The effect of intraoperative ischemia on the recovery of contractile function after free muscle transfer.
Isometric contractile function was studied after recovery in free, vascularized muscle transfer subjected to graded periods of intraoperative ischemia. Fifteen dogs had orthotopic replantation of their left gracilis muscles, with intraoperative ischemia times grouped as 0 (n = 3), 1 to 2 (n = 3), 2 to 3 (n = 4), or 3 to 4 (n = 5) hours. After recovery (mean 61.8 weeks), isometric twitch and tetanic tension and fatigue measurements were made in the replants and in the contralateral, control gracilis. On the average, replants were found to produce significantly less twitch (0.32 +/- 0.13 versus 0.49 +/- 0.24 N/g) and 75 Hz tetanic tension (2.2 +/- 0.9 versus 3.4 +/- 0.5 N/g) than controls. However, in several individual replants, 100% of control maximal tetanic tension was observed. Intraoperative ischemia time of up to 4 hours was not correlated with functional return. It is concluded that (1) full recovery is possible after free muscle transfer; (2) intraoperative ischemia, if less than 4 hours long, is not the primary determinant of functional recovery; and (3) factors besides intraoperative ischemia must be operative in producing the variability in recovery seen in this setting.


A model for non-resolvable ambiguities.
The dynamical behavior of the perception of ambiguous figures arising from the essentially nonresolvable ambiguity built in the figures themselves is analysed. Two main features of it are explored, the initial transient and the rhythmic alternation of inversions of perspective following it. The initial transient is envisaged in terms of a symmetry breaking disorder-order transformation induced by the "attention" of the observer. The rhythmic inversions of the ordered structures are classified by a model based on an ideally non linear decision equation for binary systems originally proposed to schematize the observed behavior of neurons. Finally it is suggested that the phenomena relative to the perception of ambiguous figures could represent the simplest ones among more complex situations arising in perception, in concept formation, in the sensing of emotion and in communication in general.


Survival of Cancer Patients Treated with Non-Fermented Mistletoe Extract: A Systematic Review and Meta-Analysis.
Mistletoe extracts (ME) are used in integrative cancer care to improve quality of life and to prolong survival. ME are available from different producers and differ in pharmaceutical processing, such as fermentation. In contrast to fermented ME, the impact of unfermented extracts on the survival of cancer patients has not yet been assessed in a meta-analysis. We searched the databases Embase, CENTRAL, Europe PMC, Clinicaltrials.gov, Opengrey and Google Scholar, and selected controlled studies on cancer patients treated with non-fermented ME. We included randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs). The risk of bias was assessed with Cochrane's ROB2 and ROBINS-I; a meta-analysis was conducted. Eleven RCTs and eight NRSIs met the inclusion criteria. The studies were heterogeneous and their ROB2 and ROBINS-I displayed a moderate and high risk of bias, respectively. For RCTs, the pooled effect estimate of non-fermented ME on survival was HR = 0.81 (95% CI 0.69-0.95, P = .01). Subgroup analyses as well as the NRSIs estimation support the robustness of the finding. When active comparators are added to the analysis, the effect estimates become non-significant. The results may indicate a positive impact of non-fermented ME on the overall survival of cancer patients. High quality RCTs are necessary to substantiate our results. CRD42021233177.


Antipsychotic inductors of brain hypothermia and torpor-like states: perspectives of application.
Hypothermia and hypometabolism (hypometabothermia) normally observed during natural hibernation and torpor, allow animals to protect their body and brain against the damaging effects of adverse environment. A similar state of hypothermia can be achieved under artificial conditions through physical cooling or pharmacological effects directed at suppression of metabolism and the processes of thermoregulation. In these conditions called torpor-like states, the mammalian ability to recover from stroke, heart attack, and traumatic injuries greatly increases. Therefore, the development of therapeutic methods for different pathologies is a matter of great concern. With the discovery of the antipsychotic drug chlorpromazine in the 1950s of the last century, the first attempts to create a pharmacologically induced state of hibernation for therapeutic purposes were made. That was the beginning of numerous studies in animals and the broad use of therapeutic hypothermia in medicine. Over the last years, many new agents have been discovered which were capable of lowering the body temperature and inhibiting the metabolism. The psychotropic agents occupy a significant place among them, which, in our opinion, is not sufficiently recognized in the contemporary literature. In this review, we summarized the latest achievements related to the ability of modern antipsychotics to target specific receptors in the brain, responsible for the initiation of hypometabothermia.


Treatment expectations and health-related quality of life in stone formers.
The objective of this article is to address patients' expectations of stone treatment - both surgical and medical - and their health-related quality of life (HRQOL). We present a rationale for greater inclusion of measures to assess patient expectations, satisfaction, and HRQOL into surgical and medical management for patients with recurrent urolithiasis. Patients' treatment expectations and HRQOL are fundamental and progressive new areas of interest in urolithiasis. Patients whose treatment regimens result in outcomes that match their expectations are likely to be more satisfied, which may influence their HRQOL, a valid and valuable outcome of any medical treatment or procedure. Patient perceptions of treatment effects for stones, whether surgical or medical, are complex and may not reflect only stone-free rates, surgical complication rates, and side-effects, the outcomes of traditional interest in urology. If we understand the issues of most importance to our patients, we can provide appropriate information and education that ensures the most realistic expectations, minimizes disappointment and risk, and contributes most to the patients' HRQOL.


Y-P30 promotes axonal growth by stabilizing growth cones.
The 30-amino acid peptide Y-P30, generated from the N-terminus of the human dermcidin precursor protein, has been found to promote neuronal survival, cell migration and neurite outgrowth by enhancing the interaction of pleiotrophin and syndecan-3. We now show that Y-P30 activates Src kinase and extracellular signal-regulated kinase (ERK). Y-P30 promotes axonal growth of mouse embryonic stem cell-derived neurons, embryonic mouse spinal cord motoneurons, perinatal rat retinal neurons, and rat cortical neurons. Y-P30-mediated axon growth was dependent on heparan sulfate chains. Y-P30 decreased the proportion of collapsing/degenerating growth cones of cortical axons in an Src and ERK-dependent manner. Y-P30 increased for 90 min in axonal growth cones the level of Tyr418-phosphorylated Src kinase and the amount of F-actin, and transiently the level of Tyr-phosphorylated ERK. Levels of total Src kinase, actin, GAP-43, cortactin and the glutamate receptor subunit GluN2B were not altered. When exposed to semaphorin-3a, Y-P30 protected a significant fraction of growth cones of cortical neurons from collapse. These results suggest that Y-P30 promotes axonal growth via Src- and ERK-dependent mechanisms which stabilize growth cones and confer resistance to collapsing factors.


Glutathione is present in high concentrations in cultured astrocytes but not in cultured neurons.
The levels of the antioxidants, glutathione and ascorbate were measured in primary cultures of murine astrocytes and neurons. The concentration of glutathione (reduced, GSH + oxidized, GSSG) was high in cultured, differentiated (i.e. treated with dBcAMP) and undifferentiated (i.e. untreated) astrocytes: approximately 25 (n = 2) and 16.0 +/- 5.0 (n = 7) nmol/mg protein, respectively. In contrast, glutathione levels in neurons were low: less than or equal to 1.0 (n = 7) nmol/mg protein. Ascorbate could not be detected (less than 2 nmol/mg protein) in either cell type. The apparent lack of defense mechanisms against oxidative stress may in part account for the 'fragility' of neurons in culture. The physiological implications of glutathione compartmentation in brain are discussed.


Cyclic GMP-independent mechanisms of nitric oxide-induced vasodilation.
1. The aim of the present study was to test in vitro if NO acts through a cyclic GMP-independent mechanism to activate Ca2+-dependent potassium channels (K+(Ca)), leading to membrane hyperpolarization and vasodilation in rat tail artery. 2. Acetylcholine and sodium nitroprusside stimulated a significant increase in cyclic GMP (190+/-23 and 180+/-15 pmol/g, respectively) compared with agonist-free conditions (132+/-15 and 130+/-15 pmol/g, respectively); these agonist-mediated increases in cyclic GMP were completely abolished by treatment with the guanylate cyclase inhibitor methylene blue (122+/-10 and 60+/-8 pmol/g, respectively). 3. In contrast, relaxation to acetylcholine (10(-7) mol/l; 61+/-3%) and sodium nitroprusside (10(-8) mol/l; 97+/-1%) were significantly, but not completely, attenuated by methylene blue (30+/-5 and 79+/-3%, respectively); maximum relaxation to sodium nitroprusside (10(-7) mol/l) was unaffected by methylene blue. 4. Depolarization-induced contraction of vessels with KCl inhibited relaxation to both acetylcholine (10(-7) mol/l; 18+/-4%) and sodium nitroprusside (10(-8) mol/l; 57+/-7%). Furthermore, the specific K+(Ca) antagonist charybdotoxin significantly inhibited relaxation to sodium nitroprusside (10(-8) mol/l; 52+/-7%). 5. An additive inhibitory effect on relaxation to sodium nitroprusside (10(-8) mol/l) was observed with a combination of methylene blue and KCl (26+/-6%) or charybdotoxin (34+/-3%). 6. These data suggest that NO stimulates membrane hyperpolarization via K+(Ca) activation, in addition to guanylate cyclase, to cause relaxation in rat tail artery.


Draft Genome Sequences of Five Paenibacillus Species of Dairy Origin.
Paenibacillus species are important spoilage organisms in the dairy industry. The genomes of five Paenibacillus species which were isolated from dairy products in Canada were sequenced using the Illumina MiSeq platform. Draft genomes ranging from 5.1 to 7.1 Mb with GC contents of 49 to 53% were generated.


Prescribing habits of vancomycin in the Emergency Department: are we dosing appropriately?
To prevent the development of bacterial resistance, current guidelines recommend vancomycin dosages of 15-20 mg/kg based on actual body weight. Our aim was to determine if two community teaching Emergency Departments followed the new recommendations for a weight-based dosing regimen for vancomycin. A retrospective cohort study was conducted on the prescribing habits of vancomycin in the Emergency Department. During a 6-month time period, 1,734 doses of vancomycin were dispensed and a subsequent random sample of 240 doses was reviewed. Data collection included age, gender, weight, creatinine clearance, vancomycin dose, and indication for vancomycin therapy. Mean values, standard deviations, and ranges were computed to illustrate current prescribing practices. The mean vancomycin dose was 1,117 ± 325 mg. Based on actual body weight, the calculated mean dose was 14.6 ± 5.7 mg/kg. Only 19.6% (47 of 240) of all patients received an appropriate dose based on the recommended 15-20 mg/kg vancomycin dose. Our Emergency Department is inappropriately dosing vancomycin in the majority of patients. Educating clinicians regarding appropriate vancomycin dosing is recommended to achieve compliance with the latest consensus guidelines.


Activities of caspofungin, itraconazole, posaconazole, ravuconazole, voriconazole, and amphotericin B against 448 recent clinical isolates of filamentous fungi.
We examined the in vitro activity of caspofungin, posaconazole, voriconazole, ravuconazole, itraconazole, and amphotericin B against 448 recent clinical mold isolates. The endpoint for reading caspofungin was the minimum effective concentration (MEC). Among the triazoles, posaconazole was most active, inhibiting 95% of isolates at <or=1 microg/ml, followed by ravuconazole (91%), voriconazole (90%), and itraconazole (79%). Caspofungin and amphotericin B inhibited 93% and 89% of isolates at <or=1 microg/ml, respectively, with caspofungin demonstrating an MEC 90 of 0.12 microg/ml. All three new triazoles and caspofungin inhibited >95% of Aspergillus spp. at <or=1 microg/ml compared to 83% for itraconazole and 91% for amphotericin B. Amphotericin B inhibited only 38% of Aspergillus terreus isolates at <or=1 microg/ml, whereas the three new triazoles and caspofungin inhibited all A. terreus at <or=0.5 microg/ml. The new triazoles and caspofungin have excellent in vitro activity against a very large collection of recent clinical isolates of Aspergillus spp., and some in vitro activity against selected other filamentous fungi.


Activity-adjusted crime rates show that public safety worsened in 2020.
This paper argues that changes in human activity during the COVID-19 pandemic led to an unusual divergence between crime rates and victimization risk in US cities. Most violent crimes declined during the pandemic. However, analysis using data on activity shows that the risk of street crime victimization was elevated throughout 2020. People in public spaces were 15 to 30% more likely to be robbed or assaulted. This increase is unlikely to be explained by changes in crime reporting or selection into outdoor activities by potential victims. Traditional crime rates may present a misleading view of the recent changes in public safety.


Decreased plasma orexin-A levels in obese individuals.
Orexin-A and -B stimulate appetite and food intake in rats. Orexins and orexin receptors are present in the hypothalamus as well as the enteric nervous system, the pancreas and the gut. The presence of orexins in peripheral blood, however, has not yet been reported. To determine whether orexin-A is present in human plasma and is related to body weight, we measured plasma orexin-A and leptin levels in a population with a body mass index (BMI) range from 19.8 to 59 kg/m(2). Plasma orexin-A levels correlated negatively and plasma leptin levels correlated positively with BMI. In obese and morbidly obese individuals, orexin-A levels were significantly lower and leptin levels were significantly higher when compared to normal. Our results support previous data suggesting that orexin-A acts also in a peripheral manner. The fact that lower levels of plasma orexin-A are present in obese individuals suggests that it is involved in the regulation of human energy metabolism.


Acute secretion of immunoreactive parotid hormone in response to different diets in the pig.
In pigs, feeding is a physiological stimulus for immunoreactive parotid hormone (iPH) secretion, so the chronic and acute effects of different diets on that secretion were investigated. iPH was measured by radioimmunoassay in pig plasma, in response to feeding three test meals, over 80 days, during which the maintenance diet was switched from standard pig chow to a high-sucrose diet. The maximum iPH response to feeding standard chow was high (177 +/- 32 ng/ml); it was significantly lower with crushed standard chow (58 +/- 9), and even lower with a high-sucrose diet (19 +/- 4), (p < 0.02 between all groups). After changing the maintenance diet from standard chow to high-sucrose diet, the basal iPH titre decreased by 60% and remained significantly lower. During the same time, the iPH response to the three test meals diminished, but not significantly.


ICF Core Set for patients with neurological conditions in early post-acute rehabilitation facilities.
The aim of this consensus process was to decide on a first version of the ICF Core Set for neurological patients in early post-acute rehabilitation facilities. The ICF Core Set development involved a formal decision-making and consensus process, integrating evidence gathered from preliminary studies including focus groups of health professionals, a systematic review of the literature and empiric data collection from patients. Seventeen experts selected a total of 116 second-level categories. The largest number of categories was selected from the ICF component Body Functions (54 categories or 47%). Eleven (9%) of the categories were selected from the component Body Structures, 34 (29%) were of the categories from the component Activities and Participation, and 17 (15%) from the component Environmental Factors. The Post-acute ICF Core Set for neurological patients is a clinical framework to comprehensively assess patients in early post-acute rehabilitation facilities, particularly in an interdisciplinary setting. This first ICF Core Set will be further tested through empiric studies in German-speaking countries and internationally.


Leiomyoma of the breast parenchyma: a case report and review of the literature.
Benign tumors are often seen in breast screening examinations. However, the differential diagnosis is not always simple because of radiological similarity between the different benign lesions. We present a rare case report of leiomyoma of the breast parenchyma in a 68-year-old asymptomatic patient. The mammographic and ultrasonographic findings were similar to those observed in benign lesions. The histopathological diagnosis requires careful differentiation from lesions that have smooth muscle proliferation, especially leiomyosarcoma. The most commonly performed treatment is resection of the lesion with free margins. Although breast leiomyoma is rare, it should be considered among the differential diagnoses for breast nodules of benign appearance. Resection with safety margins proved to be the only treatment needed.


Fast decolorization of azo methyl orange via heterogeneous Fenton and Fenton-like reactions using alginate-Fe2+/Fe3+ films as catalysts.
The efficiency of Fenton and Fenton-like processes can be seriously affected by the continuous loss of iron ions and by the formation of solid sludge. Here, alginate (Alg) films were synthesized to stabilize iron ions (Fe2+ and Fe3+) and to enhance their catalytic activities towards the decolorization of methyl orange via heterogeneous Fenton and Fenton-like processes. Iron ions were ionically bond to the Alg molecules resulting in a three-dimensional network with specific structural and morphological features according to the valence states of iron. Our results demonstrated that both Alg-Fe2+ and Alg-Fe3+ films show highlighted catalytic activity for the decolorization of MO and high decolorization rates. Reuse experiments demonstrated that both films could be employed in at least five consecutive decolorization processes without losing their catalytic efficiency or stability. Taken together, our findings reveal that the Alg-Fe2+ and Alg-Fe3+ films may be suitable low-cost catalysts in heterogeneous Fenton and Fenton-like processes.


Self-sampling in screening to reduce mortality from colorectal cancer: a qualitative exploration of the decision to complete a faecal occult blood test (FOBT).
To explore beliefs that might impact upon public reactions to a proposed population level faecal occult blood test (FOBT) screening invitation and acceptability of completing an FOBT home self-sampling kit. Four focus groups were conducted to explore men and women's beliefs about colorectal cancer risk, their understanding of screening and reactions to an FOBT kit. Participants were shown a kit and permitted to examine it during the focus groups. Colorectal cancer is viewed as having severe quality of life impacts and is commonly regarded as being caused by diet. Faecal blood is an expected symptom. A home self-sampling kit is viewed as highly acceptable, but some concerns were raised about collecting and storing faecal matter. The main implications for public education arising from the analysis were firstly, that communications regarding the potential to avoid quality of life impacts of colorectal cancer may motivate participation; secondly, that public education might address the ability of the test to detect asymptomatic abnormalities, in particular occult (as opposed to visible) blood; thirdly, in order to prevent avoidance responses to fear, communications need to emphasise that many abnormal test outcomes will not be cancer and early treatment may prevent cancer and associated adverse quality of life impacts; fourthly, that uptake may be promoted by emphasising messages that the test kit is very convenient; and finally, that instruction leaflets might minimise procedural concerns by suggesting simple and easy methods to collect and store faecal samples.


Why do people create imaginary worlds? The case of Fanfiction.
Dubourg and Baurmard ask why people consume fiction with imaginary worlds. We extend this inquiry to ask why people engage in creating imaginary worlds. In Fanfiction, the writing of fiction by fans involves both an immersive creative experience and a very interactive community that may explain the high (social) engagement of people with Fanfiction.


Respiratory and Cardiometabolic Comorbidities and Stages I to III NSCLC Survival: A Pooled Analysis From the International Lung Cancer Consortium.
We explored the association of respiratory and cardiometabolic comorbidities with NSCLC overall survival (OS) and lung cancer-specific survival (LCSS), by stage, in a large, multicontinent NSCLC pooled data set. On the basis of patients pooled from 11 International Lung Cancer Consortium studies with available respiratory and cardiometabolic comorbidity data, adjusted hazard ratios (aHRs) were estimated using Cox models for OS. LCSS was evaluated using competing risk Grey and Fine models and cumulative incidence functions. Logistic regression (adjusted OR [aOR]) was applied to assess factors associated with surgical resection. OS analyses used patients with NSCLC with respiratory health or cardiometabolic health data (N = 16,354); a subset (n = 11,614) contributed to LCSS analyses. In stages I to IIIA NSCLC, patients with respiratory comorbidities had worse LCCS (stage IA aHR = 1.51, confidence interval [CI]: 1.17-1.95; stages IB-IIIA aHR = 1.20, CI: 1.06-1.036). In contrast, patients with stages I to IIIA NSCLC with cardiometabolic comorbidities had a higher risk of death from competing (non-NSCLC) causes (stage IA aHR = 1.34, CI: 1.12-1.69). The presence of respiratory comorbidities was inversely associated with having surgical resection (stage IA aOR = 0.54, CI: 0.35-0.83; stages IB-IIIA aOR = 0.57, CI: 0.46-0.70). The presence of either cardiometabolic or respiratory comorbidities is associated with worse OS in stages I to III NSCLC. Patients with respiratory comorbidities were less likely to undergo surgery and had worse LCSS, whereas patients with cardiometabolic comorbidities had a higher risk of death from competing causes. As more treatment options for stages I to III NSCLC are introduced into the practice, accounting for cardiometabolic and respiratory comorbidities becomes essential in trial interpretation and clinical management.


[Effect of ambiol on stem growth in regenerants of source and transgenic potato plants].
The effects of ambiol, a new growth regulator, on stem growth and morphological features of stem development have been compared in regenerants of potato (Solanum tuberosum L., var. Desire) plants transgenic for a defensin gene and in original potato plants. The original and transgenic plants exhibited differences in shoot development, which were observed both in control settings (no ambiol) and in the presence of various ambiol concentrations. In addition to normal plants of both forms, plant regenerants with morphological deviations were present in ambiol-treated groups. It is suggested that the abnormal shoot development observed in original and transgenic potato plants treated with ambiol is associated with (a) hormonal changes caused by expression of the defensin gene in the transgenic plants and (b) effects of ambiol on the hormonal balance of the plants.


2D-Electrophoresis and Immunoblotting in Food Allergy.
Two-dimensional polyacrylamide gel electrophoresis (2DE) and Western immunoblotting have proven to be invaluable and fundamental techniques for comprehensive characterization of food allergens. Here, we describe and discuss detailed protocols used in our studies on identification of allergenic proteins in shrimp, sesame, hazelnut, and pistachio.


Comparison of MELD, HVPG, and their changes to predict clinically relevant endpoints in cirrhosis.
Identification of predictors in the natural history of cirrhosis is based on determinations at a fixed time point. However, changes of these predictors may offer more information. To evaluate the predictive value of Model for End Stage Liver Disease (MELD) and hepatic venous pressure gradient (HVPG) and their changes in cirrhosis. Patients with repeat HVPG measurements between January 2000 and December 2008 were considered for inclusion. Patients were followed until decompensation/death or July 2009. Multivariate Cox regression was used to analyze the predictive value of a single measurement of MELD and HVPG, and changes between measurements. Compensated and decompensated patients were analyzed separately. One hundred and seventeen patients were included (51 compensated, 66 decompensated). Median time between measurements and follow-up was 13 (2-24) and 11 (6-38) months in compensated and 8 (1-16) and 10 (3-21) months in decompensated patients, respectively. Fifteen compensated patients developed decompensation while twelve decompensated patients died. On multivariate analysis, MELD (HR 1.12 (95% CI 1-1.24)) and HVPG (HR 1.16 (95% CI 1.04-1.29)) were independent predictors of decompensation in compensated, while MELD (HR 1.18 (95% CI 1.09-1.27)) was the only predictor of death in the decompensated. Single and repeat measurements of MELD and HVPG are associated to outcomes in cirrhosis. Use of repeat measurements does not seem to add further information.


Azoramide prevents MPP+-induced dopaminergic neuronal death via upregulating ER chaperone BiP expression.
Progressive death of dopaminergic (DA) neurons is the main cause of Parkinson's disease (PD). The discovery of drug candidates to prevent DA neuronal death is required to address the pathological aspects and alter the process of PD. Azoramide is a new small molecule compound targeting ER stress, which was originally developed for the treatment of diabetes. In this study, pre-treatment with Azoramide was found to suppress mitochondria-targeting neurotoxin MPP+-induced DA neuronal death and locomotor defects in zebrafish larvae. Further study showed that pre-treatment with Azoramide significantly attenuated MPP+-induced SH-SY5Y cell death by reducing aberrant changes in nuclear morphology, mitochondrial membrane potential, intracellular reactive oxygen species, and apoptotic biomarkers. The mechanistic study revealed that Azoramide was able to up-regulate the expression of ER chaperone BiP and thereby prevented MPP+-induced BiP decrease. Furthermore, pre-treatment with Azoramide failed to suppress MPP+-induced cytotoxicity in the presence of the BiP inhibitor HA15. Taken together, these results suggested that Azoramide is a potential neuroprotectant with pro-survival effects against MPP+-induced cell death through up-regulating BiP expression.


Anxiety- rather than depression-like behavior is associated with adult neurogenesis in a female mouse model of higher trait anxiety- and comorbid depression-like behavior.
Adult neurogenesis has been implicated in affective disorders and the action of antidepressants (ADs) although the functional significance of this association is still unclear. The use of animal models closely mimicking human comorbid affective and anxiety disorders seen in the majority of patients should provide relevant novel information. Here, we used a unique genetic mouse model displaying higher trait anxiety (HAB) and comorbid depression-like behavior. We demonstrate that HABs have a lower rate of hippocampal neurogenesis and impaired functional integration of newly born neurons as compared with their normal anxiety/depression-like behavior (NAB) controls. In HABs, chronic treatment with the AD fluoxetine alleviated their higher depression-like behavior and protected them from relapse for 3 but not 7 weeks after discontinuation of the treatment without affecting neurogenesis. Similar to what has been observed in depressed patients, fluoxetine treatment induced anxiogenic-like effects during the early treatment phase in NABs along with a reduction in neurogenesis. On the other hand, treatment with AD drugs with a particularly strong anxiolytic component, namely the neurokinin-1-receptor-antagonist L-822 429 or tianeptine, increased the reduced rate of neurogenesis in HABs up to NAB levels. In addition, challenge-induced hypoactivation of dentate gyrus (DG) neurons in HABs was normalized by all three drugs. Overall, these data suggest that AD-like effects in a psychopathological mouse model are commonly associated with modulation of DG hypoactivity but not neurogenesis, suggesting normalization of hippocampal hypoactivity as a neurobiological marker indicating successful remission. Finally, rather than to higher depression-related behavior, neurogenesis seems to be linked to pathological anxiety.


5D imaging via light sheet microscopy reveals cell dynamics during the eye-antenna disc primordium formation in Drosophila.
5D images of engrailed (en) and eye gone (eyg) gene expressions during the course of the eye-antenna disc primordium (EADP) formation of Drosophila embryos from embryonic stages 13 through 16 were recorded via light sheet microscopy and analyzed to reveal the cell dynamics involved in the development of the EADP. Detailed analysis of the time-lapsed images revealed the process of EADP formation and its invagination trajectory, which involved an inversion of the EADP anterior-posterior axis relative to the body. Furthermore, analysis of the en-expression pattern in the EADP provided strong evidence that the EADP is derived from one of the en-expressing head segments.


CXCR2 Mediates Distinct Neutrophil Behavior in Brain Metastatic Breast Tumor.
Brain metastasis is one of the main causes of mortality among breast cancer patients, but the origins and the mechanisms that drive this process remain poorly understood. Here, we report that the upregulation of certain CXCR2-associated ligands in the brain metastatic variants of the breast cancer cells (BrM) dynamically activate the corresponding CXCR2 receptors on the neutrophils, thereby resulting in the modulation of certain key functional neutrophil responses towards the BrM. Using established neutrophil-tumor biomimetic co-culture models, we show that the upregulation of CXCR2 increases the recruitment of Tumor-Associated Neutrophils (TANs) towards the BrM, to enable location-favored formation of Neutrophil Extracellular Traps (NETs). Inhibition of CXCR2 using small molecule antagonist AZD5069 reversed this behavior, limiting the neutrophil responses to the BrM and retarding the reciprocal tumor development. We further demonstrate that abrogation of NETs formation using Neutrophil Elastase Inhibitor (NEI) significantly decreases the influx of neutrophils towards BrM but not to their parental tumor, suggesting that CXCR2 activation could be used by the brain metastatic tumors as a mechanism to program the tumor-infiltrating TANs into a pro-NETotic state, so as to assume a unique spatial distribution that assists in the subsequent migration and invasion of the metastatic tumor cells. This new perspective indicates that CXCR2 is a critical target for suppressing neutrophilic inflammation in brain metastasis.


Choriocapillary vascular density in central serous chorioretinopathy complicated by choroidal neovascularization.
To evaluate choriocapillary vascular density (CVD) in eyes with central serous chorioretinopathy (CSC) complicated by choroidal neovascularization (CNV), at baseline and after intravitreal injections (IVR) of Ranibizumab, using optical coherence tomography angiography (OCTA). Twelve eyes of 12 patients were enrolled as group 1 and 12 unaffected fellow eyes formed group 2. Twelve eyes of 12 healthy controls were the control group. CVD in Group 1 did not differ before and after treatment. CVD of Group 1 was significantly lower compared with controls at baseline (whole, parafovea and fovea p < 0.05). CVD of controls resulted significantly higher than Group 2 at baseline (whole, parafovea and fovea p < 0.05). There were not significant differences in CVD between Groups 1 and 2 at baseline (p > 0.05). OCTA revealed a choriocapillary hypoperfusion that may be responsable for the beginning of this disease and the late development of CNV.


Double filtration plasmapheresis - 10-year pediatric experience as an alternative to plasma exchange.
Double filtration plasmapheresis (DFPP) is more selective at removing antibodies compared to plasma exchange (PE), thus reducing the need for replacement blood products. We retrospectively analyzed the records of all pediatric patients whom DFPP had been performed. In total, 30 patients were treated with DFPP. Data were available for 436 sessions in 23 patients. Patients had a median of 6 (1-161) sessions. Age at start of treatment was 13.9 years (2.2-19.2) and weight 46 kg (13.4-82.8). Six patients were treated for antibody mediated rejection; 1 had full recovery, 1 CKD stage 4 and 4 required dialysis. Two patients were treated for recurrence of focal segmental glomerulosclerosis (FSGS) with good response. One successfully had an ABO-incompatible kidney transplantation. Five had anti-glomerular basement membrane disease; 3 had complete recovery, 1 CKD and 1 required transplantation. Three had granulomatosis with polyangiitis; 1 with full recovery, 1 had CKD and 1 required dialysis. Two had Type-2 Membrano-proliferative glomerulonephritis, 1 successfully treated, the other needing dialysis. One treated for rapidly progressive MPO-glomerulonephritis required dialysis. Other indications were Myasthenia Gravis, Guillain-Barré disease and autoimmune limbic encephalitis. Excluding FSGS patients (with >100 sessions), one patient had cryoprecipitate, 2 had blood transfusions, no other blood products were required. Minor complications were seen in 13 sessions (8.4%). No major complications were seen. DFPP is a safe, well tolerated form of apheresis that appears to have comparable outcomes to that of PE, without the routine need of replacement blood products.


Comparison of the Recurrence and Surgical Outcome of Spinal Hemangioblastoma in Sporadic and Von Hippel-Lindau Diseases: A Subanalysis of a Nationwide Study by the Neurospinal Society of Japan.
This study aimed to clarify the relationship between recurrence and the extent of resection in surgery for intramedullary spinal hemangioblastoma (sHB) and its impact on von Hippel-Lindau (vHL) disease. Data on sHB cases followed up for at least 6 months after surgery were extracted from a nationwide registry of 1,033 consecutive spinal intramedullary tumors surgically treated between 2009 and 2020, and were retrospectively categorized into a sporadic or vHL group. The diagnosis of vHL disease was made at each institution based on clinical findings. A total of 168 patients (sporadic group, 101; vHL group, 67) were included in the study. Compared with the sporadic group, the vHL group had a younger onset (45.4 ± 16.8 years vs. 39.6 ± 14.1 years, p = 0.02), more preoperative motor (47.5% vs. 68.7%, p < 0.01) and gait (37.6% vs. 61.2%, p < 0.01) impairments, and more patients with worsening neurological symptoms at discharge (p = 0.02). The gross total resection (GTR) rates and the recurrence rates were not statistically different between the sporadic and the vHL groups. GTR significantly improved recurrence-free survival compared to non-GTR in all patient analysis (p < 0.01) but this trend was not observed in the sporadic group. Physical functional improvement from discharge to 6 months after surgery was observed in the sporadic group (p < 0.01) but not in the vHL group. A high GTR rate may sufficiently decrease susceptibility to recurrence, especially in patients with sHB with vHL. In sporadic sHB, postoperative functional improvement can be expected, and the long-term functional prognosis is favorable.


An independent haemostatic mechanism: shear induced platelet aggregation.
We have published (1) evidence indicating that high shearing forces alone applied to platelets expose and activate a unique domain on glycoprotein IIb/IIIa (GPIIb/IIIa) at the platelet surface. In the presence of von Willebrand's factor (vWf) and divalent cations the platelets will aggregate. This paper reviews the extensive literature on high shear effects. It describes a device in which high shear produced by forcing heparinised whole blood through a complex filter normally results in platelet activation; the platelets aggregate and then block the filter. This system is inhibited by antibodies to GPIIb/IIIa and to vWf: fibrinogen is apparently not involved. The same antibodies to GPIIb/IIIa and vWf prevent high shear induced thrombosis occurring in vivo in animal models. The filter blockage is not influenced by aspirin, heparin and ticlopidine and so involves a different mechanism from the aspirin sensitive mechanisms involved in clinical thrombosis prevention in vivo in man. While there are a number of unexplained phenomena in this global test nevertheless this filter model is a simple way of studying a recently recognised pathway which is almost certainly involved in thrombogenesis in man.


Jaceidin Flavonoid Isolated from Chiliadenus montanus Attenuates Tumor Progression in Mice via VEGF Inhibition: In Vivo and In Silico Studies.
Phytochemical study of Chiliadenus montanus aerial parts afforded six compounds; Intermedeol (1), 5α-hydroperoxy-β-eudesmol (2), 5,7-dihydroxy-3,3',4'-trimethoxyflavone (3), 5,7,4'-trihydroxy-3,6,3'-trimethoxyflavone (jaceidin) (4), eudesm-11,13-ene-1β,4β,7α-triol (5) and 1β,4β,7β,11-tetrahydroxyeudesmane (6). These compounds were identified based on their NMR spectral data. The isolated compounds were tested for their cytotoxicity against liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). Jaceidin flavonoid (4) exhibited the highest cytotoxic effect in vitro. Therefore, both of jaceidin and C. montanus extract were evaluated for their in vivo anti-tumor activity against Ehrlich's ascites carcinoma (EAC). Compared to control group, jaceidin and C. montanus extract decreased the tumor weight, improved the histological picture of tumor cells, lowered the levels of VEGF and ameliorate the oxidative stress. Molecular docking and in silico studies suggested that jaceidin was a selective inhibitor of VEGF-mediated angiogenesis with excellent membrane permeability and oral bioavailability.


SIRT1 inhibits apoptosis in in vivo and in vitro models of spinal cord injury via microRNA-494.
The aim of the present study was to investigate the function and mechanism of sirtuin 1 (SIRT1) in spinal cord injury (SCI). Reverse transcription‑quantitative polymerase chain reaction was used to measure the expression levels of microRNA (miR)‑494. MTT assay, lactate dehydrogenase activity assay and flow cytometry were used to analyze the effects of miR‑494 on cell growth and apoptosis in a model of SCI. The present study demonstrated that SIRT1 expression was reduced; whereas miR‑494 expression was increased in a rat model of SCI. Overexpression of miR‑494 suppressed the protein expression levels of SIRT1, and induced p53 protein expression. Conversely, knockdown of miR‑494 induced SIRT1 protein expression in an in vitro model of SCI. Furthermore, overexpression of miR‑494 promoted cell apoptosis and decreased cell growth in an in vitro model of SCI; however, miR‑494 knockdown enhanced cell growth and inhibited cell apoptosis. Administration of a SIRT1 agonist reduced the effects of miR‑494 overexpression on cell apoptosis in an SCI model, whereas treatment with a p53 agonist reduced the effects of miR‑494 knockdown on cell apoptosis in an SCI model. Together, these findings suggested that SIRT1 may inhibit apoptosis of SCI in vivo and in vitro through the p53 signaling pathway, whereas miR‑494 suppressed SIRT1 and induced apoptosis.


Vascular dimorphism ensured by regulated proteoglycan dynamics favors rapid umbilical artery closure at birth.
The umbilical artery lumen closes rapidly at birth, preventing neonatal blood loss, whereas the umbilical vein remains patent longer. Here, analysis of umbilical cords from humans and other mammals identified differential arterial-venous proteoglycan dynamics as a determinant of these contrasting vascular responses. The umbilical artery, but not the vein, has an inner layer enriched in the hydrated proteoglycan aggrecan, external to which lie contraction-primed smooth muscle cells (SMC). At birth, SMC contraction drives inner layer buckling and centripetal displacement to occlude the arterial lumen, a mechanism revealed by biomechanical observations and confirmed by computational analyses. This vascular dimorphism arises from spatially regulated proteoglycan expression and breakdown. Mice lacking aggrecan or the metalloprotease ADAMTS1, which degrades proteoglycans, demonstrate their opposing roles in umbilical vascular dimorphism, including effects on SMC differentiation. Umbilical vessel dimorphism is conserved in mammals, suggesting that differential proteoglycan dynamics and inner layer buckling were positively selected during evolution.


The Importance of Proper Use of N95 Respirators by Health-Care Workers.
The novel coronavirus causing the COVID-19 pandemic is spread by respiratory transmission through droplets and contact. The Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) recommend the use of personal protective equipment (PPE) including a gown, gloves, and a surgical mask or N95 respirator plus a face shield and/or goggles for health-care workers who are in direct contact with COVID-19 patients. A study in China by Wang found that health-care workers on the front line of disease treatment had inadequate training in the use of PPE, particularly for respiratory infectious diseases. Instruction in the proper use of N95 respirators, with an emphasis on performing user seal checks, as well as donning and doffing, is recommended for everyone caring for COVID-19 patients.


Ex vivo-expanded baboon CD39 + regulatory T cells prevent rejection of porcine islet xenografts in NOD-SCID IL-2rγ-/- mice reconstituted with baboon peripheral blood mononuclear cells.
A high immunosuppressive burden is required for long-term islet xenograft survival in non-human primates even using genetically modified donor pigs. We aimed to investigate the capacity of baboon regulatory T cells (Treg) to suppress islet xenograft rejection, thereby developing a potential immunoregulatory or tolerance therapy that could be evaluated in NHP models of xenotransplantation. Baboon Treg expanded with stimulation by porcine peripheral blood mononuclear cells (PBMC) were characterized by cell phenotyping and suppressive activity assays in vitro. Their function in vivo was evaluated in neonatal porcine islet cell clusters (NICC) transplanted NOD-SCID IL-2rγ-/- (NSG) mice receiving baboon PBMC alone or with expanded autologous Treg. The majority of expanded Treg coexpressed Foxp3 and CD39 and were highly suppressive of the baboon anti-pig xenogeneic T cell response in vitro. Reconstitution of mice with baboon PBMC alone resulted in NICC xenograft rejection within 35 days. Cotransfer with baboon PBMC and Treg prolonged islet xenograft survival beyond 100 days, correlating with Treg engraftment, intragraft CD39 and Foxp3 gene expression, and reduced graft infiltrating effector T cells and reduced interferon-γ production. Our data supports the capacity of ex vivo expanded CD39+ baboon Treg to suppress islet xenograft rejection in primatized mice, suggesting it has potential as an adjunctive immunotherapy in preclinical NHP models of xenotransplantation.


Detecting Familial Aggregation.
In addition to characterizing the distribution of genetic features of populations (mutation and allele frequencies; measures of Hardy-Weinberg equilibrium), genetic epidemiology and statistical genetics aim to explore and define the role of genomic variation in risk of disease or variation in traits of interest. To facilitate this kind of exploration, genetic epidemiology and statistical genetics address a series of questions: 1. Does the disease tend to cluster in families more than expected by chance alone? 2. Does the disease appear to follow a particular genetic model of transmission in families? 3. Does variation at a particular genomic position tend to cosegregate with disease in families? 4. Do specific genetic variants tend to be carried more frequently by those with disease than by those without these variants in a given population (or across families)? The first question can be examined using studies of familial aggregation or correlation. An ancillary question: "how much of the susceptibility to disease (or variation in disease-related traits) might be accounted for by genetic factors?" is typically answered by estimating heritability, the proportion of variance in a trait or in risk to a disease attributable to genetics. The second question can be formally tested using pedigrees for which disease affection status or trait values are available through a modeling approach known as segregation analysis. The third question can be answered with data on genomic markers in pedigrees with affected members informative for linkage, where meiotic cross-over events are estimated or assessed. The fourth question is answerable using genotype data on genomic markers on unrelated affected and unaffected individuals and/or families with affected members and unaffected members. All of these questions can also be explored for quantitative (or continuously distributed) traits by examining variation in trait values between family members or between unrelated individuals. While each of these questions and the analytical approaches for answering them is explored extensively in subsequent chapters (heritability in Chapters 8 and 9 ; segregation in Chapter 12 ; linkage in Chapters 13 - 17 ; and association in Chapters 18 - 20 ), this chapter focuses on statistical methods to address questions of familial aggregation of qualitative phenotypes (e.g., disease status) or quantitative phenotypes.While studies exploring genotype-phenotype correlations are arguably the most important and common type of statistical genetic study performed, these studies are performed under the assumption that genetic contributors at least partially explain risk of a disease or a trait of interest. This may not always be the case, especially with diseases or traits known to be strongly influenced by environmental factors. For this reason, before any of the last three questions described above can be answered, it is important to ask first whether the disease clusters among family members more than unrelated persons, as this constitutes evidence of a possible heritable contribution to disease, justifying the pursuit of studies answering the other questions. In this chapter, the underlying principles of familial aggregation studies are addressed to provide an understanding and set of analytical tools to help answer the question if diseases or traits of interest are likely to be heritable and therefore justify subsequent statistical genetic studies to identify specific genetic causes.


Complications in the intralesional injection of triamcinolone acetonide by jet injector (Dermojet).
Two patients with lichenified eczematous lesions on the dorsal aspect of the hands were treated intralesionally with triamcinolone acetonide injected with an air-powered high-pressure device, Dermojet. The therapy was complicated by tendon rupture in one patient and by the development of a subcutaneous nodule, which was suspected to be a foreign body granulomatous reaction, in the other patient.


Cannabis use in the intensive care setting: A scoping review.
Cannabis is the most used recreational drug worldwide, and is increasingly used for medicinal purposes, however little is known about its impact on patients in intensive care units (ICU). Our objective was to identify key themes in the literature surrounding cannabis in the ICU and identify future research priorities. Four databases were systematically searched for literature investigating the impact of cannabis, and evidence for its therapeutic use, in adult ICU patients. Of 2589 articles screened, 22 articles were included for analysis. Cannabis-associated admissions were primarily related to an outbreak of vaping associated lung injury, and synthetic cannabinoid toxicity. Studies on the impact of cannabis use on outcomes were mostly limited to trauma and burns populations, with an inconsistent mortality benefit, and a trend towards increased pain scores and analgesic requirements found. There is minimal research on its therapeutic uses in ICU, with two trials investigating the use of a synthetic cannabinoid in patients with severe traumatic brain injury, with ultimately no significant effect on intracranial pressure found. There is a paucity of studies investigating the impact of cannabinoids or their therapeutic uses in critically ill patients, with further research in this area needed.


Antecedent ethanol ingestion prevents postischemic microvascular dysfunction.
Prolonged ischemia followed by reperfusion (I/R) results in impaired endothelial cell function in all segments of the microvasculature. Moreover, microcirculatory dysfunction plays a major role in the genesis of the reperfusion component of total tissue injury in I/R. Thus, preservation of endothelial function is an important therapeutic goal for ameliorating injury in tissues subjected to I/R. An accumulating body of evidence indicates that low to moderate ethanol consumption produces an adaptive transformation to a protected phenotype in both microvascular endothelium and parenchymal cells such that they are rendered resistant to the pathologic effects of I/R. The purpose of this review is to summarize our current understanding of the signaling pathways underlying the development of the preconditioned state induced by antecedent ethanol in arteriolar, capillary, and venular endothelium. In addition, we will highlight understudied areas with regard to microvascular protection afforded by antecedent ethanol in the hopes that this will stimulate investigation of its underlying mechanisms. Understanding these signaling pathways may provide a mechanistic rationale for the development of novel treatment interventions that target both the microcirculatory and parenchymal sequelae to I/R, thereby maximizing the therapeutic potential of the protected phenotypes produced by pharmacologic preconditioning.


Direct reprogramming of terminally differentiated cells into neurons: A novel and promising strategy for Alzheimer's disease treatment.
Glial activation is a common pathological process of the central nervous system (CNS) in disorders such as Alzheimer's disease (AD). Several approaches have been used to reduce the number of activated astrocytes and microglia in damaged areas. In recent years, various kinds of fully differentiated cells have been successfully reprogrammed to a desired type of cell in lesion areas. Interestingly, internal glial cells, including astrocytes and NG2 positive cells, were efficiently converted to neuroblasts and neurons by overexpression of some transcription factors (TFs) or microRNAs (miRNAs). Notably, some specific subtypes of neurons have been achieved by in vivo reprogramming and the resulting neurons were successfully integrated into local neuronal circuits. Furthermore, somatic cells from AD patients have been converted to functional neurons. Although direct reprogramming of a patient's own internal cells has revolutionized regenerative medicine, but there are some major obstacles that should be examined before using these induced cells in clinical therapies. In the present review article, we aim to discuss the current studies on in vitro and in vivo reprogramming of somatic cells to neurons using TFs, miRNAs or small molecules in healthy and AD patients.


Alkali denaturation of oxyhaemoglobins of some digenetic trematodes and their hosts.
Oxyhaemoglobins of six digenetic trematodes,--Srivastavaia indica, Gastrothylax crumenifer, Gigantocotyle explanatum, Fasciolopsis buski, Gastrodiscoides hominis, Isoparorchis hypselobagri, and of their 3 vertebrate hosts, Bubalus bubalis, Sus scrofa, Wallago attu, were subjected to alkali denaturation at a pH of 12.4. All oxyhaemoglobins from trematodes and their hosts differ from each other in the rate and extent of alkali denaturation which may be explained due to variations in the amino acid sequences of a particular haem protein in addition to other factors.


Enhanced Photochromism of Diarylethene Induced by Excitation of Localized Surface Plasmon Resonance on Regular Arrays of Gold Nanoparticles.
Localized surface plasmon resonance (LSPR) excitation on the photochromic reaction of a diarylethene derivative (DE) was studied by surface enhanced Raman scattering (SERS). UV and visible light irradiations transform reversibly DE between open-form (OF) and closed-form (CF) isomers, respectively. A mixture of PMMA and DE (either OF or CF isomer) was spin-coated onto gold nanorods (GNRs) arrays, designed by electron beam lithography, with two localized surface plasmon resonances (LSPR) at distinct wavelengths, due to their anisotropy. The photochromic reaction rates from CF to OF isomers, under LSPR excitation, were monitored from SERS spectral changes under different polarizations, on the same GNR substrate to compare the effect of LSPR field strength. It appears that the photoisomerization rate was faster when LSPR was excited with the polarization parallel to the GNR long axis. The present results highlight a potential genuine mechanism, from near field LSPR excitation, involved in the photochromic enhancement of diarylethene photochromes.


Workup and management of patients with syncope.
Syncope accounts for approximately 1% to 6% of hospital admissions and 3% of emergency room visits. Syncope is defined as a sudden transient loss of consciousness associated with a loss of postural tone with spontaneous recovery. Patients should not require electrical or chemical cardioversion to regain consciousness. Syncope must be clinically differentiated from other states of altered consciousness, such as dizziness, vertigo, seizures, coma, and nacrolepsy.


Recurrent mucosal leishmaniasis of the epiglottis in an immunosuppressed patient.
Leishmaniasis is a disease caused by the intracellular protozoan parasite Leishmania and are known more than 20 species(1) harmful for men. A 74-year-old man, with sarcoidosis treated with methotrexate and corticoid, was assessed, in 2021, by an ENT specialist due to dysphagia, dysphonia, and odynophagia with a 5-year evolution and progressive worsening. A biopsy of the right vocal cord and epiglottis was performed, and the histology demonstrated the presence of amastigotes in the tissues coloured by Giemsa making the diagnosis of Leishmaniasis. The patient was referred to the Infectious Diseases Department, with the diagnosis of mucosal leishmaniasis, and hospitalized for treatment with Liposomal Amphotericin B. The dysphagia and odynophagia improved and was discharged to Infectious Diseases Day hospital to continue treatment. He completed a total of 10 days of treatment and continued follow up in Infectious Diseases, Pneumology and ENT departments. During this time the patient stopped treatment with methotrexate but maintained deflazacort 6 mg per day. In 2023, the patient presented with worsening dysphonia and dysphagia. A new biopsy of the epiglottis was performed in the ENT department. Leishmania DNA was detected, and histology was compatible with Leishmaniasis of the left larynx. He was hospitalized in Infectious Diseases department and started treatment with Liposomal Amphotericin B. The patient completed a total of 10 days of treatment, and, by this time, the medical team decided to maintain suppressive therapy once a month with Liposomal Amphotericin B, until the patient present with a CD4 leucocyte count superior to 350/mm³ . By the time of this article, the patient maintained follow up in the Infectious Disease department with monthly sessions of therapy.


Organochlorine contaminants in water, sediment and fish of Lake Burullus, Egyptian Mediterranean Sea.
Lake Burullus is one of the Delta lakes, connected with the Mediterranean Sea through El Boughaz opening. Concentrations of organochlorine contaminants were measured in water, sediments and biota of the lake because of concerns about their effects on its productivity. The concentrations of chlorinated hydrocarbons decreased in the order of PCBs > DDTs > TC > HCHs for all water samples collected from Lake Burullus during 2006. Higher concentrations were recorded during summer season, this clearly affected by higher agricultural and sewage activities. The concentrations of DDTs in water were ranged from 0.07 to 221.9 ng L(-1); 46.3-656.5 ng L(-1); 94.3-882.6 ng L(-1) and 24.8-233 ng L(-1) during winter, spring, summer and autumn, respectively. Among DDTs metabolites p,p-DDE was the most dominant with a maximum of 520.13 ng L(-1) recorded at station 10 (El Boughaz opening). In sediment samples, PCBs concentrations were ranged from 4.6 to 213.9 ng g(-1) with an average 47.2 ng g(-1); dry weight. Total pesticides were higher than PCBs for mostly all sediment samples of Lake Burullus. Concentrations of DDTs in fish tissues were ranged from 2.76 to 24.23 ng g(-1) and from 14.16 to 45.13 ng g(-1); wet weight for Oresochromus niloticus and Clarries sp., respectively.


A Retrospective Study on the Clinicopathologic Characteristics and Outcomes of 179 Cases of Synchronous and Metachronous Bilateral Breast Cancer in China.
To investigate the clinicopathologic characteristics and outcome of bilateral breast cancer (BBC) in the Chinese population. A retrospective study was conducted on 7797 cases with primary breast cancer, including 7618 cases of unilateral breast cancer (UBC) and 179 cases of BBC. Among the latter, there were 108 cases of synchronous BBC (SBBC) and 71 cases of metachronous BBC (MBBC). In the present study, the incidence of SBBC and MBBC are 1.39% and 0.91% among the general population, respectively. In comparison of UBC and BBC, SBBC and MBBC, there are significant differences in the common clinicopathological characteristics, such as pathologic stage, hormone receptor (HR) status and molecular type. In respect of the surgical treatment of BBC, 49.72% of the patients chose mastectomy. The 3-year disease free survival (DFS) for SBBC and MBBC are 94.4% and 96.9%, respectively. There is no difference in the overall survival (OS) and DFS between SBBC and MBBC. The histological grade and type of surgery on tumors of both sides are important influencing factors of DFS in the BBC patients. There are statistical differences in the clinicopathological characteristics and outcomes between SBBC and MBBC among the Chinese population. Therefore, the treatment of BBC patients should be individualized.


Development of a genomic library of near isogenic lines (NILs) in melon (Cucumis melo L.) from the exotic accession PI161375.
A doubled haploid line (DHL) population of melon derived from a cross between the Korean cultivar "Songwhan Charmi" accession PI161375 (SC), included in the horticultural group conomon, and the Spanish cultivar "Piel de Sapo" (PS), included in the horticultural group inodorus, was used to develop a collection of near isogenic lines (NILs). These parental lines represent very different melon cultivar groups, with important differences at fruit, plant, disease response and molecular level. This cross is one of the most polymorphic ones within melon germplasm. Selected DHLs were backcrossed to PS and further backcrossing and selfing was performed, monitoring introgressions from SC using molecular markers covering the melon genetic map. A final collection of 57 NILs was obtained, containing a unique independent introgression from SC in the PS genetic background. The introgressions within the collection cover at least 85% of the SC genome with an average introgression size of 41 cM, corresponding to 3.4% of the SC genome. The average resolution for mapping genes or quantitative trait loci is 18.90 cM. This set of NILs is a potentially powerful tool for the study of quantitative trait locus involved in melon fruit quality and other important complex traits, and the introduction of new genetic variability in modern cultivars from exotic sources. The NILs can also be used as pre-competitive breeding lines in melon breeding projects.


Wnt/PCP pathway regulates the migration and neural differentiation of mesenchymal stem cells in vitro.
Mesenchymal stem cells (MSCs) are an excellent donor graft source due to their potential for self-renewal and multidirectional differentiation. However, the potential mechanisms involved in MSC homing and neural differentiation are still unclear. The purpose of this study was to explore the effects of a chemokine, SDF-1a, and Wnt3a ligand on rat MSCs' migration and b-mercaptoethanol (BME)-induced neural differentiation of MSCs. MSCs were isolated from rat bone marrow and cultured in vitro to passage 3. Scratch tests and transwell assays were used to estimate the effects of SDF-1a (25 ng/mL) and Wnt3a (10 ng/mL) on the migration of MSCs. The expression of Wnt/PCP pathway proteins RhoA, c-Jun, ATF2, and Wnt3a were assessed by Western blot. The 5 mM BME-induced neural differentiation of MSCs was determined by immunofluorescence to detect neuron- and astrocyte-specific markers such as nestin, GFAP, and Olig2. Wnt3a promoted the migration ability of MSCs and regulated the expression of RhoA, c-Jun, and ATF2 proteins. MSCs could differentiate into neural stem cells and astrocytes. Wnt3a enhanced BME induced neurogenesis in MSCs by increasing the protein expression of RhoA, c-Jun, and Wnt3a. The present study demonstrated that the Wnt/PCP pathway promotes migration and neural differentiation of rat MSC.


Acute CNS demyelination in a subject with cerebellar ataxia following the first dose of COVID-19 vaccine; a case report.
Vaccination-induced demyelination is a rare, unusual side effect of certain vaccines which can cause significant damage to patient's sensory-motor abilities within days. Although COVID-19 vaccines go through rigorous clinical trials before they are injected to the general population, certain unexpected side effects remain inevitable. We herein describe a case of a 42-year-old woman who experienced acute demyelination 10 days after the Oxford-AstraZeneca vaccination. To the best of our knowledge, this is the first case of such nature and severity described regarding COVID-19 vaccines' side effects.


Designing effective hybrid toxins.
A study of a well-designed androgen-mustard conjugate provides evidence supporting a novel mechanism for its selective toxicity in androgen-receptor-positive cancer cells. This represents a solid step forward on the path toward effective hybrid toxins for targeted cancer therapy.


[Physiotherapeutic treatment of adipose patients. Options and limitations on intensive care units].
Obese patients in the intensive care unit (ICU) represent an interesting topic, which is currently receiving increased attention from physiotherapists. The aim of this article is to present the options and limitations of physiotherapy which must be overcome in the daily routine in the ICU. The quality of therapeutic treatment of obese inpatients has shown a clear increase during the last 20 years; however, sufficient studies have not yet been carried out, international standards are not available and many therapists work differently with their patients. Additionally, the disease patterns of obesity consist of a large variety of different diseases. Despite the many demanding problems obesity is by no means an unsolvable puzzle. A literature search of lectures, studies and scientific articles was carried out to elucidate which options in the form of resources and devices are available to physiotherapists.


A branching process, its application in biology: influence of demographic parameters on the social structure in mammal groups.
Branching processes are widely used in biology. This theoretical tool is used in cell dynamics, epidemics and population dynamics. In population dynamics, branching processes are mainly used to access extinction probabilities of populations, groups or families, with the Galton-Watson branching process. Many mammal species live in socially-structured groups, and the smallest units of these groups are lineages (or families) of kin-related individuals. In many primate species, these lineages are matrilines, as females remain in their natal groups most of the time, whereas males generally disperse. Lineage parameters, such as numbers of matrilines, size of each matriline and average degree of relatedness, could strongly influence the genetic composition of groups. Evidence indicates that division along matrilines could induce substantial differentiation among fission groups. Here, we develop a novel mathematical model based on the branching process theory describing demographic dynamics of groups. The main result of this model is an explicit analytical expression of the joint distribution of numbers of lineages and sizes of socially-structured groups. We investigated the influence of parameters such as natality and mortality on the outcome of the process, including extinction probability. Finally, we discuss this theoretical result with respect to biological significance.


Family Presence during Resuscitation: A Qualitative Analysis from a National Multicenter Randomized Clinical Trial.
The themes of qualitative assessments that characterize the experience of family members offered the choice of observing cardiopulmonary resuscitation (CPR) of a loved one have not been formally identified. In the context of a multicenter randomized clinical trial offering family members the choice of observing CPR of a patient with sudden cardiac arrest, a qualitative analysis, with a sequential explanatory design, was conducted. The aim of the study was to understand family members' experience during CPR. All participants were interviewed by phone at home three months after cardiac arrest. Saturation was reached after analysis of 30 interviews of a randomly selected sample of 75 family members included in the trial. Four themes were identified: 1- choosing to be actively involved in the resuscitation; 2- communication between the relative and the emergency care team; 3- perception of the reality of the death, promoting acceptance of the loss; 4- experience and reactions of the relatives who did or did not witness the CPR, describing their feelings. Twelve sub-themes further defining these four themes were identified. Transferability of our findings should take into account the country-specific medical system. Family presence can help to ameliorate the pain of the death, through the feeling of having helped to support the patient during the passage from life to death and of having participated in this important moment. Our results showed the central role of communication between the family and the emergency care team in facilitating the acceptance of the reality of death.


Identifying bvFTD Within the Wide Spectrum of Late Onset Frontal Lobe Syndrome: A Clinical Approach.
The behavioral variant of frontotemporal dementia (bvFTD) can be difficult to diagnose because of the extensive differential diagnosis, including many other diseases presenting with a frontal lobe syndrome. We aimed to identify the diagnostic spectrum causing a late onset frontal lobe syndrome and examine the quality of commonly used instruments to distinguish between bvFTD and non-bvFTD patients, within this syndrome. A total of 137 patients fulfilling the criteria of late onset frontal lobe syndrome, aged 45 to 75 years, were included in a prospective observational study. Diagnoses were made after clinical and neuropsychological examination, and neuroimaging and cerebral spinal fluid results were taken into account. Baseline characteristics and the scores on the Mini-Mental State Exam (MMSE), frontal assessment battery (FAB), Frontal Behavioral Inventory (FBI), and Stereotypy Rating Inventory (SRI) were compared between the bvFTD and the non-bvFTD group. Fifty-five (40%) of the patients received a bvFTD diagnosis (33% probable and 7% possible bvFTD). Fifty-one patients (37%) had a psychiatric disorder, including 20 with major depressive disorder. Thirty-one patients received an alternative neurological, including neurodegenerative, diagnosis. MMSE and FAB scores were unspecific for a particular diagnosis. A score above 12 on the positive FBI subscale or a score above 5 on the SRI were indicative of a bvFTD diagnosis. A broad spectrum of both neurological and psychiatric disorders underlies late onset frontal lobe syndrome, of which bvFTD was the most prevalent diagnosis in our cohort. The commonly used MMSE and the FAB could not successfully distinguish between bvFTD and non-bvFTD, but this could be achieved with the more specific FBI and SRI.


Expandable endoprosthesis for limb-sparing surgery in children: long-term results.
Most children today with bone sarcomas undergo limb-sparing surgery. When treating children younger than 12 years of age, the result is significant limb length discrepancy (LLD). One of the solutions is the use of an expandable endoprosthesis. A retrospective analysis of 38 skeletally immature patients with bone sarcoma of the lower limb in whom different types of expandable endoprostheses were used from January 1988 to December 2005 were included. All patients were under the age of 14 years. There were 26 osteosarcoma and 12 Ewing's sarcomas. The data collected included the tumor characteristics, the surgical and other treatment modalities, complications and their treatment, and the final LLD and functional results. Fifty-five percent of the patients survived and had a mean follow-up of 113 months. All survivors reached skeletal maturity at the time of last follow-up. Seventy-one percent of the survivors had satisfactory function and 29% had a poor result. There were three secondary amputations due to local recurrence. Complications were documented in 58% of patients; the most common was infection that was diagnosed 56 times (primary 16% and secondary 84%). A significant correlation was found between function and final LLD (greater than 5 cm = inferior function), the number of complications, and the number of surgical procedures performed other than prosthesis elongation. The younger the patient was at definitive surgery, the shorter the time it took for the prosthesis to fail. In order to improve results, the number of operations must be reduced. This can be achieved by the use of novel non-invasive expandable endoprostheses or biological reconstruction.


Sphingomonas arantia sp. nov., isolated from Hoh Xil basin, China.
A Gram-negative, rod-shaped, non-motile, non-spore forming, aerobic, orange-pigmented bacterium, designated strain 6P(T), was isolated from a soil sample collected from the Hoh Xil basin, China. Strain 6P(T) grew optimally at 25 °C, pH 7.0-7.5 and NaCl concentration of 0-1 % (w/v). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 6P(T) belongs to the genus Sphingomonas, with high sequence similarity (97.1 %) to Sphingomonas fennica. The DNA-DNA hybridization homology with S. fennica DSM 13665(T) was 45.3 %. The DNA G+C content of the novel strain is 65.3 mol%. The isolate contained Q-10 as the only respiratory quinone. The major polar lipids are diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC) and sphingoglycolipid (SGL). C18:1 ω7c and C16:1 ω7c are the major fatty acids. On the basis of the polyphasic evidence presented, strain 6P(T) represents a novel species of the genus Sphingomonas, for which the name Sphingomonas arantia sp. nov. is proposed. The type strain is 6P(T) (=CGMCC 1.12702(T) = JCM 19855(T)).


Autoimmunity, alloimmunization and immunotherapy of AIDS.
The nature of clinical and physiological manifestations associated with HIV infection suggests that AIDS is an autoimmune disease. The conventional immunotherapeutic approaches aimed at enhancing the immune response against HIV have repeatedly failed when applied in the clinical practice. The results of several dozen therapeutic AIDS vaccine trials have consistently shown that while in vitro measured HIV-specific immune responses were evident as a result of vaccination the clinical improvement has been seldom observed. The clinical benefit, however, was invariably associated with the usage of vaccines that acted in accord with the principles of alloimmunization. The majority of these vaccines were derived from the blood of HIV carriers or a cell culture and thus they inherently contained alloantigens unrelated to HIV. The clinical experience with alloimmunization in a range of autoimmune diseases indicates that immune tolerization is an active immune process with benefits the vaccinees. The alloimmunization, which primarily induces tolerance rather than immune activation, might be a better strategy for the immunotherapy of AIDS.


NF-kappaB and p53 are the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope.
The coculture of cells expressing the HIV-1 envelope glycoprotein complex (Env) with cells expressing CD4 results into cell fusion, deregulated mitosis, and subsequent cell death. Here, we show that NF-kappaB, p53, and AP1 are activated in Env-elicited apoptosis. The nuclear factor kappaB (NF-kappaB) super repressor had an antimitotic and antiapoptotic effect and prevented the Env-elicited phosphorylation of p53 on serine 15 and 46, as well as the activation of AP1. Transfection with dominant-negative p53 abolished apoptosis and AP1 activation. Signs of NF-kappaB and p53 activation were also detected in lymph node biopsies from HIV-1-infected individuals. Microarrays revealed that most (85%) of the transcriptional effects of HIV-1 Env were blocked by the p53 inhibitor pifithrin-alpha. Macroarrays led to the identification of several Env-elicited, p53-dependent proapoptotic transcripts, in particular Puma, a proapoptotic "BH3-only" protein from the Bcl-2 family known to activate Bax/Bak. Down modulation of Puma by antisense oligonucleotides, as well as RNA interference of Bax and Bak, prevented Env-induced apoptosis. HIV-1-infected primary lymphoblasts up-regulated Puma in vitro. Moreover, circulating CD4+ lymphocytes from untreated, HIV-1-infected donors contained enhanced amounts of Puma protein, and these elevated Puma levels dropped upon antiretroviral therapy. Altogether, these data indicate that NF-kappaB and p53 cooperate as the dominant proapoptotic transcription factors participating in HIV-1 infection.


A case of carcinoma of the common bile duct, diagnosed at the non-icteric stage of the disease.
It is rather seldom to detect a cancer of the common bile duct at the non-icteric stage of the disease. This report presents a non-icteric case of carcinoma of the choledochus. A 70-year-old woman complained of r-hypochondralgia with occasional fever. Laboratory examination revealed an increased serum alkaline phosphatase activity without any elevation of serum bilirubin content. The oral cholecystography failed to visualize the gallbladder. By endoscopic retrograde cholangiopancreatography (ERCP), a bilateral filling defect was demonstrated at the common bile duct. Pancreatoduodenectomy was performed and the resected specimen showed a 1 X 2 cm tumor (adenocarcinoma) at the choledochus. She is now in good health over 13 months after operation.


Development and validation of an LC-MS/MS method for simultaneous determination of remdesivir and its hydrolyzed metabolite and nucleoside, and its application in a pharmacokinetic study of normal and diabetic nephropathy mice.
Remdesivir (RDV), a phosphoramidate prodrug, has broad-spectrum antiviral activity. It is the first antiviral drug approved by the US Food and Drug Administration (FDA) for the treatment of COVID-19. Remdesivir is rapidly metabolized in the body to produce derivatives: alanine metabolite (RM-442) and RDV C-nucleoside (RN). Here, the phosphatase inhibitor PhosSTOP and carboxylesterase inhibitor 5,5'-dithiobis-2-nitrobenzoic acid were used to improve stability of RDV in mouse blood. We developed a rapid and sensitive LC-MS/MS method to simultaneously quantify RDV, RM-442 and RN in mouse blood. Chromatographic separation was achieved by gradient elution on an Acquity HSS T3 column. The run time was 3.2 min. The linearity ranges of the analytes were 0.5-1,000 ng/ml for RDV and 5-10,000 ng/ml for both RM-442 and RN. The method had an acceptable precision (RSD < 8.4% for RDV, RSD < 10.7% for RM-442 and RSD < 7.2% for RN) and accuracy (91.0-106.3% for RDV, 92.5-98.6% for RM-442 and 87.5-98.4% for RN). This method was successfully applied to analyze RDV, RM-442 and RN in the blood of normal and diabetic nephropathy DBA/2 J mice after intravenous injection of RDV at 20 mg/kg. The area under the concentration-time curve of RN between the normal and diabetic nephropathy mice showed a significant difference (P < 0.01).


Thermococcus marinus sp. nov. and Thermococcus radiotolerans sp. nov., two hyperthermophilic archaea from deep-sea hydrothermal vents that resist ionizing radiation.
Enrichments for anaerobic, organotrophic hyperthermophiles were performed with hydrothermal chimney samples collected from the Mid-Atlantic Ridge at a depth of 3,550 m (23 degrees 22'N, 44 degrees 57'W) and the Guaymas Basin (27 degrees 01'N, 111 degrees 24'W) at a depth of 2,616 m. Positive enrichments were submitted to gamma-irradiation at doses of 20 and 30 kGy. Two hyperthermophilic, anaerobic, sulfur-metabolizing archaea were isolated. Strain EJ1T was isolated from chimney samples collected from the Mid-Atlantic Ridge after gamma-irradiation at 20 kGy, and strain EJ2T was isolated from the Guaymas Basin after gamma-irradiation at 30 kGy. Only strain EJ2T was motile, and both formed regular cocci. These new strains grew between 55 and 95 degrees C with the optimal temperature being 88 degrees C. The optimal pH for growth was 6.0, and the optimal NaCl concentration for growth was around 20 g l(-1). These strains were obligate anaerobic heterotrophs that utilized yeast extract, tryptone, and peptone as a carbon source for growth. Ten amino acids were essential for the growth of strain EJ1), such as arginine, aspartic acid, isoleucine, leucine, methionine, phenylalanine, proline, threonine, tyrosine, and valine, while strain EJ2T was unable to grow on a mixture of amino acids. Elemental sulfur or cystine was required for EJ2T growth and was reduced to hydrogen sulfide. Rifampicin inhibited growth for both strains EJ1T and EJ2T. The G + C contents of the genomic DNA were 52.3 and 54.5 mol% for EJ1T and EJ2T, respectively. As determined by 16S rRNA gene sequence analysis, these strains were more closely related to Thermococcus gorgonarius, T. celer, T. guaymasensis, T. profundus, and T. hydrothermalis. However, no significant homology was observed between them with DNA-DNA hybridization. These novel organisms also possess phenotypic traits that differ from those of its closest phylogenetic relatives. Therefore, it is proposed that these isolates, which are amongst the most radioresistant hyperthermophilic archaea known to date with T. gammatolerans (Jolivet et al. 2003a), should be described as novel species T. marinus sp. nov. and T. radiotolerans sp. nov. The type strain of T. marinus is strain EJ1T (= DSM 15227T = JCM 11825T) and the type strain of T. radiotolerans is strain EJ2T (= DSM 15228T = JCM 11826T).


Identification of miRNAs Contributing to the Broad-Spectrum and Durable Blast Resistance in the Yunnan Local Rice Germplasm.
MicroRNAs are 20-24 nucleotide non-coding RNAs and play important roles in plant-environment interactions. In recent years, many microRNAs (miRNAs) have been found to regulate rice immunity against rice blast fungus. However, there are limited studies about miRNAs that directly target resistance (R) genes to regulate rice immunity. In this study, by deep sequencing, small RNA libraries were constructed from four-leaf stage seedlings of the resistant variety Ziyu44 and susceptible variety Jiangnanxiangnuo (JNXN) upon Magnaporthe oryzae infection, we found that much more miRNAs were significantly differentially expressed in Ziyu44 than in JNXN. Among these miRNAs, we focused on miR9664, a newly identified rice miRNA in our sequencing, which was upregulated lightly in Ziyu44 and drastically in JNXN at 24-48 h post-inoculation (hpi). The transgenic plants overexpressing miR9664 (miR9664-oe) displayed reduced defense responses to M. oryzae, while those knocking down miR9664 (miR9664-m) displayed enhanced defense responses to M. oryzae. Most of the detected miR9664 predicted target genes were reduced in the miR9664-oe lines while increased in the miR9664-m lines. The cleavage site of LOC_Os08g07774 was confirmed by RLM-RACE. Meanwhile, after being inoculated with M. oryzae, the genes were expressed differently between Ziyu44 and JNXN. The results suggest that miR9664-mediated R gene turnover contributes to Ziyu44 broad-spectrum resistance to rice blast fungus. Taken together, our research identified a new rice miRNA that directly targets R genes to regulate rice immunity against rice blast fungus, adding significant information to the study of rice-M. oryzae interaction.


Nesfatin-1 in a reptile: its role and hormonal regulation in wall lizard testis.
Nesfatin-1 is a pleiotropic hormone implicated in various physiological functions including reproduction. Studies though limited, have established an important role of the peptide in regulation of testicular functions in mammals and fishes. However, role of nesfatin-1 in regulation of spermatogenesis and testicular steroidogenesis remains completely unexplored in reptiles. Therefore, present study aimed to develop an insight into reproductive phase-dependent testicular expression, function and regulation of nucb2/nesfatin-1 in a reptile, Hemidactylus flaviviridis. Expression of nucb2/nesfatin-1 in testis of wall lizard varied significantly depending upon reproductive phase, being highest in the active phase while lowest during regressed phase. Further, in vitro treatment of wall lizard testis with nesfatin-1 showed a concentration- and time-dependent stimulatory effect of the peptide on expression of cell proliferation and differentiation markers like scf, c-kit and pcna suggesting a spermatogenic role of nesfatin-1 in wall lizard. Also, nesfatin-1 stimulated the anti-apoptotic marker, bcl-2 while inhibited the apoptotic marker, caspase-3, suggesting its role as an inhibitor of apoptosis of testicular cells. Further, treatment with nesfatin-1 resulted in significantly higher expression of star along with a concomitant increase in testosterone production by the lizard testis. The present study also demonstrates hormonal regulation of testicular nucb2/nesfatin-1 wherein follicle-stimulating hormone (FSH) inhibited while sex steroids like dihydrotestosterone (DHT) and 17β-estradiol-3-benzoate (E2) stimulated the mRNA expression of nesfatin-1. Observations from the current study for the first time provide comprehensive evidence of spermatogenic and steroidogenic role of nesfatin-1 as well as its hormonal regulation in the testis of a reptile, H. flaviviridis.


Characterization of the first double-stranded RNA bacteriophage infecting Pseudomonas aeruginosa.
Bacteriophages (phages) are widely distributed in the biosphere and play a key role in modulating microbial ecology in the soil, ocean, and humans. Although the role of DNA bacteriophages is well described, the biology of RNA bacteriophages is poorly understood. More than 1900 phage genomes are currently deposited in NCBI, but only 6 dsRNA bacteriophages and 12 ssRNA bacteriophages genome sequences are reported. The 6 dsRNA bacteriophages were isolated from legume samples or lakes with Pseudomonas syringae as the host. Here, we report the first Pseudomonas aeruginosa phage phiYY with a three-segmented dsRNA genome. phiYY was isolated from hospital sewage in China with the clinical P. aeruginosa strain, PAO38, as a host. Moreover, the dsRNA phage phiYY has a broad host range, which infects 99 out of 233 clinical P. aeruginosa strains isolated from four provinces in China. This work presented a detailed characterization of the dsRNA bacteriophage infecting P. aeruginosa.


Complicated extremity fractures. The relation between external fixation and nonunion.
In a series of 20 tibial fractures and ten radial fractures treated by external fixation, no association was found between the development of non-union and degree of soft tissue injury, delay in fixator application, or diaphyseal versus metaphyseal fracture site. Although the absence of fracture callus on roentgenograms of long bones immobilized by external skeletal fixation portends nonunion, no obvious cause-and-effect relation could be determined.


Association of CYP1A1 gene polymorphism with chronic kidney disease: a case control study.
CYP1A1 is an important xenobiotic metabolizing enzyme, present in liver and kidney. Expression of CYP1A1 enzyme increases manifold when kidney cells are exposed to nephrotoxins/chemicals leading to oxidative stress-induced cell damage. To study the association of CYP1A1 gene polymorphism in patients of chronic kidney disease with unknown etiology (CKDU), we recruited 334 CKDU patients and 334 age and sex matched healthy controls. CYP1A1*2A and *2C polymorphisms were studied by PCR-RFLP and allele specific-PCR respectively. Subjects carrying at least one mutant allele of CYP1A1*2A (TC, CC) and *2C (AG, GG) were shown to be associated with 1.4-2-fold increased risk of CKDU. Also, genotypic combinations of hetero-/homozygous mutants of CYP1A1*2A (TC, CC) with hetero-/homozygous mutant genotypes of CYP1A1*2C (AG, GG) i.e. TC/AG (p<0.01), TC/GG (p<0.05), CC/AG (p<0.05) and CC/GG (p<0.01) were associated with CKDU with an odd ratio ranging 1.8-3.3 times approximately. This study demonstrates association of CYP1A1 polymorphisms with CKDU.


Geochemical behaviors of uranium and thorium during weathering and pedogenesis of carbonate rock: constraint from their speciation.
During weathering and pedogenesis of carbonate rock with poor-uranium (U) and thorium (Th), U and Th present the characteristics of strong leaching (especially U) and significant residual enrichment, the cause of which is still unclear. In this paper, a weathering profile developed by dolomite in karst area of Guizhou province in southwest China was selected, which showed zonation characteristics of bedrock (Y), powdery rock (Yf), and soil layer (T1 to T12) from the bottom to up. Through the determination of the occurrence speciation of U and Th in Y and weathering profile, combined with mineralogical, geochemical characteristics, and element mass balance calculation, the constraints of U and Th speciation on the geochemical behavior of U and Th during the weathering of carbonate rock were revealed. The results proved that U and Th in Y preferentially existed in acid insoluble phase, for example, the contents of U and Th in Y were 0.90 mg·kg-1 and 0.28 mg·kg-1, respectively, while those in acid insoluble matter were 2.34 mg·kg-1 and 2.57 mg·kg-1, respectively, but because the mass percentage of acid insoluble matter was extremely low (0.95%), the mass percentages of U and Th in the acid soluble phase in the whole rock were absolutely superior (96% of U and 86% Th). The U and Th in the acid soluble phase of Y were mainly adsorbed on the crystal surface of carbonate minerals or existed in the cement, and the U and Th in the carbonate lattice only accounted for a small proportion. From Y to Yf with the initial dissolution, U and Th released from the surface of carbonate minerals and cements were in carbonate-rich alkaline environment, and these portions of U and Th were leached out, resulting in strong loss of U and Th in the Yf (the loss rates are 83% of U and 65% of Th, respectively). From the Yf to the overlying soil layer T1, the carbonate components were completely dissolved, and the U and Th released from the carbonate lattice showed different behaviors, where U was completely leached and Th tended to stay in the weathered residue. Thus, in the soil layer T1 formed by Y or Yf , the residual U was the inheritance of the U in the acid insoluble phase of Y; For Th, it not only inherited the Th of acid insoluble phase of Y, but also superimposed the Th from carbonate lattice in Y. On the other hand, during the evolution process from Y to Yf and to soil layer T1, with the dissolution of carbonate, the acid insoluble phase also showed a significant tendency of chemical weathering. However, the U and Th in the Y acid insoluble phase were not leached with the decomposition of the acid insoluble phase but were redistributed among the residual phases. For the geochemical behaviors of U and Th in the evolution of soil profile (T1~T12), they were subjected to the occurrence speciation of U and Th in T1 and the change of U and Th occurrence speciation with the upward direction of soil profile. The U and Th released from the carrier minerals were mainly redistributed among the residual solid phases, which weakened the intensity of their further loss. This study deepens the understanding of the geochemical behavior of radionuclides in karst environment and provides reference for the treatment of radioactive pollution in karst areas.


Novel scheme for defining the clinical implications of TP53 mutations in myeloid neoplasia.
TP53 mutations (TP53MT) occur in diverse genomic configurations. Particularly, biallelic inactivation is associated with poor overall survival in cancer. Lesions affecting only one allele might not be directly leukemogenic, questioning the presence of cryptic biallelic subclones in cases with dismal prognosis. We have collected clinical and molecular data of 7400 patients with myeloid neoplasms and applied a novel model by identifying an optimal VAF cutoff using a statistically robust strategy of sampling-based regression on survival data to accurately classify the TP53 allelic configuration and assess prognosis more precisely. Overall, TP53MT were found in 1010 patients. Following the traditional criteria, 36% of the cases were classified as single hits, while 64% exhibited double hits genomic configuration. Using a newly developed molecular algorithm, we found that 579 (57%) patients had unequivocally biallelic, 239 (24%) likely contained biallelic, and 192 (19%) had most likely monoallelic TP53MT. Interestingly, our method was able to upstage 192 out of 352 (54.5%) traditionally single hit lesions into a probable biallelic category. Such classification was further substantiated by a survival-based model built after re-categorization. Among cases traditionally considered monoallelic, the overall survival of those with probable monoallelic mutations was similar to the one of wild-type patients and was better than that of patients with a biallelic configuration. As a result, patients with certain biallelic hits, regardless of the disease subtype (AML or MDS), had a similar prognosis. Similar results were observed when the model was applied to an external cohort. In addition, single-cell DNA studies unveiled the biallelic nature of previously considered monoallelic cases. Our novel approach more accurately resolves TP53 genomic configuration and uncovers genetic mosaicism for the use in the clinical setting to improve prognostic evaluation.


Hospital Management of Parkinson Disease Patients.
Management of patients with Parkinson disease (PD) during inpatient hospital stays is complex and poses unique challenges for physicians and ancillary staff. Patients with PD have a high risk of complications, encephalopathy, and prolonged hospital stay. Early recognition of complications and implementation of rehabilitation strategies along with appropriate management of medications are critical to improve outcomes. Patients with PD can exhibit worsening mobility and balance, insomnia, orthostatic hypotension, multiple neuropsychiatric symptoms, and gastrointestinal dysfunction while hospitalized. This review summarizes the specific in-hospital concerns observed in patients with PD and discusses potential treatment approaches.


Genetics, age, and infertility.
To review the genetics of aging specifically as it pertains to human fertility, as well as the recent advancements in the diagnosis of genetic diseases prior to embryo implantation. A review of our own experience as well as the scientific literature with regards to the decline in female fertility with age, the success of IVF in women of older reproductive age, and the role of preimplantation genetic diagnosis (PGD) in the evaluation of the patient at risk for fetal genetic anomalies. The decline in female fertility occurs primarily as a result of a decline in oocyte quality as well as quantity. The frequency of chromosomal anomalies in recognized abortuses increases in parallel with the age-specific rise in the incidence of spontaneous abortions. PGD is an accurate diagnostic tool for exclusion of genetically deficient embryos prior to initiation of pregnancy. Reproductive failure in women of older age appears to be directly related to ovarian age. Recent techniques such as cytoplasmic or germinal vesicle transfer are designed to replace the senescent cellular machinery believed to be responsible for genetic errors that occur during early cell division. PGD can accurately identify embryos with genetic deficiencies prior to implantation.


EEG and visual evoked potentials of conscious man during moderate hypothermia.
Five conscious, normal humans were cooled by water immersion until their core temperatures were near 33.5 degrees C. When hypothermic at this level, small shifts of EEG frequencies to more theta and beta and less alpha activity occurred in comparison to normothermia. There was no significant change in the amplitude of the EEG. Although 10-20% increases in the latency of peaks in the visual evoked potential occurred in some subjects when hypothermic, this was not statistically significant, nor was the slight amplitude reduction. The results confirm for conscious, unanesthetized humans that moderate hypothermia to the level of 33.5 degrees C is on the borderline for significant alteration of brain electrical activity by cold, a general conclusion that was known previously only for anesthetized or immobilized humans and other mammals.


Depressed patients' preferences for education about medications by pharmacists in Kuwait.
To assess patients' opinion toward receiving written or specialized verbal pharmacists' interventions and to determine the effect of these interventions on patients' medication knowledge. 150 newly diagnosed patients with unipolar depression and initiated with a single antidepressant were randomized into 3 groups: control, leaflet and counselling, and interviewed at initiation and after 6-8 weeks of treatment at the outpatient department of the Psychiatric Hospital in Kuwait. 50% of respondents asserted that clinicians did not give them sufficient information while 90% favoured the idea of receiving further information about therapy. Forty seven percent of participants failed to return for the second follow-up appointment. The drop-out rate was 66% in the control, 42% in the Leaflet and only 34% in the counselling groups (P=0.004). A broad support for receiving leaflets and drug counselling (97%) was found among attendees. Moreover, 94% of the counselling and 79% of the leaflets group affirmed that they received adequate information compared to 47% of the control (P=0.001). Counselling was found to be significantly associated with a much higher recall of medicine name (OR=9.6, P=0.01), how to manage missed doses (OR=8.9, P=0.007), and correct use of medication (OR=31.3, P<0.001). Leaflet use was less strongly associated than counselling and was statistically significant for recall regarding correct use of medication (OR=8.4, P=0.009). Pharmacists in a psychiatric institution can play an important role in satisfying patient demands for specialized information about their medications. Patients with depression appear very eager to receive additional drug information with modest difference between the written and the verbal counselling interventions. Patients looked at the two interventions in a very positive manner and no difference was observed between patients in the leaflets and in the counselling group with regards to how helpful, sufficient, supportive and reassuring was the educational material. However, both interventions were more informative than the control in conveying elemental drug information to patients. In contrast with the lack of enthusiasm that some clinicians express, the affirmativeness that was expressed by patients towards receiving written or verbal specialized educational interventions by pharmacists may support the psychiatric hospital pharmacists' stands in providing them for all patients which may aid in improving patients compliance and probably treatment outcome.