Determination of cadmium in whole blood and urine by Zeeman atomic absorption spectroscopy.
Direct determination of cadmium in whole blood and urine can be achieved using Zeeman effect flameless atomic absorption spectroscopy. Within-run precision studies for whole blood cadmium determinations gave relative standard deviations of 11.3% and 6.3% for 0.53 micrograms/l and 3.16 micrograms/l, respectively. Within-run precision studies for the urine analyses yielded relative standard deviations of 11.3% and 5.2% for 0.62 micrograms/l and 2.48 micrograms/l, respectively. The detection limit is 0.12 micrograms/l in the diluted specimens. Thus, this methodology may be used to quantitate normal and toxic cadmium levels in whole blood and urine.


Risk Factor-Guided Early Discharge and Potential Resource Allocation Benefits in Patients with Traumatic Subarachnoid Hemorrhage.
We sought to develop screening criteria predicting the lack of poor neurologic outcomes in patients presenting with traumatic subarachnoid hemorrhage (tSAH) and to evaluate their potential to improve resource allocation in these cases. We retrospectively reviewed patients presenting with tSAH to the emergency department (ED) of a tertiary-care institution from 2016 to 2018. We defined good neurologic outcomes as patients with stable/improving neurologic status, who did not require neurosurgical intervention, had no expanding bleed, and needed no hospital readmission. Univariate and multivariate models were generated to predict risk factors inversely associated with good neurologic outcome. A total of 167 patients presented with tSAH from 2016 to 2018. The presence of depressed skull fracture, concomitant spinal fracture, low Glasgow Coma Scale (GCS) score, cranial nerve palsies, disorientation, concomitant hemorrhages, midline shift, increased international normalized ratio (INR), and emergent medical intervention were inversely correlated with likelihood of good neurologic outcome on univariate analysis. Multivariate regression showed that midline shift (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.05-0.89; P = 0.04), GCS score <13 (OR, 0.22; 95% CI, 0.05-0.99; P = 0.05), increased INR (OR, 0.18; 95% CI, 0.03-0.85; P = 0.04), and emergent medical intervention (OR, 0.18; 95% CI, 0.04-0.63; P = 0.01) were independently associated with lower likelihood of good neurologic outcome. Forty-six patients without any factors had good outcomes but were held in the ED or admitted to the hospital. These patients (if instead discharged directly) meant a potential cost savings of $179,172. In our study, we found multiple risk factors inversely associated with good neurologic outcome, namely low GCS score, midline shift, emergent medical intervention, and INR ≥1.4. Our findings may aid clinicians in determining which tSAH patients are candidates for safe early discharge.


Factors associated with knowledge of hypertension among adolescents: implications for preventive education programs in primary care.
Hypertension (HT) amongst adolescents remains a vital issue of both a medical and social nature. There is a lack of data regarding the factors influencing the awareness of the disease among the youth. The aim of this study was to evaluate the knowledge about HT among adolescents and its level corresponding to the selected demographic, environmental and medical factors. The study was carried out among 250 adolescents of secondary schools. The authors' questionnaire poll and the psychological tests Personal Values List (PVL) and Personal Competence Scale (PCS) were performed. Only 13.2% of the youth surveyed displayed the "medium" level (defined below) of HT knowledge. Most of them present satisfactory knowledge about the causes of HT. The children from urban areas generally displayed better knowledge about HT than their peers from rural regions. Only the children who had had their blood pressure previously examined displayed good knowledge about HT. The most frequently indicated source of this knowledge was school; however, its level still remains low. There was no significant association between the level of global knowledge about HT and the feeling of one's own competences and considering the category "good health" an important personal value. Knowledge about HT among adolescents remains unsatisfactory and random, which indicates the necessity for routine education in this field, especially as it applies to HT symptoms. It seems that the consideration of such elements as blood pressure measurement and family history of HT in education programs can improve their efficiency.


Removal of dinitrotoluenes in wastewater by sono-activated persulfate.
Oxidative degradation of dinitrotoluenes (DNTs) in wastewater was performed using persulfate anions combined with ultrasonic irradiation, wherein a synergistic effect is observed. The batch-wise experiments were carried out to elucidate the influence of various operating parameters on sono-activated persulfate oxidation, including ultrasonic power intensity, persulfate anion concentration, reaction temperature and acidity of wastewater. It is noteworthy that the nitrotoluene contaminants could be almost completely eliminated by virtue of sono-activated persulfate oxidation, wherein sulfate radicals serve as principal oxidants, of which amounts are significantly enhanced via addition of sodium sulfate. Based on the results given by gas chromatograph-mass spectrometer (GC-MS), it is postulated that the methyl group of DNTs preliminarily underwent oxidation pathway into dinitrobenzoic acid, followed by decarboxylation to form 1,3-dinitrobenzene (DNB). In sum, the sono-activated persulfate oxidation is a promising method for treatment of nitrotoluenes in wastewater.


Challenges when going on excursions with children with medical complexity in Japan.
With advances in medical technology, the number of children with medical complexity (CMC) has increased. Excursions with such children encourage their social participation and have been shown to have a positive impact on their caregivers. However, the first-hand experience of the excursions has not yet been evaluated regarding the difficulties faced by CMC and their caregivers during preparation, transportation, and in the local area. Semi-structured interviews were conducted with eight informal and eight formal caregivers of CMC who attended an excursion to Tokyo Disney Land (TDL) via video conference. We investigated challenges that they had experienced through the excursion, performing inductive thematic analysis. Three themes were identified: the preparation stage (Theme 1), problems encountered while traveling to the theme park (Theme 2), and problems at the theme park (Theme 3). In the preparation stage, three subthemes, i.e. preparation for the trip, cooperation with related parties, and researching about the theme park and asking for help, are reported. Theme 2 includes four subthemes: activities of daily living, respiratory care, luggage, and weather changes. Theme 3 has three subthemes: activities of daily living, physical condition management, and issues for the theme parks. We found that securing the power supply, location, and time for daily procedures are challenges in realizing excursions for CMC, but with sufficient preparation, it is possible in Japan without major difficulty.


A new membrane-bound OprI lipoprotein expression vector. High production of heterologous fusion proteins in gram (-) bacteria and the implications for oral vaccination.
We have previously described the development of cloning vectors for the production of OprI-based outer membrane fusion proteins in E. coli (Cornelis et al., 1996) and now describe the construction of a new vector, containing a lacI(q) gene, resulting in tight repression of the promotor and allowing its use in other Gram (-) bacteria. The new pVUB3 expression vector encodes a truncated but active LacI(q)(341) repressor which binds to the single operator in the vector. A high repression of the trc promotor was observed, resulting in a very low basal leakage of expression and very high production levels of OprI or derivatives after IPTG induction in E. coli. Bacterial viability was not affected under uninduced conditions, but the number of viable cell counts decreased after production of large amounts of the outer membrane-bound OprI lipoprotein and its derivatives, both in E. coli and Salmonella typhimurium. This highly repressible system allows us to extend the use of OprI vectors in other Gram (-) bacteria, resulting in the production of outer membrane-bound lipid-modified molecules, opening the possibility for its application in the design of potential live Salmonella-based subunit vaccines.


Blood and urinary amino acids in children receiving total parenteral nutrition.
Plasma concentrations and urinary outputs of amino acids were estimated in nineteen patients receiving intravenous hyperalimentation to evaluate the adequacy of dosage and composition of the infusates for the maintenance of normal blood concentrations of essential amino acids. The use of high concentrations of branched chain amino acids seems to be appropriate for valine and isoleucine but not for leucine. The high concentration of cysteine in the infusates used induces a very high urinary excretion of cysteine and cystine and are ineffective to bring the decreased plasma cystine levels back to normal.


Bioprocess monitoring.
Electrochemical sensors for pH and dissolved oxygen remain the most commonly used in bioprocess monitoring, but continued research has resulted in improved optical sensors. Optical sensors for dissolved oxygen and dissolved carbon dioxide are now commercially available. Advances in optics and electronics are further driving down the costs of these sensors. In the near future, bioprocess optimization will change paradigms as massively parallel, fully instrumented bioreactors become available and high-throughput bioprocessing becomes a reality.


The long-term effects of school dropout and GED attainment on substance use disorders.
Epidemiologic research suggests that 14% of the population do not complete high school, and dropout has been linked to mental health conditions, substance use, chronic health problems, and criminal behavior. Few studies have assessed whether attainment of the general education development (GED) credential is protective from substance use. To assess the long-term outcomes of school dropout and GED attainment on past year substance use disorders, age of onset, and current smoking status. Longitudinal data were included for lifetime substance users who participated in the National Epidemiological Survey on Alcohol and Related Conditions (Waves I and II). Eligible participants (N=30,608) were classified as having completed high school, dropped out of high school and did not complete a GED, or completed GED at Wave I. Survey logistic regression analyses were used to determine whether high school graduation status was associated with substance use disorders and smoking at Wave II. Multivariate results suggest that participants who dropped out of high school (OR=1.53; p<.01) or attained a GED were more likely to have a past year marijuana use disorder (OR=1.62 p<.01) compared to high school graduates. High school dropouts were also more likely to be current smokers (OR=1.88; p<.05) than graduates. High school dropouts have higher long-term rates of marijuana use disorder and smoking in adulthood than graduates. Attainment of a GED does not appear to be protective from marijuana use disorders in adulthood.


Avian nucleus isthmi ventralis projects to the contralateral optic tectum.
Injections of HRP throughout the upper tectal strata led in 4 cases to the appearance of retrogradely labeled neurons within n.isthmi ventralis, contralateral to the experimental side. An additional case proved that this projection courses through the ventral supraoptic commissure. This is the first description of a crossed isthmo-tectal projection in birds.


Evaluating the impact of pulse oximetry on childhood pneumonia mortality in resource-poor settings.
It is estimated that pneumonia is responsible for 15% of childhood deaths worldwide. Recent research has shown that hypoxia and malnutrition are strong predictors of mortality in children hospitalized for pneumonia. It is estimated that 15% of children under 5 who are hospitalized for pneumonia have hypoxaemia and that around 1.5 million children with severe pneumonia require oxygen treatment each year. We developed a deterministic compartmental model that links the care pathway to disease progression to assess the impact of introducing pulse oximetry as a prognostic tool to distinguish severe from non-severe pneumonia in under-5 year olds across 15 countries with the highest burden worldwide. We estimate that, assuming access to supplemental oxygen, pulse oximetry has the potential to avert up to 148,000 deaths if implemented across the 15 countries. By contrast, integrated management of childhood illness alone has a relatively small impact on mortality owing to its low sensitivity. Pulse oximetry can significantly increase the incidence of correctly treated severe cases as well as reduce the incidence of incorrect treatment with antibiotics. We also found that the combination of pulse oximetry with integrated management of childhood illness is highly cost-effective, with median estimates ranging from US$2.97 to $52.92 per disability-adjusted life year averted in the 15 countries analysed. This combination of substantial burden reduction and favourable cost-effectiveness makes pulse oximetry a promising candidate for improving the prognosis for children with pneumonia in resource-poor settings.


The effects of tegaserod, a 5-HT receptor agonist, on gastric emptying in a murine model of diabetes mellitus.
The C57BLKS/J db/db transgenic mouse is a model of diabetes mellitus that has been shown to have delayed gastric emptying. We assessed gastric emptying rates in C57BLKS/J mice, and determined the effects of tegaserod, a new selective 5-HT(4) receptor partial agonist, on gastric emptying. Gastric emptying rates of a 20% glucose test meal were determined in 12-20-week-old female db/db mice and control littermates. The effects of tegaserod (0.1-2.0 mg kg(-1), i.p.) on gastric transit were tested in a second group of db/db mice. Pretreatment with GR11308, a specific 5-HT(4)antagonist, was used to confirm the mechanism of action of tegaserod on gastric emptying. Gastric emptying of glucose was significantly slower in db/db mice than in control littermates. Tegaserod (0.1 mg kg(-1)) significantly accelerated the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. GR11308 blocked the gastrokinetic effects of tegaserod. Gastric emptying was impaired in db/db mice. Low dose tegaserod improved gastric emptying rates in this model of gastroparesis through the activation of 5-HT(4) receptors. These findings suggest that 5-HT(4) receptor agonists may prove useful for improving delayed gastric emptying in gastroparesis.


Influences on fruit and vegetable consumption by low-income black American adolescents.
The purpose of this study was to identify personal, behavioral, and environmental factors influencing fruit and vegetable consumption among 10- to 13-year-old low-income black American youth in the lower Mississippi Delta region. Social Cognitive Theory, along with other theoretical constructs, guided focus group questions and analysis. A qualitative study using focus group methodology. Enrichment program of a sports summer camp for low-income youth. Forty-two adolescents (21 female, 21 male) participated in 6 focus groups. Personal, behavioral, and environmental influences on fruit and vegetable consumption. Content analysis methods were used by 3 independent reviewers to identify themes within the focus group transcripts. Themes were summarized and then categorized into the 3 domains of Social Cognitive Theory. The major themes were taste, availability, extended family influence, visual proof of the benefits of fruit and vegetable consumption, and the need for gender-specific behavioral skills. This formative research will aid in the development of a culturally relevant nutrition intervention for low-income black American adolescents in the lower Mississippi Delta region. The results indicate that this group is more likely to respond to interventions that use role models who can provide proof that fruit and vegetable consumption is related to improved health.


Data on synthesis and characterization of new diglycerol based environmentally friendly non-isocyanate poly(hydroxyurethanes).
This article contains original experimental data, figures and methods to the preparation of non-isocyanate poly(hydroxyurethanes) by an environmentally friendly method without the use of toxic phosgene and isocyanates from bis(2,3-dihydroxypropyl)ether dicarbonate and various diamines (Tryznowski et al., Submitted for publication) [1]. Bis(2,3-dihydroxypropyl)ether dicarbonate was obtained from a one-step procedure from commercially available diglycerol. The product was characterized by (1)H NMR, (13)C NMR, and FTIR spectroscopies and for the first time by X-Ray diffraction measurements. Then, the bis(cyclic carbonate) monomer was used as a precursor for the synthesis of various NIPUs. The NIPUs were prepared in a non-solvent process. Spectral and thermal properties of the NIPUs are compered. Here we give the procedure in order to perform bis(2,3-dihydroxypropyl)ether dicarbonate with high yield and the procedure NIPU synthesis and the complete set of monomer and NIPU analysis ((1)H NMR, (13)C NMR, FTIR, X-Ray).


Differences in Transcriptomic Profiles of Brain and Thyroid Tumors with NTRK Gene Rearrangement.
For tumors with chimeric NTRK genes, entrectinib and larotrectinib can be prescribed regardless of tumor localization. We compared changes in the transcriptional activity of genes in brain tumors (BT) and thyroid cancer (TC) with rearrangement (NTRK+) and without rearrangement (NTRK-) of the NTRK genes using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We revealed an increase in the transcription of the JUN gene in NTRK+ samples in comparison with NTRK- samples: by 1.6 times for BT (p=0.239) and by 2.5 times for TC (p=0.003). The transcription of eight HOX genes in NTRK+ BT samples was also increased (by 85-725 times, p<0.05) in comparison with NTRK-. In NTRK+ TC samples, the level of miR-31 and miR-542 was statistically significantly higher (by 3 and 2.5 times, respectively) than in NTRK-samples. For the NTRK+ BT samples, the levels of miR-10b, miR-182, and miR-21 more than 5-fold surpassed the corresponding values in NTRK-samples (p<0.05). These findings reflect differences in activation of gene transcription resulting from NTRK gene rearrangement in BT and TC.


Do Flies Count Sheep or NMDA Receptors to Go to Sleep?
The drive to sleep increases the longer that we stay awake, but this process is poorly understood at the cellular level. Now, Liu et al. show that the plasticity of a small group of neurons in the Drosophila central brain is a key component of the sleep homeostat.


Discovery of novel metabolic signatures for early identification of women at risk of developing gestational hypertension.
Gestational hypertension (GH) is defined as the presence of systolic blood pressure (BP) ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg, measured at least 4 h apart after 20 weeks of gestation. Early identification of women at high-risk of developing GH could contribute significantly towards improved maternal and fetal outcomes. To determine early metabolic biomarkers in women with GH as compared with normotensive women. Serum samples were collected from subjects during three stages of their pregnancy: 8-12 weeks, 18-20 weeks and after 28 weeks (< 36 weeks) of gestation and studied using nuclear magnetic resonance (NMR) metabolomics approach. Multivariate and univariate analyses were performed to determine the significantly altered metabolites in GH women. A total of 10 metabolites, including isoleucine, glutamine, lysine, proline, histidine, phenylalanine, alanine, carnitine, N-acetyl glycoprotein and lactic acid were observed to be significantly downregulated during all pregnancy stages in women with GH as compared with controls. Furthermore, expression of 5 metabolites in the first trimester i.e., phenylalanine [area under the curve (AUC) = 0.745], histidine [AUC = 0.729], proline [AUC = 0.722], lactic acid [AUC = 0.722], and carnitine [AUC = 0.714] exhibited highest potential in discriminating GH from normotensive women. The present study is the first of its kind to identify significantly altered metabolites that have the potential to discriminate between women at risk of developing GH and normotensive women across three trimesters of pregnancy. This opens up the possibility of exploring these metabolites as potential early predictive markers of GH.


Autoimmune myasthenia gravis.
Myasthenia gravis in children can be generalized or ocular, and associated with antibodies to acetylcholine receptors or muscle-specific kinase, but it can be negative for those antibodies (seronegative). It needs to be distinguished from congenital myasthenic syndromes and other neuromuscular diseases. In the perinatal period, transient neonatal myasthenia and arthrogryposis multiplex congenita, due to maternal antibodies, need to be considered. Juvenile myasthenia is similar in presentation and treatment to that in adults. Here we present guidelines for recognition, diagnosis, and treatment.


Pharmaceutical Approval Update.
Elbasvir/grazoprevir (Zepatier) for chronic hepatitis C virus; sumatriptin nasal powder (Onzetra Xsail) for migraine; eribulin mesylate (Halaven), now for liposarcoma; and extended-release amphetamine (Adzenys XR-ODT) for ADHD.


Black tea extract supplementation decreases oxidative damage in Jurkat T cells.
The purpose of this study was to investigate the protective effect of black tea (BT) extract against induced oxidative damage in Jurkat T-cell line. Cells supplemented with 10 or 25 mg/L BT were subjected to oxidation with ferrous ions. Malondialdehyde (MDA) production as marker of lipid peroxidation, DNA single strand breaks as marker of DNA damage, and modification of the antioxidant enzyme activity, glutathione peroxidase (GPX) were measured. Results show the efficacy of BT polyphenols to decrease DNA oxidative damage and to affect GPX activity (P<0.05), while no effect was shown on MDA production. The succeeding investigation of the activity of caffeine and epigallocatechin gallate demonstrated their antioxidant potential with respect to the cellular markers evaluated. In conclusion, this study supports the protective effect of BT against ferrous ions induced oxidative damage to DNA and the ability of BT to affect the enzyme antioxidant system of Jurkat cells.


Sand rats see the light: short photoperiod induces a depression-like response in a diurnal rodent.
The present study examined the effect of simulated change in day length on the behavior of a diurnal rodent, the fat sand rat (a species of gerbil). Animals were housed under a short photoperiod (5/19 light/dark cycle) for 3 weeks and compared with controls living under a 12/12 light/dark cycle. All sand rats then underwent the forced swim test for depression-like behavior, and the open-field test for overall activity. Sand rats exposed to the short photoperiod displayed a significantly earlier sinking in the swim test, but there was no difference between their open-field activity compared with controls. Taking these responses as indicative of depression-like behavior, we suggest that a short photoperiod may induce affective-like changes, and that the sand rat may thus offer an appropriate animal model to explore the effect of photoperiod on normal, and perhaps also abnormal, seasonal mood changes (e.g., SAD), which in humans is a prevalent disorder, with winter depression episodes and spring/summer remissions.


Complete labial fusion with urinary incontinence in a postmenopausal woman: A case report.
An 83-year-old woman presented to a rural general hospital with urinary incontinence. She was diagnosed with complete labial fusion caused by genitourinary syndrome of menopause. She was successfully treated with surgical separation followed by hydrocolloid dressings. Genitourinary syndrome of menopause often remains undiagnosed due to patient embarrassment. Greater recognition of this condition in primary care can improve patient access to appropriate treatment and improve quality of life.


Fatal Rocky Mountain spotted fever. Hematologic and lymphoreticular observations.
Generalized histiocytic proliferation with a component of phagocytosis and thrombocytopenia accompanies a number of infectious diseases and malignant neoplasms. Its extent and occurrence were studied in the hematopoietic and lymphoreticular tissues of fatal childhood cases of Rocky Mountain spotted fever. Its frequent occurrence and morphologic similarities to other associated causes were documented.


Exosomes from circRNA-Ptpn4 can modify ADSC treatment and repair nerve damage caused by cerebral infarction by shifting microglial M1/M2 polarization.
Adipose-derived stem cells (ADSCs) have been demonstrated to improve the microenvironment after a stroke. Increasing studies have confirmed that hypoxia pretreatment of ADSCs resulted in a better therapeutic effect, but the mechanism of treatment is unclear. We isolated ADSCs and exosomes. Then, constructed a middle cerebral artery occlusion (MCAO) mice model. High-throughput sequencing was used to identify the differential expression of circRNA. Immunofluorescence and ELISAs were used to detect the therapeutic effects of ADSC exosomes on MCAO. The luciferase reporter assay was used to detect the interaction relationships among circRNA-Ptpn4, miR-153-3p, and Nrf2. This study showed that exosomes from hypoxia pretreatment of ADSCs had significant effects in promoting functional recovery following in vivo MCAO, through suppressed inflammatory factor expression, and shifting the microglial from M1 to M2 polarization activation. The results showed that circRNA-Ptpn4 was highly expressed during hypoxia pretreatment of ADSCs exosomes. Exosomes from circ-Ptpn4-modified ADSCs had a greater ability to promote functional recovery. The circ-Ptpn4 delivered from ADSC exosomes induced microglia/macrophage polarization from M1 to M2 by suppressing miR-153-3p and enhancing Nrf2 expressions. Taken together, the results showed that exosomes from circRNA-Ptpn4 modified ADSC treatment repaired nerve damage caused by cerebral infarction by inducing microglial M1/M2 polarization.


Feasibility of using ultrasonic irradiation to recover active biomass from waste activated sludge.
Under typical operating conditions, the microbial fraction of activated sludge flocs is approximately 40% by weight. The objective of this research is to evaluate the feasibility of using ultrasonic irradiation to disrupt activated sludge flocs allowing for the subsequent separation of active and inactive fractions. If separation of floc components is possible, then methods may be incorporated into wastewater treatment plant operations whereby only the inactive fraction of floc is wasted (i.e., of waste activated sludge, WAS), which in turn could increase the overall effective biological solids retention time, leading to increased process robustness with no net increase in reactor size. The results indicate that ultrasonic irradiation of WAS at 800 Wl(-1) followed by 30 min of settling can produce a supernatant with heterotrophic specific oxygen uptake rates (SOURs) of over two times the SOUR measured in the bulk mixed liquor. Under these conditions 26% of the initial heterotrophic activity was recovered within only 11% of the initial volatile mass. Similarly, autotrophic analysis revealed that nitrifying organisms, while sensitive to the effects of ultrasonic irradiation, can be separated from the activated sludge floc and recovered. An irradiation density of 200 Wl(-1) with an exposure time between 1 and 2 min produced a supernatant with a specific ammonia removal rate of over two times the initial mixed liquor rate.


[Management of cerebral radionecrosis: experience in the Department of Neurology at the Mohammed V Military Teaching Hospital].
Brain radionecrosis is a rare but life-threatening complication of external-beam radiotherapy for ENT cancers, in particular of the nasopharynx, and for brain tumors. Very few studies were conducted on this complication in the African population as well as in the Maghreb population. Therefore our study aims to describe the demographic, clinical, paraclinical, therapeutic and evolutionary features of cerebral radionecrosis in the Department of Neurology at the Mohammed V Military Teaching Hospital in Rabat over a period of 18 years (2000-2017). The study involved 4 women and 13 men, with an average age of 50 years. The mean time between the end of the radiotherapy and the onset of neurological signs was 28 months. Systematic Brain MRI, sometimes complemented by spectro-MRI, allowed the diagnosis in 100% of cases. Etiologically, this complication occurred after radiotherapy for nasopharyngeal carcinoma and cancer of the larynx in all cases. Fifteen patients were treated with a combination of: bolus application of corticosteroids, platelet aggregation inhibitors associated with hyperbaric oxygen therapy with good evolution of two patients in whom oxygen therapy was contraindicated due to a lung problem and ENT cancer, received a combination of bolus application of corticosteroids and platelet aggregation inhibitors with unchanged evolution. These results demonstrate the importance of early diagnosis in patients with potentially serious conditions, in particular neuropsychiatric conditions, as well as of treatment combining bolus application of corticosteroids and hyperbaric oxygen therapy because this is the best guarantee of a favorable outcome, without omitting the crucial role of preventive measures.


Efficacy and safety of negative allosteric modulators of 5-hydroxytryptamine 2A receptors in the treatment of Alzheimer's disease psychosis: A systematic review and meta-analysis.
Psychosis is a very common feature of Alzheimer's disease (AD) that can emerge as the neurodegenerative disease progresses. The 5-hydroxytryptamine (5-HT2A) receptors are located postsynaptically to serotonergic neurons in the frontal cortex and mediate both excitatory and inhibitory neurotransmissions. However, the effectiveness and tolerance of negative modulators of 5-HT2A receptors in Alzheimer's disease psychosis (ADP) are uncertain. To detect the negative modulators of the 5-HT2A receptor as a cure for ADP. The primary outcome indicator was the total Neuropsychiatric Inventory (NPI) score. Other prognostic indicators included Mini-Mental State Examination (MMSE), the Katz Index of Independence in Activities of Daily Living (KATZ), the discontinuation rate, and adverse events. Compared to placebo, 5-HT2A inverse agonists significantly reduced the NPI total score, the KATZ and the MMSE score. The pooled odds ratio (OR) was 1.64 (95% confidence interval (95% CI): 1.01-2.65) and the heterogeneity variance was estimated at Tau2 = 0.52 with an I2 value of 90%, a χ2 value of 111.31, p = 0.04, and z-value of 2.01. The risk difference (RD) between the 5-HT2A receptor negative modulators and placebo groups was 0.12 (95% CI: 0.00-0.24) and the heterogeneity was estimated at Tau2 = 0.03, χ2 value of 127.23, degrees of freedom (df) value of 9, I2 value of 93%, z-value of 1.92, and p-value of 0.01 (<0.05). Our results suggest that negative modulators of 5-HT2A receptors are beneficial and well-tolerated in the treatment of ADP.


Fate of the great saphenous vein following endovenous laser ablation: does re-canalisation mean recurrence?
To assess changes in great saphenous vein (GSV) diameter and the significance of re-canalisation following endovenous laser ablation (EVLA). Prospective cohort study. Two groups were studied. Group A: 73 consecutive patients (84 GSVs) underwent EVLA followed by duplex ultrasound at 6, 12 and 52 weeks. Vein diameter and patency were recorded. Group B: From a prospectively maintained database 27 patients with a GSV that was found to have recanalised 6-12 weeks post-EVLA were identified and rescanned at 52 weeks. Pre- and post-treatment Aberdeen varicose vein severity scores (AVVSS) were measured. Group A: 81/84 (96%) GSVs were ablated and 3/84 (4%) had re-canalised (flash reflux <1s). GSV diameter diminished with time: pre-EVLA: mean diameter 7.7 S.D .2.0mm; 6 weeks: 5.1 S.D. 1.3mm; 12 weeks: 3.2 S.D. 1.2; 52 weeks: 85% non-visible (p<0.001). Group B: 3/27 (11%) with reflux >1s underwent repeat EVLA. 16/27 (59%) remained competent at 52 weeks and 8/27 (30%) showed trickle reflux. Vein diameter decreased in both subgroups (mean diameter 7.3 S.D. 2.5mm to 3.1 S.D. 0.8mm (p=0.006) and 7.2 S.D. 2.3mm to 3.0 S.D. 0.7mm (p=0.009) respectively) as did the AVVSS (p<0.001). Successful EVLA causes GSV shrinkage with transition from a non-compressible "thrombosed" vein to a non-visible vein by 1 year. A re-canalised GSV usually remains small with no/minimal reflux and persisting clinical benefit.


Pelvic neurofibroma in a patient presenting with pelvic pain and urinary frequency: A case report.
Pelvic neurofibromas are benign and uncommon retroperitoneal masses. They arise from Schwann cells. One of the most common types of these benign tumors is intraneural neurofibromas, which are solitary, sporadic, and not associated with neurofibromatosis type 1. Here we discuss a case of pelvic neurofibroma in a 20-year-old male who presented with chronic pelvic pain. He had no positive family history of genetic disorders. On physical exam, just a partly firm mass without mobility in the hypogastric region was detected. Ultrasound and Computed tomography scan showed pelvic retroperitoneal mass superior to the urinary bladder with extension to the rectovesical pouch and invasion of the posterior wall and dome of the bladder. The patient underwent laparotomy revealing an infiltrative retroperitoneal mass with the invasion of the posterior wall, dome, and trigone of the bladder. Histopathological findings showed neurofibroma.


Allelic association of the D2 dopamine receptor gene with cocaine dependence.
The objective of the present study was to examine allelic prevalence of the D2 dopamine receptor (DRD2) gene in male cocaine-dependent (CD) Caucasian (non-Hispanic) subjects and to determine the relationship of DRD2 alleles to family history and selected behavioral measures. The prevalence of the A1 allele in CD subjects (n = 53) was 50.9%. It was significantly higher than either the 16.0% prevalence (P < 10(-4)) in non-substance abusing controls (n = 100) or the 30.9% prevalence (P < 10(-2)) in population controls (n = 265) wherein substance abusers were not excluded. Similarly, a significantly higher prevalence (P < 10(-2)) of the B1 allele was found in CD subjects (n = 52) compared with non-substance abusing controls (n = 53); 38.5% vs. 13.2%. Logistic regression analysis of CD subjects identified potent routes of cocaine use and the interaction of early deviant behaviors and parental alcoholism as significant risk factors associated with the A1 allele. The cumulative number of these three risk factors in CD subjects was positively and significantly (P < 10(-3)) related to A1 allelic prevalence. The data showing a strong association of the minor alleles (A1 and B1) of the DRD2 with cocaine dependence suggest that a gene, located on the q22-q23 region of chromosome 11, confers susceptibility to this drug disorder.


Migration inhibition of sensitized mouse spleen cells by cell-associated transplantation antigens: effect of method of antigen presentation.
The migration of specifically sensitized mouse spleen cells following exposure to allogeneic cells (antigen) in vitro was studied. The migration inhibition recorded when sensitized cells were admixed with allogeneic cells in capillary tubes (mix method) was compared to the inhibition observed when allogeneic cells were suspended in the culture chamber media (non-mix method). Specificity as well as a higher degree of migration inhibition were obtained using the mix method, suggesting that this method is superior to the nom-mix method.


Ubiquitin folds via a flip-twist-lock mechanism.
To perform specific functional activities, the majority of proteins should fold into their distinct three-dimensional conformations. However, the biologically active conformation of a protein is generally found to be marginally stable than the other conformations that the chain can adopt. How a protein finds its native conformation from its post-synthesis unfolded structure in a complex conformational landscape is the unsolved question that still drives the protein folding community. Here, we report the folding mechanism of a globular protein, ubiquitin, from its chemically denatured state using all-atom molecular dynamics simulations. From the kinetic analysis of the simulated trajectories we show that the folding process can be described by the hydrophobic collapse mechanism, initiated by the "dewetting transition", and subsequently assisted by the origination of an N-terminal folding nucleus, and finally supported by a native salt-bridge interaction between K11 and E34. We show that ubiquitin folds via an intermediate. Finally, we confirm the presence of "biological water" and explain its role to the folding process.


Malignant cystosarcoma phylloides. Treatment and prognosis.
Twenty-six cases of malignant cystosarcoma phylloides treated at The Charity Hospital of Louisiana were reviewed. No metastases to axillary lymph nodes was observed. The lesion appears to metastasize seldom, if ever, to lymphatics, and axillary dissection is seldom required. Local recurrence was common, however, and justifies wide resection of the primary. Mortality was related more to the size of the lesion than to other findings such as skin or muscle involvement. No lesion with less than three mitoses per ten high power fields and minimal stromal atypia proved fatal. Associated neoplasia was common, particularly in the opposite breast.


The effect of smoking cessation on posterior ocular structures.
This study evaluated changes in cho-roidal and macular thickness in healthy volunteers and chronic smokers. Thirty-three eyes of 33 chronic smokers (study group) and 33 eyes of 33 healthy controls who had never smoked were prospectively evaluated. Comprehensive ophthalmic assessment included slit lamp biomicroscopy, stereoscopic fundus examination, and intraocular pressure measurement. Spectral domain optical coherence tomography was used to measure choroidal and macular thickness 1 month before smoking cessation (smoking period) and after 3 months of smoking cessation (nonsmoking period). The mean age of the participants was 41.88 ± 6.52 years (range, 26-52), and the average smoking duration was 8.6 ± 2.5 years (range, 5-16). The thickness of the paracentral choroid (nasal: 1,500 mm, p=0.001 and temporal: 1,500 mm, p=0.001) had significantly decreased after 3 months of smoking cessation. The thicknesses of the subfoveal choroid in the smoking and nonsmoking periods were not significantly different (p=0.194). The mean central macular thickness was 267.21 ± 18.42 mm in the smoking period and 268.42 ± 18.28 mm in the nonsmoking period (p=0.022). Smoking was associated with statistically significant changes in paracentral choroidal and central macular thickness in healthy volunteers. Pathological studies should be performed to evaluate the effects of smoking on posterior ocular structures.


Establishment of induced pluripotent stem cell (iPSC) line from 55-year old male patient with hemorrhagic Moyamoya disease.
Peripheral blood mononuclear cells (PBMCs) were collected from 55-year old male patient with a confirmed diagnosis of hemorrhagic Moyamoya disease (MMD). PBMCs were reprogrammed using Sendai virus particles delivering the four Yamanaka factors. A footprint-free hiPSC line was characterized by the expression of pluripotency markers and a normal karyotype. These cells were able to give rise to Embryoid Bodies and to a progeny of differentiated cells belonging to the 3 germ layers. This hiPSC line represents a suitable tool for modelling in vitro MMD disease to investigate the cellular mechanisms underlying the occurrence of this pathology.


Competition, predation and flow rate as mediators of direct and indirect effects in a stream food chain.
Using semi-natural stream channels, we estimated the effects of competition and predation exerted by juvenile and adult exotic rainbow trout (Oncorhynchus mykiss) on the diel activity pattern of juvenile native Atlantic salmon (Salmo salar), a secondary consumer. We also evaluated the direct and indirect effects of competition, predation and abiotic factors (water depth and velocity) on the growth rate of salmon, the biomass of invertebrate grazers (primary consumers) and the biomass of periphytic algae (primary producers; chlorophyll a). The presence of chemical cues emanating from adult predatory trout reduced the daily activity of juvenile Atlantic salmon. In contrast, competition imposed by juvenile rainbow trout forced Atlantic salmon to be more active during the day, even if adult rainbow trout were also present. We found no effect of either competition or of predatory cues on the growth rate of Atlantic salmon, and no evidence of indirect effects on either the biomass of invertebrates or the biomass of chlorophyll a. In contrast, we demonstrated that this food chain (fish--invertebrate grazers--periphytic algae) was under the control of a critical abiotic factor, the water velocity, and of bottom-up processes. We concluded that the exotic species directly increases the risk of predation of the native Atlantic salmon, but behavioral compensation probably limits the effects on growth rate. The competition and predation imposed by the invaders had no indirect effects on lower trophic levels. Top-down effects may have been mitigated by the dominant influence of water velocity controlling all components of the food chain and by elevated levels of primary production.


The role of radiation therapy in small cell lung cancer.
Radiotherapy (RT) is fundamental to the care of patients diagnosed with small-cell lung cancer (SCLC). In the setting of limited stage disease (LS-SCLC), the addition of thoracic RT to chemotherapy (CHT) improves survival and local control, as demonstrated in decades-worth of randomized clinical trials and subsequent meta-analyses. In extensive stage disease (ES-SCLC), thoracic RT is invaluable in the palliation of chest symptoms but there are suggestions that its use in selected patients may potentially improve overall survival . Prophylactic cranial irradiation (PCI) also improves outcomes in SCLC. For LS-SCLC patients, it reduces brain metastases rates by half and improves overall survival with minimal impact on quality-of-life. Recently, favorable results for PCI with respect to survival and prevention of symptomatic brain disease have been observed for ES-SCLC patients with any response to CHT. Current phase III trials in SCLC RT include studies looking at the optimal dose and target for limited disease and the role of thoracic RT in extensive disease.


The effect of social network sites usage in climate change awareness in Latin America.
Using data from the Latinobarómetro (Latin Barometer) survey of 2017 to analyze the effect of social network site usage on climate change awareness in 18 Latin American countries, this article makes three contributions. First, it offers results on the socioeconomic determinants of climate awareness in a region of the world where there is scant published evidence in this regard. Second, it shows the effect of social media consumption on climate change awareness by assessing the role of each of the most popular sites: YouTube, Facebook, Instagram, Twitter, LinkedIn, WhatsApp, Snapchat, and Tumblr. Third, it assesses the effects of multi-platform consumption. The results show that YouTube has the strongest and most robust positive and statistically significant effect on climate change awareness, followed by Instagram, Twitter, and WhatsApp, while being a multi-platform user also has a positive and statistically significant effect on climate change awareness. The implications of these findings for understanding the role of social media in the development of environmental awareness are discussed. The online version contains supplementary material available at 10.1007/s11111-023-00417-4.


Analysis of Aprt deficient mutants of Friend erythroleukaemia cells.
Cytogenetic analysis of mutants of the Friend Erythroleukaemia cell line deficient in adenine phosphoribosyl transferase (Aprt) was undertaken to ascertain whether non-disjunctional events were involved in the production of this mutation. All mutant clones examined were found to carry two copies of chromosome 8, the chromosome to which Aprt maps. Since the two homologues are distinguishable by silver staining, it was also clear that no mutants contained two copies of one homologue having lost the other. Treatment of mutants with 5-azacytidine failed to reactivate the Aprt locus.


Modulation of membrane-associated protein synthesis in rat brain cells by the anti-oxidant 2-ethyl-6-methyl-3-oxypyridine.
Intraperitoneal injection of different amounts of 6-methyl-2-ethyl-3-oxypyridine (6M2E3OP) to 3- and 18-month-old rats led to significant reduction of translating activity in vitro of membrane-bound polysomes of rat brain cells, but nor of free polysomes. This was more marked in the case of endoplasmic membranes of 18-month-old animals than in these of 3-month-old ones. Separation of polysomes from membranes by Triton X-100 resulted in restoration of template activity to the level of free polysomes. Forty eight hours after intraperitoneal injection of 6M2E3OP to 3- and 18-month-old rats the substance was found, by HPLC, only in endoplasmatic reticulum membranes of brain cells, but not in their cytoplasm. The xenobiotic did not change the age-dependent ratio of free and membrane-bound brain polysomes. At the same time the substance significantly inhibited the mean rate of synthesis of the longest polypeptide chains (MW 28-42,000 daltons) in cells of old animals.


Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma.
The action of retinoids on gene regulation is mediated by three distinct nuclear retinoic acid receptor (RAR) subtypes called RAR alpha, beta and gamma. Since RAR gamma is predominantly expressed in adult skin, specific ligands for this subtype could (i) represent valuable tools to evaluate the biological role of RAR gamma in skin and (ii) provide therapeutic entities with a higher therapeutic index at lower teratogenic risk. Using in vitro binding studies and a functional transactivation assay, we have identified three compounds with high RAR gamma selectivity.


Children and Adolescents with Severe Tyrannical Behaviour: Profile of Youth and Their Parents.
This study focused on a subtype of child-to-parent violence, severe tyrannical behaviour (STB). The aim was to examine the clinical characteristics of children and adolescents who physically and/or verbally abuse their parents and the sociodemographic characteristics and generalities of those families. Clinical and sociodemographic data from 73 children and adolescents with STB and their parents have been collected from a randomized control trial. Results showed a specific profile of youth with tyrannical behaviour (aggressive behaviour only in-home settings, only-child, previously mental health care), as well as differential characteristics of these families (late parenthood, high socio-economic status and conjugal family). Children with tyrannical behaviour frequently had psychiatric conditions, such as attention deficit hyperactivity disorder, separation anxiety, sleeping disorders and severe irritability was frequently described. These clinical patterns of combined neurodevelopmental, externalized and internalized symptoms suggest that the combination of individual characteristics, parenting style and parent-child relationship play essential roles in children's STB development.


Prognostic generalization of multi-level CT-dose fusion dosiomics from primary tumor and lymph node in nasopharyngeal carcinoma.
To investigate the prognostic performance of multi-level computed tomography (CT)-dose fusion dosiomics at the image-, matrix-, and feature-levels from the gross tumor volume (GTV) at nasopharynx and the involved lymph node for nasopharyngeal carcinoma (NPC) patients. Two hundred and nineteen NPC patients (175 vs. 44 for training vs. internal validation) were used to train prediction model, and 32 NPC patients were used for external validation. We first extracted CT and dose information from intratumoral nasopharynx (GTV_nx) and lymph node (GTV_nd) regions. Then, the corresponding peritumoral regions (RING_3 mm and RING_5 mm) were also considered. Thus, the individual and combination of intratumoral and peritumoral regions were as follows: GTV_nx, GTV_nd, RING_3 mm_nx, RING_3 mm_nd, RING_5 mm_nx, RING_5 mm_nd, GTV_nxnd, RING_3 mm_nxnd, RING_5 mm_nxnd, GTV + RING_3 mm_nxnd, and GTV + RING_5 mm_nxnd. For each region, 11 models were built by combining five clinical parameters and 127 features from: (1) dose images alone; (2-7) fused dose and CT images via wavelet-based fusion using CT weights of 0.2, 0.4, 0.6, and 0.8, gradient transfer fusion, and guided-filtering-based fusion (GFF); (8) fused matrices (sumMat); (9-10) fused features derived via feature averaging (avgFea) and feature concatenation (conFea); and finally, (11) CT images alone. The concordance index (C-index) and Kaplan-Meier curves with log-rank test were used to assess model performance. The fusion models' performance was better than single CT/dose model on both internal and external validation. Models that combined the information from both GTV_nx and GTV_nd regions outperformed the single region model. For internal validation, GTV + RING_3 mm_nxnd GFF model achieved the highest C-index both in recurrence-free survival (RFS) and metastasis-free survival (MFS) predictions (RFS: 0.822; MFS: 0.786). The highest C-index in external validation set was achieved by RING_3 mm_nxnd model (RFS: 0.762; MFS: 0.719). The GTV + RING_3 mm_nxnd GFF model is able to significantly separate patients into high-risk and low-risk groups compared to dose-only or CT-only models. Fusion dosiomics model combining the primary tumor, the involved lymph node, and 3 mm peritumoral information outperformed single-modality models for different outcome predictions, which is helpful for clinical decision-making and the development of personalized treatment.


Racial-Ethnic Variation in Park Use and Physical Activity in the City of Los Angeles.
Racial-ethnic disparities in physical activity present important challenges to population health. Public parks provide access to free or low-cost physical activity opportunities, but it is unclear to what extent parks are utilized by various race-ethnic groups in diverse urban settings. Here, we examine racial ethnic differences in park use and physical activity among adult residents (n = 7506) living within 1 mi of 50 parks in the city of Los Angeles. In multivariate analyses, we find few differences among race-ethnic groups in terms of their frequency of having visited the park in the past 7 days; however, we find numerous differences in how the groups used the park and in their levels of physical activity: Blacks and English-speaking Latinos were less likely than whites to report being physically active, exercising in the park, and exercising outside the park; Spanish-speaking Latinos were equally likely as whites to report exercising in park but less likely to report exercising outside the park and more likely to report using the parks for social interactions; Asians/Pacific Islanders (PI)/others were more likely than whites to report visiting the park in the past 7 days and using the parks for social interactions. Urban parks appear to be an important resource for physical activity and socialization, in particular among Spanish-speaking Latino and Asians/PI groups. Additional efforts may be needed for other racial-ethnic minorities to experience the same benefits.


Grey matter anomalies in drug-naïve childhood absence epilepsy: A voxel-based morphometry study with MRI at 3.0T.
Little is known, so far, about the cerebral structural abnormalities in drug-naïve patients with childhood absence epilepsy (CAE). We aimed to investigate regional grey matter (GM) volume differences using voxel-based morphometry (VBM) in patients and closely matched healthy control subjects. Twenty drug-naïve patients diagnosed with CAE and 20 age- and gender-matched healthy subjects were recruited. All participants underwent structural MRI scans with a 3.0T MR system. The differences in regional GM volumes between the two groups were determined by VBM analysis. Additional regression analyses were performed to identify any associations between regional GM volume and clinical seizure variables. Compared with controls, the patients with CAE showed less GM volume in the bilateral thalami. Furthermore, the GM volume in the bilateral thalami was negatively correlated with disease duration and age of onset in the CAE group. By excluding the potential effect of medication on brain structures, our study demonstrates less GM volume in the bilateral thalami in drug-naïve patients with idiopathic CAE. Our study further provides structural neuroimaging evidence on the pathophysiology of absence seizures.


Electroretinographic changes in eyes with idiopathic macular hole treated by vitrectomy.
We recorded full-field electroretinograms before and after vitrectomy in 18 eyes of 18 patients with idiopathic macular hole. The results were compared between affected and fellow eyes in the preoperative and early (within 10 days) and late (3 to 6 months) postoperative periods. No significant changes between affected and control eyes were found in the amplitude of the rod electroretinogram, mixed cone-rod electroretinogram, cone electroretinogram a- and b-waves or 30-Hz flicker electroretinogram in all stages of the study. The peak implicit times of the cone electroretinogram (a- and b-wave) and dark- and light- adapted oscillatory potential (O1-O4), however, were delayed. Also, the amplitude of the oscillatory potentials (O1+O2+O3+O4) was significantly reduced in the early postoperative period. By the late period, all of these changes had resolved. We concluded that electrophysiologic changes were derived from a transitory dysfunction of the inner retina. The possible causes of the electroretinographic changes would include mechanical trauma of the surgery, intravitreous air tamponade or the changes in vitreous electrolytes after surgery. Oscillatory potentials were more sensitive than a- and b-waves in eliciting dysfunction of the inner retina in operate on eyes.


Effect of NMDA on staurosporine-induced activation of caspase-3 and LDH release in mouse neocortical and hippocampal cells.
To achieve a better understanding of developmentally regulated NMDA- and staurosporine-induced apoptotic processes, we investigated the concerted action of these agents on caspase-3 activity and LDH release in neocortical and hippocampal cell cultures at different stages in vitro (DIV). Hoechst 33342 and MAP-2 stainings were additionally employed to visualize apoptotic changes and cell damage. The vulnerability of neocortical cells to NMDA was more prominent at later culture stages, whereas hippocampal neurons were more susceptible to NMDA treatment at earlier stages. A persistent activation of caspase-3 by staurosporine was found at all experimental stages. Despite of certain differences in susceptibility to NMDA and staurosporine, both tissues responded to regulatory action of NMDA towards staurosporine-activated caspase-3 in a similar way. Combined treatment with NMDA and staurosporine resulted in a substantial increase in caspase-3 activity in neocortical and hippocampal neurons on 2 DIV. Additive effects were also observed in neocortical cultures on 12 DIV. In contrast, NMDA substantially inhibited staurosporine-induced caspase-3 activity on 7 DIV in neocortical and hippocampal cultures. Additionally, pro-apoptotic effects of 17beta-estradiol were attenuated by NMDA on 7 DIV. Changes in vulnerability to NMDA- and staurosporine-mediated activation of caspase-3 were not strictly related to LDH release. Our data revealed that NMDA can both enhance and inhibit the staurosporine-induced neuronal cell apoptosis. The pro-apoptotic effect of NMDA was exhibited at early and late culture stages, whereas the anti-apoptotic effect was transient occurring on 7 DIV only.


A comparative study on the immune response of sheep to foot and mouth disease virus vaccine type Asia-1 prepared with different inactivants and adjuvants.
Foot and mouth disease virus type Asia-1 was inactivated either with formaldehyde or binaryethylenimine (BEI). Inactivated vaccines were prepared incorporating aluminium hydroxide gel or mineral oil as an adjuvant. The antibody response to the adult sheep was studied by ELISA and SN test for a period of 6 months. There was no difference in the antibody response between vaccines inactivated with formaldehyde or BEI. Whereas significant difference in the antibody response was observed between gel and oil vaccines. The high titres of antibody stimulated by oil vaccines persisted longer than those of gel vaccines within the period of study.


Suppression of primary antibody response by a single exposure to cadmium in mice.
Suppression of primary antibody response to sheep red blood cells (SRBC) by a single intraperitoneal (i.p.) injection of cadmium into mice was investigated by the methods of in vitro plaque-forming cell (PFC) assay. BALB/c mice were given 1.8 mg cadmium/kg body weight, and 1, 2 or 7 days later, spleen cells from exposed and control mice were cultured with SRBC. PFC responses of all exposed groups were significantly suppressed compared to those of control groups. Addition of control adherent cells to spleen cells from exposed mice failed to recover control level. In the cell-reconstitution experiments, the activity of B-cell function from the exposed group was suppressed more by cadmium than that of T-cell function. These results suggest that the suppression of primary PFC response by cadmium exposure may be caused by the inactivation of B-cells.


Pfizer-BioNTech vaccine effectiveness against Sars-Cov-2 infection: Findings from a large observational study in Israel.
Development of an effective vaccine against Covid-19 is crucial to reducing infection. mRNA BNT162b2, developed and manufactured by Pfizer-BioNTech, was one of the first FDA-approved vaccinations reporting high efficacy (95%) and minimal side effects. Evaluating effectiveness of BNT162b2 in a general population has been made possible after the implementation of a nation-wide vaccination program in Israel. This retrospective cohort study was carried out in Maccabi HealthCare services, Israel among 1.6 million members aged 16 and over. The population was divided into those who were at least seven days post- second vaccination and those who had not been vaccinated. Number of days till the end of the study or Covid-19 infection, Covid-19-related hospitalization and mortality was calculated for each participant between 18.1.2021 to 25.4.2021. Participants who had reached day eight after second vaccination during the study period could contribute days to both groups. Vaccine efficacy (VE) was calculated using a conditional Poisson model, controlling for age group, gender, hypertension, diabetes and obesity, fitted within clusters defined by geographical statistical area and calendar week. BNT162b2 was found effective for the total population group for infection, hospitalization and mortality, with adjusted VE of 93·0% (CI:92·6-93·4%), 93·4% (CI:91·9-94·7%) and 91·1% (CI:86·5-94·1%) respectively. VE for infection was lower for participants aged 75 and over, and for those with hypertension, diabetes and obesity. This study strengthens the evidence that the Pfizer-BioNTech vaccination is effective in preventing infection, hospitalization and mortality.


Bacterial origin of a diverse family of UDP-glycosyltransferase genes in the Tetranychus urticae genome.
UDP-glycosyltransferases (UGTs) catalyze the conjugation of a variety of small lipophilic molecules with uridine diphosphate (UDP) sugars, altering them into more water-soluble metabolites. Thereby, UGTs play an important role in the detoxification of xenobiotics and in the regulation of endobiotics. Recently, the genome sequence was reported for the two-spotted spider mite, Tetranychus urticae, a polyphagous herbivore damaging a number of agricultural crops. Although various gene families implicated in xenobiotic metabolism have been documented in T. urticae, UGTs so far have not. We identified 80 UGT genes in the T. urticae genome, the largest number of UGT genes in a metazoan species reported so far. Phylogenetic analysis revealed that lineage-specific gene expansions increased the diversity of the T. urticae UGT repertoire. Genomic distribution, intron-exon structure and structural motifs in the T. urticae UGTs were also described. In addition, expression profiling after host-plant shifts and in acaricide resistant lines supported an important role for UGT genes in xenobiotic metabolism. Expanded searches of UGTs in other arachnid species (Subphylum Chelicerata), including a spider, a scorpion, two ticks and two predatory mites, unexpectedly revealed the complete absence of UGT genes. However, a centipede (Subphylum Myriapoda) and a water flea and a crayfish (Subphylum Crustacea) contain UGT genes in their genomes similar to insect UGTs, suggesting that the UGT gene family might have been lost early in the Chelicerata lineage and subsequently re-gained in the tetranychid mites. Sequence similarity of T. urticae UGTs and bacterial UGTs and their phylogenetic reconstruction suggest that spider mites acquired UGT genes from bacteria by horizontal gene transfer. Our findings show a unique evolutionary history of the T. urticae UGT gene family among other arthropods and provide important clues to its functions in relation to detoxification and thereby host adaptation.


Behavioral fever in Bosk's fringe-toed lizards (Acanthodactylus boskianus) living in an industrial area in south-eastern Tunisia.
As an indicator of physiological state of lizards, thermoregulatory behavior has been proposed as an assessment tool of environmental contamination, particularly in desert ecosystems where lizards represent a major biological component. Although pesticide contamination has been shown to induce behavioral fever in lizards, the possible pyrogenic effect of heavy metals has received less attention. The objective of this study was to provide data on this issue by using Bosk's fringe-toed lizards (Acanthodactylus boskianus) living in a metal-contaminated industrial area in south-eastern Tunisia as a study model. Combining field observations of behavior with measures of thermoregulatory performance under laboratory conditions, we found that proximity to the industrial zone was associated to a different thermoregulatory behavior of lizards. There was a tendency of lizards living close to the contamination source to display behavioral fever, as they spent more time in the sun, preferred higher body temperatures, and warmed up faster, compared to lizards living far away. This heat-seeking behavior is likely a reaction to improve the functioning of physiological systems involved in the defense against toxic effects of heavy metals, possibly through the increase of metabolic rate, stimulation of enzymes involved in the detoxification process, and enhancement of immune defense systems. Our findings stress the need for further detailed studies into the physiological mechanisms linking metal contamination to behavioral fever. They also underline the usefulness of thermoregulatory behavior as a reliable, non-destructive, and inexpensive, individual-level biomarker in lizard ecotoxicology and biomonitoring of contaminated desert environments.


Training and game loads and injury risk in elite Australian footballers.
To examine the relationship between combined training and game loads and injury risk in elite Australian footballers. Prospective cohort study. Forty-six elite Australian footballers (mean±SD age of 22.2±2.9 y) from one club were involved in a one-season study. Training and game loads (session-RPE multiplied by duration in min) and injuries were recorded each time an athlete exerted an exercise load. Rolling weekly sums and week-to-week changes in load were then modelled against injury data using a logistic regression model. Odds ratios (OR) were reported against a reference group of the lowest training load range. Larger 1 weekly (>1750 AU, OR=2.44-3.38), 2 weekly (>4000 AU, OR=4.74) and previous to current week changes in load (>1250 AU, OR=2.58) significantly related (p<0.05) to a larger injury risk throughout the in-season phase. Players with 2-3 and 4-6 years of experience had a significantly lower injury risk compared to 7+ years players (OR=0.22, OR=0.28) when the previous to current week change in load was more than 1000 AU. No significant relationships were found between all derived load values and injury risk during the pre-season phase. In-season, as the amount of 1-2 weekly load or previous to current week increment in load increases, so does the risk of injury in elite Australian footballers. To reduce the risk of injury, derived training and game load values of weekly loads and previous week-to-week load changes should be individually monitored in elite Australian footballers.


Transcutaneous magnetic spinal cord stimulation for freezing of gait in Parkinson's disease.
Dopaminergic drugs partially alleviate gait problems in Parkinson's disease, but the effects are not sustained in the long-term. Particularly, the freezing of gait directly impacts patients' quality of life. Experimental epidural spinal cord stimulation (SCS) studies have suggested positive effects on locomotion among PD patients, but the effects of non-invasive stimulation have never been explored. Here, we investigated in a prospective, open-label, pilot study the efficacy and safety of non-invasive magnetic stimulation of the spinal cord in five patients with PD who experienced gait problems, including freezing of gait. A trial of transcutaneous magnetic SCS was performed at the level of the fifth thoracic vertebra. The primary outcome was the change in freezing of gait 7 days after stimulation. Secondary outcome measures included changes in gait speed and UPDRS part III. After non-invasive spinal cord stimulation, patients experienced a 22% improvement in freezing of gait (p = 0.040) and 17.4% improvement in the UPDRS part III (p = 0.042). Timed up and go times improved by 48.2%, although this did not reach statistical significance (p = 0.06). Patients' global impression of change was 'much improved' for four patients. Improvement in gait after stimulation was reversible, since it returned to baseline scores 4 weeks after stimulation. No severe side effects were recorded. This pilot study suggests that transcutaneous magnetic spinal cord stimulation is feasible and can potentially improve gait problems in PD, without severe adverse effects. Large scale phase II trials are needed to test this hypothesis.


Voltage clamp characterization of a calcium-dependent chloride conductance in a putative invertebrate motoneuron.
1. The properties of a Ca-activated Cl-current ICl(Ca) were investigated with the two electrode voltage clamp technique in the AL1 cell of the leech Haementeria ghilianii. 2. ICl(Ca) was revealed after Cl-loading of the cells, with outward K-currents eliminated by replacement of intra- and extracellular K with Cs, and with Na currents blocked by 1 microM TTX. CsCl-containing electrodes were used for recording and current passing. 3. In response to depolarizing voltage steps the cells exhibited sustained Cl-dependent currents the size and polarity of which varied with [Cl]0. The reversal potentials of tail currents of this conductance varied with [Cl]0 as predicted for the equilibrium potential of Cl by the Nernst equation and were unaffected by changes in extracellular cation concentration. 4. The decay of the Cl-dependent tail-currents followed a process which could be described by the sum of two exponentials with time constants tau 1 and tau 2 on the order of about 100 ms and 800 ms, respectively. No voltage-dependence of the time constants was apparent; however, tau 1 varied with the amount of Ca-influx. 5. The Cl-current required Ca for its activation. All current flow was abolished in Mn-containing Ringer solutions and when Ba was substituted for Ca. However, Sr could partially substitute for Ca as an activator of the current. 6. The activation curve for Cl-dependent tail currents was U-shaped directly paralleling the amount of Ca-influx, and no Cl-current flow could be induced a depolarizations below the activation threshold or beyond the apparent reversal potential for the Ca-current.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of patient selection on estimate of reproductive success after surgery for rectovaginal endometriosis: literature review.
The effect of rectovaginal endometriosis on fertility is unclear. Several authors foster radical surgery, including colorectal resection, as a fertility-enhancing procedure. However, interpretation of data is difficult, as the baseline fertility status is often undefined and it is not always possible to discriminate between spontaneous conceptions and those resulting from IVF. A systematic literature review was performed with the aim of defining the pregnancy rate specifically in patients who were infertile before surgery and who sought spontaneous pregnancy. A PubMed search was conducted to identify English language studies published between 2005 and 2011 evaluating reproductive performance after surgery for rectovaginal and rectosigmoid endometriosis. According to the results of the 11 selected studies, the mean post-operative conception rate in all women seeking pregnancy independently of preoperative fertility status and IVF performance was 39% (95% CI 35-43%; 223/571), but dropped to 24% (95% CI 20-28%; 123/510) in infertile patients who sought spontaneous conception (odds ratio 0.50, 95% CI 0.38-0.65%). Patients' selection significantly influences the estimate of the effect of rectovaginal endometriosis excision on infertility. This should be carefully taken into consideration at preoperative counselling. Rectovaginal endometriosis usually is associated with pain symptoms, but the effect of this disease form on fertility is uncertain, as burial of foci beneath rectouterine adhesions with exclusion of the deepest part of the pelvis may limit interference with fertilization processes. Several authors foster radical surgery, including colorectal resection, as a fertility-enhancing procedure. However, interpretation of data is difficult, as the baseline fertility status is often undefined and it is not always possible to discriminate between spontaneous conceptions and those resulting from IVF. A systematic literature review was performed with the aim of defining the pregnancy rate specifically in patients who were infertile before surgery and who sought pregnancy spontaneously. A PubMed search was conducted to identify English language studies published between 2005 and 2011 evaluating reproductive performance after surgery for rectovaginal and rectosigmoid endometriosis. According to the results of the 11 selected studies, the mean post-operative conception rate in all women seeking pregnancy independently of preoperative fertility status and IVF performance was 39% (223/571), but dropped to 24% (123/510) in infertile patients who sought conception spontaneously. The 15% difference is statistically significant. Infertile patients with rectovaginal endometriosis considering surgery, should be carefully informed of the real probability of post-operative conception avoiding generic overestimations.


Rat endopeptidase-24.18 alpha subunit is secreted into the culture medium as a zymogen when expressed by COS-1 cells.
Endopeptidase-24.18 (EC 184.108.40.206, E-24.18) is an oligomeric Zn-ectoenzyme. The alpha and beta subunits have been cloned from both rat and mouse kidneys. The primary structure of these subunits revealed that they both contain the consensus Zn binding site and that they are members of the astacin family. Analysis of the hydropathy plot also suggested that they are anchored by a C-terminal hydrophobic domain. In order to verify the mode of anchoring of the rat E-24.18 alpha subunit and to test the functionality of the astacin-like domain in the alpha subunit when expressed alone, COS-1 cells were transfected with a cloned cDNA for rat alpha subunit. Despite the presence of its putative transmembrane domain, the alpha subunit was not anchored in the plasma membrane but rather secreted as a dimer into the culture medium. When the enzymatic activity of the secreted recombinant protein was tested in the azocasein degradation assay, the alpha subunit was found to be inactive. Activity could, however, be revealed after mild trypsin digestion. This activity was abolished by replacing the Glu-157 in the active site by Val. Taken together our results suggest that the alpha subunit of Endopeptidase-24.18 contains a latent astacin-like Zn metallopeptidase activity which could be secreted as a soluble enzyme by kidney and intestine.


Spatiotemporal GPCR signaling illuminated by genetically encoded fluorescent biosensors.
G protein-coupled receptors (GPCRs) are ligand-activated cell membrane proteins and represent the most important class of drug targets. GPCRs adopt several active conformations that stimulate different intracellular G proteins (and other transducers) and thereby modulate second messenger levels, eventually resulting in receptor-specific cell responses. It is increasingly accepted that not only the type of active signaling protein but also the duration of its stimulation and the subcellular location from where receptors signal distinctly contribute to the overall cell response. However, the molecular principles governing such spatiotemporal GPCR signaling and their role in disease are incompletely understood. Genetically encoded, fluorescent biosensors-in particular for the GPCR/cAMP signaling axis-have been pivotal to the discovery and molecular understanding of novel concepts in spatiotemporal GPCR signaling. These include GPCR priming, location bias, and receptor-associated independent cAMP nanodomains. Here, we review such technologies that we believe will illuminate the spatiotemporal organization of other GPCR signaling pathways that define the complex signaling architecture of the cell.


The rs2302685 polymorphism in the LRP6 gene is associated with bone mineral density and body composition in Iranian children.
Some 60-80% of the variability in bone mineral density (BMD) is determined by genetic factors. In the present study, we investigated the impact of the rs2302685 polymorphism of LRP6 on BMD and body composition in Iranian children. In total, 200 children (101 boys and 99 girls) were enrolled in the study. Body composition and BMD were computed using the Hologic DXA System (Hologic, Marlborough, MA, USA). The single nucleotide polymorphism of LRP6 rs2302685 (V1062I) was determined using a polymerase chain reaction/restriction fragment length polymorphism. A generalized linear model was performed to find the association between LRP6 polymorphisms, BMD and body composition in two adjusted models. In model 1, a significant difference was found between LRP6 (rs2302685) polymorphism, trochanteric BMD (p = 0.007), intertrochanteric BMD (p = 0.007), total fat (p = 0.001), total fat (%) (p = 0.034), total lean mass (p = 0.031), total Lean + BMC (p = 0.036) and total mass (p = 0.001). In model 2, LRP6 (rs2302685) polymorphisms showed a significant effect on the trochanteric BMD (p = 0.005), intertrochanteric BMD (p = 0.005), total fat (p = 0.001), total fat (%) (p = 0.013) and total mass (p = 0.01). Total fat, total fat (%) and total body mass were higher in subjects with the CC genotype compared to the TT/CT genotype, whereas total lean mass and total Lean + BMC were higher in the TT/CT genotype. The present study shows that the LRP6 polymorphism may be associated with body composition and BMD in Iranian children.


ABO blood group is involved in the quality of the specific immune response anti-SARS-CoV-2.
Since December 2019, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. To eradicate it, it is crucial to acquire a strong and long-lasting anti-SARS-CoV-2 immunity, by either natural infection or vaccination. We collected blood samples 12-305 days after positive polymerase chain reactions (PCRs) from 35 recovered individuals infected by SARS-CoV-2. Peripheral blood mononuclear cells were stimulated with SARS-CoV-2-derived peptide pools, such as the spike (S), nucleocapsid (N) and membrane (M) proteins, and we quantified anti-S immunoglobulins in plasma. After 10 months post-infection, we observed a sustained SARS-CoV-2-specific CD4+ T-cell response directed against M-protein, but responses against S- or N-proteins were lost over time. Besides, we demonstrated that O-group individuals presented significantly lower frequencies of specific CD4+ T-cell responses against Pep-M than non O-group individuals. The non O-group subjects also needed longer to clear the virus, and they lost cellular immune responses over time, compared to the O-group individuals, who showed a persistent specific immune response against SARS-CoV-2. Therefore, the S-specific immune response was lost over time, and individual factors might determine the sustainability of the body's defenses, which must be considered in the future design of vaccines to achieve continuous anti-SARS-CoV-2 immunity.


Use of a new composite index to demonstrate improved stereoacuity after training on stimuli with dichoptically asymmetric contrast.
Many people with stereo-deficiency cannot perform stereoacuity tasks at any binocular disparity, so their threshold cannot be measured. We developed a generally useful new composite stereodepth or CSD score, with range 0 to 20, that combines stereoacuity (from 0 to 13.3) and percent correct (13.3 to 20) into a single index. CSD allows differences in stereodepth performance to be measured across groups when thresholds cannot be reliably measured, and across time when individuals gain stereodepth perception during training. We used CSD scores to assess the benefit of unequal (mixed) left- and right-eye contrast during dichoptic stereoacuity training in people with amblyopia. Nineteen adult participants with anisometropic amblyopia were assigned randomly to 10 sessions of either mixed-contrast or fixed-contrast training. Stimuli were rectangles, one above the other, viewed through a four-mirror stereoscope. Participants indicated which rectangle appeared closer. A staircase controlled disparity within the stimulus. CSD improvement was better by 1.6 CSD units for participants who received mixed-contrast training. Thus, mixed-contrast stereo training was more effective than fixed-contrast training in adults with anisometropic amblyopia.


Passage number of porcine embryonic germ cells affects epigenetic status and blastocyst rate following somatic cell nuclear transfer.
Epigenetic instability of donor cells due to long-term in vitro culture may influence the success rate of subsequent somatic cell nuclear transfer (SCNT). Therefore, the present study was designed (1) to investigate the epigenetic changes after prolonged culture in vitro of porcine embryonic germ (EG) cells, including differences in expression levels of both DNA methylation and demethylation-related genes and catalyses of histone modifications, and (2) to assess the efficiency of SCNT using EG cells from different passages. Results showed that genes either associated with DNA demethylation including DNMTs and TET1 or genes related to histone acetylation including HDACs were highly expressed in EG cells at higher passages when compared to EG cells at lower passages. In addition, the expression level of H3K27me3 functional methylase EZH2 increased while no changes were observed on H3K27me3 demethylase JMJD3 in relation to passage number. Moreover, the expression levels of both the H3K4me3 methylase MLL1 and the H3K4me3 demethylase RBP2 were increased at high passages. By using lower passage (numbers 3-5) EG cells as donor cells, the SCNT efficiency was significantly lower compared with use of fetal fibroblast donor cells. However, similar blastocyst rates were achieved when using higher passage (numbers 9-12) EG cells as donor cells. In conclusion, the present study suggests that the epigenetic status of EG cells change with increasing passage numbers, and that higher passage number EG cells are better primed for SCNT.


Analysis of the efficacy of microdissection of paravebous sinus meningiomas invading large venous sinuses.
The management of paravebous sinus meningiomas that invade major venous sinuses is a subject of debate, particularly concerning the necessity of complete resection of the tumor and reconstruction of the venous sinus. This article aims to demonstrate the outcomes of total removal of the lesion (including the invading venous sinus portion) and the effects of restoring or not restoring venous circulation in terms of recurrence of the tumor, mortality, and post-operative complications. The authors conducted a study involving 68 patients with paravebous sinus meningiomas. Of the 60 parasagittal meningiomas, 23 were located in the anterior third, 30 in the middle third, and 7 in the posterior third. Additionally, 3 lesions were located in the sinus confluence area, and 5 in the transverse sinus. All patients underwent surgery, and the degree of venous sinus involvement was classified into six types. For type I meningiomas, the outer layer of the sinus wall was stripped off. For types II to VI, two strategies were employed: non-constitutional, wherein the tumor and affected venous sinuses were removed without repair, and reconstructive, wherein the tumor was completely removed and the venous sinuses were sutured or repaired. Karnofsky Performance Status (KPS) scale and Magnetic Resonance Venography (MRV) were utilized to assess the outcomes of the surgical procedures. The study group of 68 patients underwent complete tumor resection in 97.1%, with sinus reconstruction attempted in 84.4% of cases with sinus wall and sinus cavity invasion. The recurrence rate of this group was 5.9%, with follow-up ranging from 33 to 57 months. It was found that the recurrence rate was significantly higher in cases with incomplete resection than in those with complete resection. The overall mortality rate was 4.4%, with all cases resulting from malignant brain swelling due to the failure to perform venous reconstruction after resectioning of the meningioma type VI. Furthermore, 10.3% of patients experienced worsening symptoms of neurological deficits or complete loss of neurological function, with a significantly higher incidence in those without venous reconstruction than in the venous reconstruction group (P < 0.0001, Fisher test). No statistically significant pre-operative and post-operative KPS differences were observed in patients with type I to V. However, in patients with type VI (who did not receive venous reconstruction), the post-operative KPS score was significantly worse. The results of this study suggest the necessity of a complete resection of the tumor, including the invasive venous sinus component, as the recurrence rate was found to be relatively low at 5.9%. Moreover, patients who did not undergo venous reconstruction showed significant deterioration in their clinical condition compared to other subgroups, thus highlighting the importance of venous sinus reconstruction.


The Value of a Well-Being Improvement Strategy: Longitudinal Success across Subjective and Objective Measures Observed in a Firm Adopting a Consumer-Driven Health Plan.
The objective of this study is to evaluate effectiveness of a firm's 5-year strategy toward improving well-being while lowering health care costs amidst adoption of a Consumer-Driven Health Plan. Repeated measures statistical models were employed to test and quantify association between key demographic factors, employment type, year, individual well-being, and outcomes of health care costs, obesity, smoking, absence, and performance. Average individual well-being trended upward by 13.5% over 5 years, monthly allowed amount health care costs declined 5.2% on average per person per year, and obesity and smoking rates declined by 4.8 and 9.7%, respectively, on average each year. The results show that individual well-being was significantly associated with each outcome and in the expected direction. The firm's strategy was successful in driving statistically significant, longitudinal well-being, biometric and productivity improvements, and health care cost reduction.


The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein.
The complete sequence of the human Duchenne muscular dystrophy (DMD) cDNA has been determined. The 3685 encoded amino acids of the protein product, dystrophin, can be separated into four domains. The 240 amino acid N-terminal domain has been shown to be conserved with the actin-binding domain of alpha-actinin. A large second domain is predicted to be rod-shaped and formed by the succession of 25 triple-helical segments similar to the repeat domains of spectrin. The repeat segment is followed by a cysteine-rich segment that is similar in part to the entire COOH domain of the Dictyostelium alpha-actinin, while the 420 amino acid C-terminal domain of dystrophin does not show any similarity to previously reported proteins. The functional significance of some of the domains is addressed relative to the phenotypic characteristics of some Becker muscular dystrophy patients. Dystrophin shares many features with the cytoskeletal protein spectrin and alpha-actinin and is a large structural protein that is likely to adopt a rod shape about 150 nm in length.


Effect of carbon monoxide on the cytochrome P-450-mediated metabolism of aniline and p-nitroanisole in the isolated perfused rabbit lung.
Carbon monoxide (CO), an environmental pollutant, inhibits the cytochrome P-450-mediated metabolism of xenobiotics in vitro. In recent years, the importance of the lung in the metabolic disposition of certain airborne and systemically administered xenobiotics has been demonstrated. The purpose of this investigation was to establish a threshold for the CO-induced inhibition of cytochrome P-450-mediated activities in the isolated perfused rabbit lung and to determine if these reactions are equally sensitive to this toxicant in this model. Neither the mixed-function oxidase-mediated hydroxylation nor the acetylation of aniline was altered by exposure to 7.5% CO/20% O2 for 2.5 h in the isolated perfused rabbit lung. p-Nitroanisole O-demethylation by isolated rabbit lungs ventilated with 7.5% CO/20% O2 was significantly decreased (approximately 37%) in comparison to controls. That these reactions are not similarly influenced by carbon monoxide may indicate that the constitutive isozymes of cytochrome P-450 in the rabbit lung are differentially sensitive to CO-induced inhibition.


Genetic dynamics in the sand fly (Diptera: Psychodidae) nuclear and mitochondrial genotypes: evidence for vector adaptation at the border of Iran with Iraq.
Our investigation uses nucleotide variations of the genera Phlebotomus and Sergentomyia using the EF-1α and Cyt b genotype regions to describe the sand fly fauna and genetic aspects collected at war-torn sites of the Khuzestan boundary between Iraq and Iran. All sand fly species were characterized using molecular genetics. The field work was conducted in six districts including 24 locations in remote areas for three years at the peak of sand fly activity during cutaneous leishmaniasis (CL) transmission seasons. The distribution of CL vectors was determined based on the climatic regionalization using the kriging method in ArcGIS model. DNA of sand fly pools were screened via polymerase chain reaction (PCR) using neutrality (Tajima's D) and neutral allele frequency (Fu's F s) tests to measure the effect of randomly evolving DNA sequence on the genetic diversity of sand fly populations in response to habitat fragmentation and landscape modification. Among the 1213 specimens, ten species were identified based on morphology. The non-native species Phlebotomus sergenti was unequivocally found for the first time in the studied regions. Nucleotide substitutions of sand fly sequences varied most in the most disrupted districts (Dashte-Azadegan and Abadan; disparity index test: P < 0.05). The haplotypes of Cyt b from the subgenus Sergentomyia and P. papatasi revealed more heterogeneity (Tajima's D > +2) than P. alexandri (D > +1), which suggests widespread heteroplasmic mitochondrial DNA mutations in the same mtDNA gene among different sand fly species. Subgenus Sintonius exhibited greater fitness (D = 0) and (neutrality test; P > 0.05) no evidence of selection. The sequence of the nuclear gene EF-1α indicated similar nucleotide differences, as observed for the Cyt b gene, in all sand fly species, but lower levels of polymorphisms (D > +1) were observed compared with the mitochondrial Cyt b gene (D > +2) in the subgenus Sergentomyia. Our findings describe random nucleotide diversity in the Phlebotomus and Sergentomyia population gene pools due to recent anthropogenic influence. A phylogenetic analysis showed that the closely related species are positioned in monophyletic clades, except for the subgenus Sergentomyia and P. sergenti, and highlights the importance of haplotype variations for the development of adaptability.


[Studies on Factors Influencing Influenza Vaccination Rates in Patients with Chronic Obstructive Pulmonary Disease].
BACKGROUND : With low influenza vaccination rates among the chronically ill, approaches to increase these rates among risk patients with chronic obstructive pulmonary disease (COPD) are to be uncovered. METHODS : 120 COPD patients from Magdeburg filled out a questionnaire and were analyzed regarding the influenza vaccination status 2015/2016 or 2016/2017. Vaccinated and unvaccinated were compared in socio-epidemiological factors, the health belief model (HBM), self-efficacy (GESIS-ASKU), anxiety/depression (HADS-D) and disease processing (FKV-LIS). RESULTS : 62.5 % (n = 75) were vaccinated, 31.7 % (n = 38) unvaccinated, 5.8 % (n = 7) made no statement. In over or equal to 60-year-olds 76 % were vaccinated, in under 60-year-olds 42 % were vaccinated. 60 % (n = 72) knew to belong to a risk group. Unvaccinated indicated greater concern about side effects of the vaccination (p = .004) and drew a worse benefit-expense balance (p = .001). Unvaccinated were more often uncertain about the vaccination protection and the severity of influenza (p ≤ .001). Vaccinated were highly motivated to think about vaccination themselves and more often had a positive vaccination history (p = .001). COPD patients showed a lower self-efficacy than the reference group of the German general population (p = .000), vaccinated and unvaccinated did not differ (p = .418). No difference between vaccinated and unvaccinated was found in the processing of the disease and in depression and anxiety, but unvaccinated tended to give higher anxiety values. CONCLUSION : Measures should particularly target COPD patients under 60 years of age with a negative vaccination history and sensitize them as risk patients. Widespread uncertainties about the severity of influenza and vaccination protection should be addressed. It should be communicated that influenza vaccination does not lead to exacerbation. The vaccination recommendation should increasingly be made by pulmonologists.


Bipolaron Dynamics in Graphene Nanoribbons.
Graphene nanoribbons (GNRs) are two-dimensional structures with a rich variety of electronic properties that derive from their semiconducting band gaps. In these materials, charge transport can occur via a hopping process mediated by carriers formed by self-interacting states between the excess charge and local lattice deformations. Here, we use a two-dimensional tight-binding approach to reveal the formation of bipolarons in GNRs. Our results show that the formed bipolarons are dynamically stable even for high electric field strengths when it comes to GNRs. Remarkably, the bipolaron dynamics can occur in acoustic and optical regimes concerning its saturation velocity. The phase transition between these two regimes takes place for a critical field strength in which the bipolaron moves roughly with the speed of sound in the material.


Prolongation of G1 phase in cultured glioma cells by cis-dichlorodiammineplatinum (II) (CDDP): analysis using bromodeoxyuridine (BrdU)-Hoechst technique.
The cytokinetic response of three murine (AC) and human (GB-1 and GB-2) glioma cell lines to cisdichlorodiammineplatinum (II) (CDDP) was investigated by flow cytometry. Using the 5-bromodeoxyuridine (BrdU)-Hoechst technique, percentages of cultured glioma cells in the various phases of the cell cycle, and relative phase duration were calculated. This technique proved to be a rapid and easily performed method to characterize phase length and transition rate for the complete cell cycle. In the presence of CDDP IC10 (a concentration in which 10% inhibition of cell growth be induced as compared to controls), perturbations of the cell cycle in AC and GB-1 cells included G2 delay or block, decreased transit velocity from G1 to S phase, and prolongation of G1 phase. The mean cell cycle time increased 1.4 times in AC and 1.6 times in GB-1 as compared to controls. In CDDP IC 50-treated GB-2 cells, the mean cell cycle time was prolonged three times longer than control: however, duration of each phase could not be calculated because of significant perturbation of cell cycle. These results suggest that CDDP influences glioma cells at the G1/S boundary and in the G2 phase, resulting in prolongation of the G1 phase and, to a minor degree, in block of the G2 phase.


Early detection of anastomotic leak with C-reactive protein increases the chances of anastomotic salvage.
Anastomotic leak results in increased morbidity and affects functional and oncological outcomes after colectomy. Measurement of C-reactive protein (CRP) allows early detection of anastomotic leaks. The aim of this study was to evaluate the benefit to the patient of earlier diagnosis and management of anastomotic leaks, namely avoiding takedown of the anastomosis. Patients with an anastomotic fistula after elective colorectal surgery from 2010 to 2020 were included. Three periods were defined according to progressive adherence to the CRP protocol in our department. A comparison was made between the periods 'before' (2010-2013) and 'after' (2016-2020) in terms of morbidity, mortality, anastomotic salvage, days spent in hospital within the first postoperative month, timely adjuvant chemotherapy and anastomotic stenosis. Out of 2655 elective colorectal operations, 171 patients presented with an anastomotic leak and 123 patients were included in the study. In univariate analysis, patients in the 'after' group had fewer severe complications (Clavien-Dindo Grade III to IV, 66.7% vs. 56.9; p = 0.017); the difference did not reach significance regarding timely postoperative chemotherapy (p = 0.058) and anastomotic stenosis (p = 0.682). In both, univariate and multivariate analysis, the 'after' period increased the chances of preserving the anastomosis (OR = 2.37 [1.08-5.17]) and increased the number of days out of hospital (p = 0.0002). A CRP-based protocol for the screening of anastomotic leaks after colorectal surgery was related to increased anastomotic conservation, a decreased impact and severity of the leak and a shorter length of hospital stay.


Multiple cytomegalovirus-related intestinal perforations in patients with acquired immunodeficiency syndrome. Report of two cases and review of the literature.
We present two cases of patients with acquired immunodeficiency syndrome who, in the course of their disease, suffered multiple intestinal perforations that were directly related to cytomegalovirus infection. Biopsy and surgical specimens and autopsy findings in both cases revealed extensive lesions of gastroenteritis; the gastroenteritis was characterized by randomly distributed deep ulcers, resulting in multiple perforations. The main characteristic histopathologic finding was the association of intestinal lesions with a severe form of cytomegalovirus-related occlusive vasculitis. This report provides evidence that supports the contention that cytomegalovirus is the primary causal agent of gastrointestinal lesions affecting immunocompromised patients.