Volume of hippocampal activation as a determining factor for the lateralisation of the epileptogenic zone in patients with drug-resistant mesial temporal lobe epilepsy.
Approximately 30% of patients with mesial temporal lobe epilepsy (MTLE) will develop drug resistance, which requires early surgical treatment. The success of the surgical procedure largely depends on the correct lateralisation of the epileptogenic zone, which can only be determined in 70% of patients with such conventional diagnostic tools as video electroencephalography and volumetric structural magnetic resonance imaging. We evaluated the performance of a memory functional magnetic resonance imaging (fMRI) paradigm in lateralising the epileptogenic zone in patients with drug-resistant MTLE. We included 18 patients with MTLE attended at the Instituto Neurológico Colombiano in Medellin (Colombia) between 2018 and 2019. The volume of functional activation in both temporal lobes was determined with a memory fMRI paradigm. A concordance analysis was performed to compare the performance of fMRI against that of conventional tests. In patients with left MTLE, lower total activation was found in the hemisphere ipsilateral to the epileptogenic zone as compared to the contralateral hemisphere (121.15 ± 16.48 voxels vs 170.23 ± 17.8 voxels [P < .001]), showing substantial concordance with conventional tests. Patients with right MTLE displayed lower hippocampal activation ipsilateral to the epileptogenic zone (18.5 ± 3.38 voxels vs 27.8 ± 3.77 voxels in the contralateral hippocampus [P = .048]), showing moderate concordance with conventional tests. These findings suggest that lower functional activation as determined by a memory fMRI paradigm has a high level of concordance with conventional tests for lateralising the epileptogenic zone in patients with drug-resistant MTLE.


Genetic variation for 15 autosomal STR loci (PowerPlex 16) in a population sample from northern Greece.
Fifteen autosomal STR loci were typed in a population sample of 318 unrelated individuals from northern Greece. Allele frequencies were determined, and Hardy-Weinberg equilibrium tested, for the following loci: D5S818, D7S820, TH01, TPOX, vWA, CSF1PO, D16S539, D13S317, D8S1179, D3S1358, FGA, PENTA D, PENTA E, D21S11, D18S51.


Supermarket Purchases Over the Supplemental Nutrition Assistance Program Benefit Month: A Comparison Between Participants and Nonparticipants.
The Supplemental Nutrition Assistance Program provides financial assistance for food and beverage purchases to approximately 1 in 7 Americans, with benefits distributed once monthly. Most Supplemental Nutrition Assistance Program benefits are spent early in the month, leading to decreased caloric intake later in the month. The effects of this early benefit depletion on the types of foods and beverages purchased over the course of the month is unclear. Using individually tracked sales data from 950 participants enrolled in 2 supermarket-based RCTs in Maine (October 2015-April 2016 and October 2016-June 2017), purchases of selected food categories by Supplemental Nutrition Assistance Program participants (n=248) versus nonparticipants (n=702) in the first 2 weeks compared with the last 2 weeks of the Supplemental Nutrition Assistance Program benefit month were examined. Analyses were completed in 2019. For Supplemental Nutrition Assistance Program participants, adjusted mean food spending decreased 37% from the first 2 weeks to the last 2 weeks of the Supplemental Nutrition Assistance Program benefit month (p<0.0001) compared with a 3% decrease (p=0.02) for nonparticipants. The decline in spending by Supplemental Nutrition Assistance Program participants occurred in all examined categories: vegetables (-25%), fruits (-27%), sugar-sweetened beverages (-30%), red meat (-37%), convenience foods (-40%), and poultry (-48%). Difference-in-difference estimators comparing Supplemental Nutrition Assistance Program participants with nonparticipants were statistically significant (p<0.05) for all examined categories. In the second half of the Supplemental Nutrition Assistance Program benefit month, individuals reduced purchases of all examined categories. More research is needed to understand the impact of these fluctuations in spending patterns on the dietary quality of Supplemental Nutrition Assistance Program participants.


An intriguing "silent" mutation and a founder effect in antiquitin (ALDH7A1).
Recently, alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency was shown to cause pyridoxine-dependent epilepsy in a considerable number of patients. alpha-AASA dehydrogenase deficiency is an autosomal recessive disorder characterized by a neonatal-onset epileptic encephalopathy in which seizures are resistant to antiepileptic drugs but respond immediately to the administration of pyridoxine (OMIM 266100). Increased plasma and urinary levels of alpha-AASA are associated with pathogenic mutations in the alpha-AASA dehydrogenase (ALDH7A1/antiquitin) gene. Here, we report an intriguing "silent" mutation in ALDH7A1, a novel missense mutation and a founder mutation in a Dutch cohort (10 patients) with alpha-AASA dehydrogenase deficiency.


Single injection peribulbar anesthesia with a short needle combined with digital compression.
We compare the efficacy of using a 15 mm to the standard 25 mm needle for performing peribulbar blockade. Blocks were performed on 150 patients using 15 or 25 mm needle length. Digital compression was applied by the thumb and index finger around the needle hub during injection with 15 mm needle. Anesthetic was injected until lid fullness was noted. Inadequate block was augmented. No significant differences were noted between groups with respect to local anesthetic volume, supplementation, and akinesia. Peribulbar blockade performed with a 15 mm needle with digital pressure is comparable to blockade using a 25 mm needle.


Intracranial hypertension in subarachnoid hamorrhage: outcome after decompressive craniectomy.
Intracranial hypertension can occur following aneurysmal subarachnoid haemorrhage (SAH). It can be treated with decompressive craniectomy (DC) with the aim of reducing intracranial pressure, increasing cerebral perfusion and reducing further morbidity and mortality. We studied the outcome of patients undergoing DC following SAH at our institution, to ascertain whether the use of this treatment can be rationalized.


Optogenetic stimulation of CA3 pyramidal neurons restores synaptic deficits to improve spatial short-term memory in APP/PS1 mice.
The hippocampal CA3 region, that is involved in the encoding and retrieval of spatial memory, is found to be synaptically impaired in the early-onset of Alzheimer's disease (AD). It is reported optogenetic manipulation of DG or CA1 can rescue the memory impairment of APP/PS1 mice, however, how CA3 region contributes to AD-related deficits in cognitive function is still unknown. Our work shows optogenetic stimulation of CA3 pyramidal neurons (PNs) significantly restores the impaired spatial short-term memory of APP/PS1 mice. This enhances the anatomical synaptic density/strength and synaptic plasticity as well as activates astrocytes. Chemogenetic inhibiting the activity of CA3 astrocytes reverses the effect of optogenetic stimulation of CA3 PNs that leads to reduced anatomical synaptic density/strength, decreased synaptic protein and AMPA receptors GluA3/4, thus disrupting the cognitive restoration of APP/PS1 mice. These results reveal the molecular mechanism of optogenetic activation of CA3 PNs on restoration of the spatial short-term memory of APP/PS1 mice and unveil a potential strategy of manipulating CA3 for AD treatment.


Monooxygenation of N-acetylhistamine mediated by L-ascorbate.
In the presence of molecular oxygen and a catalytic amount of copper(II) ion, ascorbate almost completely degraded histamine (approx. 72%). The reaction was shown to occur at the imidazole group but not at the primary amino group in histamine. 4-[2-(Acetylamino)ethyl]-2,3-dihydroimidazol-2-one, a monooxygenated form of N-acetylhistamine, was first isolated as the primary product.


[Medical significance and requirements of sports].
Kind and intensity of physical activity with preventive value of degenerative diseases are well known by sports medicine. The core of the problem is the transfer of established knowledge into action and the creation of attractive programs making physical activity an enjoyment and which let us forget the final objective, i.e. prevention of ill health.


Effect of preoperative coronary CT for planning of percutaneous coronary intervention for complex chronic total occlusion (CTS-C-CTOPCI): study protocol for an open-label randomised controlled trial.
Treatment of chronic total occlusion (CTO) by percutaneous coronary intervention (PCI) is associated with the difficulty of guidewire manipulation through the occluded segment, particularly when there is hard tissue due to calcification. The purpose of this randomised controlled trial is to determine whether improved planning of CTO-PCI using coronary computed tomographic angiography (CCTA) (versus conventional angiography) increases success rates of wire crossing in ≤ 60 min in difficult cases. This is a randomised controlled open-label multi-centre trial in a superiority framework with 1:1 allocation ratio. Participants (n = 130) will be randomised into two groups: the study group who will receive standard of care with the addition of preoperative coronary computed tomographic angiography (CT group), and the control group that will receive standard of care (angiography group). The primary endpoint will be the rate of successful wire crossing in ≤ 60 min in complex CTO (J-CTO ≥ 2). Wire crossing will be considered successful if TIMI flow 3 is restored and residual stenosis is < 30%. The safety endpoint will be mortality due to the intervention or major adverse cardiac events (MACE). Secondary endpoints are success rates at any time; total time of PCI; time of wire crossing; rate of PCI complications; radiation levels during PCI; volume of iodine contrast medium administered; and cost of the PCI. This randomised trial will provide insight into whether pre-procedural CCTA as opposed to conventional angiography for planning of CTO-PCI yield higher success rates of wire crossing in ≤ 60 min. Potential benefits of CCTA include shorter successful procedure times of CTO-PCI leading to less irradiation and contrast medium with lower complication rates. Clinical Trials.gov NCT04549896. Registered on December 21, 2021.


Redirecting Normal and Cancer Stem Cells to a Mammary Epithelial Cell Fate.
Tissue microenvironments, also known as stem cell niches, influence not only resident cells but also cells in surrounding tissues. Physical and biochemical intercellular signals originating from resident stem cells or non-stem cells participate in the homeostasis of the tissue regulating cell proliferation, differentiation, wound healing, tissue remodeling, and tumorigenesis. In recent publications it has been demonstrated that the normal mouse mammary microenvironment can provide development and differentiation guidance to not only resident mammary cells but also cells of non-mammary origin including tumor-derived cells. When placed in reforming mammary stem cell niches the non-mammary cells proliferate and differentiate along mammary epithelial cell lineages and contribute progeny to reforming mammary gland outgrowths. The tumor-derived cells that are redirected to assume mammary epithelial phenotypes lose their cancer-forming capacity and shift their gene expression profiles from a cancer profile towards a normal mammary epithelial expression profile. This review summarizes the recent discoveries regarding the ability of the normal mouse mammary microenvironment to dictate the cell fates of non-mammary cells introduced into mammary stem cell niches.


The human antibody response to pneumococcal capsular polysaccharides is dependent on the CD40-CD40 ligand interaction.
Protection against infections with Streptococcus pneumoniae is mediated by antibodies against the capsular polysaccharides (caps-PS). Here we show that in in vitro experiments CD4+ T lymphocytes stimulate and CD8+ T lymphocytes inhibit the human anti-caps-PS antibody response. Using antagonistic anti-CD40 and antagonistic anti-CD40 ligand (CD40L) monoclonal antibodies, we showed that the CD4+ T lymphocyte-mediated stimulation is dependent on the CD40-CD40L interaction. The role of CD40L was further illustrated by the observation that CD4+ T lymphocytes obtained from a patient with hyper-IgM syndrome were unable to enhance the immune response to caps-PS. Furthermore, CD4+ T lymphocytes from cord blood, which did not express CD40L in response to stimulation with caps-PS, failed to stimulate the antibody response of adult B lymphocytes to caps-PS. These in vitro findings were confirmed by in vivo experiments in which SCID/SCID mice were reconstituted with human mononuclear cells. Furthermore, we showed that caps-PS induce production of IL-4, IL-6, IL-10, and IFN-gamma, and that this enhanced production was inhibited by blocking the CD40-CD40L interaction. This is the first demonstration that the human immune response to caps-PS, which is markedly regulated by T lymphocytes, is dependent on the CD40-CD40L interaction.


Major genes determining yield-related traits in wheat and barley.
Current development of advanced biotechnology tools allows us to characterize the role of key genes in plant productivity. The implementation of this knowledge in breeding strategies might accelerate the progress in obtaining high-yielding cultivars. The achievements of the Green Revolution were based on a specific plant ideotype, determined by a single gene involved in gibberellin signaling or metabolism. Compared with the 1950s, an enormous increase in our knowledge about the biological basis of plant productivity has opened new avenues for novel breeding strategies. The large and complex genomes of diploid barley and hexaploid wheat represent a great challenge, but they also offer a large reservoir of genes that can be targeted for breeding. We summarize examples of productivity-related genes/mutants in wheat and barley, identified or characterized by means of modern biology. The genes are classified functionally into several groups, including the following: (1) transcription factors, regulating spike development, which mainly affect grain number; (2) genes involved in metabolism or signaling of growth regulators-cytokinins, gibberellins, and brassinosteroids-which control plant architecture and in consequence stem hardiness and grain yield; (3) genes determining cell division and proliferation mainly impacting grain size; (4) floral regulators influencing inflorescence architecture and in consequence seed number; and (5) genes involved in carbohydrate metabolism having an impact on plant architecture and grain yield. The implementation of selected genes in breeding programs is discussed, considering specific genotypes, agronomic and climate conditions, and taking into account that many of the genes are members of multigene families.


Intramolecular Cyclization During Bromination of the Quinoline Alkaloid Haplophyllidine.
Bromination of the furanoquinoline alkaloid haplophyllidine by molecular bromine and N-bromosuccinimide was accompanied by intramolecular cyclization to form mixtures of new compounds containing additional penta-, hexa-, and spirocyclic rings incorporating the prenyl group of haplophyllidine. The structures and absolute configurations of the chiral centers of all four bromo-derivatives were elucidated using a combination of NMR spectroscopic methods and X-ray crystal structure analyses.


Effect of treatment on maxillary sinus and nasal nitric oxide concentrations in patients with nosocomial maxillary sinusitis.
In maxillary nosocomial sinusitis (MNS) related to severe sepsis, nitric oxide (NO) concentration in the maxillary sinuses is drastically reduced secondarily to a downregulation of type-2 NO synthase. NO plays a major role in nonspecific immune defense of sinuses. We therefore aimed to study maxillary NO concentration during the treatment of MNS with drainage, daily lavage, and removal of any nasally introduced tube. Nine patients were studied during the first 4 days of treatment of MNS. We measured the concentration of NO gas in the maxillary sinus and in the nasal cavity, and the NO metabolite levels (nitrites/nitrates [NOx]) in the sinus lavages. Maxillary NO concentration (median [25 to 75 percentile]) increased from 70 parts per billion (ppb) [40 to 100 ppb] to 2,050 ppb (1,700 to 3,000 ppb) after 4 days of treatment of MNS (p < 0.0001). In the meantime, nasal NO increased from a median of 100 ppb (98 to 148 ppb) to 180 ppb (180 to 188 ppb) [p < 0.001]. At any time, there was a correlation between maxillary NO (logarithmic value) and nasal NO (r2 = 0.57, p < 0.0001). NOx levels remained stable in the lavages. We conclude that the treatment of the sinusitis with drainage, daily lavage, and removal of the gastric tube lead to a spectacular increase of maxillary and nasal NO concentrations.


Phenotypic and proliferative modulation of human mesenchymal stem cells via crosstalk with endothelial cells.
The purpose of this work was to investigate if a coculture system of human mesenchymal stem cells (hMSC) with endothelial cells (human umbilical vein endothelial cells, HUVEC) could modulate the phenotype and proliferation of harvested MSCs. In addition to previous investigations on the crosstalk between these two cell types, in the present work different relative cell ratios were analyzed for long, therapeutically relevant, culture periods. Moreover, MSCs osteogenic commitment was assessed in a non-osteogenic medium and in the presence of HUVECs through magnetic cell separation, cell quantification by flow cytometry, morphology by fluorescent microscopy, metabolic activity and gene expression of osteogenic markers. Collectively, the present findings demonstrate that, by coculturing MSCs with HUVECs, there was not only the promotion of osteogenic differentiation (and its enhancement, depending on the relative cell ratios used), but also a significant increase on MSCs proliferation. This augmentation in cell proliferation occurred independently of relative cell ratios, but was favored by higher relative amounts of HUVECs. Taken together, this data suggests that HUVECs not only modulate MSC phenotype but also their proliferation rate. Therefore, a coculture system of MSCs and HUVECs can a have a broad impact on bone tissue engineering approaches.


123I-5-I-R91150, a new single-photon emission tomography ligand for 5-HT2A receptors: influence of age and gender in healthy subjects.
5-HT2A receptors have been implicated in the pathophysiology of mood disorders and in the therapeutic effect of the so-called atypical antipsychotics. Recently, a new radioiodinated ligand with high affinity and selectivity for serotonin 5-HT2A receptors, 123iodinated 4-amino-N-1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl] 5-iodo-2-methoxybenzamide (123I-5-I-R91150), has been developed and has been shown to be suitable for single-photon emission tomography (SPET) imaging. In this study the influence of age and gender on the ligand binding was investigated in normal volunteers. One hundred and fifty MBq of 123I-5-I-R91150 was administered to 26 normal volunteers (13 females and 13 males) with an age range of 23-60 years. SPET imaging was performed with a triple-headed gamma camera. For semi-quantitative analysis, ratios of ligand binding in different regions of interest to the binding in the cerebellum were calculated. Mean ratios of 1.7 were obtained. No gender difference was demonstrated. 5-HT2A binding was shown to decline with age. Over an age range of 40 years a reduction in ligand binding of 42% +/- 7% was found. These results are in agreement w in vitro and positron emission tomography findings of a decline in 5-HT2A receptor binding with age. The findings confirm the suitability of 123I-5-I-R91150 for SPET imaging of 5-HT2A receptors, and highlight the necessity for age-matched controls in clinical studies.


Mouse killing in rats: a comparison of spontaneous killers and rats with lesions of the medial hypothalamus or the medial accumbens nucleus.
Mouse killing was observed and videotaped at forty-eight hr following surgery in rats with lesions of the medial hypothalamus or the medial accumbens. The initial attacks and killing bites of the lesioned rats were directed at the anterior dorsal surface, predominantly to the regions of the neck, shoulders, and thorax and did not differ from those of spontaneous mouse killing rats. The latency to attack was significantly shorter for the lesioned animals but the time required to kill following the attack tended to be longer. Lesioned animals spent significantly more time biting the prey following the kill and left significantly more bite marks on the prey than did the spontaneous killers. When the dead prey was moved about the cage following the kill, the lesioned animals showed a significantly greater tendency to attack it than did the spontaneous killers. Following the test of mouse killing, each rat was successively exposed to a freshly killed mouse, a cotton wad, and a wood block. The lesioned animals attacked the dead mouse and the cotton wad as though they were live mice whereas the spontaneous killers did not. These results suggest that while the killing is similar for lesioned and spontaneous killers, the lesioned animals show a heightened response to the killing experience. This is manifested in an exaggeration of attack behaviors toward prey and prey-like stimulus objects following an initial killing experience.


Structure-activity relationships in 2-aminodiphenylsulfides against trypanothione reductase from Trypanosoma cruzi.
In order to establish structural elements responsible for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi by 2-aminodiphenylsulfides, a series of dissymmetrical derivatives, corresponding to the replacement of one aromatic moiety by different amines, was synthesized. TR inhibition studies revealed the importance of the aromatic rings and of the amino groups in the side chains for potent inhibition. Quinonic moities were also introduced with the aim of acting as TR redox-cycling substrates.


Low Agreement Between Initial and Revised European Consensus on Definition and Diagnosis of Sarcopenia Applied to People Living With HIV.
In 2019, the European Working Group on Sarcopenia in Older People (EWGSOP2) proposed low muscle strength as the primary outcome for sarcopenia diagnosis instead of low muscle mass, as proposed in 2010 (EWGSOP1). Therefore, the aim of this study was to compare the prevalence of sarcopenia using both EWGSOP1 and EWGSOP2 operational definitions in people living with HIV (PLHIV) and to determine the agreement and correlation between different tests proposed by EWGSOP2. Cross-sectional study, where 302 PLHIV (151 men), 51.7 ± 9.0 years old were evaluated for the presence of sarcopenia using both EWGSOP1 and EWGSOP2 operational definitions. Appendicular skeletal muscle was estimated using bioimpedance analysis. Handgrip strength, chair stand, gait speed, and static balance were used as muscle function measures. Agreement was determined using Cohen kappa and Pearson correlation coefficient was calculated. Sarcopenia prevalence was 4.3% using EWGSOP1 and 1.0% using EWGSOP2. Agreement for sarcopenia diagnosis between EWGSOP1 and EWGSOP2 was fair (k = 0.37, P < 0.01). From the 13 cases of sarcopenia diagnosed using EWGSOP1, only 3 cases (23.1%) were also diagnosed using EWGSOP2. A medium correlation (r = -0.32, P < 0.01) and poor agreement (k = 0.14, P < 0.01) between muscle strength tests (handgrip strength and chair stand) were observed. Concordance between handgrip and chair stand was observed in 11 participants only, whereas 65 participants were considered to have low muscle strength using chair stand but not using handgrip. Lower sarcopenia prevalence using EWGSOP2 and low agreement between EWGSOP1 and EWGSOP2 operational definitions in diagnosing sarcopenia were observed in PLHIV.


[Surgical strategies in combined cicatricial stenosis of esophagus and stomach after chemical burn].
The results of treatment of 78 patients with the cicatricial esophageal and gastric exit stenosis are adduced. The tactics chosen have foreseen the feeding fistula and gastroenteroanastomosis conduction with subsequent substernal colonic esophagoplasty. The characteristics of different feeding fistula, the advantages and faults of every of them are adduced.


Downregulation of Wnt2 and beta-catenin by siRNA suppresses malignant glioma cell growth.
Increasing evidence suggests that aberrant activation of Wnt signaling is involved in tumor development and progression. Our earlier study on gene expression profile in human gliomas by microarray found that some members of Wnt family were overexpressed. To further investigate the involvement of Wnt signaling in gliomas, the expression of core components of Wnt signaling cascade in 45 astrocytic glioma specimens with different tumor grades was examined by reverse transcription-PCR and immunohistochemistry. Wnt2, Wnt5a, frizzled2 and beta-catenin were overexpressed in gliomas. Knockdown of Wnt2 and its key mediator beta-catenin in the canonical Wnt pathway by siRNA in human U251 glioma cells inhibited cell proliferation and invasive ability, and induced apoptotic cell death. Furthermore, treating the nude mice carrying established subcutaneous U251 gliomas with siRNA targeting Wnt2 and beta-catenin intratumorally also delayed the tumor growth. In both in vitro and in vivo studies, downregulation of Wnt2 and beta-catenin was associated with the decrease of PI3K/p-AKT expression, indicating the interplay between Wnt/beta-catenin and PI3K/AKT signaling cascades. In conclusion, the canonical Wnt pathway is of critical importance in the gliomagenesis and intervention of this pathway may provide a new therapeutic approach for malignant gliomas.


When to Initiate Antifungal Treatment in COVID-19 Patients with Secondary Fungal Co-infection.
Severe-acute respiratory coronavirus 2 (SARS-CoV-2) has been driving the health care delivery system for over 2 years. With time, many issues related to co-infections in COVID-19 patients are constantly surfacing. There have been numerous reports about various fungal co-infections in patients with COVID-19. The extent of severity of fungal pathogens has been recognized as a substantial cause of morbidity and mortality in this population. Awareness, understanding, and a systematic approach to managing fungal co-infections in COVID-19 patients are important. No guidelines have enumerated the stepwise approach to managing the fungal infections co-occurring with COVID-19. This review is intended to present an overview of the fungal co-infections in COVID-19 patients and their stepwise screening and management. The most common fungal infections that have been reported to co-exist with COVID-19 are Candidemia, Aspergillosis, and Mucormycosis. Prevalence of co-infections in COVID-19 patients has been reported to be much higher in hospitalized COVID-19 patients, especially those in intensive care units. While clear pathogenetic mechanisms have not been delineated, COVID-19 patients are at a high risk of invasive fungal infections. As secondary fungal infections have been challenging to treat in COVID-19 patients, as they tend to affect the critically ill or immunocompromised patients, a delay in diagnosis and treatment may be fatal. Antifungal drugs should be initiated with caution after carefully assessing the immune status of the patients, drug interactions, and adverse effects. The crucial factors in successfully treating fungal infections in COVID-19 patients are optimal diagnostic approach, routine screening, and timely initiation of antifungal therapy.


QT interval analysis in patients with acute biliary pancreatitis.
It has been previously proposed that electrocardiographic abnormalities may be associated with acute pancreatitis. However, there is a lack of data on the QT interval and dispersion value in patients with acute pancreatitis, and no data are also available concerning QT interval and QT dispersion in acute biliary pancreatitis (ABP). : We aimed to investigate the QT parameters in patients with ABP, to compare them with those of healthy controls, and to analyze the relationship between QT parameters and Ranson score. The present study included 32 patients with acute biliary pancreatitis and 35 healthy controls. The severity of the pancreatitis was determined by Atlanta criteria: fewer than 3 Ranson criteria or fewer than 8 APACHE II (the Acute Physiology and Chronic Health Evaluation) points indicated the mild disease (group 1); 3 or more Ranson criteria or 8 or more APACHE II points or organ failure or systemic complications or local complications indicated the severe disease (group 2). On admission, all patients underwent a standard 12-lead electrocardiogram, and corrected maximum QTc interval (QTcmax), corrected minimum QT interval (QTcmin), and corrected QTc dispersion (QTcd) values of the subjects were measured according to the Bazett formula in this study. QTcmax and QTcd were significantly longer in patients with ABP than in healthy controls (442 +/- 38 milliseconds versus 413 +/- 34 milliseconds, P < 0.05; and 67 +/- 21 milliseconds versus 42 +/- 18 milliseconds, P < 0.001, respectively). Similarly, QTcmax and QTcd were significantly longer in group 2 than in group 1 (440 +/- 38 milliseconds versus 450 +/- 34 milliseconds, P < 0.01; and 66 +/- 9 milliseconds versus 71 +/- 11 milliseconds, P < 0.01, respectively). Correlation analysis showed that there is a significant positive relationship between Ranson scores of patients and QTcmax and QTcd (P < 0.01 and P < 0.001, respectively). The effect of acute biliary pancreatitis on QT intervals and dispersion appears to be dependent not only on the disease but also on its severity, and these parameters may give additional prognostic information in ABP patients, even in the initial evaluation.


The role of accommodation in increasing the luminance of the fundus reflex during cognitive processing.
The phenomena observed during book retinoscopy include changes in the brightness of the reflex in response to changes in cognition. This experiment shows that the increase in luminance of the relfex that results from increased cognitive demand is mediated by accommodation. The luminance of the fundus reflex was monitored while subjects either read or added a series of two-digit numbers. During the addition task the luminance of the reflex increased in all cases. However, under cycloplegia the increase in luminance could not be predicted.


Hepatic arterial perfusion decreases intrahepatic shunting and maintains glucose uptake in the rat liver.
Intrahepatic shunts have an important function in the regulation of portal venous pressure in the normal rat liver. The present study determined their location, the region of confluence between the hepatic arterial and portal venous vasculatures, regions within the liver that are bypassed and the effects of hepatic arterial perfusion upon the intrahepatic redistribution of portal venous flow. Livers of male Sprague-Dawley rats were excised and perfused in vitro. Hepatic bromosulphthalein (BSP) and glucose uptake were measured in hepatic venous samples. Diversion of the hepatic arterial supply into the portal venous vasculature opened the portal venous intrahepatic shunts and resulted in a 50% reduction in portal venous glucose uptake from 29.6+/-1.6% to 14.9+/-0.9% ( P<0.0001 Student's paired t-test). Portal venous injection of 15-microm-diameter microspheres also opened the intrahepatic shunts and reduced portal venous glucose uptake to 10% from 29.0+/-1.6% to 7.8+/-0.9% ( P<0.0001 Student's paired t-test). No significant reductions in portal venous BSP uptake (43.0+/-6.9 to 48.0+/-4.8%) or hepatic arterial glucose uptake, from an average value of 94.0%, occurred. Therefore, cessation of hepatic arterial perfusion or portal venous injection of microspheres reduced portal venous glucose uptake without affecting BSP uptake. It is concluded that intrahepatic shunts divert perfusate away from the perivenous, sinusoidal (zone III) regions and into the hepatic venous vasculature, distal to zone III. The microsphere data indicate that confluence between the hepatic arterial and portal venous vasculatures occurs mainly in sinusoidal zone II.


The impact of industrial anthropization on mosquito (Diptera, Culicidae) communities in mangrove areas of Guanabara Bay (Rio de Janeiro, Brazil).
The effects of industrial anthropization on species composition and community diversity of Culicidae (Diptera) were studied in a mangrove area impacted by industrial activities as compared to a preserved area, both around Guanabara Bay in the state of Rio de Janeiro, Brazil. Diversity, equitability, and species richness in Culicidae community differed between the studied areas. Indicator species analysis and correspondence analysis were carried out and indicated that the Sabethini, especially Wyeomyia (Phoniomyia) theobaldi Lane, Wyeomyia (Phoniomyia) fuscipes (Edwards), and a non-identified species of Wyeomyia sp. were associated to the preserved area, whereas Aedes taeniorhynchus Wiedemann and Aedes scapularis (Rondani) to the impacted area.


New steroidal anti-inflammatory antedrugs bind to macrophage glucocorticoid receptors and inhibit nitric oxide generation.
In continuing efforts to synthesize potent, anti-inflammatory steroids devoid of systemic side effects, methyl 9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-3,20-dioxo-pregna-1,4-diene-16 alpha-carboxylate (FP16CM) and its 21-acetate derivative (FP16CMAc) were recently synthesized and screened in animal models of inflammation. The compounds have now been assessed for high-affinity glucocorticoid receptor binding and glucocorticoid-mediated inhibition of nitric oxide (NO) generation in an in vitro RAW 264.7 macrophage cell culture system. Relative potencies for glucocorticoid receptor binding were 1, 1.7, and 2.4 for prednisone (P) (IC50 = 287 nM), FP16CM, and FP16CMAc, respectively. Concomitant relative potencies for inhibition of NO generation by macrophages stimulated with lipopolysaccharide were 1, 0.92 and 1.9 for P (IC50 = 126 nM), FP16CM, and FP16CMAc, respectively. Collectively, results suggest that the novel antedrugs are active anti-inflammatory agents. The 9 alpha-fluoro and 21-acetate substituent may contribute to enhanced topical potency, increased receptor binding affinity and inhibitory effects on NO generation. Inhibition of vasoactive NO may be one anti-inflammatory action of the steroidal antedrugs in vivo. Collectively, results suggest that these agents may be useful for topical application in allergic/inflammatory diseases.


Associative long-term depression in the hippocampus induced by hebbian covariance.
A brief, high-frequency activation of excitatory synapses in the hippocampus produces a long-lasting increase in synaptic strengths called long-term potentiation (LTP). A test input, which by itself does not have a long-lasting effect on synaptic strengths, can be potentiated through association when it is activated at the same time as a separate conditioning input. Neural network modelling studies have also predicted that synaptic strengths should be weakened when test and conditioning inputs are anti-correlated. Evidence for such heterosynaptic depression in the hippocampus has been found for inputs that are inactive or weakly active during the stimulation of a conditioning input, but this depression does not depend on any pattern of test input activity and does not seem to last as long as LTP. We report here an associative long-term depression (LTD) in field CA1 that is produced when a low-frequency test input is negatively correlated in time with a high-frequency conditioning input. LTD of synaptic strength is also produced by activating presynaptic terminals while a postsynaptic neuron is hyperpolarized. This confirms theoretical predictions that the mechanism for associative LTD is homosynaptic and follows a hebbian covariance rule.


Angioimmunoblastic lymphadenopathy with dysproteinemia complicated by Kaposi's sarcoma.
A case of clinically and morphologically typical angioimmunoblastic lymphadenopathy (AILD) in a 68-year-old man during a prolonged antibiotic treatment for urinary infection is presented. Lymph node biopsy at first showed findings suggestive of an exhaustion of the germinal center immunological activity (like those characterizing angiofollicular lymph any clear transition into malignant lymphoma. The course of the disease was characterized by the occurrence of opportunistic infections (toxoplasmosis, herpes zoster), and finally by the onset of a cutaneous Kaposi's sarcoma. The possible relation of AILD to Kaposi's sarcoma is discussed, and the main clinical and morphological data of the case of AILD (about 200) reported in the literature are reviewed.


The Influence of Alcohol Consumption on Gambling: Do the Laboratory Study Findings Generalize to Natural Environments?
A recent meta-analysis of laboratory studies on the effects of acute alcohol consumption on risk-taking did not support that acute alcohol consumption increased risk-taking. Questions about whether this finding generalizes to those gambling in naturalistic settings remain. Therefore, we examined the gambling behavior of frequent gamblers who did and did not consume alcohol while gambling. Participants were 769 weekly gamblers (66% male) who were U.S. residents and at least 18 years old. Participants recruited via MTurk completed measures through the Qualtrics survey platform. Significant predictors of gambling under the influence of alcohol were drinking days per month and PGSI score. A linear regression model predicting percentage of time spent gambling under the influence of alcohol revealed that gambling days per week, gambling hours per day, PGSI score, and drinking days per month were significant predictors. Finally, significant predictors of spending at least 50% of gambling time gambling under the influence of alcohol included: gambling hours per day, PGSI score, and drinking days per month. These findings were consistent with the recent meta-analysis of laboratory studies. However, finding that gambling disorder symptoms and overall rates of alcohol consumption were related to gambling under the influence of alcohol replicated the frequently found relation of alcohol problems among those who also exhibit gambling problems.


Isolation and primary culture of human abdominal aorta smooth muscle cells from brain-dead donors: an experimental model for vascular diseases.
Primary cell cultures are essential tools for elucidating the physiopathological mechanisms of the cardiovascular system. Therefore, a primary culture growth protocol of cardiovascular smooth muscle cells (VSMCs) obtained from human abdominal aortas was standardized. Ten abdominal aorta samples were obtained from patients diagnosed with brain death who were organ and tissue donors with family consent. After surgical ablation to capture the aorta, the aortic tissue was removed, immersed in a Custodiol® solution, and kept between 2 and 8 °C. In the laboratory, in a sterile environment, the tissue was fragmented and incubated in culture plates containing an enriched culture medium (DMEM/G/10% fetal bovine serum, L-glutamine, antibiotics and antifungals) and kept in an oven at 37 °C and 5% CO2. The aorta was removed after 24 h of incubation, and the culture medium was changed every six days for twenty days. Cell growth was confirmed through morphological analysis using an inverted optical microscope (Nikon®) and immunofluorescence for smooth muscle alpha-actin and nuclei. The development of the VSMCs was observed, and from the twelfth day, differentiation, long cytoplasmic projections, and adjacent cell connections occurred. On the twentieth day, the morphology of the VSMCs was confirmed by actin fiber immunofluorescence, which is a typical characteristic of VSMCs. The standardization allowed VSMC growth and the replicability of the in vitro test, providing a protocol that mimics natural physiological environments for a better understanding of the cardiovascular system. Its use is intended for investigation, tissue bioengineering, and pharmacological treatments.


Dose-dependent differential effects of thrombin in allergic bronchial asthma.
Apart from its role in the coagulation system, thrombin plays an important role in the inflammatory response through its protease-activated receptors (PARs). However, the role of thrombin in the immune response is not clear. To evaluate whether thrombin has a modulatory role in allergic bronchial asthma. Bronchial asthma was induced in mice by intraperitoneal sensitization and inhalation challenge with ovalbumin. Thrombin or its inhibitors were administered by inhalation before each allergen challenge. Mice with low but sustained coagulation activation had reduced allergic inflammation, and allergic asthma was inhibited by low doses of thrombin but worsened by high doses. Allergic asthma was worsened by antithrombin, argatroban, hirudin, and anti-thrombomodulin antibody. Mice with a higher level of an inhibitor of both thrombin and activated protein C had worse disease. Heterozygous PAR-1 mice had less allergic inflammation, but PAR-1 agonist worsened it. Allergic bronchial inflammation was worsened in mice that received adoptive transfer of PAR-1 agonist-treated Th2 cells as compared with controls. Low levels of thrombin suppressed the maturation and secretion of cytokines in dendritic cells, but high levels enhanced this. The effects of thrombin on allergic asthma are dose-dependent, with detrimental effects at high doses and protective effects at low doses. These data demonstrate that thrombin modulates the outcome in allergic bronchial asthma.


ANRIL regulating the secretion of Muc5ac induced by atmospheric PM2.5 via NF-κB pathway in Beas-2B cells.
PM2.5 can cause airway inflammation and promote the excessive secretion of mucin 5ac (Muc5ac), which can further induce many respiratory diseases. Antisense non-coding RNA in the INK4 locus (ANRIL) might regulate the inflammatory responses mediated by nuclear factor kappa-B (NF-κB) signaling pathway. Beas-2B cells were used to clarify the role of ANRIL in the secretion of Muc5ac induced by PM2.5 . The siRNA was used to silence ANRIL expression. Normal and gene silenced Beas-2B cells were respectively exposed to different doses of PM2.5 for 6, 12, and 24 h. The survival rate of Beas-2B cells was detected by methyl thiazolyl tetrazolium (MTT) assay. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and Muc5ac levels were determined by enzyme linked immunosorbent assay (ELISA). The expression levels of NF-κB family genes and ANRIL were detected by real time polymerase chain reaction (PCR). The levels of NF-κB family proteins and NF-κB family phosphorylated proteins were determined using Western blot. Immunofluorescence experiments were performed to observe the nuclear transposition of RelA. PM2.5 exposure increased the levels of Muc5ac, IL-1β and TNF-α, and ANRIL gene expression (p < .05). With the dose and time of PM2.5 exposure increasing, the protein levels of inhibitory subunit of nuclear factor kappa-B alpha (IκB-α), RelA, and NF-κB1 decreased, the protein levels of phosphorylated RelA (p-RelA) and phosphorylated NF-κB1 (p-NF-κB1) increased, and RelA nuclear translocation increased, which indicated that the NF-κB signaling pathway was activated (p < .05). Silencing ANRIL could decrease the levels of Muc5ac, IL-1β, TNF-α, decrease NF-κB family genes expression, inhibit the degradation of IκB-α and the activation of NF-κB pathway (p < .05). ANRIL played a regulatory role in the secretion of Muc5ac and the inflammation induced by atmospheric PM2.5 via NF-κB pathway in Beas-2B cells. ANRIL could be a target for prevention and treatment of the respiratory diseases caused by PM2.5 .


Emergence of a NDM-1-producing ST25 Klebsiella pneumoniae strain causing neonatal sepsis in China.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) seriously threaten the efficacy of modern medicine with a high associated mortality rate and unprecedented transmission rate. In this study, we isolated a clinical K. pneumoniae strain DY1928 harboring bla NDM-1 from a neonate with blood infection. Antimicrobial susceptibility testing indicated that DY1928 was resistant to various antimicrobial agents, including meropenem, imipenem, ceftriaxone, cefotaxime, ceftazidime, cefepime, piperacillin-tazobactam, and amoxicillin-clavulanate. S1 nuclease-pulsed field gel electrophoresis (S1-PFGE), southern blot and conjugation experiment revealed that the bla NDM-1 gene was located on a conjugative plasmid of IncA/C2 type with a 147.9 kb length. Whole-genome sequencing showed that there was a conservative structure sequence (bla NDM-1-ble-trpF-dsbD) located downstream of the bla NDM-1 gene. Multilocus sequence typing (MLST) classified DY1928 as ST25, which was a hypervirulent K. pneumoniae type. Phylogenetic analysis of genomic data from all ST25 K. pneumoniae strains available in the NCBI database suggested that all bla NDM-1 positive strains were isolated in China and had clinical origins. A mouse bloodstream infection model was constructed to test the virulence of DY1928, and 11 K. pneumoniae strains homologous to DY1928 were isolated from the feces of infected mice. Moreover, we found that DY1928 had a tendency to flow from the blood into the intestine in mice and caused multiple organ damage. To our knowledge, this is the first study to report an infection caused by bla NDM-1-positive ST25 K. pneumoniae in the neonatal unit. Our findings indicated that stricter surveillance and more effective actions were needed to reduce the risk of disseminating such K. pneumoniae strains in clinical settings, especially in neonatal wards.


Effects of nursing professionalism and self-efficacy on job embeddedness in nurses.
This study aimed to investigate the effects of nursing professionalism on job embeddedness to stay in hospital nurses. This cross-sectional survey recruited 438 nurses working at four general hospitals and three small to medium hospitals in K province, South Korea. Data were collected from June 10 to September 10, 2022 using structured questionnaires and then analyzed with IBM SPSS Statistics for Windows, version 25.0. The scores, out of 5.0, were 3.30 for nursing professionalism, 3.73 for self-efficacy, and 3.15 for job embeddedness. The three variables were different according to participants' general characteristics. The correlation between self-efficacy and nursing professionalism had a positive correlation to job embeddedness. Nursing professionalism had a mediating effect on the relation between self-efficacy and job embeddedness. Self-efficacy exerted an influence on organizational commitment through the mediating effect of nursing professionalism and is expected to lay the foundation for the promotion of job embeddedness. To increase nurses' job embeddedness, nursing and hospital managers must develop and implement programs that help improve nurses' self-efficacy and nursing professionalism to adjust well in their organization.


Preliminary study of microsurgical repairs of the inferior alveolar nerve in rats using primary suturing and laser weld techniques.
A comparison of primary suturing and a new laser weld technique is described for the microsurgical repair of the inferior alveolar nerve in Wistar rats. A reliable method of exposure of the inferior alveolar nerve has been developed in order to allow intraosseous repairs of the nerve involving suturing with 10:0 nylon and a laser weld technique using an albumin-based solder, containing indocynine cardiogreen, plus an infrared (810 nm wavelength) diode laser. Seven cases of microsuture and laser weld repairs were performed with a 29.4% reduction in total operating time in the laser weld group. Histochemical analysis showed comparable mean neuron counts and mean tracer uptake by neurons for the microsuture and laser weld groups. Giant cell reactions were identified in two of the primary suture cases and axon deflection in three cases demonstrating possible advantages of the laser weld technique which showed no adverse reactions by axons or epineurium to the coagulative repair with the solder. The technique of laser weld repair, on initial analysis, therefore appears comparable with traditional suture repairs and indeed may possess several advantages. Further studies are recommended.


A survey of parasites in primary school children in Dominica, West Indies.
A study of Dominican school children aged four to twelve years showed that infection with gastrointestinal parasites was very common. Trichuris was found in the stools in 92% of the children, Ascaris in 38%, Necator in 11%, Giardia in 18% and E. histolytica in 1%. In spite of the high prevalence of parasites, the general health of the children studied was remarkably good, and only 18 of the 1000 children were found to have a haemoglobin level below 10 g/dl.


Novel detection of restriction fragment length polymorphisms in the human major histocompatibility complex.
Cosmid genomic DNA clones have been used as hybridization probes in genomic Southern blot analysis to define restriction fragment length polymorphisms (RFLPs) in the major histocompatibility complex (MHC). Using 14 different enzymes and three overlapping cosmid clones we have detected six RFLPs in a 100 kilobase (kb) segment of DNA in the class III region extending centromeric of the TNFA gene toward HLA-DR. Four of the five RFLPs, defined using the enzymes Taq I, Rsa I, Hinc II, and Hind III, and detected by the cosmid clone cosM7B, map to a 29 kb segment of DNA that includes all of the recently described G2 (BAT2) gene and a large portion of the 3' end of the G3 (BAT3) gene. The different RFLP variants were established by analyzing the DNA from three informative families and a panel of 51 HLA-homozygous typing cell lines. CosM7B detects Taq I variants of 4.3 kb, and 2.9 kb or 2.8 kb, Rsa I variants of 2.9 kb or 2.4 kb, Hinc II variants of 5.8 kb or 3.8 kb and 1.4 kb, and a Hind III variant of 4.8 kb, while cosOT2 detects Taq I variants of 4.5 kb or 4 kb. The distribution of the Rsa I, Hinc II and Taq I RFLPs detected by cosM7B, and the Taq I RFLP detected with cosOT2, within the panel of cell line DNAs was assessed by Southern blotting. The 4.3 kb Taq I variant was observed in only one cell line with the extended haplotype HLA-A29, C-, B44, SC30, DR4. The other RFLPs, however, occurred much more frequently. The 2.8 kb Taq I variant was observed in 20% of haplotypes, the 2.9 kb Rsa I variant was observed in 42% of haplotypes, and the 5.8 kb Hinc II variant was observed in 12% of haplotypes analyzed. The 4.5 kb Taq I variant detected by the overlapping cosmid cosOT2 was present in 21% of haplotypes. Analysis of the RFLP variants with each other revealed seven different haplotypic combinations. Three of the haplotypic combinations were each subdivided into two subsets on the basis of the Nco I RFLP variant they carried at the TNF-B locus. These haplotypic combinations potentially allow differentiation among different extended haplotypes such as HLA-B8, SC01, DR3, HLA-B18, F1C30, DR3, and HLA-B44, FC31, DR7. The RFLPs detected by the cosmid clones thus provide new tools which will be useful in the further genetic analysis of the MHC class III region.


Dietary specific sugars for serum protein enzymatic glycosylation in man.
All glycoprotein sugars can theoretically derive from glucose. However, dietary specific sugars could represent preferential substrates or have regulatory roles in enzymatic glycosylation. This hypothesis was tested in man using stable isotopes. Healthy subjects ingested different amounts (150, 300, or 550 mg) of artificially 13C-enriched sugar (galactose, mannose, or glucose) diluted in 200 mL water containing 50 g 13C-poor sucrose. 13C enrichment of expired CO2 was monitored for 8 hours during indirect calorimetry. Serum glycoproteins were precipitated and delipidated at various intervals. Glycoprotein neutral sugars were obtained by acidic hydrolysis, purified by ion-exchange chromatography, derivatized to alditol acetates, and analyzed by gas chromatography-isotope ratio mass spectrometry. The oxidation rate for galactose and mannose was slower than the rate for glucose. Total oxidation over the 8-hour period was less than 10% of the ingested amount of galactose or mannose. Galactose and mannose were readily incorporated into glycoprotein glycans, in the native form or after interconversion, despite ingestion of a large excess of sucrose: glycoprotein sugar 13C enrichment was strongly higher after 13C-galactose or 13C-mannose than after 13C-glucose. Thus, the metabolism of these three sugars appears to be different. Specific dietary sugars could represent a new class of non essential nutrients displaying interesting metabolic roles. This could have practical consequences especially in parenteral nutrition, where glucose is currently the only sugar available for metabolism.


Over-coupled resonator for broadband surface enhanced infrared absorption (SEIRA).
Detection of molecules is a key issue for many applications. Surface enhanced infrared absorption (SEIRA) uses arrays of resonant nanoantennas with good quality factors which can be used to locally enhance the illumination of molecules. The technique has proved to be an effective tool to detect small amount of material. However, nanoresonators can detect molecules on a narrow bandwidth so that a set of resonators is necessary to identify a molecule fingerprint. Here, we introduce an alternative paradigm and use low quality factor resonators with large radiative losses (over-coupled resonators). The bandwidth enables to detect all absorption lines between 5 and 10 μm, reproducing the molecular absorption spectrum. Counterintuitively, despite a lower quality factor, the system sensitivity is improved and we report a reflectivity variation as large as one percent per nanometer of molecular layer of PMMA. This paves the way to specific identification of molecules. We illustrate the potential of the technique with the detection of the explosive precursor 2,4-dinitrotoluene (DNT). There is a fair agreement with electromagnetic simulations and we also introduce an analytic model of the SEIRA signal obtained in the over-coupling regime.


Significance tests. Part 2.
The comparison of two means obtained from either small or large samples and the comparison of two proportions is described, together with the use of logarithmic transformation of quantitative data in order to stabilise variance.


A modification to the Kuramoto model to simulate epileptic seizures as synchronization.
The Kuramoto model was developed to describe the coupling of oscillators, motivated by the natural synchronization phenomena. We are interested in modeling an epileptic seizure considering it as the synchronization of action potentials using and modifying this model. In this article, we propose to modify this model, changing the constant coupling force for a function with logistic growth to simulate the onset and epileptic seizure level in an adult male rat caused by the administration of lithium-pilocarpine. Later, we select some frequencies and their respective amplitude values using an algorithm based on the fast Fourier transform (FFT) from an electroencephalography signal when the rat is in basal conditions. Then, we take these values as the natural frequencies of the oscillators in the modified Kuramoto model, considering every oscillator as a single neuron to simulate the emergence of an epileptic seizure numerically by increasing the synchronization value in the coupling function. Finally, using Dynamic Time Warping algorithm, we compare the simulated signal by the Kuramoto model with an FFT approximation of the epileptic seizure.


Expression of proapoptotic BAX and TP53 genes and antiapoptotic BCL-2 gene in MCF-7 and T-47D tumour cell cultures of the mammary gland after a photodynamic therapy with photolon.
Breast cancer is the most common malignant tumour in women in the whole world. Despite significant developments in the early diagnosis of breast cancer, there is no effective method which would assure total recovery of the patient. Currently available clinical data and laboratory tests indicate a possibility to introduce photodynamic therapy (PDT) to the supplementary treatment of breast cancer. The aim of this study was to assess the influence of PDT with Photolon as a photosensibilizator on the expression of apoptosis associated genes (BCL-2, BAX, TP53) in human breast cancer cell lines, preceded by assessment of survivorship and proliferative activity in the tested cells after PDT. In the present study human breast cancer cell lines MCF-7 and T-47D were used. Photolon (chlorin e6 complex: PVP 1:1) was used as a photosensitizer. Assessments of survivorship and proliferative activity of cells under the influence of PDT (WST-1 test) were conducted along with the expression of selected genes involved in the process of apoptosis: BCL-2, BAX, TP53 (RT-QPCR). PDT limited both survivorship and proliferative activity of breast cancer cells in the two tested lines. In case of T-47D cell line was found increase of BAX and BCL-2 genes expression after PDT and sustained activity of TP53 gene. Conversely, in MCF-7 cell line a decrease in expression was found for both BAX and TP53 genes, but also an increase of BCL-2 gene expression. A progressing decrease (24, 48 and 72 h after PDT) in the count of culture cells, which suggests the occurrence of apoptosis initiated by a photodynamic reaction with simultaneous increase of BCL-2/BAX index, indicates activation of a different endogenous apoptosis pathway than the one examined, namely pointing to suicidal death of cells after PDT.


A review of indoor Gaseous organic compounds and human chemical Exposure: Insights from Real-time measurements.
Gaseous organic compounds, mainly volatile organic compounds (VOCs), have become a wide concern in various indoor environments where we spend the majority of our daily time. The sources, compositions, variations, and sinks of indoor VOCs are extremely complex, and their potential impacts on human health are less understood. Owing to the deployment of the state-of-the-art real-time mass spectrometry during the last two decades, our understanding of the sources, dynamic changes and chemical transformations of VOCs indoors has been significantly improved. This review aims to summarize the key findings from mass spectrometry measurements in recent indoor studies including residence, classroom, office, sports center, etc. The sources and sinks, compositions and distributions of indoor VOCs, and the factors (e.g., human activities, air exchange rate, temperature and humidity) driving the changes in indoor VOCs are discussed. The physical and chemical processes of gas-particle partitioning and secondary oxidation processes of VOCs, and their impacts on human health are summarized. Finally, the recommendations for future research directions on indoor VOCs measurements and indoor chemistry are proposed.


Can we manipulate brain connectivity? A systematic review of cortico-cortical paired associative stimulation effects.
Cortico-cortical paired associative stimulation (ccPAS) is a form of dual-site transcranial magnetic stimulation (TMS) entailing a series of single-TMS pulses paired at specific interstimulus intervals (ISI) delivered to distant cortical areas. The goal of this article is to systematically review its efficacy in inducing plasticity in humans focusing on stimulation parameters and hypotheses of underlying neurophysiology. A systematic review of the literature from 2009-2023 was undertaken to identify all articles utilizing ccPAS to study brain plasticity and connectivity. Six electronic databases were searched and included. 32 studies were identified. The studies targeted connections within the same hemisphere or between hemispheres. 28 ccPAS studies were in healthy participants, 1 study in schizophrenia, and 1 in Alzheimer's disease (AD) patients. 2 additional studies used cortico-cortical repetitive paired associative stimulation (cc-rPAS) in generalized anxiety disorder (GAD) patients. Outcome measures include electromyography (EMG), behavioral measures, electroencephalography (EEG), and functional magnetic resonance imaging (fMRI). ccPAS seems to be able to modulate brain connectivity depending on the ISI. ccPAS can be used to modulate corticospinal excitability, brain activity, and behavior. Although the stimulation parameters used across studies reviewed in this paper are varied, ccPAS is a promising approach for basic research and potential clinical applications. Recent advances in neuroscience have caused a shift of interest from the study of single areas to a more complex approach focusing on networks of areas that orchestrate brain activity. Consequently, the TMS community is also witnessing a change, with a growing interest in targeting multiple brain areas rather than a single locus, as evidenced by an increasing number of papers using ccPAS. In light of this new enthusiasm for brain connectivity, this review summarizes existing literature and stimulation parameters that have proven effective in changing electrophysiological, behavioral, or neuroimaging-derived measures.


Diagnostic values of osteopontin combined with CA125 for ovarian cancer: a meta-analysis.
Osteopontin (OPN) is currently one of the most studied serum biomarkers of ovarian cancer (OC). This meta-analysis aims to ascertain whether OPN is a useful diagnostic biomarker for OC and determine the overall diagnostic accuracy of OPN measurement when combined with cancer antigen 125 (CA125). A systematic literature search was conducted in Cochrane Library, PubMed, EMBASE, CBM, and China National Knowledge Infrastructure databases. Information was independently extracted by two investigators. The Quality Assessment for Studies of Diagnostic Accuracy tool was applied to examine the quality of eligible studies, and a bivariate model was used to calculate the pooled estimates. We identified 17 and 10 studies that evaluated the role of OPN alone and OPN combined with CA125 in diagnosing ovarian tumor, respectively. The overall diagnostic sensitivity and specificity of OPN in OC were 0.766 (95% CI 0.685-0.831) and 0.897 (95% CI 0.849-0.931), correspondingly. When OPN was combined with CA125, the sensitivity and specificity were 0.871 (95% CI 0.788-0.924) and 0.881 (95% CI 0.837-0.914), respectively. OPN is a useful tumor biomarker in future screening tests of OC and can be a promising adjunct to CA125. Additional studies with multicenter trials and carefully selected controls are needed to further verify the results.


Immunohistochemical detection of polycyclic aromatic hydrocarbon-DNA damage in human blood vessels of smokers and non-smokers.
The presence of cigarette smoking-related polycyclic aromatic hydrocarbon (PAH)-DNA adducts was investigated in human arterial tissue using an immunoperoxidase staining method with a monoclonal antibody that recognizes benzo(a)pyrene and structurally related PAH diol epoxide-DNA adducts. This is the first time that immunohistochemical methods for detection of PAH-DNA damage have been applied to human endothelial and smooth muscle cells of blood vessels. Internal mammary artery specimens from a total of 37 smokers and non-smokers were tested. Positive nuclear staining was observed in both endothelial and smooth muscle cells, with higher staining in the endothelium. The correlation between smoking status, available for 33 subjects, and detectable PAH-DNA adducts in endothelium did not reach statistical significance (odds ratio = 3.38, 95% confidence interval is 0.47-27.60) in this small series. While no causal role can be inferred from our results, they support the theory that endothelial injury caused by cigarette smoking and other environmental exposures may be an early event in the process of atherosclerosis.


Emergency preparedness for biological and chemical incidents: a survey of anesthesiology residency programs in the United States.
We surveyed health care professionals about their preparations to manage the clinical problems associated with patients exposed to hazardous substances, including weapons of mass destruction (WMD). Training for WMD is considered a key part of public health policy and preparedness. Although such events are rare, when they do occur, they can cause mass casualties. In many models of mass casualty management, anesthesiology personnel are responsible for treating patients immediately on arrival at the hospital. We studied the extent of training offered to anesthesiology personnel in the use of WMD protective gear and patient management in United States (US) anesthesiology residency programs. Information was obtained via an online survey to all program directors and chair persons of anesthesiology programs. We polled all of the 135 US anesthesiology programs of which 90 (67%) responded. Only 37% had any form of training, and many of them did not repeat training after initial sessions. Twenty-eight percent of programs east of the Mississippi River reported some form of training whereas only 17% of programs west of it reported training available. The majority of anesthesia residency programs in the US that responded to our survey provided little or no training in the management of patients exposed to WMD. In an attack involving weapons of mass destruction or toxic chemicals, anesthesiologists will provide care. Our survey of United States anesthesiology residency programs demonstrated that there is limited training of residents regarding the anesthetic management of patients injured by weapons of mass destruction. This has serious public health implications.


Effects of cephalothin and penicillin G on platelet function in vitro.
High concentrations of cephalothin or penicillin G inhibit a number of the functions of human or rabbit platelets in citrated platelet-rich plasma (PRP) and in suspensions of washed platelets. The reactions shown to be inhibited are: ADP-induced shape change and the primary and secondary phases of aggregation and release induced by ADP or adrenaline in human cirtated PRP; release and aggregation of washed human platelets exposed to collagen, thrombin, vasopressin, or the ionophore A 23,187; aggregation of washed human platelets exposed to phytohaemagglutinin from Phaseolus vulgaris (PHA) or polylysine; release induced by concanavalin A or PHA in suspensions of washed platelets from rabbits; platelet adherence to a collagen-coated surface or to the damaged intimal surface of the rabbit aorta; platelet factor 3 availability; lysis of rabbit platelets by an antiserum directed against them; and clot retraction. Neither antibiotic affected serotonin-induced aggregation; a high concentration of cephalothin slightly inhibited the initial rate of serotonin uptake. Penicilloic acid showed about half the inhibitory effect of penicillin G on ADP-induced aggregation. In citrated human platelet-rich plasma, ampicillin and oxacillin inhibited ADP-induced aggregation to the same extent as similar concentrations of penicillin G; in suspensions of washed platelets, however, ampicillin was less inhibitory than penicillin G or oxacillin. Platelet ultrastructure, assessed by transmission electron microscopy, was not visibly altered. Evidence that the antibiotics become bound to platelets is the finding that platelets incubated with the antibiotics ans resuspended in fresh media showed less response to aggregating agents compared with control platelets. Penicillin G and related antibiotics may be inhibitory because they coat the platelet surface. Their effects on platelet functions are probably responsible for excessive bleeding and increased bleeding times observed in patients and volunteers receiving high doses of these antibiotics.


Immunohistological study on collagenous proteins of benign and malignant human cartilaginous tumours of bone.
The immunohistological distribution of collagen types I, II, III, V and VI in human benign and malignant cartilaginous tumours of bone was examined with regard to their aggressiveness. The matrix of enchondromas consisted of type II collagen distributed diffusely, and type VI predominantly localized in the immediate surroundings of the cells. Types I, III and V collagen were not found. These findings were similar to the distribution of collagenous proteins in normal hyaline cartilage where each lobule was consistently rimmed by types I and V collagen. In grade 1 chondrosarcomas, the main collagenous components of matrix were also types II and VI collagen. Type II was sometimes found in the cytoplasm of tumour cells and type VI tended to lose territorial localization. In addition, type I collagen was demonstrated consistently and type V in some cases. In grade 2 chondrosarcomas, type II collagen was demonstrated not only in the matrix but occasionally in the cytoplasm of tumour cells. Type VI was dispersed in the intercellular areas. The other collagenous proteins such as types I, III and V were also present in the matrix. In grade 3 chondrosarcomas, type II collagen was localized predominantly in the cytoplasm of tumour cells and in the adjacent matrix. Type VI was markedly decreased with complete loss of pericellular distribution, whereas types I, III and V were constantly present in the matrix. Those alterations in the distribution of collagen types correlated well with the aggressive behaviour of the tumours. The findings suggest that distribution of different collagen types in cartilaginous tumours reflects the immaturity of the tumour cells and is a useful indicator of their aggressiveness.


Infusion efficiency of sodium fluorescein into various starches.
The objective of this study was to develop new drug delivery systems (DDS) and nutrient delivery systems (NDS), using starch as a carrier material for infusion technology. Corn, waxy rice, non-waxy rice, and potato starches were used as carrier materials. Sodium fluorescein was used as an infusion material for easy detection. Each starch suspension with sodium fluorescein was reacted in a water bath at 40, 50, and 60 °C for 30 min. After each reaction, the concentration of sodium fluorescein in the supernatant was measured using a fluorescence detector. Precipitated starch was observed using fluorescence microscopy. About 70% of sodium fluorescein infused in waxy rice and corn starches at 60 °C. Additionally, the granules of these two starches were luminous by green light when exposed to a fluorescence detector, suggesting that corn and waxy rice starches can be used as carrier materials in infusion technology for DDS and NDS.


Is ryanodine receptor a calcium or magnesium channel? Roles of K+ and Mg2+ during Ca2+ release.
The ryanodine receptor (RyR) is a poorly selective channel that mediates Ca(2+) release from intracellular Ca(2+) stores. How RyR's selectivity between the physiological cations K(+), Mg(2+), and Ca(2+) affects single-channel Ca(2+) current amplitude is examined using a recent model of RyR permeation. It is found that K(+) provides the vast majority of the countercurrent (through RyR itself) that is needed to prevent the sarcoplasmic reticulum (SR) membrane potential from changing and stopping Ca(2+) release. Moreover, intra-pore competition between Ca(2+) and Mg(2+) defines single RyR Ca(2+) current amplitude. Since both [Mg(2+)] and [Ca(2+)](SR) can change during pathophysiological conditions, the RyR unitary Ca(2+) current amplitude during Ca(2+) release may change significantly due to this Ca(2+)/Mg(2+) competition. Compared to the classic action of Mg(2+) on RyR open probability, these Ca(2+) current amplitude changes have as large or larger effects on overall RyR Ca(2+) mobilization. A new aspect of RyR divalent versus monovalent selectivity is also identified where this kind of selectivity decreases as divalent concentration increases.


Atypical presentation of multicentric Castleman disease in a pediatric patient: pleural and pericardial effusion.
Castleman disease (CD) is a rare poorly understood lymphoproliferative disorder. Pediatric onset CD has been reported before. However, most of them have benign unicentric pattern. Multicentric CD (MCD) is quite rare in children. Herein, we report a 13-year-old adolescent boy with MCD of the hyaline vascular variant presenting with pleural and pericardial effusion, which is an uncommon presentation. MCD should be considered in the differential diagnosis of pleural and/or pericardial effusion with unexplained lymph nodes in children. What is Known •Pediatric Castleman disease (CD) most commonly occurs in the unicentric form, which typically is asymptomatic and cured by lymph node excision. •The diagnosis of MCD can be difficult owing to the heterogeneity of presentation and potential for nonspecific multisystem involvement. What is New •A 13-year-old adolescent boy was diagnosed with MCD of the hyaline vascular variant presenting with pleural and pericardial effusion, which is an uncommon presentation. •In a pediatric patient with fever, pleural-pericardial effusion and multiple lymph nodes, MCD should be considered in differantial diagnosis.


Advances in enantioselective analysis of chiral brominated flame retardants. Current status, limitations and future perspectives.
Enantioselective analysis is a powerful tool for the discrimination of biotic and abiotic transformation processes of chiral environmental contaminants because their environmental biodegradation is mostly stereospecific. However, it is challenging when applied to new contaminants since enantioselective analysis methods are currently available only for a limited number of compounds. The enantioselective analysis of chiral novel brominated flame retardants (NBFRs) either using gas chromatography (GC) or liquid chromatography (LC) with various chiral stationary phases (CSP) coupled with various mass spectrometric techniques was extensively discussed. The elution order of hexabromocyclododecane (HBCD) enantiomers in chiral LC was reviewed using the experimental LC data combined also with predictions from a multi-mode Hamiltonian dynamics simulation model based on interaction energies of HBCD enantiomers with β-permethylated cyclodextrin. The further development of analytical methodologies for new chiral BFRs using advanced hyphenated analytical techniques, but also the next generation mass spectrometer analyzers (i.e. GC-Qrbitrap MS-MS, LC-Qrbitrap MS-MS), will contribute to a better characterization of the transformation pathways of chiral BFRs.


Two new Erichsonius species of iSimangaliso Wetland Park in KwaZulu-Natal Province, South Africa (Coleoptera: Staphylinidae, Staphylininae).
Two new Erichsonius (Sectophilonthus) species of South Africa (type locality: KwaZulu-Natal Province: Sodwana Bay) are described, illustrated, and distinguished from similar species: E. (S.) sodwanaensis sp. nov. and E. (S.) muellerae sp. nov.


[Basic and clinical studies on AMPC (amoxicillin) in the field of surgery (author's transl)].
In the present study, amoxicillin was compared with other antibiotics with respect to sensitivity, levels achieved in the blood and various organs and clinical results. We would like to make further studies accumulated number of cases.


Endothelial nitric oxide synthase gene single-nucleotide polymorphism predicts cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
Vasospasm is a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Studies have shown a link between single-nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (eNOS) gene and the incidence of coronary spasm and aneurysms. Alterations in the eNOS T-786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm. In this prospective clinical study, 77 aSAH patients provided genetic material and were followed for the occurrence of vasospasm. In multivariate logistic regression analysis, genotype was the only factor predictive of vasospasm. The odds ratio (OR) for symptomatic vasospasm in patients with one T allele was 3.3 (95% confidence interval (CI): 1.1 to 10.0, P=0.034) and 10.9 for TT. Patients with angiographic spasm were 3.6 times more likely to have a T allele (95% CI: 1.3 to 9.6, P=0.013; for TT: OR 12.6). Patients with severe vasospasm requiring endovascular therapy were more likely to have a T allele (OR 3.5, 95% CI: 1.3 to 9.5, P=0.016; for TT: OR 12.0). Patients with the T allele of the eNOS gene are more likely to have severe vasospasm. Presence of this genotype may allow the identification of individuals at high risk for post-aSAH vasospasm and lead to early treatment and improved outcome.


Guinea pig mu opioid receptor: brainstem expression in the morphine-exposed neonate.
The mu opioid receptor (MOR) has been characterized in the mouse and rat. The guinea pig has several advantages as a model for in utero exposure to morphine; the placental structure is similar to the human; and the guinea pig metabolizes morphine to its active metabolite, morphine-6-glucuronide, at similar rates as humans. Guinea pig MOR cDNA was sequenced. To evaluate expression in respiratory control areas, a guinea pig specific cRNA probe was prepared and utilized for in situ hybridization in brainstem slices. In situ results were compared with immunohistochemistry to determine a correlation between mRNA expression and MOR protein expression. Neonatal animals exposed in utero to chronic intermittent morphine were compared with saline-exposed controls. Quantitative RT-PCR comparison of mRNA expression levels in brainstem regions was also performed. No differences were found in brainstem areas expressing mRNA or amount of mRNA expression between treatment and neonatal age groups. Immunohistochemistry showed that protein expression correlates anatomically with mRNA expression and no difference in protein levels could be detected between treatment groups. Lack of difference in mRNA or protein levels of MOR following in utero exposure to morphine suggests that differences seen between these groups with DAMGO-stimulated 35S-GTPgammaS binding involve a change in efficiency of coupling to G-proteins when MOR is activated.


Spinal subdural bleeding after attempted epidural and subsequent spinal anaesthesia in a patient on thromboprophylaxis with low molecular weight heparin.
Despite the extensive use of low molecular weight heparins (LMWH) for thromboprophylaxis, only two serious complications have thus far been reported where spinal haematomas were incurred after epidural and spinal blocks in patients on such treatment. In our patient, who was on thromboprophylaxis with the LMWH drug enoxaparin, catheter epidural anaesthesia was abandoned due to a bloody tap and superseded by spinal anaesthesia. More than 40 hours later she had developed a paraparesis and complete sensory loss in the lower extremities. The MRT image showed haematomas epi- and subdurally, as well as subarachnoidally, but no epidural bleeding was seen at laminectomy.


Comparison between blue-on-yellow and white-on-white perimetry in patients with branch retinal vein occlusion.
This study aimed to compare blue-on-yellow (B/Y) perimetry with white-on-white (W/W) perimetry in eyes with branch retinal vein occlusion (BRVO). The following measurements were performed in 29 eyes of 29 patients with resolved BRVO: W/W and B/Y perimetries using 10-2 test grid, retinal volume (RV) using optical coherence tomography (OCT), and vessel densities (VD) of the superficial capillary layer (VDs) and deep capillary layer (VDd) using OCT angiography (OCTA). First, the difference in the retinal sensitivity (RS) between BRVO-affected and unaffected areas was compared between RS_B/Y and RS_W/W in the parafoveal and extrafoveal areas. Moreover, the structure-function relationship between vessel density and RS was compared between B/Y and W/W perimetries (RS_B/Y and RS_W/W, respectively). The difference in RS between BRVO-affected and unaffected areas was significantly larger with RS_B/Y than with RS_W/W in both the parafoveal and extrafoveal areas. In the parafoveal area, VDs, VDd, and RV were significantly correlated with both RS_W/W and RS_B/Y. In contrast, in the extrafoveal area, only VDd was included in the optimal models. Our findings suggest that RS_B/Y more strongly reflects the anatomical structure and BRVO-affected area.


Current perspectives on mesenchymal stromal cell therapy for graft versus host disease.
Graft versus host disease (GvHD) is the clinical condition in which bone marrow-derived mesenchymal stromal cells (MSCs) have been most frequently studied. In this review, we summarize the experience from clinical trials that have paved the way to translation. While MSC-based therapy has shown an exceptional safety profile, identifying potency assays and disease biomarkers that reliably predict the capacity of a specific MSC batch to alleviate GvHD has been difficult. As GvHD diagnosis and staging are based solely on clinical criteria, individual patients recruited in the same clinical trial may have vastly different underlying biology, obscuring trial outcomes and making it difficult to determine the benefit of MSCs in subgroups of patients. An accumulating body of evidence indicates the importance of considering not only the cell product but also patient-specific biomarkers and/or immune characteristics in determining MSC responsiveness. A mode of action where intravascular MSC destruction is followed by monocyte-efferocytosis-mediated skewing of the immune repertoire in a permissive inflammatory environment would both explain why cell engraftment is irrelevant for MSC efficacy and stress the importance of biologic differences between responding and nonresponding patients. We recommend a combined analysis of clinical outcomes and both biomarkers of disease activity and MSC potency assays to identify patients with GvHD who are likely to benefit from MSC therapy.


Inter- and intra-specific competition of duckweed under multiple heavy metal contaminated water.
The influences of intra- and inter-species competition on ecosystems are poorly understood. Lemna aequinoctialis and Spirodela polyrhiza were used to assess the effects of exposure to different concentrations of multiple heavy metals (copper-cadmium-zinc), when the plants were grown in mixed- or mono-culture. Parameters assessed included relative growth rate (RGR), content of chlorophyll, glutathione (GSH), malondialdehyde (MDA), as well as the activity of catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD). Inter-specific competition was affected by metal concentration, with results indicating that inter-specific competition significantly affected duckweed growth and metal uptake in different heavy metal exposure conditions. Inter-specific competition increased growth rate of duckweed under high metal concentrations, although when compared with intra-specific competition, it caused no obvious differences under low metal concentrations. The growth of L. aequinoctialis was further increased in mixed culture when exposed to high metal concentrations, with inter-specific competition increasing the content of cadmium and zinc, while decreasing copper content of L. aequinoctialis compared with under intra-specific conditions. Conversely, inter-specific competition increased the content of copper and cadmium of S. polyrhiza, without causing obvious differences in zinc accumulation under high ambient concentrations. Under high metal conditions, inter-specific competition increased antioxidant enzyme activities in duckweed species, increasing resistance to heavy metals. Results show that inter-specific competition makes duckweed develop mechanisms to increase fitness and survival, such as enhancement of antioxidant enzyme activities, rather than limiting metal uptake when exposed to high concentrations of multiple metals.


Leisure-time physical activity and metabolic syndrome plus depressive symptoms in the FIN-D2D survey.
To examine the association between leisure-time physical activity (LTPA) and simultaneous presence of metabolic syndrome (MetS) and depressive symptoms (DS) based on a population-based FIN-D2D cross-sectional survey conducted in 2007. 4500 randomly selected Finnish men and women aged 45-74 years were initially enrolled; 2868 (64%) attended a health examination. Participants with complete information (n=2778) were grouped into three LTPA categories: low, moderate and high. MetS was based on the National Cholesterol Education Program criteria and DS on the Beck Depression Inventory (≥10 points). The prevalence of MetS and DS were 53% and 15%, respectively; the prevalence of simultaneous MetS and DS was 10%. The proportion of subjects with MetS, DS and simultaneous presence of MetS and DS increased with decreasing LTPA (p<0.001). On multivariate ordered analysis, LTPA was related to education years, household income, smoking, and the presence of MetS only, DS only and simultaneous MetS and DS. The prevalence of simultaneous MetS and DS was higher in participants with low LTPA compared with participants with high LTPA. Furthermore, LTPA level was associated with socioeconomic status and other health related outcomes, outlining the importance of LTPA as part of the general health promotion.


Protein profiling and classification of commercial quinoa grains by MALDI-TOF-MS and chemometrics.
Quinoa is an Andean grain that is attracting attention worldwide as a high-quality protein-rich food. Nowadays, quinoa foodstuffs are susceptible to adulteration with cheaper cereals. Therefore, there is a need to develop novel methodologies for protein characterization of quinoa. Here, we first developed a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) method to obtain characteristic mass spectra of protein extracts from 4 different commercial quinoa grains, which group different varieties marketed as black, red, white (from Peru) and royal (white from Bolivia). Then, data preprocessing and peak detection with MALDIquant allowed detecting 47 proteins (being 30 tentatively identified), the intensities of which were considered as fingerprints for multivariate data analysis. Finally, classification by partial least squares-discriminant analysis (PLS-DA) was excellent, and 34 out of the 47 proteins were critical for differentiation, confirming the potential of the methodology to obtain a reliable classification of quinoa grains based on protein fingerprinting.


Reporters for the analysis of N-glycosylation in Candida albicans.
A large proportion of Candida albicans cell surface proteins are decorated post-translationally by glycosylation. Indeed N-glycosylation is critical for cell wall biogenesis in this major fungal pathogen and for its interactions with host cells. A detailed understanding of N-glycosylation will yield deeper insights into host-pathogen interactions. However, the analysis of N-glycosylation is extremely challenging because of the complexity and heterogeneity of these structures. Therefore, in an attempt to reduce this complexity and facilitate the analysis of N-glycosylation, we have developed new synthetic C. albicans reporters that carry a single N-linked glycosylation site derived from Saccharomyces cerevisiae Suc2. These glycosylation reporters, which carry C.albicans Hex1 or Sap2 signal sequences plus carboxy-terminal FLAG₃ and His₆ tags, were expressed in C.albicans from the ACT1 promoter. The reporter proteins were successfully secreted and hyperglycosylated by C.albicans cells, and their outer chain glycosylation was dependent on Och1 and Pmr1, which are required for N-mannan synthesis, but not on Mnt1 and Mnt2 which are only required for O-mannosylation. These reporters are useful tools for the experimental dissection of N-glycosylation and other related processes in C.albicans, such as secretion.


A tumour in the cerebellopontine angle region: an unusual case.
This paper describes a nearly 60-year old patient with unilateral hearing loss, developed in one year, and complaints of tinnitus and dizziness. Additional findings were unilateral peripheral facial paresis and a diminished corneal reflex. The cause was found to be a metastasis of an anaplastic carcinoma, localized at the site of the internal acoustic porus.


[Simple rules for orientation in transcutaneous ptosis surgery--a contribution to the surgical anatomy or: how not to get lost in the upper eyelid].
Surgical preparation in the upper eyelid follows well defined anatomic structures. Nevertheless, even an experienced surgeon can loose orientation in the presence of fatty degeneration, oedema or bleeding. Some simple rules can help to stay oriented and identify the landmarks. The preaponeurotic fat has a distinct colour, structure and texture and is a landmark for the levator muscle lying underneath it. This defines a first simple rule: it is not preaponeurotic fat if it does not look like preaponeurotic fat. The orbital septum may weaken and allow orbital fat to prolapse, but it stays firmly attached at the upper orbital rim. A second simple rule therefore adresses its identification: if a structure does not move with inferior tension, it cannot be muscle or fat (it must be septum). Identifying the landmarks preaponeurotic fat, orbital septum and tarsus will facilitate anatomic correlation and surgical preparation. In summary: Rule No. 1--If it does not look like preaponeurotic fat, then it isn't. Rule No. 2--If it does not move with traction, it is neither muscle nor fat (but probably septum). Rule No. 3--If things get confusing, stop and consider rules 1 and 2.


Risk prediction in cutaneous melanoma patients from their clinico-pathological features: superiority of clinical data over gene expression data.
Risk assessment in cutaneous melanoma (CM) patients is one of the major challenges in the effective treatment of CM patients. Traditionally, clinico-pathological features such as Breslow thickness, American Joint Committee on Cancer (AJCC) tumor staging, etc. are utilized for this purpose. However, due to advancements in technology, most of the upcoming risk prediction methods are gene-expression profile (GEP) based. In this study, we have tried to develop new GEP and clinico-pathological features-based biomarkers and assessed their prognostic strength in contrast to existing prognostic methods. We developed risk prediction models using the expression of the genes associated with different cancer-related pathways and got a maximum hazard ratio (HR) of 2.52 with p-value ~10-8 for the apoptotic pathway. Another model, based on combination of apoptotic and notch pathway genes boosted the HR to 2.57. Next, we developed models based on individual clinical features and got a maximum HR of 2.45 with p-value ~10-6 for Breslow thickness. We also developed models using the best features of clinical as well as gene-expression data and obtained a maximum HR of 3.19 with p-value ~10-9. Finally, we developed a new ensemble method using clinical variables only and got a maximum HR of 6.40 with p-value ~10-15. Based on this method, a web-based service and an android application named 'CMcrpred' is available at (https://webs.iiitd.edu.in/raghava/cmcrpred/) and Google Play Store respectively to facilitate scientific community. This study reveals that our new ensemble method based on only clinico-pathological features overperforms methods based on GEP based profiles as well as currently used AJCC staging. It also highlights the need to explore the full potential of clinical variables for prognostication of cancer patients.


βhCG mediates immune suppression through upregulation of CD11b+ Gr1+ myeloid derived suppressor cells, CD206+ M2 macrophages, and CD4+ FOXP3+ regulatory T-cells in BRCA1 deficient breast cancers.
BRCA1 mutation is reported in about 70% of all triple negative breast cancers (TNBC), while BRCA1 defect due to promoter hypermethylation is seen in about 30%-60% of sporadic breast cancers. Although PARP inhibitors and platinum-based chemotherapy are used to treat these cancers, more efficient therapeutic approaches are required to overcome the resistance to treatment. Our previous findings have reported elevated βhCG expression but not αhCG in BRCA1 deficient breast cancers. As βhCG causes immune suppression in pregnancy, this study explored the immunomodulatory effect of βhCG in BRCA1mutated/deficient TNBC. We observed that Th1, Th2, and Th17 cytokines are upregulated in the presence of βhCG in BRCA1 defective cancers. In NOD-SCID and syngeneic mouse models, βhCG increases the frequency of Myeloid-derived suppressor cells in tumour tissues and contributes to macrophage reprogramming from antitumor M1 to pro-tumour M2 phenotype. βhCG reduces the CD4+ T-cell infiltration while increasing the density of CD4+ CD25+ FOXP3+ regulatory T-cell in BRCA1 deficient tumour tissues. In contrast, xenograft tumours with βhCG knocked down TNBC cells did not show these immune suppressive effects. We have also shown that βhCG upregulates pro-tumorigenic markers arginase1(Arg1), inducible nitric oxide synthase, PD-L1/PD-1, and NFκB in BRCA1 defective tumours. Thus, for the first time, this study proves that βhCG suppresses the host antitumor immune response and contributes to tumour progression in BRCA1 deficient tumours. This study will help develop new immunotherapeutic approaches for treating BRCA1 defective TNBC by regulating βhCG.


Objectively Measured Physical Activity Is Associated with Vertebral Size in Midlife.
Vertebral fractures reduce the quality of life and are a major burden to the health care sector. Small vertebral size is associated with increased vertebral fracture risk. Previous studies have investigated the relationship between physical activity (PA) and vertebral size, but their results seem somewhat contradictory. In this population-based birth cohort study, we aimed to evaluate the relationship between objectively measured PA and vertebral size. The study population consisted of 1202 cohort participants who underwent PA and vertebral size measurements at the age of 46 to 48 yr. Moderate-to-vigorous PA (MVPA, ≥3.5 METs) was measured by a wrist-worn accelerometer (Polar Active; Polar Electro, Finland) for 14 d. The vertebral axial cross-sectional area (CSA) of the L4 vertebra was measured and calculated from lumbar magnetic resonance imaging scans at 46 to 48 yr. We analyzed the association between the daily amount of MVPA (min·d) and vertebral CSA using multivariable linear regression analysis. The daily amount of MVPA was significantly and positively associated with CSA in both sexes. For every minute per day of MVPA, men had 0.71 mm (95% confidence interval, 0.36-1.06) and women 0.90 mm (95% confidence interval, 0.58-1.21) larger CSA. Physical activity of at least moderate intensity is positively associated with vertebral size and may thus prevent future vertebral fractures.


Principles of pulmonary artery catheterization in the critically ill.
The pulmonary artery catheter (PAC) may be helpful in determining the etiology of shock, lactic acidosis, pulmonary edema, oliguric renal failure, pulmonary hypertension, and a number of cardiac abnormalities. In addition, it may also be useful in guiding fluid and vasoactive therapy. However, although hemodynamic data from the pulmonary artery catheter (PAC) is widely used diagnostically and therapeutically in the care of critically ill patients, the use of the catheter has not been shown to provide outcomes benefit. In fact, there is some evidence to suggest that placement of the PAC may actually be detrimental. The reasons for this are unclear, but it has been shown that both physicians and nurses frequently misinterpret waveforms and other data obtained from the PAC. Presently, there are a number of ongoing randomized, controlled trials investigating the use of the PAC in specific clinical situations and/or patient populations as well as using specific treatment strategies. In the meantime, if any benefit is to be achieved, it is imperative that clinicians have a thorough understanding of the indications, contraindications, complications, and pitfalls of data interpretation prior to using the catheter. These are reviewed in this article.


Bromocriptine for the treatment of postoperative cerebellar mutism syndrome in pediatric patients: Three case reports.
Cerebellar mutism syndrome (CMS) is a common complication after posterior fossa tumor resection. It is characterized by a significant lack or loss of speech. Its biological origin remains unclear and there are no standardized treatments. However, bromocriptine seems to be a possible treatment for this condition. In this paper, we present three cases of pediatric patients (4, 5, and 17-year old) who developed CMS after posterior fossa tumor surgery. They were treated with bromocriptine to improve neurological symptoms.Management and outcome: Bromocriptine was started at a low dose and was progressively increased to reach the minimum effective dose. After four months of treatment, a normal and fluid speech was observed in the three patients. No discontinuation due to adverse events were reported. Bromocriptine has shown to be an effective and safe treatment for CMS in pediatric patients after posterior fossa tumor resection.


Procalcitonin in preoperative diagnosis of abdominal sepsis.
The present study attempted to identify the diagnostic significance of procalcitonin (PCT) in acute abdominal conditions as well as the range of concentrations relating to diagnosis of abdominal sepsis. This was prospective clinical study. The study included 98 consecutive patients with acute abdominal conditions, divided in sepsis and systemic inflammatory response syndrome (SIRS) group. PCT concentrations on admission were significantly higher in the sepsis group than in the SIRS group (median [interquartile range] 2.32 [7.41] vs 0.45 ng/ml [2.62]). A cutoff value of 1.1 ng/ml yielded 72.4% sensitivity and 62.5% specificity. In a group of patients with abdominal symptoms lasting for more than 24 h, a cut-off value of 1.1 ng/ml yielded higher sensitivity (82.9%) and higher specificity (77.3%). Our results suggest that PCT measurements may be useful for early, preoperative diagnosis of abdominal sepsis.