow donor. The high matching rate of this successful search is attributed to homozygosity and the extreme frequency of certain antigens in this small ethnic community. It is emphasized that smaller donor pools are required in searches within a minority population. GM and KM allotype typing as well as blood group Diego typing show patterns similar to those reported in other North American Indian groups.


Disparities and Racism Experienced Among Older African Americans Nearing End of Life.
The purpose of this review is to examine racism in healthcare as it relates to older African American adults. We focus on health disparities in old age and medical mismanagement throughout their lifespan. In the United States there have been extensive medical advances over the past several decades. Individuals are living longer, and illnesses that were deemed terminal in the past are now considered chronic illnesses. While most individuals living with chronic illness have experienced better quality of life, this is not the case for many African American older adults. Older African American adults are less likely to have their chronic illness sufficiently managed and are more likely to die from chronic illnesses that are well controlled in Whites. African American older adults also continue to suffer from poorer healthcare outcomes throughout the lifespan to end-of-life.


Effects of Lactobacillus combined with semidry flour milling on the quality and flavor of fermented rice noodles.
To shorten the fermentation time and reduce the contamination with heterozygous bacteria during the process of fermenting rice noodles, pure bacterial fermentation combined with semidry flour milling was used to produce fermented rice noodles. The changes in the pH value and microbial community diversity of the rice slurries, the physicochemical properties of the rice flours, and the texture, cooking qualities, sensory qualities and volatile components of the rice noodles prepared with different fermentative methods were investigated. The results showed that the pure bacterial fermentation required 18 h to reach a stable pH value, while the natural fermentation required 54 h. In addition, compared with naturally fermented rice slurry, the bacterial community diversity of the pure bacterial fermented rice slurry was significantly lower, while the fungal community diversity did not differ significantly. Significant differences were observed in the content of the damaged starch, amylose and protein between semidry milled pure bacterial fermented (SP) and wet milled naturally fermented (WN) rice flours (P < .05), while these differences had no significant effect on the texture and cooking qualities of the SP and WN rice noodles (P > .05). In addition, the types of volatile components of the SP noodles were significantly lower than those of other noodles, while the primary volatile component categories of the SP noodles were consistent with that of the WN noodles, and they had a similar flavoring substance.


Differentiation of the humoral immune response in inflammatory diseases of the central nervous system.
The three main immunoglobulin classes obey the basic principles of passive protein transfer at the blood-CSF barrier and the serum-derived portions could therefore be quantified with the help of the permeability marker albumin. The Ig fractions secreted into the CSF by sessile plasma cell clones have been determined in various inflammatory diseases of the central nervous system. The humoral immune response in multiple sclerosis and chronic encephalitis of unknown cause was dominated by IgG antibodies. In most other inflammatory diseases IgA and IgM were concomitantly synthesized, e.g. in neurosyphilis and meningoencephalitis caused by viruses of the herpes group. In tick-borne meningopolyneuritis Bannwarth, only IgM and in bacterial meningitis only IgA may be produced locally. The detection of a secretory immunoglobulin fraction in the CSF may be the sole laboratory parameter in chronic inflammatory processes of the nervous system.


The effect of lead (Pb) exposure and iron (Fe) deficiency on intestinal lactobacilli, E. coli and yeast: A study in experimental rats.
The current study investigated the additive effect of oral lead (Pb) exposure and dietary iron (Fe) deficiency on intestinal lactobacilli, E. coli, and yeast in SD rats. Weanling rats were fed on control diet (CD) or iron deficient diet (ID) for 4 weeks, followed by oral Pb exposure for another 4 weeks. Lead exposure was withdrawn for 2 weeks, and then resumed after 2 weeks. Blood samples were collected to determine haemoglobin (Hb), serum iron, blood Pb and δ-Aminolevulenic acid dehydratase (ALAD) activity. Fecal samples were collected to enumerate the lactobacilli, E. coli and yeast population on selective agar media and determine Pb levels. Hb and serum Fe levels decreased significantly in iron deficient rats. Pb exposed rats had a significant increase in blood Pb levels and decreased ALAD activity. The lactobacilli population was significantly decreased (p<0.05) in ID rats compared to the CD group. Further, a significant decrease in the lactobacilli population was observed in Pb exposed rats irrespective of the dietary regimen. Upon withdrawal of Pb exposure, lactobacilli increased significantly in both the CD+Pb and ID+Pb groups, whereas re-exposure to Pb decreased lactobacilli population. The E. coli and yeast populations were inconsistent among both the ID and Pb exposed rats compared to controls. Fecal Pb levels increased significantly in Pb exposed rats irrespective of diet. An additive effect of dietary Fe deficiency and oral Pb exposure resulted in greater reductions in the intestinal lactobacilli population compared to either treatment alone. In addition, transient withdrawal of Pb exposure led to improved lactobacilli population irrespective of Fe status.


Distribution of beta-globin haplotypes among the tribes of southern Gujarat, India.
The present study was carried out in Indo-European speaking tribal population groups of southern Gujarat (India) to elucidate the allelic and haplotypic content of β-globin system in individuals with HbAA genotypes. 6 neutral restriction sites of the β-globin system were analysed and various statistical parameters were estimated to draw meaningful interpretations. All the 6 sites were found to be polymorphic and most were in Hardy-Weinberg Equilibrium in the studied group. Haplotypes were constructed using two different combinations of the 6 restriction sites analysed. Analysis of the 5 sites revealed a set of three predominant haplotypes, '+----', '-++-+' and '-+-++'; and haplotypes '+--', '++-' and '+++' were found to be the most frequent when the 3 sites were used to construct the haplotypes. Haplotypic heterozygosity levels (>83%) observed in the present study group were comparable to those observed in African and Afro-American populations and greater than other world populations. All the ancestral haplotypes, +-----, -++-+, -+-++ and ----+ were found in the study group. The distribution pattern of various haplotypes was consistent with the global pattern. The paucity of comparable data from other Indian populations restricted one from making interpretations about the study group's relationships with other Indian populations but the results were indicative of older population histories or experience of gene flow by the study group and their affinities with populations of southern India.


Muscle microvascular hemoglobin concentration and oxygenation within the contraction-relaxation cycle.
Inability to directly measure microvascular oxygen distribution and extraction in striated muscle during a contraction/relaxation cycle limits our understanding of oxygen transport to and utilization by contracting muscle. We examined muscle microvascular hemoglobin concentration (total [Hb/Mb]) and oxygenation within the contraction-relaxation cycle to determine if microvascular RBC volume would be preserved and if oxygen extraction continued during the actual contraction phase. Eight subjects performed dynamic knee extension exercise (40 contractions/min) at moderate ( approximately 30% of peak work rate) and heavy ( approximately 80% of peak) work rates. Total hemoglobin/myoglobin (total [Hb/Mb]) and deoxy-hemoglobin/myoglobin (deoxy-[Hb/Mb]) were measured in the rectus femoris using NIRS to determine if microvascular total [Hb/Mb] would be preserved during the contraction, and to estimate microvascular oxygen extraction, respectively. Mean values during the relaxation (RP) and contractile phases and the peak values during the contractile phase for both moderate and heavy exercise were calculated. Total [Hb/Mb] increased from rest to steady-state exercise (6.36+/-5.08 microM moderate; 5.72+/-4.46 microM heavy exercise, both P<0.05), but did not change significantly within the contraction/relaxation cycle. Muscle contractions were associated with a significant (1.29+/-0.98 microM moderate; 2.16+/-2.12 microM heavy exercise, P<0.05) increase in deoxy-[Hb/Mb] relative to RP. We conclude that (a) microvascular RBC volume is preserved during muscle contractions (i.e., RBCs are present in the capillaries), and (b) the cyclical pattern of deoxygenation/oxygenation during the respective contraction/relaxation phases of the contraction cycle suggests that oxygen extraction is not restricted to the relaxation phase but continues to occur during muscle contractions.


Cellular expression of Noc2, a Rab effector protein, in endocrine and exocrine tissues in the mouse.
Noc2 is a Rab effector which participates in regulated exocytosis. It is expressed abundantly in endocrine cells but at low levels in exocrine tissues. Noc2-deficient mice, however, exhibit marked accumulation of secretory granules in exocrine cells rather than endocrine cells. In the present study, we investigated localization of Noc2 immunohistochemically in various endocrine and exocrine tissues in normal mice. Western blotting detected a Noc2-immunoreactive band of 38 kDa in isolated pancreatic islets, the adrenal gland, pituitary gland, and thyroid gland. Immunostaining for Noc2 labeled endocrine cells in the adrenal medulla and adenohypophysis, pancreatic islet cells, thyroid parafollicular cells, and gut endocrine cells, supporting the notion that Noc2 is a Rab effector protein shared by amine/peptide-secreting endocrine cells. Besides endocrine tissues, granular ducts in salivary glands contained Noc2. Although immunostaining failed to detect Noc2 in acinar cells of all exocrine glands examined, reverse transcriptase-polymerase chain reaction analysis detected the mRNA expression in exocrine pancreas. Ultrastructurally, Noc2 immunoreactivity was associated with the limiting membrane of granules in both pancreatic endocrine and salivary duct exocrine cells. The cellular and subcellular localizations of Noc2 should yield key information on its functional significance as well as account for the phenotype in Noc2-deficient mice.


Kinetics and mechanism of BAL 31 nuclease action on small substrates and single-stranded DNA.
Kinetic and mechanistic aspects of the action of two forms of the BAL 31 nuclease (EC 3.1.11) from Alteromonas espejiana on model substrates, small oligonucleotides, larger oligonucleotides and poly[d(A)] have been examined. The minimal oligonucleotide substrate is a 5'-phosphorylated dinucleotide and a phosphodiester not containing a nucleotide residue is not cleaved. Both forms act predominantly in an exonucleolytic fashion on single-stranded DNA polymers in a highly processive manner; however, the mechanism becomes distributive for small oligomers (3-4 nucleotide residues). The direction of attack is from the 5' end, in contrast to the mode of digestion of duplex DNA which involves attack at the 3' termini. An endonucleolytic mode of attack also exists, but at a level 2-3% or less of that of the terminally directed cleavage. Apparent values for the catalytic efficiency of the action on long DNA polymers are too large to fit a simple kinetic scheme involving a direct enzyme-substrate encounter and lead to an interpretation in which nuclease molecules are non-productively bound away from the 5' ends and undergo facilitated diffusion to yield productive (terminally bound) enzyme-substrate complexes.


A 10-Year Retrospective Clinical Analysis of Fungal Keratitis in a Portuguese Tertiary Centre.
To determine the microbiological profile, risk factors, treatment and surgical intervention rates of fungal keratitis at a tertiary referral centre. A retrospective review of microbiological and medical records from hospitalised patients treated for fungal keratitis at Centro Hospitalar Universitário de São João from 2009 to 2019 was conducted. Overall, 43 patients were included in our study. The mean age of patients was 63.7 years and 46.5% were men. In culture were isolated 22 (51.2%) filamentous fungi and 21 (48.8%) yeast. Candida species (n = 20, 46.5%), Fusarium species (n = 10, 23.4%) and Aspergillus species (n = 4, 9.3%) were the most common isolated species. Important risk factors were contact lens use (n = 24, 55.8%), long-term users of topical corticosteroids (n = 19, 44.2%) and previous keratitis (n = 19, 44.2%). Yeast isolates had a statistically significant higher prevalence in long-term users of topical corticosteroids compared to filamentous ones (p = 0.043). Twenty-four cases (55.8%) required surgical intervention, of which 23 cases underwent therapeutic penetrating keratoplasty. Ocular complications, such as evisceration was noted in 12 patients (27.9%) and endophthalmitis in 5 (11.6%). No statistically significant changes of best corrected visual acuity (BCVA) were found after treatment (p = 0.687). Most patients with fungal keratitis have associated risk factors. Filamentous and yeast species have equally prevalent etiologies. In general, our results mirror how difficult and challenging the approach and treatment of fungal keratitis could be.


Adolescent alcohol exposure alters the rat adult hypothalamic-pituitary-adrenal axis responsiveness in a sex-specific manner.
Exposure to alcohol during adolescence exerts long-term effects on the adult brain stress circuits, causing many changes that persist into adulthood. Here we examined the consequences of adolescent intermittent ethanol (AIE, administered from postnatal day (PND) 28-42) on the hypothalamic-pituitary-adrenal (HPA) axis-related brain circuitry of rats challenged with intragastric (ig) administration of alcohol in adulthood (PND 70-71). Both male and female adolescent rats were exposed to alcohol vapors, while controls did not receive the drug, to assess whether AIE alters adult alcohol response in a sex-specific manner. We demonstrated that AIE increased paraventricular nucleus (PVN) Avp mRNA levels during late (PND 42) but not middle (PND 36) adolescence in males. While an alcohol challenge administered to 70-71-day-old rats increased Crf mRNA levels in males and Avp mRNA levels in females, AIE blunted both effects. These results suggest that AIE produced long-lasting changes in the responsiveness of the HPA axis to a subsequent alcohol challenge in a sex-specific manner. Furthermore, AIE altered adrenergic brain stem nuclei involved in stress responses in adulthood, resulting in increased numbers of phenylethanolamine N-methyltransferase (PNMT) neurons in male C2 and female C1 regions. This tended to enhance activation of the male C2 nucleus upon alcohol challenge. Collectively, these results suggest that AIE exerts long-term effects on the ability of the PVN to respond to an alcohol challenge in adulthood, possibly mediated by catecholaminergic input from the brain stem to the PVN.


Custodian of Oxygen Monitoring: Is There a Winner?
How to cite this article: Praveen Kumar G, Kakar V. Custodian of Oxygen Monitoring: Is There a Winner? Indian J Crit Care Med 2021;25(9):967-968.


Association between indoor air pollutant exposure and blood pressure and heart rate in subjects according to body mass index.
This study investigates the effects of high body mass index (BMI) of subjects on individual who exhibited high cardiovascular disease indexes with blood pressure (BP) and heart rate (HR) when exposed to high levels of indoor air pollutants. We collected 115 office workers, and measured their systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR at the end of the workday. The subjects were divided into three groups according to BMI: 18-24 (normal weight), 24-27 (overweight) and >27 (obese). This study also measured the levels of carbon dioxide (CO2), total volatile organic compounds (TVOC), particulate matter with an aerodynamic diameter less than 2.5μm (PM2.5), as well as the bacteria and fungi in the subjects' work-places. The pollutant effects were divided by median. Two-way analysis of variance (ANOVA) was used to analyze the health effects of indoor air pollution exposure according to BMI. Our study showed that higher levels of SBP, DBP and HR occurred in subjects who were overweight or obese as compared to those with normal weight. Moreover, there was higher level of SBP in subjects who were overweight or obese when they were exposed to higher levels of TVOC and fungi (p<0.05). We also found higher value for DBP and HR with increasing BMI to be associated with exposure to higher TVOC levels. This study suggests that individuals with higher BMI have higher cardiovascular disease risk when they are exposed to poor indoor air quality (IAQ), and specifically in terms of TVOC.


Detection of discrete subaortic stenosis by 3-dimensional transesophageal echocardiography.
We present a case with discrete subaortic stenosis diagnosed by 2D and 3D echocardiography. 3D echocardiography was useful to demonstrate its morphology and dynamic change of the left ventricular outflow tract area, providing important information for surgical intervention.