Is total pelvic exenteration reasonable primary treatment for rectal carcinoma?
Total pelvic exeneration (TPE) is reasonable primary surgical therapy in select patients with large bulky locally invasive rectal cancers that can be removed en bloc. Many do not have either nodal or distant metastasis. Furthermore, TPE can be curative and often is palliative for similar lesions that are recurrent or nonresponsive to radiation therapy. Operative mortality rates should be under 10% and can be under 5% for primary cases. Although improvement in preoperative management and operative technique, especially with urinary conduits and postoperative care is clear, both early and late complications are significant. Unfortunately, preoperative identification of those patients requiring TPE rather than abdominoperineal or low anterior resection remains poor. Furthermore, recent improvements in techniques for pelvic slings to prevent small bowel entrapment and protection from irradiation or myocutaneous flaps to obliterate the massive dead space are not yet clearly established as preventors of either early or later complications.


A non-cholinergic function for acetylcholinesterase in the substantia nigra: behavioural evidence.
Acetylcholinesterase is released from substantia nigra neurons, independently of cholinergic transmission. In an attempt to discover the functional significance of this phenomenon, the behavioural effects of injecting acetylcholinesterase into one substantia nigra of the rat were investigated. Following a single injection of the enzyme, intraperitoneal amphetamine evoked circling behaviour in a direction away from the side of injection. Purified acetylcholinesterase with a similar electrophoretic mobility to the endogenous secreted form, was far more potent in eliciting circling than much higher activities of commercial enzyme, consisting of several molecular species of acetylcholinesterase. Similar infusions of butyrylcholinesterase did not induce circling. Depending upon the amount of enzyme initially given, the behavioural effects of a single injection of acetylcholinesterase persisted for up to thirty days. During this period apomorphine, administered systemically, induced transient circling towards the acetylcholinesterase-treated side. It is concluded that secreted acetylcholinesterase has a functional significance within the substantia nigra, independent of cholinergic transmission. This released enzyme could exert long-term changes in the activity of the nigrostriatal system, involving modification of dopamine striatal receptors.


Characterization of denitrifying phosphate-accumulating organisms cultivated under different electron acceptor conditions using polymerase chain reaction-denaturing gradient gel electrophoresis assay.
To investigate the characteristics and the microbial diversity of denitrifying phosphate-accumulating organisms (DNPAOs) that are capable of conducting enhanced biological phosphorus removal (EBPR) using nitrate as electron acceptor, three sequencing batch reactors were operated under three different electron acceptor conditions, i.e., only oxygen, oxygen together with nitrate and only nitrate. Based on the chemical analysis concerning the biochemical transformation of each reactor, it was found that phosphate-accumulating organisms responsible for EBPR consisted of at least three populations including DNPAOs, and that the microbial community structure was changed according to the electron acceptor conditions. Also, the sludge cultivated with oxygen together with nitrate showed a drastic increase in the amount of phosphorus uptake under anoxic conditions, which suggested that a proportion of DNPAOs capable of utilizing nitrate under aerobic conditions were present. On the other hand, the change in microbial community structure depending on the type of electron acceptor was demonstrated by the analysis of the results of denaturing gradient gel electrophoresis of polymerase chain reaction-amplified 16S ribosomal DNA fragments. It was found that the bacteria commonly contained in all the reactors were Rhodocyclus sp. (96% identity) and Dechlorimonas sp. (97% identity) that belonged to the beta subclass of Proteobacteria on the basis of the analysis of the sequence excised from DGGE bands and the determination of phylogenetic affiliation. However, only the presence of Rhodocyclus sp. in all the reactors was demonstrated by fluorescent in situ hybridization analysis.


The six-minute walk test is an excellent predictor of functional ambulation after total knee arthroplasty.
The Six-minute walk (6 MW) and Timed-Up-and-Go (TUG) are short walk tests commonly used to evaluate functional recovery after total knee arthroplasty (TKA). However, little is known about walking capacity of TKA recipients over extended periods typical of everyday living and whether these short walk tests actually predict longer, more functional distances. Further, short walk tests only correlate moderately with patient-reported outcomes. The overarching aims of this study were to compare the performance of TKA recipients in an extended walk test to healthy age-matched controls and to determine the utility of this extended walk test as a research tool to evaluate longer term functional mobility in TKA recipients. The mobility of 32 TKA recipients one year post-surgery and 43 healthy age-matched controls were assessed using the TUG, 6 MW and 30-minute walk (30 MW) tests. The latter test was repeated one week later. Self-reported function was measured using the WOMAC Index and a physical activity questionnaire. 30 MW distance was significantly shorter amongst TKA recipients (mean 2108 m [95% CI 1837 to 2381 m]; Controls 3086 m [2981 to 3191 m], P < 0.001). Test-retest repeatability was high (ICC = 0.97, TKA; 0.96, Controls). Amongst TKA recipients, the 30 MW distance correlated strongly with the shorter tests (6 MW, r = 0.97, P < 0.001; TUG, r = -0.82, P < 0.001). Multiple regression modeling found 6 MW distance to be the only significant predictor (P < 0.001) of 30 MW distance, explaining 96% of the variability. The TUG test models were moderate predictors of WOMAC function (55%) and physical activity (36%) and were stronger predictors than 6 MW and 30 MW tests. Though TKA recipients are able to walk for 30 minutes one year post-surgery, their performance falls significantly short of age-matched norms. The 30 MW test is strongly predicted by 6 MW test performance, thus providing strong construct validity for the use of the 6 MW test in the TKA population. Neither a short nor long walk test is a strong predictor of patient-reported function after TKA.


Young scientist perspective-microbiology trainees and social media: making science go viral during a pandemic.
This perspective looks at how social media has become even more critical since the pandemic and provides tips on how to market research outputs from a trainee viewpoint better.


Cisplatin interaction with cysteine and methionine, a theoretical DFT study.
Interactions of hydrated cisplatin complexes with sulphur-containing amino acids cysteine and methionine were explored. The square-planar cis-[Pt(NH3)2(H2O)X]+ complexes (where X=Cl- and OH-) were chosen as mono- and dihydrated reactants. Calculations using density functional theory (DFT) techniques with B3LYP functional were performed. The isolated molecules and the supermolecular approaches were employed for the determination of the reaction energies. Bond dissociation energies (BDE) were estimated in the model of isolated molecules and supermolecules were used for the determination of the association energies between the two interacting parts. Formation of monodentate complexes by replacing the aqua-ligand with the S, N, and O-sites of both amino acids represents an exothermic process. The highest BDE was found in cysteine structures for the Pt-S coordination. The bonding energy is about 114 kcal/mol, which is comparable with cisplatin-guanine adducts. Analogous BDE for methionine complexes is smaller by about 40 kcal/mol. This correlates well with the known fact that cysteine forms irreversible cisplatin adducts while similar adducts in the methionine case are reversible. The formation of chelate structures is an exothermic reaction only for the hydroxo-form of reactants in the supermolecular approach where additional association interactions between the released water and chelate molecules sufficiently stabilize the final product.


The development of the Language-Independent Speech in Noise and Reverberation test (LISiNaR) and evaluation in listeners with English as a second language.
Create a language-independent, ecologically valid auditory processing assessment and evaluate relative stimuli intelligibility in native and non-native English speakers. The Language-Independent Speech in Noise and Reverberation Test (LISiNaR) targets comprised consonant-vowel (CVCV) pseudo-words. Distractors comprised CVCVCVCV pseudo-words. Stimuli were presented over headphones using an iPad either face-to-face or remotely. Scoring occurred adaptively to establish a participant's speech reception threshold in noise (SRT). The listening environment was simulated using reverberant and anechoic head-related transfer functions. In four test conditions, targets originated from 0°. Distractors originated from either ±90°, ±67.5° and ±45° (spatially separated) or 0° azimuth (co-located). Reverberation impact (RI) was calculated as the difference in SRTs between the anechoic and reverberant conditions and spatial advantage (SA) as the difference between the spatially separated and co-located conditions. Young adult native speakers of Australian (n = 24) and Canadian (25) and non-native English speakers (34). No significant effects of language occurred for the test conditions, RI or SA. A small but significant effect of delivery mode occurred for RI. Reverberation impacted SRT by 5 dB relative to anechoic conditions. Performance on LISiNaR is not affected by the native language or accent of groups tested in this study.


Speckle intensity statistics for chromatic scattering media under partially polarized illumination.
Intensity contrast in a fully developed speckle pattern resulting from the elastic scattering of a partially polarized light from a strongly scattering medium is theoretically and numerically studied. Simple expressions are derived when the illumination bandwidth is much smaller or larger than the chromatic length of the scattering medium.


The hemagglutinins of the human influenza viruses A and B recognize different receptor microdomains.
A cryptically I-active sialylglycoprotein (glycoprotein 2) isolated from bovine erythrocyte membranes as Sendai virus receptor (Suzuki, Y., Suzuki, T. and Matsumoto, M. (1983) J. Biochem. 93, 1621-1633) contains N-glycolylneuraminic acid (NeuGc) as its predominate sialic acid and exhibits poor receptor activity for a variety of influenza viruses. Enzymatic modification of asialoglycoprotein-2 to contain N-acetylneuraminic acid (NeuAc) in the NeuAc alpha 2-3Gal and NeuAc alpha 2-6Gal sequences using specific sialyltransferase resulted in the appearance of receptor activity toward human influenza viruses A and B. The biological responsiveness chicken erythrocytes treated with sialidase and then reconstituted with derivatized glycoprotein 2 showed considerable recovery to influenza virus hemagglutinin-mediated agglutination, low-pH fusion and hemolysis. Specific hemagglutination inhibition activity of derivatized glycoprotein 2 was 5-16-times higher than that of human glycophorin. A/PR/8/34 (H1N1) virus preferentially recognized derivatized glycoprotein 2 containing NeuAc alpha 2-3Gal sequence over that containing NeuAc alpha 2-6Gal while the specificity of A/Aichi/2/68 (H3N2) for the sialyl linkages was reversed. B/Lee virus recognized both sequences almost equally. The biological responsiveness to the viruses of the erythrocytes labeled with the derivatized glycoprotein 2 containing NeuGc was considerably lower than that of derivatized glycoprotein 2 containing NeuAc. The results demonstrate that the hemagglutinins of human isolates of influenza viruses A and B differ in the recognition of microdomains (NeuAc, NeuGc) of the receptors for binding and fusion activities in viral penetration and the sequence to which sialic acid (SA) is attached (SA alpha 2-3Gal, SA alpha 2-6Gal). Inner I-active neolacto-series type II sugar chains may be important in revealing the receptor activity toward the hemagglutinin of both human influenza viruses A and B.


Entangling of Peptide Nanofibers Reduces the Invasiveness of SARS-CoV-2.
The viral spike (S) protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors on the host cells, facilitating its entry and infection. Here, functionalized nanofibers targeting the S protein with peptide sequences of IRQFFKK, WVHFYHK and NSGGSVH, which are screened from a high-throughput one-bead one-compound screening strategy, are designed and prepared. The flexible nanofibers support multiple binding sites and efficiently entangle SARS-CoV-2, forming a nanofibrous network that blocks the interaction between the S protein of SARS-CoV-2 and the ACE2 on host cells, and efficiently reduce the invasiveness of SARS-CoV-2. In summary, nanofibers entangling represents a smart nanomedicine for the prevention of SARS-CoV-2.


Prediction of complications associated with general surgery using a Bayesian network.
Numerous attempts have been made to identify risk factors for surgery complications, but few studies have identified accurate methods of predicting complex outcomes involving multiple complications. We performed a prospective cohort study of general surgical inpatients who attended 4 regionally representative hospitals in China from January to June 2015 and January to June 2016. The risk factors were identified using logistic regression. A Bayesian network model, consisting of directed arcs and nodes, was used to analyze the relationships between risk factors and complications. Probability ratios for complications for a given node state relative to the baseline probability were calculated to quantify the potential effects of risk factors on complications or of complications on other complications. We recruited 19,223 participants and identified 21 nodes, representing 9 risk factors and 12 complications, and 55 direct relationships between these. Respiratory failure was at the center of the network, directly affected by 5 risk factors, and directly affected 7 complications. Cardiopulmonary resuscitation and sepsis or septic shock also directly affected death. The area under the receiver operating characteristic curve for the ability of the network to predict complications was >0.7. Notably, the probability of other severe complications or death significantly increased when a severe complication occurred. Most importantly, there was a 141-fold higher risk of death when cardiopulmonary resuscitation was required. We have created a Bayesian network that displays how risk factors affect complications and their interrelationships and permits the accurate prediction of complications and the creation of appropriate preventive guidelines.


Brain Barriers and Multiple Sclerosis: Novel Treatment Approaches from a Brain Barriers Perspective.
Multiple sclerosis (MS) is considered a prototypic organ specific autoimmune disease targeting the central nervous system (CNS). Blood-brain barrier (BBB) breakdown and enhanced immune cell infiltration into the CNS parenchyma are early hallmarks of CNS lesion formation. Therapeutic targeting of immune cell trafficking across the BBB has proven a successful therapy for the treatment of MS, but comes with side effects and is no longer effective once patients have entered the progressive phase of the disease. Beyond the endothelial BBB, epithelial and glial brain barriers establish compartments in the CNS that differ in their accessibility to the immune system. There is increasing evidence that brain barrier abnormalities persist during the progressive stages of MS. Here, we summarize the role of endothelial, epithelial, and glial brain barriers in maintaining CNS immune privilege and our current knowledge on how impairment of these barriers contributes to MS pathogenesis. We discuss how therapeutic stabilization of brain barriers integrity may improve the safety of current therapeutic regimes for treating MS. This may also allow for the development of entirely novel therapeutic approaches aiming to restore brain barriers integrity and thus CNS homeostasis, which may be specifically beneficial for the treatment of progressive MS.


[Clinical and histological study of a case of facial Afro-Caribbean childhood eruption (FACE)].
The term Facial Afro-Caribbean childhood eruption (FACE) was coined in 1990 to describe a perioral granulomatous eruption in black-skinned children. We present a typical case of this condition, together with a histological and immunohistochemical study. A seven-year-old boy with black skin was referred for numerous nonpruritic papules that appeared on his face several months prior to the consultation. He had a past history of atopic dermatitis, but his mother denied any use of steroids or other topical treatment on his face. Examination showed numerous small lupoid and flesh-colored papules localised in the perioral, perinasal and periocular areas. Biopsy revealed a diffuse granulomatous infiltrate of the dermis comprising histiocytes, multinucleated giant cells and a heavy lymphocytic component. Histiocytes were CD68+ and CD1a-, while the majority of lymphocytes were CD3+ (70% CD8+ and 30% CD4+). This particular type of perioral dermatitis is seen chiefly in male children with black skin. Our histologic study revealed a diffuse and massive granulomatous infiltrate of the dermis, in contrast with the small size of the papules. Expression of CD68, absence of necrosis and dense CD3+ infiltrate in this disease resembles findings in the granulomatous variant of rosacea. This entity must be differentiated from lupus miliaris disseminatus faciei and from sarcoidosis.


The small conductance calcium-activated potassium channel 3 (SK3) is a molecular target for Edelfosine to reduce the invasive potential of urothelial carcinoma cells.
Metastasis is the survival-determining factor in urothelial carcinoma (UC) of the urinary bladder. The small conductance calcium-activated potassium channel 3 (SK3) enhances tumor cell invasion in breast cancer and malignant melanoma. Since Edelfosine, a glycerophospholipid with antitumoral properties, effectively inhibits SK3 channel activity, our goal was to evaluate SK3 as a potential molecular target to inhibit the gain of an invasive phenotype in UC. SK3 protein expression was analyzed in 208 tissue samples and UC cell lines. Effects of Edelfosine on SK3 expression and intracellular calcium levels as well as on cell morphology, cell survival and proliferation were assessed using immunoblotting, potentiometric fluorescence microscopy, and clonogenic/cell survival assay; furthermore, we analyzed the effect of Edelfosine and SK3 RNAi knockdown on tumor cell migration and invasion in vitro and in vivo. We found that SK3 is strongly expressed in muscle-invasive UC and in the RT112 cellular tumor model. Higher concentrations of Edelfosine have a strong antitumoral effect on UC cells, while 1 μM effectively inhibits migration/invasion of UC cells in vitro and in vivo comparable to the SK3 knockdown phenotype. Taken together, our results show strong expression of SK3 in muscle-invasive UC, consistent with the postulated role of the protein in tumor cell invasion. Edelfosine is able to effectively inhibit migration and invasion of UC cells in vitro and in vivo in an SK3-dependent way, pointing towards a possible role for Edelfosine as an antiinvasive drug to effectively inhibit UC cell invasion and metastasis.


Immunohistochemical study of cerebral amyloid angiopathy: use of an antiserum to a synthetic 28-amino-acid peptide fragment of the Alzheimer's disease amyloid precursor.
A polyclonal antibody to a synthetic peptide representing a 28-amino-acid sequence of the previously isolated and described Alzheimer's disease amyloid precursor was raised in rabbits. The antibody was used in conjunction with an avidin-biotin-peroxidase technique to stain cerebral microvessels involved by amyloid angiopathy and senile "neuritic" plaque amyloid cores. The staining method has significant advantages over standard histologic techniques used to demonstrate brain amyloid and might have important practical applications in the study of microvascular lesions associated with cerebral amyloid angiopathy, as well as in studies on the pathogenesis of Alzheimer's disease or senile dementia of Alzheimer type.


Bile salt-stimulated lipase in human milk from 2 to 16 weeks postpartum.
Our objectives were to determine the change in bile salt-stimulated lipase (BSSL) activity in mature milk with time postpartum and to determine if BSSL activity was related to total lipid in the milk. Milk samples were collected from 12 mothers at 2, 6, 12 and 16 weeks postpartum. A significant (P less than .05) decrease in BSSL activity with time was observed. The average values expressed as mumol free fatty acids released/min/ml milk were 5.3, 4.5, 4.1 and 3.6 at 2, 6, 12 and 16 weeks postpartum. Total lipid in the milk increased significantly (P less than .05) from 4.1 g/dl at 2 weeks to 5.4 g/dl at 16 weeks postpartum but was not significantly correlated with BSSL activity.


Corrigendum to 'Oral Azvudine for hospitalised patients with COVID-19 and pre-existing conditions: a retrospective cohort study.' [EClinicalMedicine 59 (2023) 101981].
[This corrects the article DOI: 10.1016/j.eclinm.2023.101981.].


Ultrasound-guided intra-articular tenotomy of the long head of the biceps: a cadaveric feasibility study.
Isolated tenotomy of the long head of the biceps (LHB) is known to improve function in patients with massive and non-reparable cuff tears without osteoarthritis. This two step cadaveric study was performed with the purpose to identify the best surgical technique for isolated LHB tenotomy under USG guidance (pilot study) and evaluate its feasibility (subsequent study). Pre-operative ultrasonographic evaluation of the rotator cuff was performed and any specimens whose long head of the biceps was not found to be intact during the pre-operative ultrasound evaluation were excluded. In the pilot study, nine scar-free cadaveric shoulders underwent ultrasound-guided tenotomy through a single percutaneous portal to determine the best instrument and approach which ensure elective and complete LHB tenotomy. Using it, a second series of 12 cadaveric shoulders were operated following a similar protocol to evaluate the feasibility of this technique. Pilot study: The use of a backward endoscopic cutter through a posterior percutaneous portal was found to be the safest. Control of the tenotomy was possible by manipulating the intra-articular part of the tendon with the instrument ("Groove Alone" test). Subsequent study: The tenotomy of the LHB was complete in all cases. Mean length of the proximal LHB stump was 0.3 cm (range, 0-0.8 cm). No iatrogenic lesion was observed when using the backward endoscopic cutter. On the other hand, the use of straight endoscopic scissors led to severe damage to the rotator cuff and the conjoined tendon. The "Groove Alone" test checked against iatrogenic injury. This was not done in one of the cases and it led to a partial section of the superior half of the tendon of the subscapularis. By the use of both appropriate endoscopic instrumentation and the newly described "Groove Alone" test, ultrasound-guided LHB tenotomy through a single percutaneous portal appears to be a feasible and reliable procedure that could be an alternative to isolated arthroscopic tenotomy. The choice of a posterior portal (soft point) may increase the safety and precision of this procedure and decrease the length of the proximal stump of the LHB.


Carcinogenic potencies of polycyclic aromatic hydrocarbons for back-door neighbors of restaurants with cooking emissions.
In the present study, 21 polycyclic aromatic hydrocarbon (PAH) congeners were measured in the exhaust stack of 3 types of restaurants: 9 Chinese, 7 Western, and 4 barbeque (BBQ). The total PAH concentration of BBQ restaurants (58.81 ± 23.89 μg m(-3)) was significantly higher than that of Chinese (20.99 ± 13.67 μg m(-3)) and Western (21.47 ± 11.44 μg m(-3)) restaurants. The total benzo[a]pyrene potency equivalent (B[a]P(eq)) concentrations, however, were highest in Chinese restaurants (1.82 ± 2.24 μg m(-3)), followed by Western (0.86 ± 1.43 μg m(-3), p<0.01) and BBQ-type restaurants (0.59 ± 0.55 μg m(-3), p<0.01). We further developed a probabilistic risk model to assess the incremental lifetime cancer risk (ILCR) for people exposed to carcinogenic PAHs. Because the exhaust stack directly affected the back-door neighbors of these restaurants, we were concerned with the real exposure of groups near the exhaust stack outlets of these restaurants. The ILCRs for total exposure of the neighbors (inhalation+dermal contact+ingestion) were 2.6-31.3, 1.5-14.8, and 1.3-12.2 × 10(-6) in Chinese, Western, and BBQ restaurants, respectively. We suggest that the maximum acceptable exposure time to the exhaust stack outlet area for Chinese, Western, and BBQ restaurants ranges between 5-19, 17-42, and 18-56 h month(-1), respectively, based on an ILCR of less than 10(-6).


[Front tooth trauma--endodontic aspects].
In a short review indication, possibilities and frontiers of modern endodontic treatment concepts for traumatized teeth are summarized.


Ants of three adjacent habitats of a transition region between the cerrado and caatinga biomes: the effects of heterogeneity and variation in canopy cover.
Habitat heterogeneity and complexity associated with variations in climatic conditions are important factors determining the structure of ant communities in different terrestrial ecosystems. The objective of this study was to describe the horizontal and vertical distribution patterns of the ant community associated with three adjacent habitats in a transition area between the Cerrado and Caatinga biomes at the Pandeiros River, state of Minas Gerais, Brazil. We tested the following hypotheses: (1) the richness and composition of ant species and functional group structure changes between different habitats and strata; (2) habitats with higher tree species richness and density support higher ant species richness; and (3) habitats with lower variation in canopy cover support higher ant species richness. Sampling was conducted in three adjacent habitats and at three vertical strata. Ant species richness was significantly different among vertical strata. Ant species composition was different among both habitats and vertical strata and functional group structure was divergent among habitats. Partitioning of the diversity revealed that the diversity for the three components was statistically different from the one expected by the null model; α and β 2 were higher and β 1 was lower than the values expected by chance. Tree density and variation in canopy cover negatively affected ant species richness. The occurrence of different species and the changing of functional group structures in different habitats and strata suggest an ecological-evolutionary relationship between ants and their habitats and emphasize the need to implement local conservation strategies in the ecotones between biomes.


Association between waist circumference change and incident chronic obstructive pulmonary disease among Chinese adults: a 10-year cohort study.
The aim of our study was to investigate waist circumference (WC) change and the risk of incident chronic obstructive pulmonary disease (COPD) among Chinese adults. A total of 8164 participants aged > 18 years who attended health examinations with repeat measurements of WC and lung function [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1)] from 2010 to 2019 were recruited. WC change was categorized as ≤ - 2.5%, - 2.5 to 2.5%, 2.5% to 5% and > 5% according to sex. Modified Poisson regression models were used to assess the association of WC gain and the risk of COPD. During the 10-year follow-up, a total of 917 COPD cases were identified. From baseline to follow-up, the mean FEV1 decreased from 3.20 to 2.79L among male participants and 2.28-1.95L among female participants. Compared with participants who did not have abdominal obesity, at either, baseline or follow-up, participants with abdominal obesity of both sexes after the follow-up were associated with a greater risk of COPD regardless of abdominal obesity at baseline. The risk of incident COPD increased 19% among male participants (RR = 1.19, 95%CI = 1.04-1.48) and 14% among female participants (RR = 1.14, 95%CI = 1.01-1.40) when WC gain increased > 5% during the 10-year follow-up. The COPD risk decreased 18% among male participants with a WC change ≤ - 2.5% (RR = 0.82, 95%CI = 0.67-0.99). The risk of incident COPD was positively associated with increasing WC among Chinese adults of both sexes.


Groundwater hydrogeochemical formation and evolution in a karst aquifer system affected by anthropogenic impacts.
Karst groundwater, an important water source, is often highly influenced by human impacts, causing environmental damage and threats to human health. However, studies on the anthropogenic influences on the hydrogeochemical evolution of karst groundwater are relatively rare. To assess hydrogeochemical formation and evolution, we focused on a typical karst groundwater system (Jinan, China) which is composed of cold groundwater (av. temperature 13-17 °C), springs and geothermal water (av. temperature > 30 °C) and is significantly affected by human activities. The study was performed by means of water samples collecting and analyzing and isotope analysis (2H, 18O and 14C). The statistical analysis and inverse models were also applied to further understand geochemical processes and anthropogenic influences. The 2H, 18O and 14C results indicate that the cold karst groundwater is easily influenced and contaminated by the local environment, while geothermal water is relatively old with a slow rate of recharge. The hydrochemical types of cold karst groundwater are mainly HCO3-Ca and HCO3·SO4-Ca, while geothermal water hydrochemical types are SO4-Ca·Na and SO4-Ca. Groundwater Ca2+, Mg2+, HCO3- and SO42- are mainly controlled by carbonate equilibrium, gypsum dissolution and dedolomitization. Groundwater Na+, K+ and Cl- are mainly derived from halite dissolution, and in geothermal water, they are also affected by incongruent dissolution of albite and K-feldspar. Anthropogenic nitrogen produces ammonium resulting in nitrification and reduction in CO2(g) consumption and HCO3- release from carbonate dissolution. Principal component analysis and inverse models also indicate that nitrification and denitrification have significantly affected water-rock interactions. Our study suggests that karst groundwater quality is dominated by water-rock interactions and elucidates the influence of anthropogenic nitrogen. We believe that this paper will be a good reference point to study anthropogenic influences on the groundwater environment and to protect karst groundwater globally.


Synthesis of Acylated Xylan-Based Magnetic Fe₃O₄ Hydrogels and Their Application for H₂O₂ Detection.
Acylated xylan-based magnetic Fe₃O₄ nanocomposite hydrogels (ACX-MNP-gels) were prepared by fabricating Fe₃O₄ nanoctahedra in situ within a hydrogel matrix which was synthesized by the copolymerization of acylated xylan (ACX) with acrylamide and N-isopropylacrylamide under ultraviolet irradiation. The size of the Fe₃O₄ fabricated within the hydrogel matrix could be adjusted through controlling the crosslinking concentrations (C). The magnetic hydrogels showed desirable magnetic and mechanical properties, which were confirmed by XRD, Raman spectroscopy, physical property measurement system, SEM, TGA, and compression test. Moreover, the catalytic performance of the magnetic hydrogels was explored. The magnetic hydrogels (C = 7.5 wt %) presented excellent catalytic activity and provided a sensitive response to H₂O₂ detection even at a concentration level of 5 × 10-6 mol·L-1. This approach to preparing magnetic hydrogels loaded with Fe₃O₄ nanoparticles endows xylan-based hydrogels with new promising applications in biotechnology and environmental chemistry.


Improving "Life Chances": Surveying the Anti-Transgender Backlash, and Offering a Transgender Equity Impact Assessment Tool for Policy Analysis.
Transgender inclusion within policy is critical yet often missing. We propose a policy tool to assesses human rights, access to resources and opportunities, language, and implications for transgender and nonbinary individuals. Acknowledging trans communities as standard policy practice can serve as an essential practice to shift dialogue and norms.


Blended municipal compost and biosolids materials for mine reclamation: Long-term field studies to explore metal mobility, soil fertility and microbial communities.
Application of stable soil amendments is often the key to successful phytostabilization and rehabilitation of mine tailings, and microbial guilds are primary drivers of many geochemical processes promoted by these amendments. Field studies were set up at a tailings management area near Sudbury, Ontario to examine performance of blends of lime stabilized municipal biosolids and compost at nine different rates over thick (1 m) municipal compost covers planted with agricultural crops. Based on biogeochemical variability of the substrates four and ten years after application of the initial compost cover, the experimental plots could be classified into three categories: "Low" rate (0-100 t ha-1 biosolids), "Medium" rate (200-800 t ha-1), and "High" rate (1600-3200 t ha-1) treatments. The addition of biosolids materials to the thick compost cover at rates higher than 100 t ha-1 significantly reduced C:N ratio of the substrates, available phosphorus, and some of the nutrient cations, while notably increasing inorganic carbon and the potential solubility of Ni and Cu. This suggests that increasing biosolids application rates may not equivalently ameliorate soil quality and geochemical stability. Correspondingly, microbial communities were altered by biosolids additions, further intensifying the negative impacts of biosolids on long-term efficiency of the initial compost cover. Abundance of cellulose, hemicellulose, and lignocellulose decomposers (as key drivers of mineralization and humification) was significantly reduced by "Medium" and "High" rate treatments. Most DNA sequences with high affinity to denitrifiers were detected in "High" rate treatments where geochemical conditions were optimal for higher microbial denitrification activities. These findings have implications for improving the long-term efficiency of reclamation and environmental management programs in mine tailings of northern temperate climates.


Multiple sclerosis presenting at 4 years of age: clinical and MRI correlations.
The authors present a patient with multiple sclerosis (MS) whose onset of illness was at 4 years of age. Three separate and distinct episodes of central nervous system (CNS) dysfunction associated with cerebrospinal fluid (CSF) pleocytosis, electroencephalographic (EEG) abnormalities, and extensive CNS white matter demyelination on both computerized tomography (CT) and magnetic resonance imaging (MRI) characterized her clinical course. Two episodes responded well to prednisone therapy.


Establishment of immortalized Schwann cells from Sandhoff mice and corrective effect of recombinant human beta-hexosaminidase A on the accumulated GM2 ganglioside.
We have established spontaneously immortalized Schwann cell lines from dorsal root ganglia and peripheral nerves of Sandhoff mice. One of the cell lines exhibited genetically and biochemically distinct features of Sandhoff Schwann cells. The enzyme activities toward 4-methylumbelliferyl N-acetyl-beta-D-glucosamine (beta-hexosaminidases A, B, and S) and 4-methylumbelliferyl N-acetyl-beta-D-glucosamine-6-sulfate (beta-hexosaminidases A and S) were decreased, and GM2 ganglioside accumulated in lysosomes of the cells. Incorporation of recombinant human beta-hexosaminidase isozymes expressed in Chinese hamster ovary cells into the cultured Sandhoff Schwann cells via cation-independent mannose 6-phosphate receptors was found, and the incorporated beta-hexosaminidase A degraded the accumulated GM2 ganglioside. The established Sandhoff Schwann cell line is useful for investigation and development of therapies for Sandhoff disease.


Expression of Marek's disease virus in producer and non-producer lymphoblastoid cell lines.
Continuous in vitro propagation of a producer Marek's disease (MD) lymphoblastoid cell line reduced the number of cells producing virus antigens and the inducibility of these antigens to 5-iododeoxyuridine (IUDR) but did not change the oncogenicity of the cells for chickens. In contrast, propagation of a non-producer MD cell line did not change the non-productivity of the cell line, but decreased the transplantability of the cells. The MD lines were free of replicating avian leukosis sarcoma viruses (LSV) and were susceptible to infection with LSV of subgroup A.


The augmented anticancer potential of AP9-cd loaded solid lipid nanoparticles in human leukemia Molt-4 cells and experimental tumor.
AP9-cd, a novel lignan composition from Cedrus deodara has significant anticancer potential, and to further enhance its activity, it was lucratively encumbered into solid lipid nanoparticles (SLNs). These nanoparticles were formulated by micro-emulsion technique with 70% drug trap competence. AP9-cd-SLNs were regular, solid, globular particles in the range of 100-200 nm, which were confirmed by electron microscopic studies. Moreover, AP9-cd-SLNs were found to be stable for up to six months in terms of color, particle size, zeta potential, drug content and entrapment. AP9-cd-SLNs have 30-50% higher cytotoxic and apoptotic potential than the AP9-cd alone. The augmented anticancer potential of AP9-cd-SLNs was observed in cytotoxic IC50 value, apoptosis signaling cascade and in Ehrlich ascites tumor (EAT) model. AP9-cd-SLNs induce apoptosis in Molt-4 cells via both intrinsic and extrinsic pathway. Moreover, the dummy nanoparticles (SLNs without AP9-cd) did not have any cytotoxic effect in cancer as well as in normal cells. Consequently, SLNs of AP9-cd significantly augment the apoptotic and antitumor potential of AP9-cd. The present study provides a podium for ornamental the remedial latent via novel delivery systems like solid lipid nanoparticles.


Cortical neuronal counts in normal elderly controls and demented patients.
The purposes of the investigation were to determine whether there was significant neuronal loss in dementia, and if so, whether it was general or localised, and to examine the relationship between neuronal counts, senile plaques and neurofibrillary change. Neuronal counts were made in nine cortical areas in the brains of 25 patients with senile dementia of the Alzheimer type and twenty-five age-matched controls, with the aid of an image analysing computer. Neuronal counts per square millimetre were significantly lower in the demented group of patients in the inferior frontal and superior temporal gyri. Neuronal counts in four columns of cortex were significantly reduced in superior, middle and inferior frontal gyri, cingulate gyrus and superior and middle temporal gyri. There was no significant difference in the parietal (Brodmann area 7) or occipital (Brodmann area 17) cortex. Corresponding glial counts per square millimetre show a significant increase in the demented group only in the middle and inferior temporal gyri. Neuronal counts correlated weakly but significantly with plaque counts in the same cortical area in the middle frontal gyrus and the superior and middle temporal gyri. High correlations between neuronal counts and estimates of neurofibrillary change were found in superior, middle and inferior frontal gyri, cingulate gyrus and superior and middle temporal gyri.


Structure in a desert rodent community: use of space around Dipodomys spectabilis mounds.
In an earlier paper (Bowers et al. 1987) we reported patterns of microhabitat use by desert rodents among 0.25-ha plots where seeds were added or certain rodent species removed. We used the results to make inferences about the spatial organization of the whole rodent community. Here we change our focus to test for spatial usage patterns at a smaller (within-plot) scale. Specifically, we examine to what extent spatial use varies with proximity to mounded burrows of the large kangaroo rat, Dipodomys spectabilis. Capture frequency of five of nine rodent species was correlated with distance from D. spectabilis mounds, while six species showed correlations with vegetative cover that also increased with distance from mounds. In general, sites nearer mounds were underutilized, and sites further away overutilized by the rodent community as a whole. Logistic regression analyses showed for six species that vegetative cover and particularly, distance to nearest mound accounted for more of the variation in whether a station captured a species than did plot-to-plot (i.e., treatment) effects. Similar analyses using two plots where D. spectabilis was removed (where vacant mounds persited for years) suggested that the selection of microhabitats with contrasting vegetation structure was more pronounced in the absence than in the presence of D. spectabilis, and that in most cases distance from mounds was important only if mounds were occupied. Spatial structure in this community appears to revolve around the occupation of space by dominant individuals that partially modify/obscure large scale patterns involving the selection of particular structural microhabitats.


[Health and investment: How are the 237 billion euro of the German professional pension funds invested?]
Exceeding ecological limits through climate crisis, loss of biodiversity, altered biogeochemical cycles and novel substances is dangerous and leads to increased morbidity. Hence, financial assets should be divested from hazardous industries and re-allocated to support the transformation to an economy that keeps activities within ecological limits. The present study investigates how sustainability criteria are applied to the assets of German pension funds. A survey containing 26 items on 1) business practice, 2) implementation of sustainability strategies, 3) application of ESG criteria to investment decisions, and 4) projects and goals was sent to each and every of 93 German professional pension funds. Furthermore, their annual business reports and publications were analyzed for information on sustainability efforts. 37 of 93 pension funds responded to our survey, 8 of them returned the query. All agreed that ESG criteria are part of their business culture. Predominantly, they adhere to common standards for sustainable investments (UNPRI [United Nations Principles for Responsible Investment], 75% approval); yet, they do not exclude the production of goods that are potentially harmful to health (e.g., tobacco and alcohol). A minority of the participating pension funds agrees that ESG criteria are part of their business culture. However, only few of them provide information about their actual application. Nevertheless, there are pension funds that do not respect sustainability criteria in an appropriate way, and thus take unnecessary financial risks and invest in harmful industries.


Loss of "pacemaker's identity" following activation of the emergency VVI feature.
Electromagnetic signals coming from the pacemaker programmer can permanently damage multiprogrammable pacemakers. At a follow-up of a sixfold programmable VVI pacemaker (Phoenix 251-6, Pacesetter), the emergency VVI button was activated on the programmer after the programming of the pacing impulse had induced a loss of capture. The next telemetrical interrogation revealed an alteration to a threefold programmable Programmalith III. The inadvertent programming of the model number occurred, because the programming head was removed at one very specific time in the programming sequence of the emergency VVI command.


The new method, the old problem - role of contrast-enhanced spectral mammography in the diagnosis of breast cancer among Polish women.
The aim of the study was to evaluate spectral mammography (CESM) in diagnosing breast cancer, which is based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The study included a group of 547 women who underwent spectral mammography and histopathological verification of the lesion, previously seen in mammography and/or ultrasound. In the group of 547 women, 593 focal lesions were diagnosed. All CESM examinations were carried-out with a digital mammography device dedicated to performing dual-energy CESM acquisitions. An intravenous injection of 1.5 ml/kg of body mass of non-ionic contrast agent was performed. The analysis includes 593 breast lesions, in this group cancer was detected in 327 (55.14%) lesions, and in 256 (43.17%) cases benign lesions were confirmed by histopathological examination and at least 12 months of observation. The method shows differentiation of benign and malignant lesions in the breast: sensitivity of 97.86%, specificity of 59.4%, PPV - 74.76%, NPV - 95.76%. Spectral mammography could be an ideal method to detect breast cancer. Thanks to the high NPV (95.76%), it facilitates the exclusion of cancer in situations where pathological contrast enhancement is not observed. The unsatisfactory specificity of the study (59.4%) would not make it safe to avoid a core needle biopsy of lesions that undergo contrast enhancement.


Modifying the Stöber Process: Is the Organic Solvent Indispensable?
The Stöber method is one of the most important and fundamental processes for the synthesis of inorganic (nano)materials but has the drawback of using a large amount of organic solvent. Herein, ethanol was used as an example to explore if the organic solvent in a typical Stöber method can be omitted. It was found that ethanol increases the particle size of the obtained silica spheres and aids the formation of uniform silica particles rather than forming a gel. Nevertheless, the results indicated that an organic solvent in the initial synthesis mixture is not indispensable. An initially immiscible synthesis method was discovered, which can replace the organic solvent-based Stöber method to successfully synthesize silica particles with the same size ranges as the original Stöber process without addition of organic solvents. Moreover, this process can be of further value for the extension to synthesis processes of other materials based on the Stöber process.


Humanistic and economic burden of depression and anxiety among adults with migraine: A systematic review.
Depression and anxiety are well-recognized comorbid health conditions among adults with migraine due to their humanistic and economic burden. This review was conducted to systematically assess the humanistic and economic burden of comorbid depression and/or anxiety disorder among adults with migraine. A systematic literature search was conducted using MEDLINE and CINAHL via EBSCO, EMBASE, and Cochrane Database of Systematic Reviews via OVID. Studies evaluating the humanistic burden and the economic burden of comorbid depression and anxiety among adults with migraine that were published in peer-reviewed English language journals from inception until January 2020 were included. Out of the 640 identified articles, 23 studies were found eligible and included in this review. Regarding the humanistic burden, health-related quality of life (HRQoL) was examined by 11 studies, 7 studies examined disability, while 2 studies evaluated both HRQoL and disability measures. These studies reported an association between depression and/or anxiety and lower HRQoL and higher disability among adults with migraine. Regarding the economic burden, only three studies were identified and all concluded that depression and/or anxiety are significantly associated with higher healthcare expenditures and utilization among adults with migraine. Results of this review highlight the substantial burden of depression and/or anxiety for adults with migraine. Healthcare providers need to identify and treat anxiety and depression for patients living with migraine.


Allergenic components of a novel food, Micronesian nut Nangai (Canarium indicum), shows IgE cross-reactivity in pollen allergic patients.
New foods may present a risk for food hypersensitive patients. Several examples exist of allergic reactions caused by cross-reactive plant-derived foods, and new foods should be scrutinised before introducing them to the market. We have evaluated the clinical and serological relevance of cross-reactivity between Nangai and pollen allergens. Cross-reactivity was examined with Maxisorp RAST (radioallergosorbent test), RAST inhibition and Western blot, using sera from patients allergic to grass, birch and mugwort pollen. None of the patients reported having seen or eaten Nangai previously. To determine the biological and clinical relevance of the cross-reactivity, histamine release (HR) test, skin prick test (SPT) and food challenge were used. There was prevalence for reactivity against Nangai in the group of pollen allergic patients. This cross-reactivity seems to be related--at least in part--to carbohydrate epitopes. Three out of 12 patients tested with Nangai were positive upon open challenge, but using double blind placebo controlled food challenge (DBPCFC) this could not be confirmed in two patients. The biological effects of Nangai on allergic patients were confirmed using HR and SPT. The Nangai specific IgE found among pollen allergic patients addresses the need for control of new or changed foods before introduction to the market.


Prevalence of abnormal findings on brain magnetic resonance (MR) examinations in adult participants of brain docking.
To determine the prevalence of abnormal findings on brain magnetic resonance (MR) examinations in adult participants of brain docking in order to assess its usefulness. We analyzed screening brain MR examinations for 1113 adults (age, 52.6+/-8.5 years; range, 22-84; 761 male and 352 female) performed during 6-year period from April 1998 to March 2004. All participants voluntarily sought a brain MR examination at their own expense. All subjects were studied using the same 1.0-T MR scanner, on axial T1-weighted spin echo (SE) images, proton-density-weighted and T2-weighted fast SE images, and intracranial MR angiography (MRA). All abnormal findings were classified into three basic categories: (1) findings with no referral necessary; (2) findings not requiring further evaluation, but which needed to be reported to the referring physician; (3) findings requiring further evaluation. Participants with abnormal MR findings requiring further evaluation accounted for 1.3 %, but five of seven suspected intracranial aneurysms were not confirmed by other imaging modalities (false positive). No malignant tumors or other life-threatening pathology was detected, and only three participants (0.27 %) with abnormalities underwent surgical treatment. No participant groups were identified from our data as being high risk for MR abnormal findings requiring further evaluation. Brain-docking participants had a variety of abnormalities on brain MR examinations, but only a small percentage of these findings required further evaluation. The usefulness of the brain docking with MRI and MRA has yet to be proven, and at this time we cannot approve this screening procedure.


Sapovirus infections in Japan before and after the emergence of the COVID-19 pandemic: An alarming update.
An increasing trend of sapovirus (SaV) infections in Japanese children during 2009-2019, particularly after the introduction of the voluntary rotavirus (RV)-vaccination program has been observed. Herein, we investigated the epidemiological situation of SaV infections from 2019 to 2022 when people adopted a precautionary lifestyle due to the emergence of the COVID-19 pandemic, and RV vaccines had been implemented as routine vaccines. Stool samples were collected from children who attended outpatient clinics with acute gastroenteritis and analyzed by reverse transcriptase-polymerase chain reaction to determine viral etiology. Among 961 stool samples, 80 (8.3%) were positive for SaV: 2019-2020 (6.5%), 2020-2021 (0%), and 2021-2022 (12.8%). The trend of SaV infection in Japanese children yet remained upward with statistical significance (p = 0.000). The major genotype was GI.1 (75%) which caused a large outbreak in Kyoto between December 2021 and February 2022. Phylogenetic, gene sequence and deduced amino acid sequence analyses suggested that these GI.1 strains detected in the outbreak and other places during 2021-2022 or 2019-2020 remained genetically identical and widely spread. This study reveals that SaV infection is increasing among Japanese children which is a grave concern and demands immediate attention to be paid before SaV attains a serious public health problem.


Novel MAO-B inhibitors: potential therapeutic use of the selective MAO-B inhibitor PF9601N in Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disease that is characterized by preferential loss of dopaminergic neurons in the substantia nigra pars compacta, leading to declining levels of dopamine in the striatum. In our search for compounds able not only to extend the effects of dopamine by preventing its degradation but also to halt or slow the neurodegenerative process, we designed, synthesized, and biologically tested a series of propargylamines for their potential use as therapeutic agents for PD. Among them, PF9601N, [N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine], showed high potency and selectivity as a MAO-BI (monoamine oxidase type B inhibitor) and also demonstrated remarkable neuroprotective properties in several in vivo and cellular models of PD. In this chapter, we describe the preclinical evidence revealing the novel MAO-BI PF9601N as an interesting candidate for the treatment of PD.


Cartilage formation in a hollow fiber bioreactor studied by proton magnetic resonance microscopy.
The ideal in vitro system for investigating the regulation of cartilage formation and maintenance would allow for three-dimensional tissue growth, a wide range of biochemical interventions, and non-destructive evaluation. We have developed a hollow fiber bioreactor (HFBR) system which meets these criteria. After injection with embryonic chick sternal chondrocytes, neocartilage is elaborated around the hollow fibers, reaching a thickness of up to a millimeter after four weeks of growth. This process was monitored over time with nuclear magnetic resonance (NMR) microimaging and correlative biochemical and histologic analyses. Tissue volume and cellularity increased greatly during development. This was accompanied by changes in magnetic resonance properties consistent with increased macromolecular content. Further, tissue heterogeneity, observed as regional variations in cell size in histologic sections, was also observed in quantitative NMR images.


O-ATRP synthesized poly(β-pinene) blended with chitosan for antimicrobial and antioxidant bio-based films production.
Antioxidant and antimicrobial activities are important characteristics of active film packaging designed to extend food preservation. In this study, functional bio-based films were produced using different concentrations of antioxidant poly(β-pinene) bio-oligomer synthesized via organocatalyzed atom transfer radical polymerization (O-ATRP) and blended with chitosan of different molecular weights. The structural, mechanical, thermal, solubility, antioxidant, and antimicrobial properties of the films were investigated. The poly(β-pinene)-chitosan blends presented significant pores and irregularities with the increase of poly(β-pinene) concentration over 30%. Chitosan molecular weight did not show any important influence in the physical properties of the blends. Poly(β-pinene) load decreased the materials' tensile strength and melting temperature, exhibiting a plasticizing effect on chitosan chains. The antioxidant and antimicrobial activities of the films were improved by poly(β-pinene) incorporation and mainly depended on its concentration. Therefore, the incorporation of poly(β-pinene) in chitosan films can be an alternative for active packaging production.


Differential susceptibility to epithelial-mesenchymal transition (EMT) of alveolar, bronchial and intestinal epithelial cells in vitro and the effect of angiotensin II receptor inhibition.
The generation of myofibroblasts via epithelial-mesenchymal transition (EMT), a process through which epithelial cells lose their polarity and become motile mesenchymal cells, is a proposed contributory factor in fibrosis of a number of organs. Currently, it remains unclear to what extent epithelia of the upper airways and large intestine are susceptible to this process. Herein, we investigated the ability of model cell lines of alveolar (A549), bronchial (Calu-3) and colonic (Caco-2) epithelial cells to undergo EMT when challenged with transforming growth factor-β1 (TGF-β1) and other pro-inflammatory cytokines. Western blot and immunofluorescence microscopy demonstrated that A549 cells readily underwent EMT, as evidenced by a spindle-like morphology, increase in the mesenchymal marker, vimentin, and down-regulation of E-cadherin, an epithelial marker. In contrast, neither Calu-3 nor Caco-2 cells exhibited morphological changes nor alterations in marker expression associated with EMT. Moreover, whilst stimulation of A549 cells enhanced migration and reduced their proliferative capacity, no such effect was observed in epithelial cell lines of the bronchus or colon. In addition, concomitant treatment of A549 cells with telmisartan, an angiotensin II receptor antagonist with antifibrotic properties, was found to reduce cytokine-induced collagen I production and cell migration, although expression levels of vimentin and E-cadherin remained unaltered. Mechanistically, telmisartan failed to inhibit phosphorylation of Smad2/3. Together, these results, using representative in vitro models of the alveolus, bronchus and colon, tentatively suggest that epithelial cell plasticity and susceptibility to EMT may differ depending on its tissue origin. Furthermore, our investigations point to the beneficial effect of telmisartan in partial abrogation of alveolar EMT.


Reproductive health issues in rural Western Kenya.
We describe reproductive health issues among pregnant women in a rural area of Kenya with a high coverage of insecticide treated nets (ITNs) and high prevalence of HIV (15%). We conducted a community-based cross-sectional survey among rural pregnant women in western Kenya. A medical, obstetric and reproductive history was obtained. Blood was obtained for a malaria smear and haemoglobin level, and stool was examined for geohelminths. Height and weight were measured. Of 673 participants, 87% were multigravidae and 50% were in their third trimester; 41% had started antenatal clinic visits at the time of interview and 69% reported ITN-use. Malaria parasitemia and anaemia (haemoglobin < 11 g/dl) were detected among 36% and 53% of the women, respectively. Geohelminth infections were detected among 76% of the 390 women who gave a stool sample. Twenty percent of women were underweight, and sixteen percent reported symptoms of herpes zoster or oral thrush in the last two months. Nineteen percent of all women reported using a contraceptive method to delay or prevent pregnancy before the current pregnancy (injection 10%, pill 8%, condom 0.4%). Twenty-three percent of multigravidae conceived their current pregnancy within a year of the previous pregnancy. More than half of the multigravidae (55%) had ever lost a live born child and 21% had lost their last singleton live born child at the time of interview. In this rural area with a high HIV prevalence, the reported use of condoms before pregnancy was extremely low. Pregnancy health was not optimal with a high prevalence of malaria, geohelminth infections, anaemia and underweight. Chances of losing a child after birth were high. Multiple interventions are needed to improve reproductive health in this area.


tert-butyl hydroperoxide-dependent microsomal release of iron and lipid peroxidation. I. Evidence for the reductive release of nonheme, nonferritin iron.
Rat liver microsomes were found to contain a small pool of nonheme, nonferritin iron. In the presence of ADP, low concentrations of tert-butyl hydroperoxide promoted the reductive release of nonheme, nonferritin iron, as evidenced by mobilization of bathophenanthroline-chelatable Fe2+. Iron release was inhibited by SKF 525-A and metyrapone, which are known to interfere with cytochrome P450-catalyzed reactions. Iron release was also inhibited by high concentrations of t-BOOH, which caused rapid and extensive destruction of cytochrome P450. These observations suggested that iron release was catalyzed by cytochrome P450. Treatment of rats with phenobarbital (PB) caused simultaneous increase of cytochrome P450 and decrease of nonheme, nonferritin iron. The effects of PB were minimized by simultaneous administration of hematin, an inhibitor of heme synthesis, indicating that the nonheme iron was utilized for the synthesis of the heme iron of inducible cytochrome P450 isozymes. Consistently, microsomes from the liver of PB-treated rats were found to release low amounts of Fe2+, unless rats had also been treated with hematin to prevent utilization of nonheme, nonferritin iron for the synthesis of heme iron.


Computational insights into the substrate recognition mechanism of cartilage extracellular matrix degradation.
Articular cartilage is connective tissue that forms a slippery load-bearing joint surface between bones. With outstanding mechanical properties, it plays an essential role in cushioning impact and protecting the ends of bones. Abnormal mechanical stimulation, such as repetitive overloading or chondral injury, induces excessive cartilage extracellular matrix (ECM) degradation, leading to osteoarthritis and other joint disorders. A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) is an aggrecanase that dominates the catalysis of aggrecan, the major proteoglycan in the cartilage ECM. Intriguingly, unlike its critical cleavage site Glu373-374Ala, another potential cleavage site, Glu419-420Ala, composed of the same amino acids in the aggrecan interglobular domain, is not a major cleavage site. It remains unclear how ADAMTS-5 distinguishes between them and hydrolyzes the correct scissile bonds. This research introduces a bottom-up in silico approach to reveal the molecular mechanism by which ADAMTS-5 recognizes the cleavage site on aggrecan. It is hypothesized that the sequence in the vicinity assists ADAMTS-5 in positioning the cleavage site. Specific residues were found to serve as binding sites, helping aggrecan bind more stably and fit into the enzyme better. The findings provide insight into the substrate binding and recognition mechanism for cartilage ECM degradation from a brand new atomic-scale perspective, laying the foundation for prophylaxis and treatment of related joint diseases.


Repeated administration of AC-5216, a ligand for the 18 kDa translocator protein, improves behavioral deficits in a mouse model of post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD) is a severely disabling anxiety disorder that may occur following exposure to a serious traumatic event. It is a psychiatric condition that can afflict anyone who has experienced a life-threatening or violent event. Previous studies have shown that changes in 18 kDa translocator protein (TSPO) expression (or function), a promising target for treating neurological disorders without benzodiazepine-like side effects, may correlate with PTSD. However, few studies have investigated the anti-PTSD effects of TSPO ligands. AC-5216, a ligand for TSPO, induces anxiolytic- and anti-depressant-like effects in animal models. The present study aimed to determine whether AC-5216 ameliorates PTSD behavior in mice. Following the training session consisting of exposure to inescapable electric foot shocks, animals were administered AC-5216 daily during the behavioral assessments, i.e., situational reminders (SRs), the open field (OF) test, the elevated plus-maze (EPM) test, and the staircase test (ST). The results indicated that exposure to foot shocks induced long-term behavioral deficiencies in the mice, including freezing and anxiety-like behavior, which were significantly ameliorated by repeated treatment with AC-5216 but without any effect on spontaneous locomotor activity or body weight. In summary, this study demonstrated the anti-PTSD effects of AC-5216 treatment, suggesting that TSPO may represent a therapeutic target for anti-PTSD drug discovery and that TSPO ligands may be a promising new class of drugs for the future treatment of PTSD.


Ruder syndrome. Clinical and pathologic correlation.
Ruder syndrome is an unusual varient of adrenal hyperfunction characterized clinically by debilitating osteopenia, and pathologically by bilateral micronodular adrenal hyperplasia. A unique case resembling Ruder syndrome is described in which the dominant pathologic feature was unilateral adrenal adenomatosis.


Voltage-gated sodium channels confer excitability to human odontoblasts: possible role in tooth pain transmission.
Odontoblasts are responsible for the dentin formation. They are suspected to play a role in tooth pain transmission as sensor cells because of their close relationship with nerve, but this role has never been evidenced. We demonstrate here that human odontoblasts in vitro produce voltage-gated tetrodotoxin-sensitive Na(+) currents in response to depolarization under voltage clamp conditions and are able to generate action potentials. Odontoblasts express neuronal isoforms of alpha2 and beta2 subunits of sodium channels. Co-cultures of odontoblasts with trigeminal neurons indicate a clustering of alpha2 and beta2 sodium channel subunits and, at the sites of cell-cell contact, a co-localization of odontoblasts beta2 subunits with peripherin. In vivo, sodium channels are expressed in odontoblasts. Ankyrin(G) and beta2 co-localize, suggesting a link for signal transduction between axons and odontoblasts. Evidence for excitable properties of odontoblasts and clustering of key molecules at the site of odontoblast-nerve contact strongly suggest that odontoblasts may operate as sensor cells that initiate tooth pain transmission.


Healthy lifestyles in pre-service teachers in Israel: the impact of academic institutions.
This study examines the impact of academic institutions on changes to students' awareness and habits regarding a healthy lifestyle, specifically through nutrition and physical exercise, following the Covid-19 pandemic. In May 2020, quantitative online questionnaires were completed by 266 pre-service teachers (83.5% female), aged 19-63, who were studying at an academic institution in Israel. The questionnaire, which included health-related 15 items, as well as a number of demographic questions, was distributed via social media, academic mailing lists, and the researchers' colleagues. The respondents were asked to provide socio-demographic data and information regarding their health-related habits, such as smoking and exercising, at two timepoints: prior to the Covid-19 pandemic and during the first lockdown in Israel (March-May 2020). Statistical analysis included paired t-tests, Wilcoxon and McNemar tests, Pearsons's correlations, and hierarchical regressions. The academic institution's promoting of a healthy lifestyle, as perceived by students, was found to contribute to the explained variance (EPV) of their maintaining a healthy lifestyle, prior to and during the Covid-19 pandemic (R2 = 9.4%, p < .001and R2 = 2.4%, p = 0.009, respectively), beyond the respondents' demographic characteristics. Moreover, correlations were found between the institution's promoting of a healthy lifestyle at both timepoints. Respondents who perceived their institution as promoting a healthy lifestyle prior to the pandemic maintained healthier lifestyles than their peers; healthier lifestyles were also maintained by respondents who were unmarried, non-smokers, more educated, and watched less television. Finally, the institution's promoting of a healthy lifestyle prior to the pandemic significantly contributed to the students' maintaining a healthy lifestyle and healthy nutrition during the pandemic. The findings of this study highlight the impact of academic institutions on maintaining healthy lifestyles, even in times of crises and emergencies, thereby contributing to public health.


Fractionation and characterization of saccharides and lignin components in wood prehydrolysis liquor from dissolving pulp production.
Saccharides and lignin components in prehydrolysis liquor (PHL) from kraft-based dissolving pulp production was characterized after being fractionated using membrane filtration. The results showed that the membrane filtration provided a method for organics fractionation with considerable recovery rate, but exhibited some disadvantages. Besides the limited ability in purifying oligosaccharides (OS) due to the overlaps of molecular weight distribution with lignin components, the membrane filtration could not improve the homogeneity of OS as indicated by the analysis of chemical compositions and the degree of polymerization (DP), which may be ascribed to the linear conformation of OS. The characterization of lignin components indicated a great potential for polymer industry because of the remarkable content of phenolic hydroxyl groups (PhOH), especially for low molecular weight (LMW) fraction. It was concluded the organics in PHL provided streams of value-added chemicals. However, the practical significance thereof can be realized and maximized only when they are successfully and completely fractionated.


Erythema elevatum diutinum, cryoglobulinaemia, and fixed urticaria on cooling.
A mixed cryoglobulin (IgG/IgM) was detected in a patient with erythema elevatum diutinum. Cold exposure activated the complement system and provoked a fixed urticarial reaction with the histology of a leukocytoclastic vasculitis.


The permeation and activation properties of brain sodium channels change during development.
BTX-modified sodium channels from 15-day embryonic (E15) rat forebrains were studied in planar lipid bilayers. Compared to postnatal sodium channels, E15 channels had a lower maximal single channel conductance, whereas their permeation pathway sensed a comparable surface charge density and had a similar apparent binding affinity for sodium ions. The steady-state activation curve of E15 channels was significantly more hyperpolarized and had a shallower slope than postnatal channels. The apparent BTX binding affinity was significantly lower for E15 channels than for postnatal channels. Finally, E15 channel alpha-subunits displayed a lower apparent molecular weight, and a lower sialylation level than postnatal sodium channel alpha-subunits. Together with previous studies, our data suggested that the observed functional differences between E15 and postnatal voltage-dependent sodium channels cannot be explained solely by the observed differences in channel sialylation, and hence they also appeared to reflect the presence of other channel structural differences.


Introduction of a New Interesting Walnut Cultivar "Leto".
Ιn an effort to create walnut cultivars (Juglans regia) with high productivity, fruit quality and lateral bearing, a new cultivar, named "Leto", was created by the cross "Gustine" × "Pedro". Its main phenological and pomological characteristics were assessed according to the criteria of IPGR (1994) and UPOV-TG/125/6 (1999), for 10 consecutive years and compared with its maternal cultivars and "Chandler". Observations showed that "Leto" has high lateral bearing habit (90%) and presents satisfactory yield at the full production age. The tree size is smaller than that of its parents and "Chandler", female flowers bloom from 11 to 22 of April and male from 3 to 6 of April. "Leto" nuts are harvested at the end of September, present easy hull dehiscence and high kernel percentage. Other positive nut characteristics of "Leto" are light kernel color, well kernel filling and easy removal of the kernel halves. "Leto" is a mid-early cultivar of great interest due to its high- quality nuts, suitable for dense plantings, in regions where the last spring frosts occur in late March to early April, thus, making it a promising cultivar for Greece, but also for other regions with similar geomorphological and climatic conditions.


A potentially crucial role of the PKD1 C-terminal tail in renal prognosis.
Autosomal dominant polycystic disease (ADPKD) often results in renal failure. Recently, allelic influences of PKD1 mutation types on renal survival were extensively investigated. Here, we analyzed integrated influences of PKD1 mutation types and positions on renal survival. We included 338 (82 pedigrees) and 72 (12 pedigrees) patients with PKD1 and PKD2 mutations, respectively, identified through comprehensive gene analysis of 101 probands with ADPKD. Genetic testing was performed using next-generation sequencing, long-range PCR, and multiplex ligation-dependent probe amplification. Pathogenic mutations were identified by a software package-integrated seven databases and provided access to five cloud-based computing systems. Mean renal survivals of carriers with PKD1 non-truncating-type mutations at positions upstream of G-protein-coupled receptor proteolytic site (GPS-upstream domain), transmembrane domain, or cytoplasmic C-terminal tail (CTT) domain were 70.2, 67.0, and 50.1 years, respectively (P < 0.0001); renal survival was shorter for mutation positions closer to CTT domain, suggesting its crucial role in renal prognosis. Furthermore, in truncating-type mutations, strong inactivation is anticipated on nucleotides downstream from the mutation site, implying CTT domain inactivation irrespective of mutation site. Shorter mean renal survival was found for PKD1 truncating-type than non-truncating-type mutation carriers (P = 0.0348); mean renal survival was not different between PKD1 3'- and 5'-region truncating-type mutation carriers (P = 0.4375), but was shorter in PKD1 3'-region than in 5'-region non-truncating-type mutation carriers (P = 0.0014). Variable strength of CTT domain inactivation might account for these results. Aforementioned findings indicate that CTT domain's crucial role in renal prognosis needs further investigation by larger studies (ClinicalTrials.gov; NCT02322385).


Successful endoscopic cyanoacrylate injection therapy for ruptured duodenal varices immediately after balloon-occluded retrograde transvenous obliteration.
We present a rare case of acute duodenal variceal rupture after B-RTO that was successfully treated with endoscopic CA injection therapy. A 74-year-old Japanese woman was transferred to our hospital due to progressive general malaise and hematemesis. Gastroduodenoscopy (GDS) showed duodenal varices without active bleeding in the second portion of duodenum. Balloon-occluded retrograde transvenous obliteration (B-RTO) was carried out to prevent duodenal variceal rebleeding. Good pooling of ethanolamine oleate with iopamidol (EOI) was observed in duodenal varices using balloon catheters. However, massive melena was observed immediately after B-RTO. Emergent GDS revealed a white plug on the treated varix, thus endoscopic cyanoacrylate (CA) injection therapy was performed. We speculated that the injection of EOI increased the pressure in the duodenal varices which resulted in rupture of duodenal varices. B-RTO was effective therapy to prevent duodenal variceal rebleeding, but postprocedural monitoring is required as illustrated by this case. We suggest that careful monitoring and backup system for endoscopy are required during or after B-RTO.


Neonatal extracorporeal renal replacement therapy-a routine renal support modality?
Peritoneal dialysis (PD) is generally considered the preferred extracorporeal therapy for neonates with acute kidney injury (AKI). However, there are situations when PD is not suitable, such as in patients with previous abdominal surgery, hyperammonemia and significant ascites or anasarca. Additionally, with a need to start PD soon after catheter placement, there is increased risk of PD catheter leak and infection. Extracorporeal continuous renal replacement therapy (CRRT) is challenging in severely ill neonates as it requires obtaining adequately sized central venous access to accommodate adequate blood flow rates and also adaptation of a CRRT machine meant for older children and adults. In addition, ultrafiltration often cannot be set in sufficiently small increments to be suitable for neonates. Although CRRT practices can be modified to fit the needs of infants and neonates, there is a need for a device designed specifically for this population. Until that becomes available, providing the highest level of care for neonates with AKI is dependent on the shared experiences of members of the pediatric nephrology community.


Cloning and characterization of the peroxisomal acyl CoA oxidase ACO3 gene from the alkane-utilizing yeast Yarrowia lipolytica.
The ACO3 gene, which encodes one of the acyl-CoA oxidase isoenzymes, was isolated from the alkane-utilizing yeast Yarrowia lipolytica as a 10 kb genomic fragment. It was sequenced and found to encode a 701-amino acid protein very similar to other ACOs, 67.5% identical to Y. lipolytica Aco1p and about 40% identical to S. cerevisiae Pox1p. Haploid strains with a disrupted allele were able to grow on fatty acids. The levels of acyl-CoA oxidase activity in the ACO3 deleted strain, in an ACO1 deleted strain and in the wild-type strain, suggested that ACO3 encodes a short chain acyl-CoA oxidase isoenzyme. This narrow substrate spectrum was confirmed by expression of Aco3p in E. coli.


A highly tumor-specific light-triggerable drug carrier responds to hypoxic tumor conditions for effective tumor treatment.
Light-triggered drug delivery is among the most investigated stimulus-response strategies and has been widely explored in cancer treatment. However, the limited specificity of light-triggered drug delivery reduces the therapeutic efficacy and causes considerable undesirable side effects. In this work, we demonstrate a highly tumor-specific light-triggerable drug carrier (H-LTDC) induced by a combination of internal (i.e., tumor hypoxia) and external stimuli (i.e., light). The doxorubicin (DOX)-loaded H-LTDC was self-assembled from type-1-reactive oxygen species (ROStype1)-mediated degradable chondroitin sulfate (CS) conjugated with a photosensitizer (PS), Pheophorbide-a, which has a spherical shape and a uniform size distribution. Under hypoxic conditions, ROSType1 was mainly generated due to the electron-rich sulfate groups in the polysaccharide backbone. The ROStype1 generated by H-LTDC allowed laser-triggered drug release at low oxygen concentrations. From the in vitro cytotoxicity tests with colon cancer cells (HCT-116), under laser irradiation, DOX-loaded H-LTDCs showed higher toxicity under hypoxic conditions than that under normoxic conditions. In vivo and ex vivo biodistribution studies demonstrated that H-LTDCs selectively accumulated in the tumor tissues. As a result, drug-loaded H-LTDCs exhibited high anti-tumor activity in vivo. Overall, we believe that this approach could represent a promising platform for the treatment of tumor and hypoxia-associated diseases without undesirable side effects.


Calmodulin and cyclic AMP. Possible different sites of action of these two regulatory agents in exocytotic hormone release.
It may now be possible to identify certain intracellular events that impact specifically on secretion-granule fusion to the plasma membrane or on granule lysis. Secretion vesicles in isolated rat islets appear to translocate somatostatin (SRIF) receptors from the Golgi apparatus to the plasma membrane. We have proposed that secretion granule fusion to the plasma membrane can be determined by measuring recruitment of SRIF receptors to the surface membrane. Granule lysis can be assessed by measuring insulin release. To activate cyclic AMP (cAMP)-dependent pathways, we employed isobutylmethylxanthine (IBMX, 400 microM), glucagon (10 microM), and forskolin (20 microM), a diterpene activator of adenylate cyclase. These agents evoked rapid release of insulin (from 0.41 +/- 0.02 to 1.88 +/- 0.02; 0.41 +/- 0.02 to 1.93 +/- 0.08; and 0.41 +/- 0.02 to 1.66 +/- 0.03 microU/islet/min, respectively, P less than 0.001). There was no concomitant recruitment of SRIF receptors. Somatostatin (10 micrograms/ml), which inhibits cAMP-stimulated protein phosphorylation, suppresses insulin release evoked by IBMX, glucagon, or forskolin (inhibition: 80, 75, or 82%, respectively). In contrast, trifluoperazine (10 microM), an inhibitor of calmodulin, did not suppress insulin release induced through cAMP-dependent pathways. Trifluoperazine suppresses glucose-induced insulin release and the recruitment of SRIF receptors to the surface membrane, suggesting the possible role of calmodulin in promoting secretion-granule fusion with the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of Glottal Inverse Filtering in the Presence of Source-Filter Interaction.
The validity of glottal inverse filtering (GIF) to obtain a glottal flow waveform from radiated pressure signal in the presence and absence of source-filter interaction was studied systematically. A driven vocal fold surface model of vocal fold vibration was used to generate source signals. A one-dimensional wave reflection algorithm was used to solve for acoustic pressures in the vocal tract. Several test signals were generated with and without source-filter interaction at various fundamental frequencies and vowels. Linear Predictive Coding (LPC), Quasi Closed Phase (QCP), and Quadratic Programming (QPR) based algorithms, along with supraglottal impulse response, were used to inverse filter the radiated pressure signals to obtain the glottal flow pulses. The accuracy of each algorithm was tested for its recovery of maximum flow declination rate (MFDR), peak glottal flow, open phase ripple factor, closed phase ripple factor, and mean squared error. The algorithms were also tested for their absolute relative errors of the Normalized Amplitude Quotient, the Quasi-Open Quotient, and the Harmonic Richness Factor. The results indicated that the mean squared error decreased with increase in source-filter interaction level suggesting that the inverse filtering algorithms perform better in the presence of source-filter interaction. All glottal inverse filtering algorithms predicted the open phase ripple factor better than the closed phase ripple factor of a glottal flow waveform, irrespective of the source-filter interaction level. Major prediction errors occurred in the estimation of the closed phase ripple factor, MFDR, peak glottal flow, normalized amplitude quotient, and Quasi-Open Quotient. Feedback-related nonlinearity (source-filter interaction) affected the recovered signal primarily when f o was well below the first formant frequency of a vowel. The prediction error increased when f o was close to the first formant frequency due to the difficulty of estimating the precise value of resonance frequencies, which was exacerbated by nonlinear kinetic losses in the vocal tract.


Regional changes in myocardial acid production during ischemic arrest: a comparison of sanguineous and asanguineous cardioplegia.
Regional differences in myocardial acid production have not been characterized during administration of either asanguineous or sanguineous cardioplegia. To investigate this, miniature glass pH electrodes were placed in the right ventricular (RV) myocardium, the left ventricular subendocardial (LV endo) region, and the subepicardial (LV epi) region in a canine model. Multiple doses of either blood cardioplegia (Group 1; N = 11) or crystalloid cardioplegia (Group 2; N = 11) were administered during 4 hours of aortic cross-clamping. The accumulation of hydrogen ions during the cross-clamp period was greater in Group 2 than Group 1 in the LV endo region (629 +/- 79 nm/L versus 66 +/- 31 nm/L; p less than 0.001), the LV epi region (623 +/- 66 nm/L versus 72 +/- 32 nm/L; p less than 0.001), and the RV myocardium (814 +/- 296 nm/L versus 150 +/- 54 nm/L; p less than 0.05). Within each group, the time course of myocardial pH and the accumulation of hydrogen ions did not differ among the LV endo region, LV epi region, and the RV myocardium (p = not significant). These data indicate that transmural and interventricular differences in myocardial pH and hydrogen ion accumulation are not produced in the vented, arrested canine heart. In addition, when compared with asanguineous cardioplegia, blood cardioplegia globally and transmurally reduces acid accumulation during ischemic arrest.


Nitric oxide is involved in establishing the balance between cell cycle progression and cell death in the developing neural tube.
Endogenous nitric oxide (NO) has recently been shown to affect cell cycle progression in the neural tube (NT) of the chick embryo. High NO levels trigger entry into S phase basally, while low NO levels facilitate mitosis apically. Here, we further explore the involvement of NO in determining cell numbers in the chick NT. In addition to the effect of short-term (6 h) NOS inhibition, we have observed a concomitant decrease in programmed cell death (PCD). Paradoxically, long-term (12 h) NOS inhibition caused an increase in PCD to compensate for the high proliferation rate under these conditions. Long-term treatment with a NO donor caused a decrease in S phase and increased PCD. The effects produced by the NO donor could be alleviated by folic acid that facilitated entry into S phase and prevented PCD. The effects produced by NOS inhibition (12 h) could be overcome by an embryo extract, used as a source of extracellular survival factors that enhanced proliferation and prevented PCD. Taken together, these data demonstrate that changing endogenous NO levels affect the balance between cell proliferation and PCD in NT of the developing chick embryo.


A cholangiocellular carcinoma nude mouse strain showing histologic alteration from adenocarcinoma to squamous cell carcinoma.
Adenosquamous carcinoma and squamous cell carcinoma (SCC) occur rarely in the liver compared with adenocarcinoma, and the histogenesis and biologic behaviors of these tumors remain unknown. The authors addressed these issues in the current article. A specimen aseptically obtained from the surgically resected cholangiocellular carcinoma (CCC) was cut into pieces and inoculated into the back of a nude mouse, bilaterally. The developed tumors were resected and serially transplanted into nude mice. The morphologic features and growth kinetics of the nude mouse tumors at different passages were compared. The authors established a new human CCC nude mouse strain, designated nuKMC-2, from a 64-year-old woman. The original tumor of the patient showed the features of moderately differentiated tubular adenocarcinoma with small sheet-like arrangement of polygonal cells. The initial tumor developed in a nude mouse showed morphologic features similar to the original tumor. With the serial transplantation to nude mice, the components of tubular adenocarcinoma diminished, and all of the nuKMC-2 was replaced by SCC. Doubling times of nuKMC-2 at the 5th and 11th passages were 9.9 and 7.4 days, respectively, which suggested that the tumor with squamous components were more aggressive biologically than the adenocarcinoma. The results suggested that adenosquamous carcinoma might be a transitional form from adenocarcinoma to SCC and that some of the primary hepatic SCC might originate from adenocarcinomas.


Ca2+ uptake during capacitation of mouse spermatozoa and the effect of an anion transport inhibitor on Ca2+ uptake.
With a specially constructed chamber, Ca2+ uptake by mouse spermatozoa was monitored continuously during capacitation and the acrosome reaction. It was shown, using calcium ion-selective microelectrodes, that there was an initial uptake of Ca2+ by spermatozoa undergoing capacitation. Such net transport was also promoted by the divalent cation ionophores A23187 or ionomycin. An anion inhibitor, SITS, produced dose-dependent inhibition of Ca2+ uptake. This inhibitor reduced the incidence of capacitation as revealed by a reduction in the B pattern by chlortetracycline (CTC) assay and thus inhibited fertilization, suggesting that anions are involved in calcium uptake in mouse spermatozoa.


Neonatal benign sacrococcygeal teratoma with N-type rectobulbar fistula.
A unique case of benign sacrococcygeal teratoma associated with an N-type rectobulbar fistula is reported.


Potential association between prediabetic conditions and gingival and/or periodontal inflammation.
Prediabetic conditions, which include impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), might be associated with chronic gingival and/or periodontal inflammation. However, the occurrence of this oral inflammation in prediabetic conditions is poorly understood. The present study aimed to assess the association between prediabetes and gingival and/or periodontal inflammation. A total of 94 Puerto Rican men and women aged 40-65 years, who were residents of San Juan, Puerto Rico, and free of diabetes, were included in the study. All participants had at least one tooth site with clinical attachment loss ≥3 mm. Fasting and 2-h plasma glucose were collected. Gingival/periodontal inflammation was assessed by bleeding on gentle probing of the sulcus at six sites per tooth. Participants with the percentage of teeth with bleeding on probing (BOP) equal to or greater than the median were compared with those with the percentage of teeth with BOP less than median. Participants with high BOP tended to present higher IFG (odds ratio [OR] 5.5, 95% confidence interval [CI] 1.2-25.3) and/or prediabetic condition (OR 3.6, 95% CI 1.0-13.2) than those with a low percentage of BOP, adjusting for age, sex, smoking, alcohol consumption, waist circumference and number of missing teeth. Using the continuous form of the outcome, the corresponding adjusted least squares means of percentage of BOP were 26.8 (standard error of the mean [SEM] 2.3) and 43.8 (SEM 6.0) in normal and IFG, respectively (P = 0.01), and 27.0 (SEM 2.4) and 39.0 (SEM 5.3) among healthy and prediabetic individuals, respectively (P = 0.05). IFG and/or prediabetes are strongly associated with BOP, a marker of chronic gingival/periodontal inflammation.


IMA-graft patency control by thermal coronary angiography during coronary bypass surgery.
Thermal coronary angiography (TCA) was evaluated for the intraoperative assessment of graft patency and flow in internal mammary artery (IMA) bypass grafts. TCA was performed in 210 patients undergoing 460 vein and 153 IMA bypass grafts after completion of the distal anastomoses. The IMA grafts and the recipient coronary arteries were delineated by the temperature differential between a cold epimyocardium and the perfusing warm blood after bulldog clamp release. TCA provided information about graft and anastomosis patency, initial flow patterns, and native coronary stenoses. TCA was performed in all studied IMA bypass grafts: 142 grafts were patent. Low flow but patency was observed in 24 IMA grafts and 11 IMA grafts showed no flow. Subsequently, 8 anastomotic failures and 3 proximal IMA graft occlusions were encountered. Based on these findings, 8 anastomoses were successfully revised and 7 additional vein grafts were added. One low flow IMA graft was not revised leading to postoperative ST elevation. Thirty-one distal native coronary stenoses were detected in the recipient LADs, 3 of which were not seen in the preoperative cineangiogram. In 20 instances, TCAs were obscured by an excess of fat or myocardium impeding image analysis. In 8 cases, TCA results were confirmed by conventional angiography postoperatively showing an excellent correlation in all cases. We conclude that intraoperative TCA demonstrates early IMA graft function and initial flow patterns. During our study, TCA documented a 7.2% IMA graft early failure rate. Intraoperative decision making was aided by TCA in 9.2% of all IMA grafts; this confirmed the clinical relevance of TCA.


Possible route of antigen uptake by the Harderian gland of the domestic fowl.
India ink and colloidal gold dropped on to the eyeball of chickens travelled up the secretory duct to reach the Harderian gland. 2. It is suggested that this is the route by which exogenous antigens reach the gland.


An activated-platelet-sensitive nanocarrier enables targeted delivery of tissue plasminogen activator for effective thrombolytic therapy.
It remains a major challenge to develop a selective and effective fibrinolytic system for thrombolysis with minimal undesirable side effects. Herein, we report a multifunctional liposomal system (164.6 ± 5.3 nm in diameter) which can address this challenge through targeted delivery and controlled release of tissue plasminogen activator (tPA) at the thrombus site. The tPA-loaded liposomes were PEGylated to improve their stability, and surface coated with a conformationally-constrained, cyclic arginine-glycine-aspartic acid (cRGD) to enable highly selective binding to activated platelets. The in vitro drug release profiles at 37 °C showed that over 90% of tPA was released through liposomal membrane destabilization involving membrane fusion upon incubation with activated platelets within 1 h, whereas passive release of the encapsulated tPA in pH 7.4 PBS buffer was 10% after 6 h. The release of tPA could be readily manipulated by changing the concentration of activated platelets. The presence of activated platelets enabled the tPA-loaded, cRGD-coated, PEGylated liposomes to induce efficient fibrin clot lysis in a fibrin-agar plate model and the encapsulated tPA retained 97.4 ± 1.7% of fibrinolytic activity as compared with that of native tPA. Furthermore, almost complete blood clot lysis was achieved in 75 min, showing considerably higher and quicker thrombolytic activity compared to the tPA-loaded liposomes without cRGD labelling. These results suggest that the nano-sized, activated-platelet-sensitive, multifunctional liposomes could facilitate selective delivery and effective release of tPA at the site of thrombus, thus achieving efficient clot dissolution whilst minimising undesirable side effects.


Transaxillary Subcutaneouscopic Excision of Fibroadenoma of the Breast in Children: The Covert Scar Approach.
Fibroadenoma is a common condition in adolescent girls. Most tumors are excised either through a periareolar approach or the inframammary approach. Both approaches produce visible scars in adolescent girls. We propose a new cosmetic approach to this lesion and report our experience with the transaxillary subcutaneouscopic approach for excision of the fibroadenoma of the breast. The purpose of this case report is to delineate an innovative surgical approach to resection of a breast fibroadenoma that yields an adequate resection without possible damage to the ductal system while optimizing cosmetic results by avoiding scars. We retrospectively reviewed the medical records of four adolescent girls who underwent the above approach for excision of fibroadenoma of the breast. The age range was 14-16 years. There were no complications in all 4 patients. The final result at the 3-month follow-up revealed an esthetically pleasing skin incision that healed well and was hidden by the natural skin fold of the axilla. Transaxillary subcutaneouscopic excision of fibroadenoma of the breast in children is a safe and effective technique and should be considered for excision of benign breast lesions in children.


Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to CRL4-DCAF15.
Indisulam and related sulfonamides recruit the splicing factor RBM39 to the CRL4-DCAF15 E3 ubiquitin ligase, resulting in RBM39 ubiquitination and degradation. Here, we used a combination of domain mapping and random mutagenesis to identify domains or residues that are necessary for indisulam-dependent RBM39 ubiquitination. DCAF15 mutations at Q232 or D475 prevent RBM39 recruitment by indisulam. RBM39 is recruited to DCAF15 by its RRM2 (RNA recognition motif 2) and is ubiquitinated on its N terminus. RBM23, which is an RBM39 paralog, is also recruited to the CRL4-DCAF15 ligase through its RRM2 domain and undergoes sulfonamide-dependent degradation. Indisulam alters the expression of more than 3,000 genes and causes widespread intron retention and exon skipping. All of these changes can be attributed to RBM39, and none are the consequence of RBM23 degradation. Our findings demonstrate that indisulam selectively degrades RBM23 and RBM39, the latter of which is critically important for splicing and gene expression.