Nutrition Management of High-Risk Neonates After Discharge.
Nutrition management of the high-risk infant after hospital discharge is complicated by the infant's dysfunctional or immature oral feeding skills, nutritional deficits, and the family's feeding plan. Although evidence is limited, available studies point to developing an individualized nutritional plan, which accounts for these factors; protects and prioritizes the family's plan for breastfeeding; and promotes an acceptable growth pattern. Further research is needed to identify the type and duration of posthospital discharge nutrition to optimize high-risk infant neurodevelopment and body composition. Attention to infant growth, lactation support, and safe feed preparation practices are critical in the transition to home.


Association of C3953T transition in interleukin 1β gene with idiopathic male infertility in an Iranian population.
In this study we investigate the association of C3953T transition single nucleotide polymorphism in the fifth exon of the interleukin 1β gene with idiopathic male infertility. In a case-control study, blood samples were collected from 230 fertile and 207 infertile men who referred to the Kashan IVF centre. Genotypes of samples at the C3953T location were determined by polymerase chain reaction-restriction fragment length polymorphism. The data showed a significant association of TT genotype (OR = 2.49, 95%CI = 1.02-6.10; p = 0.0452) and T allele (OR = 1.46, 95%CI = 1.07-1.99; p = 0.0174) with male infertility. In a subgroup analysis, we found that the TT genotype (OR = 3.28, 95%CI = 1.16-9.26; p = 0.0249) and T allele (OR = 1.63, 95%CI = 1.10-2.41; p = 0.0142) were associated with oligozoospermia. Our findings suggest that the C3953T polymorphism could be considered as a potential biomarker for a genetic diagnosis of male infertility.


Anaerobic whey treatment by a stirred sequencing batch reactor (ASBR): effects of organic loading and supplemented alkalinity.
An assessment was made of cheese whey treatment in a mechanically stirred anaerobic sequencing batch reactor (ASBR) containing granular biomass. The effect of increasing organic load and decreasing influent alkalinity supplementation (as sodium bicarbonate) was analyzed. The reactor operated on 8-h cycles with influent COD concentrations of 500, 1000, 2000 and 4000 mg/L, corresponding to volumetric organic loads of 0.6 to 4.8 mgCOD/L.d. Organic COD removal efficiencies were always above 90% for filtered samples. These results were obtained with an optimized alkalinity supplementation of 50% (ratio between mass of NaHCO3 added and mass of influent mgNaHCO3/mgCOD) in the assays with 500 and 1000 mgCOD/L and of 25% in the assays with 2000 and 4000 mgCOD/L. Initial alkalinity supplementation was equal to the mass of influent COD (100%). The system showed formation of viscous polymer-like substances. These were probably of microbiological origin occurring mainly at influent CODs of 2000 and 4000 mg/L and caused some biomass flotation. This could, however be controlled to enable efficient and stable reactor operation.


"Pseudocatheter" due to inadvertent ventricular catheter placement.
Ultrasound is frequently used in the routine follow-up of patients who have been shunted for obstructive hydrocephalus. We report a case with "pseudocatheter" appearance due to the initial incorrect placement of the ventricular catheter. To our knowledge, such an appearance has not been previously described.


Therapeutic applications of catheter cholangiography.
Percutaneous transhepatic catheterization of the biliary tree was performed in 23 patients. In 21 the catheter was advanced past an obstructing lesion into the distal common bile duct and duodenum to establish antegrade biliary drainage. The catheter was left permanently in place as a form of endoprosthesis in 5 patients.


Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo.
The tissue-specific distribution of tissue-type and urokinase-type plasminogen activator (t-PA and u-PA) and their inhibitor type 1 (PAI-1) was analyzed at mRNA level in five major rat organ tissues. t-PA mRNA was detected in lung, kidney, heart, and liver. u-PA mRNA was detected in kidney and lung. Presence of PA mRNA correlated with the detection of PA activity in extracts of these tissues. PAI-1 mRNA was detected predominantly in heart and lung. Although PAI activity could not be measured directly in tissue extracts, the presence of PAI-1 mRNA correlated with the occurrence of PA.PAI complex in fibrin autography of tissue extracts. Endotoxin injection caused a very large increase in plasma PAI activity. This increase correlated with a marked increase in PAI-1 mRNA in nearly all tissues studied. The increase in PAI-1 mRNA is most pronounced in lung and liver. Endotoxin injection also caused an increased level of t-PA mRNA in heart and kidney, and an increased u-PA mRNA level in kidney. mRNA analysis of freshly isolated and separated subfractionated liver cells showed that the marked increase in PAI-1 mRNA in the liver after endotoxin injection may be due mainly to a strong increase of PAI-1 mRNA in the liver endothelial cells.


Cyanoacrylate microbial sealants for skin preparation prior to surgery.
Surgical site infections (i.e. incisions that become infected) are a continuing concern in health care. Microbial sealant is a liquid that can be applied to the skin immediately before surgery and is thought to help reduce the incidence of surgical site infections (SSIs) by sealing in the skin flora, thus preventing contamination and infection of the surgical site. To assess the effects of the preoperative application of microbial sealants (compared with no microbial sealant) on rates of SSI in people undergoing clean surgery. For this first update we searched the following electronic databases in July 2013: the Cochrane Wounds Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid MEDLINE - In-Process & Other Non-Indexed Citations, Ovid EMBASE and EBSCO CINAHL. Randomised controlled trials (RCTs) were eligible for inclusion if they involved people undergoing clean surgery (i.e. surgery that does not involve the breathing system, gut, genital or urinary tract or any part of the body with an existing infection) in an operating theatre and compared the use of preoperative microbial sealants with no microbial sealant. All review authors independently extracted data on the characteristics, risk of bias and outcomes of the eligible trials. Three trials (524 participants undergoing clean surgery) met the inclusion criteria. The trials all compared cyanoacrylate microbial sealant with no sealant, and, when pooled, we found there were fewer SSIs with the use of microbial sealant (10/261 participants) than with the control comparison (29/274 participants). The difference between the two groups was statistically significant (risk ratio (RR) 0.36, 95% CI 0.18 to 0.72) but given the number of participants and quality of the studies, they should be treated with caution. There were some adverse events in one study, but these were not judged to be a result of the use of microbial sealant. In this first update there is still insufficient evidence available to determine whether the use of microbial sealants reduces the risk of surgical site infection or not. Further rigorous, adequately-powered RCTs are required to investigate this properly.


Levan-type fructooligosaccharides synthesis by a levansucrase-endolevanase fusion enzyme (LevB1SacB).
We describe here the enzymatic production of levan type-fructooligosaccharides (L-FOS) with a DP from 2 to 10, through simultaneous synthesis and hydrolysis reactions. This was accomplished by LevB1SacB, a new enzyme resulting from the fusion of SacB, a levansucrase from Bacillus subtilis and LevB1, an endolevanase from B. licheniformis. In the fusion enzyme, SacB retains its catalytic behavior with a decrease in kcat from 164 to 108s-1. LevB1 in LevB1SacB kinetic behavior improves considerably reaching saturation with levan and following Michaelis-Menten kinetics, quite differently from the previously reported first order kinetic behavior. We also report that LevB1SacB or both enzymes (LevB1 & SacB) at equimolar concentrations in simultaneous reactions result in an optimal, wide and diverse L-FOS profile, including 6-kestose, levanbiose and blastose among other L-FOS and 1-kestose, which accumulates as by-product of SacB levan synthesis. Yields of around 40% (w/w) were obtained from 600g/l sucrose with either LevB1SacB or LevB1 & SacB. The reaction was successfully scaled up to a stirred 2l bioreactor.


Increasing attractiveness of baits with venom gland extract for Atta sexdens rubropilosa (Forel) (Hymenoptera: Formicidae).
The effect of larval cuticle extract (larval pheromone) and venom gland extract (trail pheromone) on transport of formulated baits by Atta sexdens rubropilosa (Forel) was studied in the field and under laboratory conditions. In the laboratory, we observed the transport to the nest of baits impregnated with 10 μL of venom gland extract (0.01 gland/bait) or 10 μL of larval cuticle extract (0.05 larva/bait). The most transported impregnated bait was then tested in the field placing rubber septa impregnated with 100 mL of extract or with 100 mL of solvent with the baits at 0.2, 1.0, 5.0, and 10.0 m away from the trail and from the nest entrance. Baits impregnated with venom gland extract were transported more often than baits formulated with larval cuticle extract. In field tests, the venom gland extract reduced the time required for ants to detect baits and increased the transport of baits displayed at 0.2 m from the foraging trail or nest entrance. The increase in the transport of impregnated baits and the lower time to be transported might help to reduce the loss of bait in the field and decrease the risk of active ingredient contacts with non-target species.


The effect of two different root canal sealers on treatment outcome and post-obturation pain in single-visit root canal treatment: A prospective randomized clinical trial.
This randomized clinical trial aimed to evaluate and compare the effect of mineral trioxide aggregate (MTA)-based bioceramic- and resin-based sealers on the incidence and intensity of post-obturation pain and treatment outcome in asymptomatic vital molar teeth in single-visit root canal treatment. One hundred asymptomatic mandibular molar teeth with vital pulp were randomly assigned into two groups according to the sealer used: MTA Fillapex or AH Plus sealer. WaveOne Gold instruments were used for root canal preparations. Root canals were obturated with WaveOne Gold gutta-percha cones corresponding in size and taper to the last instrument used. MTA Fillapex was used in the first group and AH Plus was used in the second group as the root canal sealer. The effects of age, gender, tooth types and the level of root canal filling on the treatment outcome were evaluated after 1 and 2 years. Postoperative pain at 6, 12, 24, 48, 72 h, 4, 5, 6, 7 and 30 days after root canal treatment was measured with the Numerical Rating Scale. Chi-square test was used for the treatment outcome and Mann-Whitney U, chi-Square and Spearman correlation analyses were used for postoperative pain. α = .05 was the level of significance. Twelve patients did not complete the 2-year follow-up and the study finished with 88 patients. In the MTA Fillapex group 41 correct, one short, two extruded, and in the AH Plus group 40 correct, one short and three extruded root canal fillings were detected. No significant differences were observed between the first- and second-year treatment outcomes between the groups (p > .05).There was no association between age, gender, tooth number, root canal filling length and the treatment success in all evaluated teeth (p > .05). The differences between the groups in terms of postoperative pain incidence and intensity at all time-points were not significant (p > .05). There was no correlation between the age and postoperative pain (p > .05), but pain was statistically higher in women (p < .05). Mineral trioxide aggregate Fillapex showed similar success rate and post-obturation pain incidence and intensity as AH Plus sealer and can be used as a root canal sealer in asymptomatic mandibular molars with irreversible pulpitis.


Development of disposable lipid biosensor for the determination of total cholesterol.
A prototype chronoamperometric biosensor for the determination of total cholesterol was developed that consists of a homemade potentiostat and disposable strips immobilized with Fe(3)O(4), cholesterol oxidase (ChOx), and cholesterol esterase (ChE). The principle of sensing cholesterol is based on the detection of reduction signal of hydrogen peroxide generated in two enzymatic reactions. The co-immobilization of ChE and ChOx allows the sensor to detect both concentrations of esterified and free cholesterol. The effects of biosensor on catalyst, enzymes, applied potential, and buffer pH was investigated, and the operation conditions were optimized. The detection of cholesterol can be accomplished in one step, a 10 microL of sample was dropped onto the area of sensing strip and the reduction signal was obtained at an applied potential of -200 mV (vs. Ag/Ag(+)). The pre-reaction time was set at 15s before applying potential on the strip and the sampling time was 5s. The sensing device displays a linear response over the range of 100-400mg/dL (R(2)=0.999) for cholesteryl oleate. The coefficient variation was determined as 5.06% (N=20) for 100mg/dL cholesteryl oleate and the detection limit is 19.4 mg/dL (S/N=3). The probable interferences in bio-matrix were selected to test the selectivity and no significant response was observed in the biosensor.


Agricultural subsidies and the American obesity epidemic.
Government-issued agricultural subsidies are worsening obesity trends in America. Current agricultural policy remains largely uninformed by public health discourse. Although findings suggest that eliminating all subsidies would have a mild impact on the prevalence of obesity, a revision of commodity programs could have a measurable public health impact on a population scale, over time. Policy reforms will be important determinants of the future of obesity in America, primarily through indemnity program revisions, and the allocation of increasing amounts of resources to sustainable agriculture. Public health intervention will be required at the policy level to promote healthy behavioral changes in consumers. The 2013 Farm Bill will be the key mechanism to induce such policy change in the near future.


Prevalence and correlates of cognitive impairment in schizophrenia: a cross-sectional study from a teaching hospital southern Sri Lanka.
This study assessed the prevalence of cognitive impairment, the degree of impairment in individual cognitive domains and sociodemographic and clinical correlates among patients attending to psychiatry clinics at Teaching Hospital, Karapitiya, Sri Lanka. A cross-sectional study was carried out at the psychiatry outpatient clinics of Teaching Hospital, Karapitiya, Sri Lanka. Their cognitive functions were assessed using the culturally validated Sinhala version of Addenbrooke's Cognitive Examination - III (ACE-III-S). ACE-III-S score below 85.5 was considered as significant cognitive impairment. Linear regression analysis was used to assess the factors associated with cognitive impairment. A P value of 0.05 is considered significant. One hundred forty patients with schizophrenia were assessed. Of this, 125 patients had significant cognitive impairment with a prevalence of 89.3% (95% CI:84.1-94.5). Impairment in each cognitive domain was as follows: 60% in attention, 65.7% in memory, 55% in fluency, 61.4% in language, and 63.6% in visuospatial skills. Impairment was not different between cognitive domains. Advancing age (P < 0.001), shorter duration of formal education (P = < 0.001), longer duration of illness (P = < 0.001) and not having a full-time employment (P = 0.020) showed a positive association with cognitive impairment. Nine out of ten patients with schizophrenia experienced significant cognitive impairment. Patients showed more than 50% impairment in all cognitive domains. The cognitive domains did not show disproportionate impairment. This study highlights the importance of introducing routine cognitive assessment protocols in patients with schizophrenia.


Sustainable valorization of paper mill sludge into cellulose nanofibrils and cellulose nanopaper.
As a kind of agro-industrial wastes, paper mill sludge (PMS) has posed serious environmental and economic challenges for disposal due to the more stringent regulations and diminishing land availability in recent years. The present study is aimed at providing a sustainable approach to efficiently convert PMS to cellulose nanofibrils (CNFs) and cellulose nanopaper (CNP) by formic acid (FA) hydrolysis pretreatment and the followed microfluidization. It is found that FA hydrolysis (4-6 h) could swell and shorten PMS fibers, and only two-pass microfluidization is sufficient to get uniform CNFs from the collected cellulose residual. Results indicate that the obtained CNFs show high thermal stability and crystallinity index, surface functionality (ester groups), as well as a high yield of over 75 wt.%. Notably, more than 90 % FA can be recovered and the hydrolyzed sugars could be potentially used to produce platform chemicals (e.g. lactic acid, furfural). Finally, transparent CNP is prepared from the CNFs suspension via a simple vacuum filtration technique. The resultant CNP shows good mechanical properties with the maximum tensile strength and toughness of 106.4 MPa and 6.62 MJ/m3, respectively. Therefore, the current work provides a green and sustainable method to valorize PMS for the production of valuable CNFs and CNP.


Feeling the sound - short-term effect of a vibroacoustic music intervention on well-being and subjectively assessed warmth distribution in cancer patients-A randomized controlled trial.
So far, the effects of vibroacoustic music therapy in cancer patients are unknown. However, used in anthroposophic medicine, it could be an approach to enhance well-being. The goal of this study was to evaluate the immediate effects of a sound-bed music intervention with respect to the subjective well-being as well as body warmth and pain. We treated 48 cancer patients with 10 min of sound-bed intervention in a cross-over design. Primary outcome was the total sum of the Basler Mood Questionnaire (BMQ), secondary outcomes were subscales of the BMQ and questions addressing body warmth and pain. The EORTC-QLQ C30 was used as baseline assessment for quality of life (QOL). Patients had lower QOL values than the EORTC reference samples (p < .001, d = 0.90). The primary outcome increased after music (p < .001, d = 0.47), no changes were seen in the control condition (p = .73, d = 0.04), the time by condition interaction was significant (p < .05). Increase after music for the BMQ subscales inner balance (p < .001, d = 0.73), vitality (p < .001, d = 0.51) and vigilance (p < .001, d = 0.37) as well as for the additional questions satisfaction (p < .001, d = 0.43), current mood (p < .001, d = 0.43), body warmth (p < .05, d = 0.44) and warmth distribution (p < .01, d = 0.49). No significant changes were seen in pain levels and social extroversion. Sound-bed intervention improved momentary well-being and caused self-perceived physiological changes associated with relaxation beyond the benefits of simple resting time (control condition). Thus, it might be a promising approach to improve well-being in cancer patients.


Prescription drug advertising: medical journal practices under different types of control.
Medication is one important aspect of health care delivery. The sources of information used to select appropriate medication include drug advertisements which appear in professional journals. There is a need to monitor the quality of these advertisements. The study reported in this paper includes a longitudinal (1961 to 1977) and cross-societal (Britain, United States and Australia) content analysis of drug advertisements. Such a comparison contributes to the debate concerning the type of regulation likely to be effective for this form of advertising.


Households' willingness to adopt greywater treatment technologies in a developing country - Exploring a modified theory of planned behaviour (TPB) model including personal norm.
This study explored willingness of households to adopt a greywater treatment and reuse system using the theory of planned behaviour in its original form and an extended model including personal norms. The study was conducted among 478 household heads in the central region of Ghana. The results indicate the original theory of planned behaviour (TPB) model explained about 54% of the variance in respondents' intentions to adopt this system and the extended model which includes personal norms explained 59% of the intentions. The extended model turned out to be the better model to predict willingness to adopt this household greywater and treatment system. The findings of this study shed more light on the role of personal norms in households' willingness to adopt a greywater treatment and reuse system and may inform interventions aimed at promoting such systems.


Enhanced visible light driven photoelectrochemical degradation of tetracycline hydrochloride using a BiOI photoanode modified with MnO2 films.
Removal of pharmaceuticals in wastewater has been the focus of many research due to the recalcitrant nature and hazardous effects of these compounds. The photoelectrochemical degradation process has proven to be suitable to harness solar energy for the mineralization of organic compounds in wastewater. Herein, we report the application of BiOI/MnO2 heterostructured anode for the photoelectrochemical degradation of tetracycline hydrochloride in aqueous solution. The photoanode was prepared through electrodeposition technique and fully characterized through microscopic, spectroscopic and electrochemical techniques. The results showed that formation of p-n heterojunction between BiOI and MnO2 in the photoanode led to improved charge separation which was evident in improved optical and photoelectrochemical properties. The FTO-BiOI/MnO2 electrode attained a photocurrent density of 0.104 mA cm-2 with applied potential of 1.0 V (vs Ag/AgCl) which was almost double that of pristine BiOI suggesting efficient charge separation. The heterostructured photoanode achieved 94% removal of tetracycline hydrochloride after 120 min through the PEC degradation process with 61% mineralization efficiency. The electrode showed good reusability and stability with 92% PEC removal after eight cycles. Hence, the FTO-BiOI/MnO2 has a great potential as anode for PEC wastewater treatments.


Invadopodia: at the cutting edge of tumour invasion.
Invasion of tissues by malignant tumours is facilitated by tumour cell migration and degradation of extracellular matrix (ECM) barriers. Several invasive neoplasms, including head and neck squamous cell carcinoma, breast carcinoma, melanoma and glioma, contain tumour cells that can form actin-rich protrusions with ECM proteolytic activity called invadopodia. These dynamic organelle-like structures adhere to, and digest, collagens, laminins and fibronectin. Invadopodia are dependent on multiple transmembrane, cytoplasmic and secreted proteins engaged in cell adhesion, signal transduction, actin assembly, membrane regulation and ECM proteolysis. Strategies aimed at disrupting invadopodia could form the basis of novel anti-invasive therapies for treating patients. Here we review the molecular basis of invadopodia formation with particular emphasis on the intracellular signaling networks that are essential for invadopodia activity and examine the potential role of these structures in glioma invasion.


Observations on aggregated lymphoid nodules in the cardiac glandular areas of the Bactrian camel (Camelus bactrianus).
Aggregated lymphoid nodules are an important part of the gut-associated lymphoid tissue (GALT). They are mainly distributed in the ileum and appendix of animals and humans but their distribution in the cardiac glandular area has not been reported. A study of stomach histology in the Bactrian camel has revealed that the nodules are distributed as a band-like region along the ventral wall of the stomach neck, at the beginning of the cranial enlargement and on the lesser curvature. The mucous folds are thicker in these regions than where there are no aggregated lymphoid nodules. The nodules appeared similar to ileal aggregated lymphoid nodules found in other animals and consisted of typical polymorphological lymphatic nodules arranged in a single continuous row occupying the submucosa and forming mucosal folds together with the mucous membrane. The whole mucous membrane with cardiac glands, diffuse lymphatic tissue and solitary lymphoid nodules in the lamina propria were found to cover the aggregated lymphoid nodule regions, but some nodules with a typical corona extended into the lamina propria and were covered with follicle-associated epithelium devoid of cardiac glands. These findings indicate that the stomach of the Bactrian camel possesses not only a special structure of digestion but also has characteristic immunological morphology.


Method and complexity in bioethics: the example of community genetics.
This article describes the need to develop a new methodology in bioethics that can consider multiple interactions, creativity and the organisation specific to complex systems. Community genetics is taken as an example of complexity in bioethics. Community genetics involves large populations and illustrates certain characteristics of complex adaptive systems which are discussed in the article.


Isospora lutrae n. sp. (Apicomplexa: Eimeriidae), a new coccidium from the European otter Lutra lutra (L.) (Carnivora: Mustelidae) from Spain.
Parasitological examination of European otter originating from Extremadura, Spain revealed the presence of a new isosporan species. Oöcysts of Isospora lutrae n. sp. are spherical to subspherical, 31.2 (27.5-32) x 29.6 (28-31) microm and have a smooth wall c. 1 microm thick. Sporocysts are ellipsoidal, 18.2 (17-19) x 14.4 (14-16) microm and lack Stieda and substieda bodies. A spherical sporocyst residuum is present, consisting of granules scattered among the sporozoites. Sporozoites are spindle-shaped, 12.4 x 2.5 microm and have anterior and posterior refractile bodies. Based on its unique morphologic structure and host, I. lutrae is considered to be new.


[Relationship between procalcitonin serum levels and complications and outcome of patients with hematological malignancy admitted to Intensive Care Unit].
Patients with hematological neoplasms transferred to an Intensive Care Unit (ICU) for a life-threatening complication have a poor outcome. In these patients, it is crucial to identify clinical and biologic parameters with potential prognostic significance. This study prospectively evaluated the usefulness of serum procalcitonin (PCT) levels as a predictor of complications (infectious or not) and outcome in these patients. One hundred patients with hematological malignancy were admitted to the ICU from October 2004 until August 2009. In 59 of them serum PCT levels were daily measured from the ICU admission until a maximum period of 10 consecutive days. Hematological diseases were acute leukemia (n=30), lymphoma and other lymphoproliferative disorders (n=18), multiple myeloma (n=7) and other (n=4). Twenty-five patients (42%) had received hematopoietic stem cell transplantation. Thirty-seven patients (63%) presented neutropenia. Those patients who could not be discharged alive from the ICU presented higher PCT levels on days 1, 2 and 3. PCT levels were significantly higher in those patients with neutropenia or septic shock or other causes of hemodynamic instability. The presence of a microbiologically documented infection, respiratory failure or the need of mechanical ventilation support did not significantly affect PCT levels in this study. Early serum PCT levels measurement might be useful for predicting mortality in patients with hematological malignancy requiring advanced life support.


Neuroanatomical mapping of DNA repair and antioxidative responses in mouse brain: Effects of a single dose of MPTP.
The primary objective of this study was to map the normal distribution of the base excision enzyme oxyguanosine glycosylase (OGG1) across mouse-brain regions as a prelude to assessing the effects of various neurotoxicants, ranging from highly selective molecules like MPTP to more global toxic agents. This research is based on the hypothesis that regional brain vulnerability to a toxicant is determined, in part, by variation in the intrinsic capacity of cellular populations to successfully repair oxidative DNA damage. After mapping the normal distributions of OGG1 and superoxide dismutase (SOD) across 44 loci dissected from mouse brain, MPTP, a mitochondrial toxicant with selective dopamine (DA) neuron cytotoxicity was used to elicit focal oxidative stress and DNA repair responses. A single dose of MPTP (20mg/kg, i.p.) elicited time- and region-dependent changes in both SOD and OGG1, with early increases in DNA repair and anti-oxidant activities throughout all regions of brain. In some sampled loci, notably the substantia nigra (SN) and hippocampus, the heightened DNA repair and antioxidant responses were not maintained beyond 48h. Other loci from cerebellum, cerebral cortex and pons maintained high levels of activity up to 72h. Levels of dopamine (DA) were decreased significantly at all time points and remained below control levels in nigro-striatal and mesolimbic systems (ventral tegmental area and nucleus accumbens). Assessment of apoptosis by TUNEL staining revealed a significant increase in number of apoptotic nuclei in the substantia nigra at 72h and not in other loci. The marked degree of apoptosis that became evident in SN at 72h was associated with large decreases in SOD and DNA repair activity at that locus. In conclusion, MPTP elicited global effects on DNA repair and antioxidant activity in all regions of brain, but the most vulnerable loci were unable to maintain elevated DNA repair and antioxidant responses.


Silver nanoparticles uptake by salt marsh plants - Implications for phytoremediation processes and effects in microbial community dynamics.
This study investigated the uptake of silver nanoparticles (AgNPs) by a salt marsh plant, Phragmites australis, as well as AgNPs effects on rhizospheric microbial community, evaluating the implications for phytoremediation processes. Experiments were carried out with elutriate solution doped with Ag, either in ionic form or in NP form. Metal uptake was evaluated in plant tissues, elutriate solutions and sediments (by AAS) and microbial community was characterized in terms of bacterial community structure (evaluated by ARISA). Results showed Ag accumulation but only in plant belowground tissues and only in the absence of rhizosediment, the presence of sediment reducing Ag availability. But in plant roots Ag accumulation was higher when Ag was in NP form. Multivariate analysis of ARISA profiles showed significant effect of the absence/presence of Ag either in ionic or NP form on microbial community structure, although without significant differences among bacterial richness and diversity. Overall, P. australis can be useful for phytoremediation of medium contaminated with Ag, including with AgNPs. However, the presence of Ag in either forms affected the microbial community structure, which may cause disturbances in ecosystems function and compromise phytoremediation processes. Such considerations need to be address regarding environmental management strategies applied to the very important estuarine areas. The form in which the metal was added affected metal uptake by Phragmites australis and rhizosediment microbial community structure, which can affect phytoremediation.


A field trial of suppression of Aedes aegypti population by releasing sterile males into a domestic population.
After release of an average of 1260 sterile male each day for a period of sixty two days, the average fertility of Aedas aegypti population remained above 50% in Ererwani village. It is concluded that the irradiated sterile males may not be suitable as a control measure, despite the fact that irradiation was carried out in nitrogen atmosphere.


NAD+ levels control Ca2+ store replenishment and mitogen-induced increase of cytosolic Ca2+ by Cyclic ADP-ribose-dependent TRPM2 channel gating in human T lymphocytes.
Intracellular NAD(+) levels ([NAD(+)](i)) are important in regulating human T lymphocyte survival, cytokine secretion, and the capacity to respond to antigenic stimuli. NAD(+)-derived Ca(2+)-mobilizing second messengers, produced by CD38, play a pivotal role in T cell activation. Here we demonstrate that [NAD(+)](i) modifications in T lymphocytes affect intracellular Ca(2+) homeostasis both in terms of mitogen-induced [Ca(2+)](i) increase and of endoplasmic reticulum Ca(2+) store replenishment. Lowering [NAD(+)](i) by FK866-mediated nicotinamide phosphoribosyltransferase inhibition decreased the mitogen-induced [Ca(2+)](i) rise in Jurkat cells and in activated T lymphocytes. Accordingly, the Ca(2+) content of thapsigargin-sensitive Ca(2+) stores was greatly reduced in these cells in the presence of FK866. When NAD(+) levels were increased by supplementing peripheral blood lymphocytes with the NAD(+) precursors nicotinamide, nicotinic acid, or nicotinamide mononucleotide, the Ca(2+) content of thapsigargin-sensitive Ca(2+) stores as well as cell responsiveness to mitogens in terms of [Ca(2+)](i) elevation were up-regulated. The use of specific siRNA showed that the changes of Ca(2+) homeostasis induced by NAD(+) precursors are mediated by CD38 and the consequent ADPR-mediated TRPM2 gating. Finally, the presence of NAD(+) precursors up-regulated important T cell functions, such as proliferation and IL-2 release in response to mitogens.


A simple and rapid flow injection chemiluminescence determination of cysteine with Ru(phen)3(2+)-Ce(IV) system.
A new chemiluminescence system was developed for the determination of cysteine by flow injection system. This method is based on the reaction of L-cysteine with Ru(phen)3(2+) and Ce(IV) to produce chemiluminescence. The calibration curve was linear over the range 8.0x10(-7) to 4.0x10(-5) and 4.0x10(-5) to 1.0x10(-3) M with a detection limit of 7.0x10(-7) M (S/N=3). The relative standard deviation of 4.0x10(-6) M cysteine was found 3.5% (n=10). The influence of potential interfering substances was studied. The proposed method was successfully applied for the flow injection determination of cysteine in the real samples with minimum sampling rate of 90 sample/h.


Association of the COVID-19 Pandemic With Rates of Prostate Cancer Biopsies and Diagnoses in Black vs White US Veterans.
Several studies have assessed the negative effect of the COVID-19 pandemic on cancer screening and diagnosis rates. However, this has not been evaluated for prostate biopsy and prostate cancer (PC) diagnosis in an equal-access health care system. To determine the association of the pandemic with prostate biopsy and PC diagnosis rates among Black vs White patients in the Veterans Affairs Health Care System (VAHCS). This cohort study included a retrospective analysis of all prostate biopsies performed on patients in the VAHCS without a preexisting PC diagnosis between January 2018 and March 2021. The base population included all living male patients who had at least 1 visit to the VAHCS during the 3 years prior to each month of the study. The COVID-19 pandemic. The main outcomes were the number of prostate biopsies and PC diagnoses by month. The influence of the pandemic on prostate biopsy volume and the incidence of PC diagnoses was modeled using an interrupted time-series analysis. Poisson generalized linear models were fitted to project the expected number of prostate biopsies and PC diagnoses had there been no pandemic interruption. Additional models were used to test for differences by race. Prior to the pandemic (January 2018 through February 2020), monthly biopsy numbers among 51 606 included men ranged between 1230 and 1695, of which 56% to 60% of results were positive for PC. The estimated number of missed PC diagnoses from March 2020 through March 2021 ranged from 97 cases (October 2020: 752 cases expected, 655 cases observed) to 573 cases (April 2020: 794 cases expected, 221 cases observed). Prior to the pandemic, biopsy rates were statistically significantly higher among Black vs White men (incidence rate ratio, 2.25; 95% CI, 2.06-2.46; P < .001). There was no change in biopsy rates associated with race at the onset of the pandemic nor during the recovery period from March 2020 to March 2021. Similar trends were observed for PC diagnosis rates. Results of this cohort study demonstrate that during the COVID-19 pandemic, prostate biopsy and PC diagnosis rates decreased, particularly during the peak of the pandemic. However, there were no statistically significant changes in rates by race.


S1P prophylaxis mitigates acute hypobaric hypoxia-induced molecular, biochemical, and metabolic disturbances: A preclinical report.
Sphingosine-1-phosphate (S1P) is emerging to have hypoxic preconditioning potential in various preclinical studies. The study aims to evaluate the preclinical preconditioning efficacy of exogenously administered S1P against acute hypobaric hypoxia (HH)-induced pathological disturbances. Male Sprague Dawley rats (200 ± 20 g) were preconditioned with 1, 10, and 100 μg/kg body weight (b.w.) S1P (i.v.) for three consecutive days. On the third day, S1P preconditioned animals, along with hypoxia control animals, were exposed to HH equivalent to 7,620 m (280 mm Hg) for 6 h. Postexposure status of cardiac energy production, circulatory vasoactive mediators, pulmonary and cerebral oxidative damage, and inflammation were assessed. HH exposure led to cardiac energy deficit indicated by low ATP levels and pronounced AMPK activation levels, raised circulatory levels of brain natriuretic peptide and endothelin-1 with respect to total nitrate (NOx), redox imbalance, inflammation, and alterations in NOx levels in the pulmonary and cerebral tissues. These pathological precursors have been routinely reported to be coincident with high-altitude diseases. Preconditioning with S1P, especially 1 µg/kg b.w. dose, was seen to reverse the manifestation of these pathological disturbances. The protective efficacy could be attributed, at least in part, to enhanced activity of cardioprotective protein kinase C and activation of small GTPase Rac1, which led to further induction of hypoxia-adaptive molecular mediators: hypoxia-inducible factor (HIF)-1α and Hsp70. This is a first such report, to the best of our knowledge, elucidating the mechanism of exogenous S1P-mediated HIF-1α/Hsp70 induction. Conclusively, systemic preconditioning with 1 μg/kg b.w. S1P in rats protects against acute HH-induced pathological disturbances. © 2016 IUBMB Life 68(5):365-375, 2016.


Lymphokines facilitate maturation of oligodendrocytes in vitro.
As oligodendrocytes develop in vitro, A2B5+ progenitor cells acquire the oligodendrocyte-specific marker, galactocerebroside (GalC), to become A2B5+ GalC+ cells. They then gradually lose reactivity to A2B5, to become A2B5- GalC+ mature oligodendrocytes. By examining this developmental surface antigen expression with and without lymphokine stimuli we found that crude lymphokines, but not interleukin-2 or gamma-interferon, facilitate this maturation process. Thus, lymphokines may have a role in differentiation of oligodendrocytes. The same lymphokine stimuli, however, did not enhance the proliferation of oligodendrocytes.


Synthesis of desthio prenylcysteine analogs: sulfur is important for biological activity.
N-Acetyl-S-farnesyl cysteine (AFC) is the minimal synthetic substrate for the enzyme Icmt, which methylates prenylated proteins. The desthio-AFC isostere 2 has been synthesized in racemic form. This analog was not an Icmt substrate, but instead a weak inhibitor with an IC50 of approximately 325 microM.


Establishment of a human oligodendroglial cell line.
A human oligodendroglial cell line has been established from a mixed glioma. Over a period of 22 months, the cell consisted of cells with the morphologic features of such a strong perinuclear halo, dichotomous branching, and a tendency to aggregate and float in the medium. In small aggregates, most cells are bipolar. The cell line also continues to synthetize the S-100 protein specific to neural tissue. The response of this cell line to dibutyryl-cyclic AMP is striking, resulting in a remarkable narrowing and elongation of the cell processes. This cell line could be used for studies on glial differentiation and neuron-glia interaction.


Effects of Ca on microstructure, mechanical and corrosion properties and biocompatibility of Mg-Zn-Ca alloys.
Zn and Ca were selected as alloying elements to develop an Mg-Zn-Ca alloy system for biomedical application due to their good biocompatibility. The effects of Ca on the microstructure, mechanical and corrosion properties as well as the biocompatibility of the as-cast Mg-Zn-Ca alloys were studied. Results indicate that the microstructure of Mg-Zn-Ca alloys typically consists of primary α-Mg matrix and Ca₂Mg₆Zn₃/Mg₂Ca intermetallic phase mainly distributed along grain boundary. The yield strength of Mg-Zn-Ca alloy increased slightly with the increase of Ca content, whilst its tensile strength increased at first and then decreased. Corrosion tests in the simulated body fluid revealed that the addition of Ca is detrimental to corrosion resistance due to the micro-galvanic corrosion acceleration. In vitro hemolysis and cytotoxicity assessment disclose that Mg-5Zn-1.0Ca alloy has suitable biocompatibility.


The murine pan T cell marker CD96 is an adhesion receptor for CD155 and nectin-1.
The CD155 ligand CD96 is an immunoglobulin-like protein tentatively allocated to the repertoire of human NK receptors. We report here that the CD96/CD155-interaction is preserved between man and mouse although both receptors are only moderately conserved in amino acid sequence. Moreover, murine CD96 (mCD96) binds to nectin-1, a receptor related to CD155. Applying newly generated monoclonal antibodies specifically recognizing mCD96, an expression profile is revealed resembling closely that of human CD96 (hCD96) on cells of hematopoietic origin. A panel of anti-mCD96 but also recently established anti-mCD155 antibodies effectively prevents formation of CD96/CD155-complexes. This was exploited to demonstrate that the only available receptor for mCD96 present on thymocytes is mCD155. Moreover, T cell adhesion to insect cells expressing mCD155 is blocked by these antibodies depending on the T cell subtype. These results suggest a function of the CD96/CD155-adhesion system in T cell biology.


Breaking the Invisible Barriers: Unleashing the Full Potential of Immune Checkpoint Inhibitors in Oncogene-Driven Lung Adenocarcinoma.
The rapid development of targeted therapy paved the way toward personalized medicine for advanced non-small cell lung cancer (NSCLC). Lung adenocarcinoma (ADC) harboring actionable genetic alternations including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), Kirsten rat sarcoma virus (ALK) and c-ros oncogene 1 (ROS1) treated with tyrosine kinase inhibitors (TKIs) incurred lesser treatment toxicity but better therapeutic responses compared with systemic chemotherapy. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) have also shown an increase in overall survival (OS) for NSCLC patients. However, acquired resistance to these targeted therapies remains a major obstacle to long-term maintenance treatment for lung ADC patients. The emergence of immune checkpoint inhibitors (ICIs) against programmed cell death protein 1 (PD-1) or programmed cell death-ligand 1 (PD-L1) has changed the treatment paradigm for NSCLC tumors without actionable genetic alternations. Clinical studies have suggested, however, that there are no survival benefits with the combination of targeted therapy and ICIs. In this review, we will summarize and discuss the current knowledge on the tumor immune microenvironment and the dynamics of immune phenotypes, which could be crucial in extending the applicability of ICIs for this subpopulation of lung ADC patients.


Major depression in women: a review of the literature.
To promote pharmacists' understanding and recognition of major depression in women and to review gender/sex-specific differences in its prevalence, etiology, risk factors, clinical features, course, and management. Clinical literature on this topic in the English language since 1990, searched through MEDLINE. Selected review articles and clinical trials from peer-reviewed journals. Epidemiologic data from diverse cultures indicate that the lifetime prevalence of major depression is twice as high in women as in men. The artifact, biological, and psychosocial hypotheses have each been proposed to explain the predominance of lifetime depression in women. Major depression is a multifactorial disorder and is influenced by numerous risk factors, including age, socioeconomic status, childhood history of sexual abuse, and recent stressful life events. Clinical course and presentation tend to differ between women and men. Women may experience different types of depression during various reproductive or life stages, including premenses, pregnancy, postpartum, and menopause. Treatment for major depression includes psychosocial therapy, pharmacotherapy, and electroconvulsive therapy. The literature indicates that major depression is often underrecognized and undertreated. Biological and psychosocial factors contribute to the higher vulnerability of women to major depression. The biological-psychosocial origins of depression in women may require a multidimensional approach to treatment. By providing education about this disease, referring individuals with signs and symptoms of depression for evaluation, and encouraging appropriate use of antidepressants, pharmacists can improve the detection and treatment of major depression.


[Diagnosis of foot and mouth disease].
Because foot-and-mouth disease has the potential for an explosive spread, instant and reliable diagnosis is of special importance. In this article the clinical examination, types and shipment of samples as well as the current methods of laboratory diagnosis by detection of FMD-virus, antigen, nucleic acid and antibodies are reviewed. Special emphasis is laid on the differentiation between vaccinated and infected animals, in respect to conventional as well as novel vaccines.


Alcoholic Ketoacidosis: Etiologies, Evaluation, and Management.
Alcoholic ketoacidosis (AKA) is defined by metabolic acidosis and ketosis in a patient with alcohol use. This is a common presentation in the emergency department (ED) and requires targeted therapies. This narrative review evaluates the pathogenesis, diagnosis, and management of AKA for emergency clinicians. AKA is frequently evaluated and managed in the ED. The underlying pathophysiology is related to poor glycogen stores and elevated nicotinamide adenine dinucleotide and hydrogen. This results in metabolic acidosis with elevated beta-hydroxybutyrate levels. Patients with AKA most commonly present with a history of alcohol use (acute or chronic), poor oral intake, gastrointestinal symptoms, and ketoacidosis on laboratory assessment. Patients are generally dehydrated, and serum glucose can be low, normal, or mildly elevated. An anion gap metabolic acidosis with ketosis and electrolyte abnormalities are usually present on laboratory evaluation. Management includes fluid resuscitation, glucose and vitamin supplementation, electrolyte repletion, and evaluation for other conditions. Emergency clinician knowledge of the evaluation and management of AKA is essential in caring for these patients.


Generation of a human induced pluripotent stem cell (iPSC) line from a Bernard-Soulier syndrome patient with the mutation p.Asn45Ser in the GPIX gene.
Bernard Soulier Syndrome (BSS) is an inherited rare platelet disorder characterized by mutations in the platelet glycoprotein complex GPIb-IX-V. We generated an induced pluripotent stem cell (iPSC) line from a BSS patient with a mutation p.Asn45Ser in the GPIX locus (BSS2-PBMC-iPS4F24). Peripheral blood mononuclear cells were reprogrammed using non-integrative viral transduction. Characterization of BSS2-PBMC-iPS4F24 included mutational analysis of GPIX locus, analysis of conventional pluripotency-associated factors at mRNA and protein level and in vitro and in vivo differentiation studies. This iPSC line will provide a powerful tool to study the biology of BSS disease.


Adaptive variation in offspring size in the terrestrial isopod, Armadillidium vulgare.
Variation in the birth size of offspring of the terrestrial isopod, Armadillidium vulgare, was observed in laboratory experiments and in field populations. In the laboratory, larger offspring were produced when the mother's food supply was reduced. In field populations, larger offspring were produced during the summer, a period of reduced food availability. Smaller offspring are produced in the spring, when food is readily available. Females may be making larger young to increase survival during the more severe conditions of the summer breeding period.


Remote psychophysical testing of smell in patients with persistent olfactory dysfunction after COVID-19.
Olfactory dysfunction associated with coronavirus 2 (SARS-CoV-2) infection is in most cases transient, recovering spontaneously within a few days. However, in some patients it persists for a long time, affects their everyday life and endangers their health. Hence, we focused on patients with persistent loss of smell. The aim of this study was to evaluate olfactory dysfunction using a standardized test. Due to the pandemic, olfactory testing was performed online. Smell tests (Odorized Markers Test, OMT) were sent home to the patients. Together with the smell self-testing, participants reported and assessed several parameters (age, sex, subjective assessment of smell and taste, nasal patency, etc.) in an online questionnaire. Based on the questionnaire outcomes, the results were sent to the patients along with a list of participating otolaryngologists who provided them with professional care. From March to June 2021, 1025 patients requested smell testing, of these, 824 met the inclusion criteria of this study. The duration of the olfactory dysfunction at the time of testing ranged from 1 month to 1 year. Using the OMT, impaired smell ability-anosmia or hyposmia-was confirmed in 82.6% of participants. A total of 17.4% of participants were determined to be normosmic however, more than 50% of them complained of parosmia and/or phantosmia. Our study demonstrates the relevance of psychophysical smell testing and its suitability for remote use during the pandemic. This study also revealed several correlations between prolonged olfactory dysfunction and the monitored parameters.


Glycosylation of internal sugar residues of oligosaccharides catalyzed by alpha-galactosidase from Aspergillus fumigatus.
Purified alpha-galactosidase from a thermotolerant fungus Aspergillus fumigatus IMI 385708 was found to catalyze efficiently transgalactosylation reactions using 4-nitrophenyl alpha-D-galactopyranoside as glycosyl donor. Self-transfer reactions with this substrate afforded in low yields several 4-nitrophenyl galactobiosides. Monosaccharides also served as poor glycosyl acceptors. Disaccharides and particularly higher oligosaccharides of alpha-1,4-gluco- (maltooligosaccharides), beta-1,4-gluco- (cellooligosaccharides) and beta-1,4-manno-series were efficiently galactosylated, the latter being the best acceptors that were also doubly galactosylated. With mannooligosaccharides product yields increased with polymerization degree of acceptors reaching 50% at DP of 4-6. Longer oligosaccharide acceptors were galactosylated at internal sugar residues. All galactosyl residues were transferred exclusively to the primary hydroxyl group(s) at C-6 position of oligosaccharide acceptors. This is in accordance with the inability of the enzyme to transfer galactose to beta-1,4-linked xylooligosaccharides. This is the first report of glycosyl transfer reaction to internal sugar residues of oligosaccharides catalyzed by a glycosidase. High affinity to oligosaccharide acceptors also opens a way toward enzymatic glycosylation of polysaccharides, thus modulating their physico-chemical and biological properties.


Phase separation and zinc-induced transition modulate synaptic distribution and association of autism-linked CTTNBP2 and SHANK3.
Many synaptic proteins form biological condensates via liquid-liquid phase separation (LLPS). Synaptopathy, a key feature of autism spectrum disorders (ASD), is likely relevant to the impaired phase separation and/or transition of ASD-linked synaptic proteins. Here, we report that LLPS and zinc-induced liquid-to-gel phase transition regulate the synaptic distribution and protein-protein interaction of cortactin-binding protein 2 (CTTNBP2), an ASD-linked protein. CTTNBP2 forms self-assembled condensates through its C-terminal intrinsically disordered region and facilitates SHANK3 co-condensation at dendritic spines. Zinc binds the N-terminal coiled-coil region of CTTNBP2, promoting higher-order assemblies. Consequently, it leads to reduce CTTNBP2 mobility and enhance the stability and synaptic retention of CTTNBP2 condensates. Moreover, ASD-linked mutations alter condensate formation and synaptic retention of CTTNBP2 and impair mouse social behaviors, which are all ameliorated by zinc supplementation. Our study suggests the relevance of condensate formation and zinc-induced phase transition to the synaptic distribution and function of ASD-linked proteins.


Psychosocial determinants of physical activity in children attending afterschool programs: a path analysis.
Physical activity (PA) is important for controlling childhood obesity, but a comprehensive PA model for school-aged children is lacking. Guided by the youth PA promotion (YPAP) model, this study estimated the direct and indirect effects of self-efficacy, enjoyment, parental influence, and environment on self-reported PA and pedometer steps. A secondary purpose was to explore the association between self-reported PA and pedometer steps. An observational and prospective study was conducted among 133 children, aged 8-11 years old, from 10 elementary schools with afterschool programs in a Midwestern U.S. school district from August through October 2013. PA was assessed by a 7-day recall scale and pedometers. Other variables were assessed by validated questionnaires. Approximately 65 (49%) children were overweight or obese-only 17 (13%) met national PA recommendations-and body mass index z-score was negatively correlated with pedometer steps (r = -.18 p = .04). A path analysis showed that self-efficacy had a direct effect on self-reported PA and pedometer steps, enjoyment had only a direct effect on self-reported PA, and parental influence had a direct effect on pedometer steps and an indirect effect on self-reported PA through self-efficacy and enjoyment. The association between self-reported PA and pedometer steps was not significant. Because this study only partially supports the YPAP model, studies with a larger sample size and longitudinal design are essential to further examine this model. The nonsignificant relationship of self-reported PA with pedometer steps may be due to the systematic error resulting from a common method artifact of self-report. Given the importance of parental influence, enjoyment, and self-efficacy, targeting these three determinants in future interventions to increase PA among children is recommended.


Endocrine dysfunction in hereditary hemochromatosis.
Hereditary hemochromatosis (HH) is a genetic disorder of iron overload and subsequent organ damage. Five types of HH are known, classified by age of onset, genetic cause, clinical manifestations and mode of inheritance. Except for the rare form of juvenile haemochromatosis, symptoms do not usually appear until after decades of progressive iron loading and may be triggered by environmental and lifestyle factors. Despite the last decades discovery of genetic and phenotype diversity of HH, early studies showed a frequent involvement of the endocrine glands where diabetes and hypogonadism are the most common encountered endocrinopathies. The pathogenesis of diabetes is still relatively unclear, but the main mechanisms include the loss of insulin secretory capacity and insulin resistance secondary to liver damage. The presence of obesity and/or genetic predisposition may represent addictive risk factor for the development of this metabolic disease. Although old cases of primary gonad involvement are described, hypogonadism is mainly secondary to selective deposition of iron on the gonadotropin-producing cells of the pituitary gland, leading to hormonal impaired secretion. Cases of hypopituitarism or selected tropin defects, and abnormalities of adrenal, thyroid and parathyroid glands, even if rare, are reported. The prevalence of individual gland dysfunction varies enormously within studies for several bias due to small numbers of and selected cases analyzed, mixed genotypes and missing data on medical history. Moreover, in the last few years early screening and awareness of the disease among physicians have allowed hemochromatosis to be diagnosed in most cases at early stages when patients have no symptoms. Therefore, the clinical presentation of this disease has changed significantly and the recognized common complications are encountered less frequently. This review summarizes the current knowledge on HH-associated endocrinopathies.


Consolidation of obstetric services in a public health emergency.
Though much of routine healthcare pauses in a public health emergency, childbirth continues uninterrupted. Crises like COVID-19 put incredible strains on healthcare systems and require strategic planning, flexible adaptability, clear communication, and judicious resource allocation. Experiences from obstetric units affected by COVID-19 highlight the importance of developing new teams and workflows to ensure patient and healthcare worker safety. Additionally, adapting a strategy that combines units and staff from different areas and hospitals can allow for synergistic opportunities to provision care appropriately to manage a structure and workforce at maximum capacity.


Correlation between liver volume, portal vascular anatomy, and hepatic perfusion in dogs with congenital portosystemic shunt before and after placement of ameroid constrictors.
To correlate changes in hepatic volume, hepatic perfusion, and vascular anatomy of dogs with congenital extrahepatic portosystemic shunts, before and after attenuation with an ameroid constrictor. Prospective study. Dogs (n = 22) with congenital extrahepatic portosystemic shunts. CT angiography and perfusion scans were performed before and after attenuation of a portosystemic shunt with an ameroid constrictor. Changes in hepatic volume, hepatic perfusion, and vascular anatomy were measured. Portal scintigraphy was performed in 8 dogs preoperatively and 22 dogs postoperatively. Dogs with smaller preoperative liver volumes had greater increases in liver volume postoperatively compared with those with larger preoperative liver volumes. Hepatic arterial fraction was increased in dogs preoperatively and returned to normal range after shunt attenuation, and was correlated with increase in liver size and decreased shunt fraction. Three dogs with no visible portal vasculature preoperatively developed portal branches postoperatively. Dogs with smaller preoperative liver volumes had the largest postoperative increase in liver volume. Hepatic arterial perfusion and portal scintigraphy correlate with liver volume and are indicators of successful shunt attenuation. Dogs without visible vasculature on CT angiography had visible portal vasculature postoperatively.


KN-93 inhibits IKr in mammalian cardiomyocytes.
Calcium/calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 is widely used in multiple fields of cardiac research especially for studying the mechanisms of cardiomyopathy and cardiac arrhythmias. Whereas KN-93 is a potent inhibitor of CaMKII, several off-target effects have also been found in expression cell systems and smooth muscle cells, but there is no information on the KN93 side effects in mammalian ventricular myocytes. In this study we explore the effect of KN-93 on the rapid component of delayed rectifier potassium current (IKr) in the ventricular myocytes from rabbit and guinea pig hearts. Our data indicate that KN-93 exerts direct inhibitory effect on IKr that is not mediated via CaMKII. This off-target effect of KN93 should be taken into account when interpreting the data from using KN93 to investigate the role of CaMKII in cardiac function.


Rt-PCR increases detection of submicroscopic peritoneal metastases in gastric cancer and has prognostic significance.
Positive peritoneal cytology confers the same prognosis as clinical stage IV disease in gastric cancer. Conventional cytology examination, however, has low sensitivity. We hypothesize that real-time polymerase chain reaction (RT-PCR) may have increased sensitivity and provide more accurate staging information. From February 2007 to April 2009, peritoneal lavage samples were collected prospectively from 156 patients with biopsy-proven gastric cancer undergoing staging laparoscopy. These washings were analyzed by both Papanicolaou staining and RT-PCR for the tumor marker carcinoembryonic antigen (CEA). Visible peritoneal disease was seen at laparoscopy in 38 patients (LAP+, 24%). Cytology was positive (CYT+) in 23 patients, while RT-PCR was positive (PCR+) in 30. The sensitivity of CYT for the detection of visible disease was 61% compared to 79% for PCR (P = 0.02). No visible peritoneal disease was seen at laparoscopy (LAP-) in 118 (76%) patients. Eight (7%) were CYT+, while 28 (24%) were PCR+. Predictors of PCR positivity included advanced-stage disease (T3-4 vs. T1-2 tumors) and poor pathologic features such as vascular or perineural invasion. Long-term follow-up demonstrated a worse survival of LAP-CYT-PCR+ (P = 0.0003) and LAP-CYT+PCR+ (P = 0.0004) compared to LAP-CYT-PCR- patients. There was no significant difference in survival between CYT-PCR+ and CYT+PCR+ patients. PCR positivity also predicted a higher likelihood of disease recurrence after resection. An R0 resection was performed in 85 LAP- patients (54%): only 1 (1%) was CYT+, while 13 (15%) were PCR+. Of this group, PCR+ demonstrated a worse survival than PCR- patients (P = 0.02). Further analysis showed that, in R0 resection, stage III/IV, CYT- subgroup, PCR+ was associated with a trend towards worse survival (P = 0.09) compared to PCR- patients. RT-PCR for CEA increases the detection of subclinical peritoneal disease and is more sensitive than cytology. Predictors of positive PCR included advanced-stage disease, vascular invasion, and perineural invasion. PCR positivity was associated with increased disease recurrence and decreased survival. Further follow-up is required to determine if PCR positivity alone is an independent predictor of poor survival in gastric cancer.


The Role of the Nervous System in the Pathophysiology of Psoriasis: A Review of Cases of Psoriasis Remission or Improvement Following Denervation Injury.
As most efforts in the last decade have focused on the immunologic basis of inflammatory skin disease, there has been less emphasis on the role of the nervous system in the disease process of psoriasis. Evidence in support of the neurocutaneous pathway has come from observations of patients experiencing unilateral improvement and even complete remission following nerve damage in the affected dermatomal region. The aim of this review was to investigate the role of neuropeptides in the intricate pathophysiology of psoriasis. The PubMed database was searched for individual case reports or case series that reported clearance or significant improvement in psoriatic disease in patients following documented nerve injury. A total of 11 cases were found that reported improvement of psoriatic lesions in areas afflicted by central or peripheral nerve injury. The most common causes of denervation were inadvertent surgical interruption, cerebrovascular accident, and poliomyelitis. In four cases the patients eventually regained neurologic function, which was associated with a recurrence of skin lesions. In cases of permanent nerve damage, there was remission of psoriasis. The cases reported in the literature to date provide clinical evidence that absence of neural input leads to psoriasis improvement, suggesting a crucial role of the nervous system in the pathophysiology of psoriatic disease. In fact, neuropeptides such as nerve growth factor, substance P, calcitonin gene-related peptide, and vasoactive intestinal peptide may be important contributors of psoriatic disease and potential targets for future therapies.


Delayed metabolism of postprandial triglyceride-rich lipoproteins in subjects with echolucent carotid plaques.
Subjects with echolucent carotid plaques have an increased risk of ischemic cerebrovascular events independent of degree of stenosis. Low plasma lipoprotein lipase (LPL) activity promotes a proatherogenic lipid profile, and delayed chylomicron clearance is a risk factor for atherosclerosis. This study was conducted to determine plasma LPL activity and postprandial metabolism of triglycerides in relation to carotid plaque morphology. Plaque echogenicity was assessed by B-mode ultrasound and analysis of the grey scale median (GSM). Echolucent plaques were defined as GSM < or = 63 (the median) and echogenic plaques as GSM > 63, and 57 subjects with carotid plaques and 38 subjects without carotid plaques were recruited. Blood samples were collected before and at 2-h interval for 8 h after a standard high fat meal. LPL activity and mass was determined before and after heparin administration. Postheparin LPL activity was decreased in subjects with echolucent plaques compared to subjects with echogenic plaques (P = 0.06) and to controls (P = 0.04). Plaque echogenicity increased linearly with increasing levels of postheparin LPL activity (P = 0.02) and mass (P = 0.03). Subjects with echolucent plaques had delayed postprandial clearance of chylomicron triglycerides compared to controls (P = 0.04). Low postheparin LPL activity due to attenuated mobilization of LPL from capillary endothelium may play an important role in the formation of echolucent plaques by modulation of postprandial lipids and subsequent fat accumulation in the arterial wall.


Environmentally-relevant concentrations of atrazine induce non-monotonic acceleration of developmental rate and increased size at metamorphosis in Rhinella arenarum tadpoles.
Despite of the various studies reporting on the subject, anticipating the impacts of the widely-used herbicide atrazine on anuran tadpoles metamorphosis remains complex as increases or decreases of larval period duration are almost as frequently reported as an absence of effect. The aim of the present study was to examine the effects of environmentally-relevant concentrations of atrazine (0.1, 1, 10, 100, and 1000μg/L) on the timings of metamorphosis and body size at metamorphosis in the common South American toad, Rhinella arenarum (Anura: bufonidae). None of the atrazine concentrations tested significantly altered survival. Low atrazine concentrations in the range of 1-100μg/L were found to accelerate developmental rate in a non-monotonic U-shaped concentration-response relationship. This observed acceleration of the metamorphic process occurred entirely between stages 25 and 39; treated tadpoles proceeding through metamorphosis as control animals beyond this point. Together with proceeding through metamorphosis at a faster rate, tadpoles exposed to atrazine concentrations in the range of 1-100μg/L furthermore transformed into significantly larger metamorphs than controls, the concentration-response curve taking the form of an inverted U in this case. The no observed effect concentration (NOEC) was 0.1μg atrazine/L for both size at metamorphosis and timings of metamorphosis. Tadpoles exposed to 100μg/L 17β-estradiol presented the exact same alterations of developmental rate and body size as those treated with 1, 10 and 100μg/L of atrazine. Elements of the experimental design that facilitated the detection of alterations of metamorphosis at low concentrations of atrazine are discussed, together with the ecological significance of those findings.


Association between state physical education (PE) requirements and PE participation, physical activity, and body mass index change.
To determine if state physical education (PE) laws are associated with student physical education attendance and physical activity (PA), and whether physical education and competitive food laws, in conjunction, are associated with lower BMI change. State laws regarding physical education time requirements and competitive foods in 2003 and 2006 were classified as strong, weak, or none, based on codified law ratings obtained from the Classification of Laws Associated with School Students. Laws were linked to student data on PE attendance and physical activity (8th grade, Spring 2007) and BMI change (5th-8th grade, 2004-2007), obtained from the Early Childhood Longitudinal Study (n=5510 students in 40 states). Girls reported 0.31 more days of activity (95% CI: 0.02, 0.61) and were more likely to attend physical education ≥ 3 days/week (74.1% versus 52.1%, difference=22.0, 95% CI: 2.1, 42.0) if they resided in states with strong physical education laws compared to no physical education laws. Weak physical education laws had modest associations with PE and activity, and there was no evidence that weak laws reduce BMI gain regardless of competitive food laws. Strong physical education laws with specific time requirements may increase physical education attendance and activity in girls. There is insufficient evidence that physical education laws reduce student weight gain.


Modulation of neutrophil functions by activated platelet release factors.
Platelets activated with physiological agonists, such as thrombin, ADP, or collagen, released products able to modulate neutrophil functions. In particular, platelet supernatant contained an inhibitor of superoxide anion generation induced by phorbol ester and a chemotactic factor for human neutrophils. The proteolytic digestion of platelet supernatant completely abrogated chemotactic activity without interfering with the inhibitory effect, indicating the presence of different molecules involved in the modulation of different neutrophil functions. This was further confirmed by the pretreatment of platelets with aromatic benzamidine which abolished chemotactic activity, but did not affect superoxide inhibition of neutrophils. This report provides evidence for interaction of platelets and inflammatory cells, suggesting that platelets are able to induce accumulation of neutrophils and control their respiratory burst, which also has a critical role in tissue damaging in inflammation.


Acute high-intensity interval exercise attenuates incubation of craving for foods high in fat.
Food-seeking behaviors can be driven by food-associated cues, and palatable food seeking in response to food cues is a risk factor for obesity development. Cue-induced food seeking increases following a period of abstinence, a behavioral phenomenon known as "incubation of craving," which may contribute to an individual's difficulty abstaining from palatable foods. Pharmacological and environmental manipulations have been employed to try and reduce incubation of craving, albeit primarily in drug abuse paradigms. The goal of this study was to determine whether forced exercise can attenuate incubation of high-fat food craving. Male Sprague Dawley rats learned to self-administer high-fat pellets (60%) in combination with a compound cue (light + tone). The influence of high-intensity interval exercise on the time-dependent increase in cue-induced lever responding was investigated 30 days after the first cue test. Rats exposed to exercise during abstinence did not express incubation of craving. The results suggest that high-intensity exercise can prevent the establishment of incubation of craving for foods high in fat and may reduce cue-induced maladaptive food-seeking behaviors that contribute to overeating and obesity.


2D Ca3 Sn2 S7 Chalcogenide Perovskite: A Graphene-Like Semiconductor with Direct Bandgap 0.5 eV and Ultrahigh Carrier Mobility 6.7 × 104 cm2 V-1 s-1.
Graphene, a star 2D material, has attracted much attention because of its unique properties including linear electronic dispersion, massless carriers, and ultrahigh carrier mobility (104 -105 cm2 V-1 s-1 ). However, its zero bandgap greatly impedes its application in the semiconductor industry. Opening the zero bandgap has become an unresolved worldwide problem. Here, a novel and stable 2D Ruddlesden-Popper-type layered chalcogenide perovskite semiconductor Ca3 Sn2 S7 is found based on first-principles GW calculations, which exhibits excellent electronic, optical, and transport properties, as well as soft and isotropic mechanical characteristics. Surprisingly, it has a graphene-like linear electronic dispersion, small carrier effective mass (0.04 m0 ), ultrahigh room-temperature carrier mobility (6.7 × 104 cm2 V-1 s-1 ), Fermi velocity (3 × 105 m s-1 ), and optical absorption coefficient (105 cm-1 ). Particularly, it has a direct quasi-particle bandgap of 0.5 eV, which realizes the dream of opening the graphene bandgap in a new way. These results guarantee its application in infrared optoelectronic and high-speed electronic devices.


[Application of computer systems in perinatology. I. Review of computer systems].
The main elements of the computer system used in medical practice are discussed. Typical application possibilities of microcomputers in perinatal medicine are described.


Photo-electrooxidation treatment of Acetaminophen in aqueous solution using BDD-Fe and BDD-Cu systems.
In this study, acetaminophen (ACT) in aqueous solution was treated with electrooxidation and photo-electrooxidation processes (PEO). An electrochemical cell was used for the treatment of different concentrations of ACT (10, 50 and 80 mg L-1). A 23 factorial design was proposed, and the variables studied were current intensity 0.5 A (45.45 mA cm-2) and 1.0 A (90.91 mA cm-2), electrode configuration (anode:BDD, cathode:Fe or Cu) and presence/absence of UV light; NaCl 0.043 M (2.5 g L-1) was used as supporting electrolyte, the initial pH was 5.5, and the treatment time was 3 h. The aqueous solutions were characterized before and after the treatment using infrared spectroscopy (FT-IR), Ultraviolet-visible spectroscopy (UV-Vis), chemical oxygen demand (COD), total organic carbon (TOC), total carbon (TC), and fluorescence spectroscopy. The optimal operating conditions using an initial ACT concentration of 80 mg L-1 were 1.0 A, BDD-Fe configuration and UV light (254 nm). The removal efficiencies were 100% of ACT and 82.75% of TOC after 15 min of treatment. At concentrations of 50 and 10 mg L-1, 77.16% and 50.29% of TOC were removed after 10 and 5 min of treatment, respectively. Finally, the kinetic study showed an increase in the rate constants when the UV light was applied.


Glutamate receptor subunits at mossy fiber-unipolar brush cell synapses: light and electron microscopic immunocytochemical study in cerebellar cortex of rat and cat.
The present study provides a survey of the immunolocalization of ionotropic glutamate receptor subunits throughout the rat and cat cerebellar cortex, with emphasis on the unipolar brush cell (UBC), a hitherto neglected cerebellar cell that is densely concentrated in the granular layer of the vestibulocerebellum and that forms giant synapses with mossy fibers. An array of nine previously characterized antibodies has been used, each of which stained a characteristic profile of cerebellar cells. The UBCs of both rat and cat were strongly immunostained by an antibody against the alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) receptor subunits, GluR2 and GluR3; were moderately immunostained by a monoclonal antibody to kainate receptor subunits, GluR5/6/7; were weakly immunostained by antibodies to NR1 subunits; and were not stained by antibodies to GluR1, GluR4, GluR6/7, KA-2, and NR2A/B. Postsynaptic densities of the giant mossy fiber-UBC synapses were GluR2/3, GluR5/6/7, and NR1 immunoreactive. The other cerebellar neurons were all immunolabeled to some extent with the GluR2/3 and NR1 antibodies. In addition, Purkinje cells were immunopositive for GluR1 and GluR5/6/7; granule cells were immunopositive for GluR5/6/7, GluR6/7, KA-2, and NR2A/B. The Golgi-Bergmann glia was densely stained by GluR1 and GluR4 antibodies, whereas astrocytes of the granular layer were stained by the GluR4 antiserum. Data provided herein may guide further electrophysiological and pharmacological studies of cerebellar cells in general and the UBCs in particular.


Pregnancy loss history at first parity and selected adverse pregnancy outcomes.
To evaluate the association between pregnancy loss history and adverse pregnancy outcomes. Pregnancy history was captured during a computer-assisted personal interview for 21,277 women surveyed in the National Survey of Family Growth (1995-2013). History of pregnancy loss (<20 weeks) at first parity was categorized in three ways: number of losses, maximum gestational age of loss(es), and recency of last pregnancy loss. We estimated risk ratios for a composite measure of selected adverse pregnancy outcomes (preterm, stillbirth, or low birthweight) at first parity and in any future pregnancy, separately, using predicted margins from adjusted logistic regression models. At first parity, compared with having no loss, having 3+ previous pregnancy losses (adjusted risk ratio (aRR) = 1.66 [95% CI = 1.13, 2.43]), a maximum gestational age of loss(es) at ≥10 weeks (aRR = 1.28 [1.04, 1.56]) or having experienced a loss 24+ months ago (aRR = 1.36 [1.10, 1.68]) were associated with increased risks of adverse pregnancy outcomes. For future pregnancies, only having a history of 3+ previous pregnancy losses at first parity was associated with increased risks (aRR = 1.97 [1.08, 3.60]). Number, gestational age, and recency of pregnancy loss at first parity were associated with adverse pregnancy outcomes in U.S. women.


Intestinal ultrasound detects an increased diameter and submucosal layer thickness in the appendix of patients with ulcerative colitis compared to healthy controls - a prospective cohort study.
Increasing evidence suggests that appendicectomy as alternative treatment for ulcerative colitis (UC), especially in patients with histopathological appendiceal inflammation. Intestinal ultrasound (IUS) is a non-invasive diagnostic modality to characterise appendiceal inflammation. To assess appendiceal IUS characteristics in UC patients and compare findings to healthy controls (HC). In this prospective study, appendiceal IUS was performed in consecutive UC patients with active (A; n = 35) or quiescent (Q; n = 30) disease and in HC (n = 30). Transverse appendiceal diameter (TAD) and additional IUS parameters (bowel wall thickness, submucosal layer thickness and colour Doppler signal) were assessed. The appendix was visualised in 41/65 UC patients (63.1%; A vs. Q: 23/35 vs. 18/30, p = 0.67) and 18/30 (60%) HC. UC patients had a higher TAD (A: 5.5 mm, Q: 5.0 mm, HC: 4.3 mm; A-HC p < 0.01; Q-HC p = 0.01, A-Q p = ns) and submucosal layer thickness (A: 1.0 mm, Q: 1.0 mm, HC: 0.7 mm; A-HC p < 0.01, Q-HC: p = 0.01, A-Q: p = ns) when compared to HC. A TAD ≥6 mm corresponding to an ultrasonographic suspicion of acute appendicitis was mainly reported in A-UC patients (A: 43%; Q: 6%; HC: 0%, p = 0.01) and occurred irrespective of disease extent. However, none of the patients had a clinical suspicion of acute appendicitis. A TAD ≥6 mm was predominantly seen in A-UC. TAD was higher in UC patients compared to HC irrespective of disease activity and was characterised by an increased submucosal layer thickness. IUS therefore has the potential to identify UC patients with appendiceal inflammation.


Individual housing does not influence the adaptation of the pituitary-adrenal axis and other physiological variables to chronic stress in adult male rats.
Although the influence of housing conditions on the physiological response to stress has been extensively studied for several years, no attempts have been made to investigate the effect of this variable on the capacity for adaptation to chronic stress. To this end, adult male rats were housed either individually or in groups of four per cage and subjected to 2 hr of daily immobilization stress for 14 days. Housing did not influence any of the physiological variables measured either in unstressed or in stressed rats except the corticosterone response to stress which was higher in individually housed rats. Of the behavioral measures, individual housing significantly decreased defecation rate in the novel environment. Other behavioral measures were not influenced by housing. Chronic stress significantly reduced ambulation but no significant interaction between housing and chronic stress was observed. Taken together, these data indicate that a short period of individual housing did not affect the physiological and behavioral consequences of repeated exposure to chronic stress.


Calsyntenin-3 C-terminal fragment accumulates in dystrophic neurites surrounding aβ plaques in tg2576 mouse and Alzheimer disease brains: its neurotoxic role in mediating dystrophic neurite formation.
Dystrophic neurites surrounding β-amyloid (Aβ) plaques precede neuronal death in Alzheimer disease. These neuritic alterations may be one of the initial stages for synaptic loss and dysfunction. However, intracellular pathways that cause local disruption of neuronal processes by Aβ remain to be fully elucidated. The identification of Aβ-induced genes that mediate neuritic pathology would provide considerable insight into the mechanisms of Alzheimer's disease. Previously, we reported that selective up-regulation of calsyntenin-3 (Cst-3) by Aβ and accumulation of neurotoxic Cst-3 in dystrophic neurites surrounding Aβ plaques may lead to local disruption of these neurites. Like amyloid precursor protein, Cst-3 undergoes two-step proteolytic processing: the primary cleavage with α-secretase generates an N-terminal ectodomain and a C-terminal fragment (CTF). The CTF is subsequently cleaved into p3 peptide and an intracellular domain via γ-secretase. It would be interesting to know whether accumulated Cst-3 in dystrophic neurites surrounding Aβ plaques is the full-length version or a CTF. Herein, we show that the CTF but not full-length Cst-3 accumulated in dystrophic neurites surrounding Aβ plaques in Tg2576 mouse and Alzheimer disease brains. In vitro experiments with Cst-3 fragments have revealed that only the CTF resulted in acceleration of neuronal death. These results indicate that accumulation of the neurotoxic CTF in neurites surrounding Aβ plaques may lead to local disruption of neuronal processes and development of dystrophic neurites.


High-resolution genetic mapping with pooled sequencing.
Modern genetics has been transformed by high-throughput sequencing. New experimental designs in model organisms involve analyzing many individuals, pooled and sequenced in groups for increased efficiency. However, the uncertainty from pooling and the challenge of noisy sequencing data demand advanced computational methods. We present MULTIPOOL, a computational method for genetic mapping in model organism crosses that are analyzed by pooled genotyping. Unlike other methods for the analysis of pooled sequence data, we simultaneously consider information from all linked chromosomal markers when estimating the location of a causal variant. Our use of informative sequencing reads is formulated as a discrete dynamic Bayesian network, which we extend with a continuous approximation that allows for rapid inference without a dependence on the pool size. MULTIPOOL generalizes to include biological replicates and case-only or case-control designs for binary and quantitative traits. Our increased information sharing and principled inclusion of relevant error sources improve resolution and accuracy when compared to existing methods, localizing associations to single genes in several cases. MULTIPOOL is freely available at http://cgs.csail.mit.edu/multipool/.


Deep learning in head & neck cancer outcome prediction.
Traditional radiomics involves the extraction of quantitative texture features from medical images in an attempt to determine correlations with clinical endpoints. We hypothesize that convolutional neural networks (CNNs) could enhance the performance of traditional radiomics, by detecting image patterns that may not be covered by a traditional radiomic framework. We test this hypothesis by training a CNN to predict treatment outcomes of patients with head and neck squamous cell carcinoma, based solely on their pre-treatment computed tomography image. The training (194 patients) and validation sets (106 patients), which are mutually independent and include 4 institutions, come from The Cancer Imaging Archive. When compared to a traditional radiomic framework applied to the same patient cohort, our method results in a AUC of 0.88 in predicting distant metastasis. When combining our model with the previous model, the AUC improves to 0.92. Our framework yields models that are shown to explicitly recognize traditional radiomic features, be directly visualized and perform accurate outcome prediction.


Reactions of denatured proteins with other cellular components to form insoluble aggregates and protection by lactoferrin.
Elucidation of the mechanism of formation of insoluble protein aggregates is essential to resolve problems such as protein folding diseases. In this study the effects of various types of biomolecules on the aggregation of denatured proteins were investigated. Denatured alpha-lactalbumin, an acidic protein, was found to be precipitated by lactoferricin, a basic peptide derived from lactoferrin. Denatured lysozyme, a basic protein, by itself showed aggregation, which was promoted by addition of native alpha-lactalbumin. Heparin and nucleic acids caused almost instant aggregation of denatured lysozyme. Native lactoferricin was also found to aggregate with heparin or nucleic acids. The results show that denatured/misfolded proteins as well as peptides are highly reactive with other cellular components to form insoluble aggregates and suggest a possible mechanism by which protein folding diseases progress. Most of the above aggregation reactions were inhibited by lactoferrin, which could form soluble complexes with denatured alpha-lactalbumin, heparin, and nucleic acids.


2-({[(Pyridin-1-ium-2-ylmeth-yl)carbamo-yl]form-amido}-meth-yl)pyridin-1-ium bis-(3,5-di-carb-oxy-benzoate): crystal structure and Hirshfeld surface analysis.
The asymmetric unit of the title salt, C14H16N4O2 (2+)·2C9H5O6 (-), comprises half a dication, being located about a centre of inversion, and one anion, in a general position. The central C4N2O2 group of atoms in the dication are almost planar (r.m.s. deviation = 0.009 Å), and the carbonyl groups lie in an anti disposition to enable the formation of intra-molecular amide-N-H⋯O(carbon-yl) hydrogen bonds. To a first approximation, the pyridinium and amide N atoms lie to the same side of the mol-ecule [Npy-C-C-Namide torsion angle = 34.8 (2)°], and the anti pyridinium rings are approximately perpendicular to the central part of the mol-ecule [dihedral angle = 68.21 (8)°]. In the anion, one carboxyl-ate group is almost coplanar with the ring to which it is connected [Cben-Cben-Cq-O torsion angle = 2.0 (3)°], whereas the other carboxyl-ate and carb-oxy-lic acid groups are twisted out of the plane [torsion angles = 16.4 (3) and 15.3 (3)°, respectively]. In the crystal, anions assemble into layers parallel to (10-4) via hy-droxy-O-H⋯O(carbon-yl) and charge-assisted hy-droxy-O-H⋯O(carboxyl-ate) hydrogen bonds. The dications are linked into supra-molecular tapes by amide-N-H⋯O(amide) hydrogen bonds, and thread through the voids in the anionic layers, being connected by charge-assisted pyridinium-N-O(carboxyl-ate) hydrogen bonds, so that a three-dimensional architecture ensues. An analysis of the Hirshfeld surface points to the importance of O-H⋯O hydrogen bonding in the crystal structure.


One pot phytosynthesis of gold nanoparticles using Genipa americana fruit extract and its biological applications.
In this article, rapid one pot synthesis of gold nanoparticles (GNPs) using an eco-friendly extract of Genipa americana L. fruit is described. Electrospray ionization mass spectrometry (ESI-MS) and Fourier transform infrared (FTIR) spectroscopic studies demonstrated that small molecules such as genipin, genipaol, geniposide and ranolazine can act as reducer as well as stabilizers. The monodispersed, spherical GNPs were further characterized by UV-vis spectroscopy at λmax=535 nm, transmission electron microscopy (TEM), dynamic light scattering (DLS) and X-ray diffraction (XRD) analysis. This synthetic approach offers a greener and alternate route to the preparation of GNPs free from toxic chemical components and stable for 6-7 months under room temperature. The green synthesized GNPs showed weak antioxidant efficacy against 1,1-diphenyl-2-picrylhydrazyl and no cytotoxicity against A-549 and HeLa human cancer cell lines, from lung and cervix. This study opens a new industrial scope of G. americana fruit in nanoscience and as surface modified GNPs can be developed into a successful drug carrier for future pharmaceutical products.


The protective effect of hypothermia on reversibility in the neuronal function of the hippocampal slice during long lasting anoxia.
The reversibility of neuronal function (postsynaptic potential and level of high energy phosphates) during deprivation of oxygen and/or glucose at 37, 28 and 21 degrees C was studied using hippocampal slices. The resistance of the neurons per se against anoxia could be well determined in the brain slice free from post-anoxic circulatory disturbance. During deprivation of oxygen and glucose the survival time, the period of deprivation of oxygen and glucose during which neurons of the tissue slice can survive for recovery, was at 10, 15 and 45 min at 37, 28 and 21 degrees C, respectively. During deprivation of glucose only it was 1.5, 3 and 5 h at 37, 28 and 21 degrees C. During deprivation of oxygen only the survival time was 2.5, 5 and 15 h at 37, 28 and 21 degrees C. Deep hypothermia (21 degrees C) and the presence of glucose prolonged tremendously the survival time of the neurons of tissue slice during long-lasting anoxia.


Cost effectiveness of Mohs micrographic surgery.
Chren's study provides further evidence that for primary facial nonmelanoma skin cancers (NMSCs), recurrence rates with Mohs micrographic surgery (MMS) are modestly better than those for excision surgery. In 20 years, use of MMS has grown ∼10-fold and its cost now exceeds two billion dollars annually. Clinical experience and available data suggest that the skill of the treating physician is at least as important a determinant of outcome as the choice of MMS or excision. As patients and referring physicians increasingly share in the cost of more expensive procedures, evidence-based guidelines that establish the clinical circumstances in which the additional benefits of MMS outweigh its higher cost are needed, still lacking, and unlikely to become available.


[Apoptosis of human oral epidermoid carcinoma KB cells and multidrug resistant KBv200 cells induced by matrine].
To investigate the induction of apoptosis on human oral epidermoid carcinoma KB cells and multidrug resistant KBv200 cells by Matrine. MTT assay was used to investigate the inhibition ability of Matrine on the cells in vitro. Transmission electron microscope was used to observe the ultrastructure feature of cells. after treated by Matrine. Acridine orange (AO)/Ethidium bromide (EB) fluorescent staining and flow cytometry were used to observe apoptosis induced by Matrine. Flow cytometry was applied to study the effects of the drug on cell cycles of the cells. When 0.50, 1.00, 1.50, 2.00 mg/ml of Matrine was used, the vital rates of KB and KBv200 cells were decreased according to Matrine's concentration. The IC50 concentrations of Matrine on KB and KBv200 cells were 1.35 mg/ml and 1.43 mg/ml individually. The results of AO/EB fluorescent staining and flow cytometry showed that Matrine could induce apoptosis of two kinds of cells. While observed by transmission electron microscope, there were more contraction of cells, condensation of nuclei, bubble of cytoplasm in both kinds of cells after treated by Matrine. Matrine could stop the growth of KB and KBv200 cells at S period and restrain mitosis of cells. Matrine can inhibit the growth of KB and KBv200 cells by inducing apoptosis. The apoptosis effect is dose-dependent and it has certain relation to the blocking of S period cells.


Serum peptidome: diagnostic window into pathogenic processes following occupational exposure to carbon nanomaterials.
Growing industrial use of carbon nanotubes and nanofibers (CNT/F) warrants consideration of human health outcomes. CNT/F produces pulmonary, cardiovascular, and other toxic effects in animals along with a significant release of bioactive peptides into the circulation, the augmented serum peptidome. While epidemiology among CNT/F workers reports on few acute symptoms, there remains concern over sub-clinical CNT/F effects that may prime for chronic disease, necessitating sensitive health outcome diagnostic markers for longitudinal follow-up. Here, the serum peptidome was assessed for its biomarker potential in detecting sub-symptomatic pathobiology among CNT/F workers using label-free data-independent mass spectrometry. Studies employed a stratified design between High (> 0.5 µg/m3) and Low (< 0.1 µg/m3) inhalable CNT/F exposures in the industrial setting. Peptide biomarker model building and refinement employed linear regression and partial least squared discriminant analyses. Top-ranked peptides were then sequence identified and evaluated for pathological-relevance. In total, 41 peptides were found to be highly discriminatory after model building with a strong linear correlation to personal CNT/F exposure. The top-five peptide model offered ideal prediction with high accuracy (Q2 = 0.99916). Unsupervised validation affirmed 43.5% of the serum peptidomic variance was attributable to CNT/F exposure. Peptide sequence identification reveals a predominant association with vascular pathology. ARHGAP21, ADAM15 and PLPP3 peptides suggest heightened cardiovasculature permeability and F13A1, FBN1 and VWDE peptides infer a pro-thrombotic state among High CNT/F workers. The serum peptidome affords a diagnostic window into sub-symptomatic pathology among CNT/F exposed workers for longitudinal monitoring of systemic health risks.


Cytogenetic mapping and orientation of the rhesus macaque MHC.
Applying fluorescence in situ hybridisation (FISH), six cosmid clones of rhesus macaque origin containing the genes SACM2L, RING1, BAT1 and MIC2, MIC3, MICD, and MOG of the major histocompatibility complex (MHC) were localised to the long arm of the rhesus macaque chromosome 6 in 6q24, the orthologous region to human 6p21.3. Furthermore, centromere to telomere orientation of the rhesus macaque MHC as well as the internal order of the MHC genes tested are the same as in human. Fiber-FISH allows a rough estimate of distances between these MHC genes in the rhesus macaque, and, as in the human, the rhesus macaque MHC comprises about 3 to 4 Mb.


Perfusion abnormality in neuronal intranuclear inclusion disease with stroke-like episode: A case report.
Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease. Some patients with NIID occasionally present with acute symptoms. However, its mechanism remains unclear. We report a patient with NIID who presented with a stroke-like episode. Arterial spin labeling magnetic resonance imaging revealed hypoperfusion in the focal cerebral region at the onset while no apparent arterial occlusion was observed. The abnormal perfusion area was normalized 6 days after admission. Therefore, the perfusion abnormality was likely the main cause of acute neurologic deficits in NIID. NIID should be considered in the differential diagnosis of stroke mimics.


Evaluation of contaminants of emerging concern attenuation through a vegetation filter managed using different operating conditions.
In wastewater treatment using Vegetation Filters (VFs), natural processes reduce contaminants present in water although some of them can reach the environment. In this study, 39 contaminants of emerging concern (CECs) are evaluated in a pilot VF under different operating conditions during almost four years. The use of woodchip amendments and the change from surface irrigation through furrows to drip irrigation (and from weekly to daily water application) provide CEC concentration reductions in the water infiltrating through the vadose zone. Biodegradation is the main process taking place and has been favoured mainly by woodchip soil amendments and the increased residence. Median attenuation percentages of the CECs most frequently detected with highest concentrations in applied wastewater vary between 52% and 100% at the end of the study (at 45 cm depth). Among targeted CECs, caffeine, and its transformation product paraxanthine are the most attenuated. Flecainide and venlafaxine show a persistent behaviour. However, their leaching concentrations are very low (< 31 ng/L). Concerning the underlying aquifer, the groundwater quality in terms of CEC concentrations is conditioned by the surrounding area rather than the operation of the VF. Levels in groundwater are always below those in wastewater and infiltrating water.