Insight into PCR testing for surgeons.
The most commonly used molecular diagnostic technique is the polymerase chain reaction (PCR). PCR detects a short section of genetic code of interest, a cancer gene, human mRNA or a pathogen's genome. It is used by every specialty in medicine and surgery, with increasing frequency and importance. In this article, the history, steps of the cycle, uses, forms, advantages and disadvantages of PCR are discussed. With the SARS coronavirus-2 pandemic having such an enormous impact on the delivery of elective surgery, decisions to proceed or defer are made by surgeons on a daily basis, based on PCR results. An understanding of these results is provided, what they tell us, what they do not and what other information is required to make these decisions. It is imperative to also look beyond PCR results, seeing the patient within the context of their symptoms, other pathology and imaging results, with the assistance of a medical virologist or microbiologist, in complex cases.


Effect of ergometrine on contractile force of guinea-pig isolated heart: antagonism by cimetidine.
The action of ergometrine on contractile force of guinea-pig isolated heart was investigated and the effect of receptor antagonists on the inotropic effect of ergometrine, isoproterenol, dopamine and histamine was evaluated. Ergometrine was found to have a good dose-dependent inotropic effect and the antagonism of cimetidine toward this action is reported. Experiments carried out in hearts in which a massive depletion of mast-cells histamine was produced are in favour of a direct action of the drug on H2-receptors.


Real-world effectiveness of vedolizumab compared to anti-TNF agents in biologic-naïve patients with ulcerative colitis: A two-year propensity-score-adjusted analysis from the prospective, observational VEDOIBD -study.
This observational real-world evidence (RWE) study is based on prospectively collected data from the VEDOIBD registry study. To compare the effectiveness of vedolizumab and anti-TNF agents in biologic-naïve patients with ulcerative colitis (UC) at the end of induction and during maintenance treatment. Between 2017 and 2020, we enrolled 512 patients with UC starting therapy with vedolizumab or an anti-TNF agent in 45 IBD centres across Germany. We excluded biologic-experienced patients and those with missing partial Mayo (pMayo) outcomes; this resulted in a final sample of 314 (182 on vedolizumab and 132 on an anti-TNF agent). The primary outcome was clinical remission measured using pMayo score; any switch to a different biologic agent was considered an outcome failure (modified ITT analysis). We used propensity score adjustment with inverse probability of treatment weighting to correct for confounding. During induction therapy, clinical remission was relatively low and similar in vedolizumab- and anti-TNF-treated patients (23% vs. 30.4%, p = 0.204). However, clinical remission rates after two years were significantly higher for vedolizumab-treated patients than those treated with an anti-TNF agent (43.2% vs. 25.8%, p < 0.011). Among patients treated with vedolzumab, 29% switched to other biologics, versus 54% who had received an anti-TNF agent. After two years of treatment, vedolizumab resulted in higher remission rates than anti-TNF agents.


Converting human carbonic anhydrase II into a benzoate ester hydrolase through rational redesign.
Enzymes capable of benzoate ester hydrolysis have several potential medical and industrial applications. A variant of human carbonic anhydrase II (HCAII) was constructed, by rational design, that is capable of hydrolysing para-nitrophenyl benzoate (pNPBenzo) with an efficiency comparable to some naturally occurring esterases. The design was based on a previously developed strategy [G. Höst, L.G. Mårtensson, B.H. Jonsson, Redesign of human carbonic anhydrase II for increased esterase activity and specificity towards esters with long acyl chains, Biochim. Biophys. Acta 1764 (2006) 1601-1606.], in which docking of a transition state analogue (TSA) to the active site of HCAII was used to predict mutations that would allow the reaction. A triple mutant, V121A/V143A/T200A, was thus constructed and shown to hydrolyze pNPBenzo with k(cat)/K(M)=625 (+/- 38) M(-1) s(-1). It is highly active with other ester substrates as well, and hydrolyzes para-nitrophenyl acetate with k(cat)/K(M)=101,700 (+/- 4800) M(-1) s(-1), which is the highest esterase efficiency so far for any CA variant. A parent mutant (V121A/V143A) has measurable K(M) values for para-nitrophenyl butyrate (pNPB) and valerate (pNPV), but for V121A/V143A/T200A no K(M) could be determined, showing that the additional T200A mutation has caused a decreased substrate binding. However, k(cat)/K(M) is higher with both substrates for the triple mutant, indicating that binding energy has been diverted from substrate binding to transition state stabilization.


[Related factors in the elderly's use of municipal institutions: basic study for promoting participation in a care prevention program].
This study was performed to examine factors related to the use of municipal institutions with the focus on 'Accessibility'. The data used in this analysis were from the AGES (Aichi Gerontological Evaluation Study) Project, conducted by Nihon Fukushi University located in Aichi Prefecture, Japan. A self-administrated questionnaires was mailed to 5,759 persons aged 65 years and older who were not disabled in 2006, and 2,795 persons responded. A dependent variable in the analysis was the use of municipal institutions (a Public Health Center, Welfare Center for the elderly and City Hall). Independent variables were age, disease, employment status, IADL (instrumental activities of daily living), depression (GDS: geriatric depression scale), self-rated feeling of health and 'Accessibility' (transportation mode and distance from municipal institutions). Multivariate logistic analysis was used to provide adjusted relative risk estimates for the associations between use of municipal institutions and related factors. In multivariate logistic analysis, 'Accessibility' showed a significant relative risk for the use of municipal institutions after controlling for other related factors. Compared with the elderly whose places of residence was located less than 250 meters from the municipal institutions, the relative risk for the elderly who resided more than 1,500 meters from the municipal institutions was around 0.4 (male: RR = 0.358; female: RR = 0.378). 'Accessibility' is significantly related to the use of municipal institutions. To promote use of the municipal institutions, improving elderly access may well be effective.


Soil acidification and the liming potential of biochar.
Soil acidification in managed ecosystems such as agricultural lands principally results from the increased releasing of protons (H+) from the transformation reactions of carbon (C), nitrogen (N) and sulphur (S) containing compounds. The incorporation of liming materials can neutralize the protons released, hence reducing soil acidity and its adverse impacts to the soil environment, food security, and human health. Biochar derived from organic residues is becoming a source of carbon input to soil and provides multifunctional values. Biochar can be alkaline in nature, with the level of alkalinity dependent upon the feedstock and processing conditions. This review covers the fundamental aspects of soil acidification and of the use of biochar to address constraints related to acidic soil. Biochar is increasingly considered as an effective soil amendment for reducing soil acidity owing to its liming potential, thereby enhancing soil fertility and productivity in acid soils. The ameliorant effect on acid soils is mainly because of the dissolution of carbonates, (hydro)-oxides of the ash fraction of biochar and potential use by microorganisms.


Mouse spider bites (Missulena spp.) and their medical importance. A systematic review.
To determine the clinical significance of definite bites by mouse spiders (Actinopodidae: Missulena spp.) from published case reports/series and museum records. A computerised literature search of MEDLINE and EMBASE was undertaken. All cases reported to major Australian museums and reports from venom researchers working with mouse spiders were also reviewed. Textbooks on clinical toxinology were searched and further reports of cases were located. All cases of definite spider bites where the spider was collected and identified by an expert as a mouse spider were included. All reports were evaluated and the following data extracted: patient demographics (age, sex, geographical location, season), bite site, local and systemic effects, and hospital attendance. Clinical effects were classified into three groups: severe neurotoxic envenoming, local neurotoxic effects or mild systemic effects, and minor local effects. Forty definite bites were identified from around Australia, with only one case of severe envenoming (a 19-month-old child). Local neurotoxic effects occurred in six cases and minor systemic effects in five. There was no evidence of envenoming in most bite victims, and the rate of severe envenoming was 2.5% (95% CI, 0-13%). There were no recorded deaths. In most cases, bites by mouse spiders cause only minor or moderate effects. Severe envenoming is rare and far less common than for funnel-web spider bites. Mouse spider bites do not appear to be a major medical problem.


Near-infrared NIR irradiation and sodium hypochlorite: An efficacious association to counteract the Enterococcus faecalis biofilm in endodontic infections.
New strategies are necessary for the prevention of endodontic infections caused by Enterococcus faecalis, a common resistant pathogen and biofilm producer. Aim of the present study was to compare the effects of Near-Infrared (NIR) Light-Emitting Diode (LED) irradiation and different concentrations of sodium hypochlorite (NaOCl) alone or combined to each other on the E. faecalis biofilm, on artificial and human dentin surfaces. E. faecalis ATCC 29212 preformed biofilms, on polystyrene wells and on dentin discs, were treated with 880 nm NIR irradiation and NaOCl at 4%, 2.5%, 1% and 0.5% alone and combined to each other (NIR irradiation plus NaOCl 1% or 0.5%) at 5 and 10 min. Treated biofilms were compared to the controls for (i) biofilm biomass evaluation, (ii) CFU count for the quantification of cultivable cells and (iii) cells viability. All the detected experimental conditions displayed a significant reduction of biofilm biomass (p < 0.001) and CFUs/mL (p < 0.01) in respect to the controls on both tested surfaces. The effects on the E. faecalis biomass, colony count and cell viability were not time-dependent except for NaOCl 2.5% and 1% in the biofilm biomass reductions on human dentin discs. NIR-LED irradiation alone showed a reduction of E. faecalis aggregates without interfering with cell viability whereas NaOCl alone expressed a killing effect in a concentration dependent way. The combination of NIR-LED irradiation with NaOCl 1% and 0.5% displayed a double effect of cluster disaggregation and cell killing. In particular, NIR-LED irradiation combined with NaOCl 0.5% displayed an anti-biofilm activity major than those expressed by NaOCl 0.5% alone (p = 0.001) with a reduction of biomass 93% vs 71% and 97% vs 25% after 10 min, on polystyrene wells and human dentin discs, respectively. The innovative use of NIR-LED irradiation combined at short times with low concentration of NaOCl (1% and 0.5%) is capable to reach a significant effect on E. faecalis biofilm, especially on human dentin discs.


Uranium deposition and retention in a USTUR whole body case.
This report describes a whole body donation from a person with a documented occupational intake of uranium. USTUR Case 1002 was an adult male who died from an acute cerebellar infarct at the age of 83. He worked as a power operator, utility operator, and metal operator for 28 years in a facility that processed and handled radioactive materials. Although he suffered a number of burns from hot metal and acids, cuts, abrasions, and puncture wounds during his many years of work, there were no corresponding health physics or medical records to indicate that these occurrences needed or required excision or decontamination due to the suspicion of the deposition of radioactive material. Over the course of his employment, USTUR Case 1002 submitted numerous urine samples for uranium, plutonium, and fission product analysis. The highest single uranium value measured during this time period was approximately 30 microg L(-1) recorded during the second year of his employment. A urinary bioassay sample taken before termination of employment measured 4.3 microg L(-1). The mean urinary uranium concentration per liter per year calculated from the employee's bioassay records covering the first eleven years of monitoring averaged less than 3 microg L(-1). The ratio of 234/238U activity in the lung tissue was about 1, the same as that found in natural uranium. The highest concentration of uranium was found in a tracheobronchial lymph node. The uranium content in the various tissues of the body followed a rank order lung > skeleton > liver > kidney. Concentration of uranium in the kidney tissue was approximately 1.98 ng g(-1), about 3 orders of magnitude less than the generally accepted threshold level for permanent kidney damage of 3 microg U g(-1) and roughly equal to the 1.4 ng g(-1) reported for Reference Man. The autopsy disclosed findings not uncommon in the aged: severe atherosclerosis, areas of sclerotic kidney glomeruli with stromal fibrous scarring, and moderate to severe arterionephrosclerosis. Lung sections contained parenchymal areas of acute vascular congestion and a mild degree of anthracosis.


A holistic picture of spatial distribution of river polluting loads in a highly anthropized area.
For many years, there has been a debate on the polluting loads affecting the Gulf of Naples, one of Italy's most spectacular and iconic landscape. The wide territory bordering the Gulf includes the Sarno river basin (SRB) managed by the Southern Apennines River Basin District Authority in the framework of Unit of Management Sarno (UoM-Sarno). The paper investigated the anthropogenic pressures and their spatial distribution in the UoM-Sarno, revealing as SRB represents a hotspot of pollution mainly due to the high population density and widespread hydro-demanding activities which are responsible of high organic and eutrophication loads. The pollution sources, variably distributed on the area, and potentially conveyed to the wastewater treatment plants (WWTPs) located into SRB, were estimated considering the WWTPs treatment capacity as well. Results revealed a holistic picture of UoM-Sarno area allowing to establish the priorities of the interventions aimed at safeguarding the coastal marine resources. In particular, 2590 tons BOD/year were directly discharged into the Gulf of Naples due to the missing of sewers, and other 10,600 tons BOD/year are potentially discharged in the Sarno river reaching the sea, considering the contribution of population, industrial activity, and livestock.


Three new species of myrmecophilous scutacarid mites (Acari: Scutacaridae) from Western Siberia, Russia.
Three new species of myrmecophilous mites of the genus Scutacarus Gros, 1845 (Acariformes: Pygmephoroidea: Scutacaridae), S. lasiophilus sp. nov., S. myrmicinus sp. nov., and S. crinitus sp. nov. are described from ants and their nests in Tyumen Province, Western Siberia, Russia.


Differences and similarities among experts' opinions on Salmonella enterica dynamics in swine pre-harvest.
A workshop was conducted to elicit expert opinion on infection status and transmission of salmonella in pigs at the farm of origin, during transport and during lairage. A second objective was to compare opinions regarding risk factors for salmonella introduction and control at the farm level between experts from different countries. Thirty-six experts from 11 countries filled in a paper-and-pencil questionnaire during an international conference. Experts from all countries agreed on the risk of salmonella introduction related to live animals and the importance of general hygiene and all-in/all-out management for salmonella control. However, workshop participants from Denmark put more weight on factors related to feed while experts from USA rated factors related to rodents and people contact higher. The experts believed that 21-33% of pigs coming from a chronically infected farm would be infected with salmonella, but only one-third of the infected pigs would be shedders. Regarding transport and lairage, the US participants believed that contamination was occurring in the majority of pigs regardless of initial infection status and particularly during lairage; in contrast, the Danish experts were more optimistic with respect to the contamination and infection risk. US experts believed that the incidence of salmonella shedding would be high among pigs infected during transport and lairage and that an important proportion of 'carrier' pigs would start shedding. Our results reflect the differences in the level of salmonella infection and implemented control strategies between countries as well as the different philosophies that professionals have. The differences in opinion regarding salmonella dynamics could be due either to true differences in risk as a consequence of distinct management and transport practices in Denmark and USA or to a difference in perception.


Female Mice Exposed to Postnatal Neglect Display Angiotensin II-Dependent Obesity-Induced Hypertension.
Background We have previously reported that female mice exposed to maternal separation and early weaning (MSEW), a model of early life stress, show exacerbated diet-induced obesity associated with hypertension. The goal of this study was to test whether MSEW promotes angiotensin II-dependent hypertension via activation of the renin-angiotensin system in adipose tissue. Methods and Results MSEW was achieved by daily separations from the dam and weaning at postnatal day 17, while normally reared controls were weaned at postnatal day 21. Female controls and MSEW weanlings were placed on a low-fat diet (LF, 10% kcal from fat) or high-fat diet (HF, 60% kcal from fat) for 20 weeks. MSEW did not change mean arterial pressure in LF-fed mice but increased it in HF-fed mice compared with controls (P<0.05). In MSEW mice fed a HF, angiotensin II concentration in plasma and adipose tissue was elevated compared with controls (P<0.05). In addition, angiotensinogen concentration was increased solely in adipose tissue from MSEW mice (P<0.05), while angiotensin-converting enzyme protein expression and activity were similar between groups. Chronic enalapril treatment (2.5 mg/kg per day, drinking water, 7 days) reduced mean arterial pressure in both groups of mice fed a HF (P<0.05) and abolished the differences due to MSEW. Acute angiotensin II-induced increases in mean arterial pressure (10 μg/kg SC) were attenuated in untreated MSEW HF-fed mice compared to controls (P<0.05); however, this response was similar between groups in enalapril-treated mice. Conclusions The upregulation of angiotensinogen and angiotensin II in adipose tissue could be an important mechanism by which female MSEW mice fed a HF develop hypertension.


The depth distribution of optimal stimulus orientations for neurones in cat area 17.
Neurones recording during penetrations through cat area 17 as near parallel to the radial fibre bundles as possible have been quantitatively tested as to their optimal orientation. Optimal orientation within any one penetration was similar though considerable variability was observed. Histological reconstruction and other considerations showed that this variability could not be attributed to poor penetration angle or limitations of the microelectrode technique. These results confirm that neurones with similar optimal orientations are found in all cortical layers at one cortical locus, but it is difficult to reconcile the variability observed with a mosaic-like distribution of orientation across the cortical surface. The findings were consistent, however, with the assumption of a continuous distribution of orientation sensitivity across the cortical surface with considerable superimposed scatter.


Kaposi's sarcoma in an HIV-negative chronic lymphocytic leukemia patient without immunosuppressive therapy: A case report.
Kaposi's sarcoma is a neoplasm of endothelial cells. That vascular tumor is usually limited to the skin, but it may involve mucous membranes, visceral organs, and lymph nodes. Serological evidence has shown that human herpesvirus 8 infection is required for the development of Kaposi's sarcoma. Chronic lymphocytic leukemia is the most common leukemia all over the world. Increased skin cancer risk has been reported for patients with chronic lymphocytic leukemia. The relation between these two pathologies has not yet been clarified. We report a case of Kaposi's sarcoma along with chronic lymphocytic leukemia in a patient who did not receive therapy for chronic lymphocytic leukemia.


Alpha 2-macroglobulin 'fast' forms inhibit superoxide production by activated macrophages.
Mouse peritoneal macrophages activated by bacillus Calmette-Guerin (BCG) were incubated with human alpha 2-macroglobulin converted to its 'fast' form with either trypsin or methylamine before being stimulated with phorbol myrystate acetate. Both alpha 2-macroglobulin-trypsin and alpha 2-macroglobulin-methylamine inhibited macrophage production of superoxide anion (O2-) while native alpha 2-macroglobulin had little effect except at high concentration. The alpha 2-macroglobulin 'fast' forms, which bind with a Kd of about 8 nM, inhibited 50% generation of O2- (ID50) at a concentration of 7 nM while alpha 2-macroglobulin inhibited O2- production with an ID50 of 141 nM. The 'fast' forms of alpha 2-macroglobulin may play a role in the feedback regulation of inflammatory reactions.


Elderly patients with altered mental status.
Mental status changes in the elderly are a source of concern and a challenge for the emergency physician. A variety of medical conditions and psychiatric disturbances are potential causes of those symptoms. Acute changes must be differentiated from mental status alterations occurring as a result of chronic conditions. This article focuses on the emergency evaluation, treatment, and differential diagnosis of this symptom complex.


Doula, Sister, Aunt, Storyteller: A Midwife's Retelling of Birth.
As a midwife, delivering hundreds of babies a year in a busy city hospital, I rarely have the opportunity to reconnect with what made me pursue the path of midwifery. This is the story of the birth of my niece.


[Studies on the constituents of trichosanthes root. I. Constituents of roots of Trichosanthes kirilowii Maxim. var. japonicum Kitam].
From the fresh roots of Trichosanthes kirilowii Maxim. var. japonicum Kitam., the following substances were identified: methyl palmitate, palmitic acid, suberic acid, alpha-spinasterol, stigmast-7-en-3 beta-ol, alpha-spinasterol 3-O-beta-D-glucopyranoside, stigmast-7-en-3 beta-ol 3-O-beta-D-glucopyranoside, bryonolic acid, cucurbitacin B, cucurbitacin D, vomifoliol, ethyl alpha-L-arabinofranoside and D-glucose. The bitter taste of Trichosanthes Root was considered to be due to cucurbitacin B and D.


Improvement of Vicia-micronucleus test for assessment of soil quality: a proposal for international standardization.
The Viciafaba root tip micronucleus test is one of the most employed plant genotoxicity assays, and has been used on various types of contaminated materials. This test has been standardized by AFNOR, the French member organization of ISO. However, this test is usually performed with a water extraction step but soil genotoxicity assessment would be more relevant when performed directly in the soil itself. In order to harmonize these protocols, an ISO standard for the V.faba micronucleus test in both liquid phase (exposure of plants to different liquid matrix, including soil water extracts) and solid phase (direct exposure of plants to the soil) would be very useful. In this context, we compared two exposure durations in the solid phase (48 h and 5 d) for the V.faba micronucleus test with two different well-known genotoxicants, maleic hydrazide and copper sulfate. We concluded that these two durations induced equivalent sensitivity: the micronucleus frequency was significantly increased with 5 μmol maleic hydrazide per kg dry soil and with 2 mmol copper sulfate per kg dry soil with both exposure durations. However, exposing roots to soil during 48 h is more practical. Moreover, organically and conventionally cultured seeds were employed to determine whether the seed provenance influenced the test sensitivity. Organic seeds were less sensitive to copper, possibly because copper-based treatments are permitted, and often applied, in organic farms. Therefore, in the absence of completely non-treated seeds, organically-cultured seeds did not appear to offer any advantages over conventional seeds.


Comparison of coherence and phase synchronization of the human sleep electroencephalogram.
Potential differences between coherence and phase synchronization analyses of human sleep electroencephalogram (EEG) are assessed and occurrences of phase vs. complete synchronization between EEG signals from different locations during different sleep stages are investigated. Linear spectral coherence, mean phase coherence (MPC) z-score and Pearson's correlation coefficient of analytic amplitudes were evaluated for different spectral bands of whole-night EEG recordings from 25 healthy subjects. Coherence and MPC z-score demonstrated practically the same statistical differences between vigilance stages, confirming the findings of previous coherence-based studies. MPC z-score and amplitude correlations were most correlated (>0.5) between homologous interhemispheric positions and least correlated between nonhomologous interhemispheric positions and between fronto-occipital positions. Coherence and phase synchronization provided essentially the same information. Complete synchronization was manifested by highly coherent phases and correlated amplitudes, as well as by correlated changes of phase synchronization, coherence and amplitude correlations between vigilance states. In cases of weaker coupling, phase synchronization and coherence change in agreement, while behaviour of amplitude correlations differs. Phase synchronization analysis is not superior to coherence analysis, although the coupling between EEG signals is dominated by phase synchronization which turns into complete synchronization in the most strongly coupled EEG signals.


Intercellular CO2 concentration and water-use efficiency of temperate plants with different life-forms and from different microhabitats.
Photosynthesis and transpiration were measured simultaneously, under near-optimum and constant environmental conditions, in intact leaves of plants native to the temperate forest region. A linear relationship between photosynthetic rate and stomatal conductance was found in every species tested irrespective of leaf age or season, indicating that the calculated intercellular CO2 concentration and water-use efficiency were fairly constant within a species. The values of intercellular CO2 concentration and water-use efficiency ranged from 221 to 271 μl l-1 [Formula: see text] and 4.46 to 8.20 μmol CO2 mmolH2O-1 (6.24±0.90 μmol CO2 mmolH2O-1), respectively. The variations in intercellular CO2 concentration and water-use efficiency were not directly related to photosynthetic capacities, life-forms, or microhabitat preferences. The intercellular CO2 concentrations found in this study were close to values reported from cultivated plants and plants native to more arid regions, suggesting a common mechanism to maintain the stomatal conductance proportional to photosynthetic capacity over a wide variety of C3 plants.


Prognostic Impact of Immune-Related Gene Expression in Preoperative Peripheral Blood from Gastric Cancer Patients.
Anti-PD-1 therapy has shown a promising clinical outcome in gastric cancer (GC). We evaluated the clinical significance of systemic immune-related gene expression in GC patients who underwent surgery. The correlation between the preoperative PD-1, PD-L1, and CD8 mRNA levels in peripheral blood (PB) and clinicopathological factors, including survival, in 372 GC patients was evaluated using quantitative RT-PCR. PD-1- and PD-L1-expressing cells were identified by flow cytometric analysis. The PD-1, PD-L1, and CD8 mRNA levels in GC patients were significantly higher than those in normal controls, respectively (all P < 0.0001). The levels of each gene were positively correlated with those of the other two genes (all P < 0.0001). GC patients with low PD-1, high PD-L1, and low CD8 mRNA levels had significantly poorer overall survival (OS) than those with high PD-1, low PD-L1, and high CD8 mRNA levels, respectively (P < 0.01, P < 0.05, and P < 0.05, respectively). Multivariate analysis showed that low PD-1 and high PD-L1 mRNA levels were independent poor prognostic factors for OS (PD-1: HR 2.38, 95% CI 1.27-4.78, P < 0.01; PD-L1: HR 1.81, 95% CI 1.15-2.78, P < 0.05). PD-1 and PD-L1 expression occurred on T cells (> 90%) and T cells or monocytes (> 70%), respectively. The PD-1, PD-L1, and CD8 mRNA levels in preoperative PB reflected the anti-tumour immune response, and the low PD-1 and high PD-L1 mRNA levels in PB were independent poor prognostic markers in GC patients who underwent surgery.


[The traditions of "the saint doctor" Gaas in Russian clinic: A.N. Kazem-Bek and V.A. Kazem-Bek (Kazan-Harbin)].
The article retrace the process of maintaining and passing on the humanistic traditions of Russian medicine founded by Doctor F.P. Gaas in the late XIXth - early XXth centuries. The biographies of Kazan physicians are presented, including eminent therapist professor A.N. Kazem-Bek (the representative of N.A. Vinogradov clinical school) from Kazan University and his son, Doctor V.A. Kazem-Bek, who practised medicine in Harbin.


Evaluation of residual level and distribution characteristics of organochlorine pesticides in agricultural soils in South Korea.
In this study, we evaluated the residual levels and distribution characteristics of 10 organochlorine pesticides (OCPs) in the soil of agricultural lands (paddy field, vegetable field, and orchard, n = 150) nationwide. As a result of the investigation, 3-10 types of OCPs were detected in combination in 144 locations (96%) of the total 150 locations. Among those OCPs, dichlorodiphenyltrichloroethane (DDT) and endosulfan were detected in high amounts. The geometric mean concentrations of DDT and endosulfan were ∑DDT 0.31 ng g-1 (ND-2187.18 ng g-1) and ∑endosulfan 0.33 ng g-1 (ND-312.68 ng g-1), respectively. OCP concentrations were generally higher in orchards than in other agricultural fields due to a large amount of pesticides used. DDT in two orchards was detected at 2187.18 ng g-1 and 1061.78 ng g-1, exceeding the levels stated in the Canadian DDT Soil Quality Guidance (SQG, 700 ng g-1). The result of applying the isomer ratio to evaluate the recent or past use of DDT, endosulfan, and hexachlorocyclohexane (HCH), which had a high detection rate, showed that it could be attributable to historical usage. DDT and HCH showed statistically similar residual distribution patterns; however, endosulfan did not show a clear correlation with DDT and HCH due to the effect of its recent use. Thus, the results of evaluation of OCP residual levels and distribution characteristics can be used for the soil management policy of OCPs in agricultural lands in Korea.


Inhibitors of cyclic nucleotide phosphodiesterases inhibit protein carboxyl methylation in intact blood platelets.
The cycle of protein-carboxyl methylation and demethylation was studied in intact blood platelets. Platelets rapidly incorporated L-[methyl-3H]methionine and after a delay of about 20 min, they evolved [3H]methanol. This evolution, and the amount of [3H] methanol liberated by treatment with base, was inhibited in a dose-dependent fashion by the cyclic nucleotide phosphodiesterase inhibitors 3-isobutyl-1-methylxanthine, papaverine, dipyridamole, and RA233 (2,6-bis(diethanolamino)-4-piperidinopyrimido[5,4-d] pyrimidine). Each of these compounds increased the incorporation of [3H]methionine into platelets. The effects of RA233 were studied in more detail. Inhibition of [3H]methanol production was not potentiated by stimulators of the adenylate cyclase or the guanylate cyclase. The majority of the base-labile radioactivity was trichloroacetic acid precipitable. Thin layer chromatography of extracts of platelets incubated with L-[35S]methionine showed that RA233 did not induce a cellular accumulation of [35S]S-adenosylhomocysteine, and that it actually increased the amount of cellular [35S]S-adenosylmethionine. Discontinuous polyacrylamide gel electrophoresis at acid pH using the cationic detergent benzyldimethyl-n-hexadecylammonium chloride of platelets incubated with [3H]methionine showed incorporation of radioactivity into more than 30 protein bands, including one which co-migrates with calmodulin. The incorporation into the majority of these bands was inhibited by RA233 in a dose-dependent fashion. It is suggested that caution should be used in ascribing the pharmacological effects of known phosphodiesterase inhibitors to increases in cyclic nucleotides, because some of these effects could be due to inhibition of protein carboxyl methylation.


Resolving uncertainty in the spatial relationships between passive benzene exposure and risk of non-Hodgkin lymphoma.
Benzene is a known occupational carcinogen associated with increased risk of hematologic cancers, but the relationships between quantity of passive benzene exposure through residential proximity to toxic release sites, duration of exposure, lag time from exposure to cancer development, and lymphoma risk remain unclear. We collected release data through the Environmental Protection Agency's Toxics Release Inventory (TRI) from 1989 to 2003, which included location of benzene release sites, years when release occurred, and amount of release. We also collected data on incident cases of non-Hodgkin lymphoma (NHL) from the Georgia Comprehensive Cancer Registry (GCCR) for the years 1999-2008. We constructed distance-decay surrogate exposure metrics and Poisson and negative binomial regression models of NHL incidence to quantify associations between passive exposure to benzene and NHL risk and examined the impact of amount, duration of exposure, and lag time on cancer development. Akaike's information criteria (AIC) were used to determine the scaling factors for benzene dispersion and exposure periods that best predicted NHL risk. Using a range of scaling factors and exposure periods, we found that increased levels of passive benzene exposure were associated with higher risk of NHL. The best fitting model, with a scaling factor of 4 kilometers (km) and exposure period of 1989-1993, showed that higher exposure levels were associated with increased NHL risk (Level 4 (1.1-160kilograms (kg)) vs. Level 1: risk ratio 1.56 [1.44-1.68], Level 5 (>160kg) vs. Level 1: 1.60 [1.48-1.74]). Higher levels of passive benzene exposure are associated with increased NHL risk across various lag periods. Additional epidemiological studies are needed to refine these models and better quantify the expected total passive benzene exposure in areas surrounding release sites.


Outcomes of Transcatheter Aortic Valve Replacement in Mixed Aortic Valve Disease.
The aim of this study was to compare outcomes after transcatheter aortic valve replacement (TAVR) in patients with pure aortic stenosis (AS) (i.e., no or trivial associated aortic regurgitation [AR]) with those in patients with AS and mild or more severe AR (i.e., mixed aortic valve disease [MAVD]). TAVR is indicated in treating patients with severe AS. Limited data exist regarding the outcomes of TAVR in patients with MAVD. A total of 1,133 patients who underwent TAVR between January 2014 and December 2017 were included. The primary outcome was all-cause mortality. The comparison was adjusted to account for post-TAVR AR development in both groups. The secondary outcomes included composite endpoints of early safety and clinical efficacy as specified in the Valve Academic Research Consortium-2 criteria. Variables were compared using Mann-Whitney, chi-square, and Fisher exact tests, while Kaplan-Meier analyses were used to compare survival. A total of 688 patients (61%) had MAVD (median age 83 years , 43% women). Among these, 17% developed mild, 2% moderate, and <1% severe post-TAVR AR. Overall, patients with MAVD had better survival compared with patients with pure AS (p = 0.03). Among patients who developed post-TAVR AR, those in the MAVD group had better survival (p = 0.04). In contrast, in patients who did not develop post-TAVR AR, pre-TAVR AR did not improve survival (p = 0.11). Patients with MAVD who underwent TAVR had better survival compared with patients with pure AS. This is explained by the better survival of patients with MAVD who developed post-TAVR AR, likely due to left ventricular adaptation to AR.


Efficacy of new class I medical device for actinic keratoses: a randomized controlled prospective study.
The presence of Actinic Keratoses (AKs) represent the most important warning sign of subclinical ultraviolet radiation. Currently, the regular use of sunscreens is considered essential for the prevention of the development of AKs. We evaluated the effectiveness of a new class I Medical Device (MD) for the prevention and treatment of AKs vs traditional sunscreen alone (SPF 100+). We conducted a randomized controlled prospective study in 90 Caucasian patients: 62 immunocompetent and 28 Organ Transplant Recipients (OTRs). We randomly assigned subjects to the MD group or sunscreen alone in a 1:1 assignment ratio. The patients have been reevaluated after three and six months. In immunocompetent patients treated with MD, at the end of the study the reduction of the mean number of AKs was 54.7 vs. 9.43% with photoprotector. In OTRs, the global reduction was of 36.7% after MD use compared to 14.3% with the sunscreen. The prevalence of NMSCs, in the patients treated with MD, was 11.11 and 17.18 with sunscreen; the incidence was 19.7 in patients treated with MD and 32.1 in those treated with sunscreen. The MD has demonstrated good efficacy in the reduction of visible AKs, encouraging its use also in high-risk category, like OTRs.


Assessment of virulence factors characteristic of human Escherichia coli pathotypes and antimicrobial resistance in O157:H7 and non-O157:H7 isolates from livestock in Spain.
The distribution of virulence factors (VFs) typical of diarrheagenic Escherichia coli and the antimicrobial resistance (AMR) profiles were assessed in 780 isolates from healthy pigs, broilers, and cattle from Spain. VF distribution was broader than expected, although at low prevalence for most genes, with AMR being linked mainly to host species.


Impact of code stroke on thrombolytic therapy in patients with acute ischemic stroke at a secondary referral hospital in Taiwan.
Efficacy of thrombolytic therapy decreases with time elapsed from symptom onset. We sought to identify the impact of code stroke on the thrombolytic therapy. Code stroke is activated by the emergency physician when a patient is eligible for thrombolytic therapy. We retrospectively reviewed patients with acute ischemic stroke between January 2011 and December 2014. In total, 1809 patients were enrolled. Code stroke was activated in 233 of 351 patients arriving at the emergency room (ER) within 3 h of symptom onset, and in 21 patients arriving >3 h. The sensitivity, specificity, and positive and negative predictive values of code stroke were 76%, 46%, 72%, and 51%, respectively. Thrombolytic therapy was provided to 58 patients, accounting for 3.4% of all cerebral infarcts. Code stroke was activated in 40 of these patients. The most common reasons for excluding thrombolytic therapy were: National Institute of Health Stroke Scale (NIHSS) < 6, intracranial hemorrhage (ICH), and age >80 years. Mean liaison-to-neurological evaluation time was only 6 min. Code stroke activation significantly reduced all the intervals, except for the onset-to-ER and door-to-order times. During the 4-year study period, there were significant reductions of the door-to-neurology liaison time by 28 min and door-to-laboratory time by 22 min. The proportion of door-to-needle time within 60 min improved from 33% in 2011 to 67% in 2014. Improved NIHSS scores during hospitalization were most prominent in tPA-treated patients. Symptomatic ICH occurred in 3.6% patients arriving within 3 h. Death occurred in 50% of patients received tPA treatment on family's request, and only 13% of those patients had favorable outcome. Code stroke is effective in reducing in-hospital delays. The accuracy of code stroke activation has acceptable sensitivity but low specificity. Rapid patient assessment by neurologists increases the number of patients eligible for thrombolytic therapy.


Injuries due to deliberate violence in areas of Argentina. II. Lesions. Copenhagen Study Group.
As part of a transcultural investigation of violent behavior in Argentina and Denmark, the lesions from accidents involving deliberate violence registered in the emergency wards of Hospital Fernandez and Hospital Pinero in Capital Federal Buenos Aires over a period of 13 and 17 months, respectively, were studied. Among the 281 victims entering the two emergency wards blunt violence without use of instruments was most often reported to be the violation method. Frequently indicated violation instruments against the male victims were batons (18.7%), sharp instruments (17.7%), and firearms (17.7%), the corresponding figures for female victims being 9.6%, 8.4% and 4.8%. The use of firearms and batons was considerably more pronounced in Argentina than in Denmark, particularly against male victims. A total of 373 primary and secondary diagnoses were reported from the patients, the most frequent diagnoses being contusions and open wounds in the head/neck region. Forty-three percent of the diagnoses were related to the head/neck region, being the most frequently injured region and the trunk the second most frequently injured region (30%). The degree of predominance of lesions in the head/neck region was much less than in the Danish material. Injuries of internal organs of the trunk were considerably more frequent in Argentina than in Denmark. Eighty-five percent of the victims had moderate or less serious lesions when assessed on the basis of the scores in the Abbreviated Injury Scale (AIS), (score less than or equal to 2). The AIS scores of the lesions in female victims were on average only slightly higher than those recorded in the Danish study, while 16.1% of the male Argentinian victims had lesions scored greater than or equal to 3 compared to 1.8% in male Danish victims. The need for treatment and hospitalization was more pronounced than in the Danish study. It may be concluded that the frequency of serious cases of deliberate violence probably would decrease if more restrictive rules for the possessing of firearms were enacted and enforced.


Genetic and environmental contributions to perfectionism and its common factors.
The aims of this study: (1) To evaluate the relative contributions of genetics and environment to perfectionism and it's two constructs: self-oriented, and socially prescribed perfectionism. (2) To clarify genetic and environmental common origins of both personal and social components. Participants were 258 pairs of adolescent Spanish twins. Socially prescribed and self-oriented perfectionism were assessed using the perfectionism subscale of the Eating Disorder Inventory. univariate and bivariate twin models, according to sex. Results; Heritability of self-oriented perfectionism was 23% in boys and 30% in girls, and of socially prescribed perfectionism 39% in boys and 42% in girls. Bivariate analysis suggested a common genetic and environmental pathway model. The genetic correlation between both perfectionisms was 0.981 in boys and 0.704 in girls. The non-shared environmental correlation was 0.254 in boys and 0.259 in girls. Conclusions; genetic influences on perfectionism are moderate during adolescence. Our results point toward a shared genetic component underlying both kind of perfectionism. These findings generate doubts about the hypothesis of a leading role of genetics in the pathogenesis of Self-oriented perfectionism and of environment in socially prescribed. The high genetic correlation seems to indicate that self-oriented and socially prescribed are the same dimension of perfectionism.


High density lipoprotein infusion and partial plasma exchange in Tangier disease.
High density lipoprotein (HDL) infusion and partial plasma exchange were undertaken in two patients homozygous for Tangier disease. Serum samples and ultracentrifugally isolated serum fractions were analysed over a period of 7 days post infusion by agarose electrophoresis, two-dimensional immunoelectrophoresis (employing antibodies to HDL, HDL3, Apoprotein A-I, and Apoprotein A-II), Apoprotein A radioimmunoassay, and analytical polyacrylamide electrophoresis. The following observations were made: (a) immediately after HDL substitution the broad-beta band, normally visible upon agarose electrophoresis of Tangier plasma, resolved into a distinct beta and pre-beta band; (b)as HDL was catabolized, an abnormal alpha-migrating lipoprotein was generated which contained Apoprotein A-II as protein constituent; and (c) there was a proferential loss of Apoprotein A-I from HDL and the plasma compartment in the course of HDL catabolism. The results suggest that the defect in Tangier disease resides with enhanced catabolism or defective synthesis of Apoprotein A-I.


Single-rater reliability of a three-dimensional instrument for decision-making in tertiary triage and ICU- prioritization-a case vignette simulation study.
Disconcerting reports from different EU countries during the first wave of the COVID-19 pandemic demonstrated the demand for supporting decision instruments and recommendations in case tertiary triage is needed. COVID-19 patients mainly present sequentially, not parallelly, and therefore ex-post triage scenarios were expected to be more likely than ex-ante ones. Decision-makers in these scenarios may be highly susceptible to second victim and moral injury effects, so that reliable and ethically justifiable algorithms would have been needed in case of overwhelming critical cases.To gather basic information about a potential tertiary triage instrument, we designed a three-dimensional instrument developed by an expert group using the Delphi technique. The instrument focused on three parameters: 1) estimated chance of survival, 2) estimated prognosis of regaining autonomy after treatment, and 3) estimated length of stay in the ICU. To validate and test the instrument, we conducted an anonymous online survey in 5 German hospitals addressing physicians that would have been in charge of decision-making in the case of a mass infection incident. Of about 80 physicians addressed, 47 responded. They were presented with 16 fictional ICU case vignettes (including 3 doublets) which they had to score using the three parameters of the instrument.We detected a good construct validity (Cronbach's Alpha 0.735) and intra-reliability (p < 0.001, Cohens Kappa 0.497 to 0.574), but a low inter-reliability (p < 0.001, Cohen's Kappa 0.252 to 0.327) for the three parameters. The best inter-reliability was detected for the estimated length of stay in the ICU. Further analysis revealed concerns in assessing the prognosis of the potentially remaining autonomy, especially in patients with only physical impairment.In accordance with German recommendations, we concluded that single-rater triage (which might happen in stressful and highly resource-limited situations) should be avoided to ensure patient and health care provider safety. Future work should concentrate on reliable and valid group decision instruments and algorithms and question whether the chance of survival as a single triage parameter should be complemented with other parameters, such as the estimated length of stay in the ICU.


Human IgM+IgD+ B cells, the major B cell subset in the peripheral blood, express V kappa genes with no or little somatic mutation throughout life.
Peripheral blood B cells of a 67-year-old person were separated into IgM+IgD+, IgM+IgD-, and IgM-IgD- subsets, and nucleotide sequences of expressed immunoglobulin light chain variable (V) regions encoded by V kappa 3 and V kappa 4 gene family members were determined from amplified cDNA. V region sequences from IgM+IgD+ cells (the major B cell population in the blood) showed no or little somatic mutation (0.3%), in contrast to V kappa sequences from IgM+IgD- and IgM-IgD- B cells (2.0% and 3.9%, respectively). This suggests that in the human like in the mouse, and independently of age, somatically mutated memory B cells accumulate in the compartment of IgM-IgD- cells, whereas the IgM+IgD+ subpopulation consists of cells whose antibody repertoire is mainly determined by V region gene rearrangements and N-region insertion, at the molecular level. The somatically mutated IgM+IgD- cells may represent early descendants of IgM+IgD+ cells recruited into the memory cell compartment.


Massive osteolysis of the skull and its therapeutic implications: a case report.
A case of massive osteolysis of the skull and its histology is described. Removal of the bone defect with a margin of normal bone and covering of the defect by cranioplasty is advised and may arrest the disease.


Altered regulation of c-jun and its involvement in anchorage-independent growth of human lung cancers.
The c-jun oncogene is frequently overexpressed in non-small-cell lung cancers (NSCLC), but its functional involvement in lung cancer development has not been clearly elucidated. In this study, we found that among the immediate-early serum responsible genes, exemplified by c-jun, c-fos and c-myc, induction of c-jun in a human bronchial epithelial cell line, BEAS-2B, was dependent on anchorage, in contrast to clear induction of c-fos and c-myc under both anchorage-dependent and -independent conditions. In fact, forced expression of c-jun in BEAS-2B cells significantly increased cell viability and colony formation in soft agar. Furthermore, we also found that such anchorage-dependent regulation of c-jun was lost in a significant fraction of human lung cancer cell lines. Interestingly, suppressed anchorage-independent but not anchorage-dependent growth was noted by constitutive expression of a dominant-negative c-jun mutant in a lung cancer cell line showing dysregulated and sustained c-jun expression in the absence of anchorage. These findings suggest that dysregulated c-jun expression may be involved in the acquisition of anchorage independence in the process of human lung carcinogenesis.


The C-terminal end of the capsid protein of Avian Nephritis Virus is antigenic and induces broadly cross-reactive antibodies.
Avian nephritis virus (ANV) has been isolated frequently from commercial broilers in many countries. The prevalence and economic impact of ANV however has been difficult to ascertain due to the lack of convenient serological techniques. In this study the full-length and fragments of the ANV capsid protein were expressed in Baculovirus and affinity purified recombinant proteins used for the detection of ANV antibodies in ELISA. The crystal structure of Human Astrovirus (HAstV) was used as a model to determine potential homologous C-terminal antigenic regions in ANV. The rp37 fragment from three ANV strains NSW_3, ANV-1 and ANV-2, and a shorter NSW_3 fragment (rp33) were compared for their ability to detect ANV antibodies in seven reference chicken sera. The ANV-1 rp37 antigen was the most strain specific whereas the NSW_3 rp37 and rp33 antigens detected antibodies in all heterologous sera, including ANV-1 serum. Irrespective of the strain used, the two NSW_3 protein fragments rp37 and rp33 were found to be superior as antigens for ELISA when compared to the full-length capsid protein rp75. An ELISA designed using the NSW_3 rp33 could reliably differentiate between uninfected and infected commercial broiler flocks, as demonstrated by statistically significant differences between the OD values. This study identified an ANV immunogenic region and successfully used recombinant protein expression of this region to detect cross-reactive ANV antibodies. The results of this study facilitate future studies into the epidemiology and importance of ANV infections in commercial poultry.


Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.
We conducted a two-phase clinical trial in patients with progressive malignant glioma (MG). The first phase of this trial was designed to determine the dose of O6-BG effective in producing complete depletion of tumor AGT activity for 48 hours. The second phase of the trial was designed to define the maximum tolerated dose (MTD) of a single dose of temozolomide when combined with O6-BG. In addition, plasma concentrations of O6-BG and O6-benzyl-8-oxoguanine were evaluated after O6-BG. For our first phase of the clinical trial, patients were scheduled to undergo craniotomy for AGT determination after receiving a 1-hour O6-BG infusion at 120 mg/m2 followed by a continuous infusion at an initial dose of 30 mg/m2/d for 48 hours. The dose of the continuous infusion of O6-BG escalated until tumor AGT was depleted. Once the O6-BG dose was established a separate group of patients was enrolled in the second phase of clinical trial, in which temozolomide, administered as a single dose at the end of the 1-hour O6-BG infusion, was escalated until the MTD was determined. The O6-BG dose found to be effective in depleting tumor AGT activity at 48 hours was an IV bolus of 120 mg/m2 over 1 hour followed by a continuous infusion of 30 mg/m2/d for 48 hours. On enrolling 38 patients in six dose levels of temozolomide, the MTD was established at 472 mg/m2 with dose-limiting toxicities limited to myelosuppression. This study provides the foundation for a phase II trial of O6-BG plus temozolomide in temozolomide-resistant MG.


Occurrence and characterization of oils rich in gamma-linolenic acid part II: fatty acids and squalene from Macaronesian Echium leaves.
Leaves from 25 Macaronesian Echium (Boraginaceae) species have been surveyed for hydrocarbon compounds. These plants were previously reported as the major source of gamma-linolenic acid so far found in nature. In addition, six European Echium species and the common Borago officinalis have been analysed for comparative purposes. High squalene amounts were found in all Echium plants from the Macaronesia, ranging from 3.73%, in E. simplex to 20.1% in E. fastousum. Squalene was almost absent from all European Echium species, and the same is true for B. officinalis. The relatively high oil content (2.27%) in leaves of E. fastuosum raises the total squalene amount to about 0.46% within this tissue. The main fatty acid component in the leaf was alpha-linolenic acid (ALA, 18:3omega3), ranging in the Macaronesian Echium from 9.32% in E. acanthocarpum to 54.45% in E. simplex. Possible utilisation of these plants as a commercial source of squalene and hypotheses about its physiological role in the plant are discussed.


Education in nursing diagnosis: evaluating clinical outcomes.
This article describes the development, implementation, and evaluation of an educational program to update the knowledge and skills of nurses in the use of the nursing process and nursing diagnoses. Results 1 year later suggest improvement in participants' knowledge of the phases of the nursing process. Chart audits demonstrated this knowledge was more specifically applied to improved documentation of nursing diagnoses.


Isolation of Chlamydia trachomatis from throat and rectum of homosexual men.
Isolation of Chlamydia trachomatis is reported from homosexual men: from the throat with no abnormal symptoms and from the rectum in two cases of proctitis.


Copy number variants in the sheep genome detected using multiple approaches.
Copy number variants (CNVs) are a type of polymorphism found to underlie phenotypic variation, both in humans and livestock. Most surveys of CNV in livestock have been conducted in the cattle genome, and often utilise only a single approach for the detection of copy number differences. Here we performed a study of CNV in sheep, using multiple methods to identify and characterise copy number changes. Comprehensive information from small pedigrees (trios) was collected using multiple platforms (array CGH, SNP chip and whole genome sequence data), with these data then analysed via multiple approaches to identify and verify CNVs. In total, 3,488 autosomal CNV regions (CNVRs) were identified in this study, which substantially builds on an initial survey of the sheep genome that identified 135 CNVRs. The average length of the identified CNVRs was 19 kb (range of 1 kb to 3.6 Mb), with shorter CNVRs being more frequent than longer CNVRs. The total length of all CNVRs was 67.6Mbps, which equates to 2.7 % of the sheep autosomes. For individuals this value ranged from 0.24 to 0.55 %, and the majority of CNVRs were identified in single animals. Rather than being uniformly distributed throughout the genome, CNVRs tended to be clustered. Application of three independent approaches for CNVR detection facilitated a comparison of validation rates. CNVs identified on the Roche-NimbleGen 2.1M CGH array generally had low validation rates with lower density arrays, while whole genome sequence data had the highest validation rate (>60 %). This study represents the first comprehensive survey of the distribution, prevalence and characteristics of CNVR in sheep. Multiple approaches were used to detect CNV regions and it appears that the best method for verifying CNVR on a large scale involves using a combination of detection methodologies. The characteristics of the 3,488 autosomal CNV regions identified in this study are comparable to other CNV regions reported in the literature and provide a valuable and sizeable addition to the small subset of published sheep CNVs.


Calcitonin gene-related peptide containing autonomic efferent pathways to the pelvic ganglia of the rat.
Indirect immunofluorescence method was employed to investigate the involvement of calcitonin gene-related peptide (CGRP) in the autonomic efferent innervations of the pelvic visceral organs of the rat. Cells labeled with Fast blue (FB) injected into the pelvic ganglia were observed in the sacral parasympathetic nucleus; about 30% of these neurons showed CGRP-like immunoreactivity. These CGRP-like immunoreactive neurons were located in the dorsomedial part of the sacral parasympathetic nucleus, extending their dendrites mediolaterally. FB-labeled cells were also found in the upper lumbar level (L1, L2) of the spinal cord. Some of these neurons also showed CGRP-like immunoreactivity. CGRP-like immunoreactive varicose fibers were seen in the pelvic ganglia surrounding individual ganglion cells. Considerable amount of these fibers were not affected by sensory deafferentation, so they probably originated from autonomic efferent neurons.


Clinical and endoscopic predictors for intraprocedural mucosal injury during per-oral endoscopic myotomy.
Mucosal injury (MI) is one of the most common perioperative adverse events of per-oral endoscopic myotomy (POEM). Severe undertreated MI may lead to contamination of the tunnel and even mediastinitis. This study explored the characteristics, predictors, and management approaches of intraoperative MI. A retrospective review of the prospectively collected database at a large tertiary referral endoscopy unit was conducted for all patients undergoing POEM between August 2010 and March 2016. MI was graded according to the difficulty of repair (I, easy to repair; II, difficult to repair). The primary outcomes were the incidence and predictors of intraoperative MI. Secondary outcomes were MI details and the corresponding treatment. POEM was successfully performed in 1912 patients. A total of 338 patients experienced 387 MIs, for an overall frequency of 17.7% (338/1912). Type II MI was rare, with a frequency of 1.7% (39/1912). Major adverse events were more common in patients with MI than in those without MI (6.2% vs 2.5%, P < .001). On multivariable analysis, MI was independently associated with previous Heller myotomy (odds ratio [OR], 2.094; P = .026), previous POEM (OR, 2.441; P = .033), submucosal fibrosis (OR, 4.530; P < .001), mucosal edema (OR, 1.834; P = .001), and tunnel length ≥13 cm (OR, 2.699; P < .001). Previous POEM (OR, 5.005; P = .030) and submucosal fibrosis (OR, 12.074; P < .001) were significant predictors of type II MI. POEM experience >1 year was a protective factor for MI (OR, .614; P = .042) and type II MI (OR, .297; P = .042). MI during POEM is common, but type II injury is rare. Previous POEM and submucosal fibrosis were significant predictors of type II mucosal injury. POEM experience after the learning curve reduces the risk of MI.


Pets as social facilitators.
Pets not only interact directly with people but, through their presence alone, may also modify the social behavior between two or more people. Examples of this latter effect are offered from the literature on pet-facilitated therapy, pets and children, and pets in the community. An attempt is made to develop a theoretical framework to explain this phenomenon.


[The impact of religious coping on adaptation strategy among the sick].
The influence of religious practice on sick people's adaptation processes has been demonstrated in many studies. It is important for the clinical reasoning implemented by caregivers to integrate this aspect in a context defined by the principle of "laïcité" as understood in France.


Cold application for pain and anxiety reduction following chest tube removal: A systematic review and meta-analysis.
To conduct a systematic review and meta-analysis to evaluate the effects of cold application on pain and anxiety reduction after chest tube removal (CTR). The act of removing the chest tube often causes pain among cardiothoracic surgery patients. Most guidelines regarding CTR do not mention pain management. The effects of cold application on reducing pain and anxiety after CTR are inconsistent. Systematic review and meta-analysis. We searched six databases, including Embase, Ovid Medline, Cochrane Library, Scopus, the Index to Taiwan Periodical Literature System and Airiti Library, to identify relevant articles up to the end of February 2021. We limited the language to English and Chinese and the design to randomised controlled trials (RCTs). All studies were reviewed by two independent investigators. The Cochrane Collaboration's tool was used to assess the risk of bias, Review Manager 5.4 was used to conduct the meta-analysis. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology was used for assessing certainty of evidence (CoE). Ten RCTs with 683 participants were included in the meta-analysis. The use of cold application could effectively reduce pain and anxiety after CTR. The subgroup showed that a skin temperature drops to 13°C of cold application was significantly more effective for the immediate reduction in pain intensity after CTR compared with control group. The GRADE methodology demonstrated that CoE was very low level. Cold application is a safe and easy-to-administer nonpharmacological method with immediate and persistent effects on pain and anxiety relief after CTR. Skin temperature drops to 13°C or lasts 20 min of cold application were more effective for immediate reduction of pain intensity following CTR. In addition to pharmacological strategy, cold application could be used as evidence for reducing pain intensity and anxiety level after CTR.


Leachability and analytical speciation of antimony in coal fly ash.
The present study assesses the single extraction of Sb from two coal fly ashes with aqueous solutions at a range of pHs (1-12) and with citrate 1 mol L(-1) at pH 5, in order to obtain preliminary information about Sb leaching from this matrix. Speciation analysis of the coal fly ash extracts by HPLC-ICP-MS and HPLC-HG-AFS was carried out in order to identify the presence of individual Sb species. Sb(V) was the main Sb species in the leachates, although minor amounts of Sb(III) were also detected in some extracts. Citrate at pH 5 gave the best extraction efficiency for both samples whereas Sb species were also fairly soluble in aqueous solutions at acidic pHs. Analysis by HPLC-ICP-MS provided the most accurate results in some extracts (aqueous solution at pH 1 and citrate at pH 5) when both coupled techniques used were compared. The presence in these leachates of higher content of interfering metal ions (Ca, Fe and Pb) than those obtained for the Sb species reduced stibine generation in the HPLC-HG-AFS analysis. The proposed methodology can be considered reliable and useful for antimony speciation in environmental studies.


Correction to: Environmental efficiency and the role of energy innovation in emissions reduction.
The correct affiliation of the 1st Author is shown in this paper.


Hexamethylene amiloride binds the SARS-CoV-2 envelope protein at the protein-lipid interface.
The SARS-CoV-2 envelope (E) protein forms a five-helix bundle in lipid bilayers whose cation-conducting activity is associated with the inflammatory response and respiratory distress symptoms of COVID-19. E channel activity is inhibited by the drug 5-(N,N-hexamethylene) amiloride (HMA). However, the binding site of HMA in E has not been determined. Here we use solid-state NMR to measure distances between HMA and the E transmembrane domain (ETM) in lipid bilayers. 13 C, 15 N-labeled HMA is combined with fluorinated or 13 C-labeled ETM. Conversely, fluorinated HMA is combined with 13 C, 15 N-labeled ETM. These orthogonal isotopic labeling patterns allow us to conduct dipolar recoupling NMR experiments to determine the HMA binding stoichiometry to ETM as well as HMA-protein distances. We find that HMA binds ETM with a stoichiometry of one drug per pentamer. Unexpectedly, the bound HMA is not centrally located within the channel pore, but lies on the lipid-facing surface in the middle of the TM domain. This result suggests that HMA may inhibit the E channel activity by interfering with the gating function of an aromatic network. These distance data are obtained under much lower drug concentrations than in previous chemical shift perturbation data, which showed the largest perturbation for N-terminal residues. This difference suggests that HMA has higher affinity for the protein-lipid interface than the channel pore. These results give insight into the inhibition mechanism of HMA for SARS-CoV-2 E.


Inhibition of PDGF BB stimulated DNA synthesis in rat aortic vascular smooth muscle cells by the expression of a truncated PDGF beta receptor.
Rat aortic vascular smooth muscle cells (VSMCs) were transfected with a vector encoding a truncated human PDGF beta receptor or the full-length human PDGF beta receptor. Cells stably expressing the truncated human PDGF beta receptor or the full-length human PDGF beta receptor were selected and the effect of PDGF BB on DNA synthesis in these cells was studied. Cells expressing the full-length PDGF beta receptor entered DNA synthesis normally, however, cells expressing the truncated PDGF beta receptor failed to enter DNA synthesis in response to PDGF BB. These data show that the mitogenic response of rat aortic vascular smooth muscle cells to PDGF BB can be inhibited by the expression of a truncated PDGF beta receptor.


Neutrophils, nitric oxide, and microvascular permeability in severe sepsis.
Alterations in microvascular permeability are prevalent in patients with sepsis; a recent study reported that patients with septic shock had increased capillary filtration coefficient (Kf), a noninvasive index of microvascular permeability. We aimed to determine whether patients with severe sepsis had increased Kf, and whether the magnitude of Kf correlated with indexes of nitric oxide activity and neutrophil activation. Single-center, prospective study. Twenty-five-bed ICU of a medical college-affiliated teaching hospital. Fifteen ICU patients with severe sepsis based on the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria of 1992, and 10 nonseptic ICU patients as control subjects. Kf was measured by venous congestion plethysmography, plasma nitrate/nitrite (NOx) by chemiluminescence, and neutrophil expression of alpha4-integrin (an index of neutrophil activation) by flow cytometry. Septic patients had higher Kf than nonseptic control subjects. Kf of septic patients was 5.6 +/- 0.6 x 10(-3) mL.min(-1).100 mL tissue(-1).mm Hg(-1) (mean +/- SEM, mL.min(-1).100 mL tissue(-1).mm Hg(-1) = Kf units [KfU]) as compared to 3.9 +/- 0.5 x 10(-3) KfU in nonseptic ICU patients (p < 0.05). There was no correlation between plasma NOx and Kf, or between neutrophil alpha4-integrin expression and Kf in patients with sepsis. Septic patients with clinical evidence of edema had significantly higher Kf (p < 0.05) than nonedematous septic patients. ICU patients with severe sepsis have increased Kf, a noninvasive index of microvascular water permeability. The magnitude of hyperpermeability did not correlate with NOx levels or one index of neutrophil activation (alpha4-integrin expression). Presence of peripheral edema in these patients was associated with increased Kf, and may represent a simple, clinical indicator of altered microvascular permeability in sepsis.


Multivariate genome-wide analysis of aging-related traits identifies novel loci and new drug targets for healthy aging.
The concept of aging is complex, including many related phenotypes such as healthspan, lifespan, extreme longevity, frailty and epigenetic aging, suggesting shared biological underpinnings; however, aging-related endpoints have been primarily assessed individually. Using data from these traits and multivariate genome-wide association study methods, we modeled their underlying genetic factor ('mvAge'). mvAge (effective n = ~1.9 million participants of European ancestry) identified 52 independent variants in 38 genomic loci. Twenty variants were novel (not reported in input genome-wide association studies). Transcriptomic imputation identified age-relevant genes, including VEGFA and PHB1. Drug-target Mendelian randomization with metformin target genes showed a beneficial impact on mvAge (P value = 8.41 × 10-5). Similarly, genetically proxied thiazolidinediones (P value = 3.50 × 10-10), proprotein convertase subtilisin/kexin 9 inhibition (P value = 1.62 × 10-6), angiopoietin-like protein 4, beta blockers and calcium channel blockers also had beneficial Mendelian randomization estimates. Extending the drug-target Mendelian randomization framework to 3,947 protein-coding genes prioritized 122 targets. Together, these findings will inform future studies aimed at improving healthy aging.


Progress and prospects of arthropod chitin pathways and structures as targets for pest management.
Chitin is a structural component of the arthropod cuticular exoskeleton and the peritrophic matrix of the gut, which play crucial roles in growth and development. In the past few decades, our understanding of the composition, biosynthesis, assembly, degradation, and regulation of chitinous structures has increased. Many chemicals have been developed that target chitin biosynthesis (benzoyphenyl ureas, etoxazole), chitin degradation (allosamidin, psammaplin), and chitin regulation (benzoyl hydrazines), thus resulting in molting deformities and lethality. In addition, proteins that disrupt chitin structures, such as lectins, proteases, and chitinases have been utilized to halt feeding and induce mortality. Chitin-degrading enzymes, such as chitinases are also useful for improving the efficacy of bio-insecticides. Transgenic plants, baculoviruses, fungi, and bacteria have been engineered to express chitinases from a variety of organisms for control of arthropod pests. In addition, RNA interference targeting genes involved in chitin pathways and structures are now being investigated for the development of environmentally friendly pest management strategies. This review describes the chemicals and proteins used to target chitin structures and enzymes for arthropod pest management, as well as pest management strategies based upon these compounds, such as plant-incorporated-protectants and recombinant entomopathogens. Recent advances in RNA interference-based pest management, and how this technology can be used to target chitin pathways and structures are also discussed.


The conformational flexibility of the C-terminus of histone H4 promotes histone octamer and nucleosome stability and yeast viability.
The protein anti-silencing function 1 (Asf1) chaperones histones H3/H4 for assembly into nucleosomes every cell cycle as well as during DNA transcription and repair. Asf1 interacts directly with H4 through the C-terminal tail of H4, which itself interacts with the docking domain of H2A in the nucleosome. The structure of this region of the H4 C-terminus differs greatly in these two contexts. To investigate the functional consequence of this structural change in histone H4, we restricted the available conformations of the H4 C-terminus and analyzed its effect in vitro and in vivo in Saccharomyces cerevisiae. One such mutation, H4 G94P, had modest effects on the interaction between H4 and Asf1. However, in yeast, flexibility of the C-terminal tail of H4 has essential functions that extend beyond chromatin assembly and disassembly. The H4 G94P mutation resulted in severely sick yeast, although nucleosomes still formed in vivo albeit yielding diffuse micrococcal nuclease ladders. In vitro, H4G4P had modest effects on nucleosome stability, dramatically reduced histone octamer stability, and altered nucleosome sliding ability. The functional consequences of altering the conformational flexibility in the C-terminal tail of H4 are severe. Interestingly, despite the detrimental effects of the histone H4 G94P mutant on viability, nucleosome formation was not markedly affected in vivo. However, histone octamer stability and nucleosome stability as well as nucleosome sliding ability were altered in vitro. These studies highlight an important role for correct interactions of the histone H4 C-terminal tail within the histone octamer and suggest that maintenance of a stable histone octamer in vivo is an essential feature of chromatin dynamics.


Water use patterns of four co-occurring chaparral shrubs.
Mixed stands of chaparral in California usually contain several species of shrubs growing close to each other so that aerial branches and subterranean roots overlap. There is some evidence that roots are stratified relative to depth. It may be that root stratification promotes sharing of soil moisture resources. We examined this possibility by comparing seasonal water use patterns in a mixed stand of chaparral dominated by four species of shrubs: Quercus durata, Heteromeles arbutifolia, Adenostoma fasciculatum, and Rhamnus californica. We used a neutron probe and soil phychrometers to follow seasonal depletion and recharging of soil moisture and compared these patterns to seasonal patterns of predawn water potentials, diurnal leaf conductances, and diurnal leaf water potentials. Our results indicated that 1) Quercus was deeply rooted, having high water potentials and high leaf conductances throughout the summer drought period, 2) Heteromeles/Adenostoma were intermediate in rooting depth, water potentials, and leaf conductances, and 3) Rhamnus was shallow rooted, having the lowest water potentials and leaf conductances. During the peak of the drought, predawn water potentials for Quercus corresponded to soil water potentials at or below a depth of 2 m, predawn water potentials of Heteromeles/ Adenostoma corresponded to a depth of 0.75 m, and predawn water potentials of Rhamnus corresponded to a depth of 0.5 m. This study supports the concept that co-occurring shrubs of chaparral in California utilize a different base of soil moisture resources.


Effects of combining retrieval practice and tDCS over long-term memory: A randomized controlled trial.
The ability to retain new information is important in daily life. In particular, two techniques have shown promise for improving long-term retention: retrieval practice (RP), which consists of actively retrieving information from long-term memory to make it more accessible in the future; and transcranial direct current stimulation (tDCS), which consists of non-invasive brain stimulation that modulates cognitive processes by increasing and decreasing neuronal excitability. Previous studies have implicated the left dorsolateral prefrontal cortex (l-dlPFC) in memory encoding and memory organization. We examined whether RP associated with a single 20-min tDCS session over the l-dlPFC could improve long-term memory retention. Participants (N = 119) repeatedly studied a list of related words either via RP or via restudy, while undergoing either anodal or sham stimulation. Participants returned 2 days later for a free-recall test. Results showed that the RP group outperformed the restudy group in all measures, regardless of stimulation type. Also, recall organization was higher in the RP group than in the restudy group. The data support previous findings and indicate that RP may enhance performance by improving the organization of the to-be-remembered list items.


Barriers and enablers in implementing an electronic incident reporting system in a teaching hospital: A case study from Saudi Arabia.
Widespread recognition of the impact of healthcare adverse events has triggered incident reporting system implementation to promote patient safety. The aim was to assess the effectiveness, usability, enablers, and barriers of the Electronic Occurrence Variance Reporting System (eOVR) in addition to end user satisfaction. This study comprised a cross-sectional survey two years after implementation of the eOVR. Secondary data analysis evaluated the volume of incident reporting before and after implementing the eOVR. Primary outcome measures: satisfaction and system usability, system security, workplace safety culture, training, and reporting trends. An overall satisfaction was collected. rate of reported OVRs per 1000 admissions. Furthermore, barriers and enablers to the reporting process were explored. Study findings indicate that the eOVR has been successful in terms of high satisfaction according to respondents. Most of the respondents found the system easy to access, maintained patient confidentiality and reporting anonymity. Around half the respondents indicated having a non-punitive culture of reporting in their hospital. Physicians had significantly lower scores in all primary outcomes Incident reporting increased by 33.6% (p < 0.0001) after implementing the eOVR. Successful incident reporting systems should be easy and simple to use, accessible and include features that guarantee anonymity and confidentiality. End-users should be trained prior to launching such a system. The implementation of such systems needs to be combined with promoting a just culture in the organization, timely feedback, more involvement and focus on physicians and junior staff which will improve user satisfaction and reporting rates.


Transcatheter arterial chemoembolization for hepatocellular carcinoma: Comparison of the therapeutic efficacies between miriplatin and epirubicin.
The therapeutic efficacy of transcatheter arterial chemoembolization (TACE) using miriplatin was evaluated in comparison with that using epirubicin in patients with hepatocellular carcinoma (HCC). Two hundred and eight-nine HCC patients receiving TACE were retrospectively enrolled; none of the patients gave a previous TACE history. The short-term therapeutic efficacy was evaluated by computed tomography (CT) performed 1 month later. In patients showing TE-4, CT and/or magnetic resonance imaging examinations were performed repeatedly and the long-term therapeutic efficacy was assessed based on local tumor recurrence. After exclusion of 68 patients (CT not performed at 1 month), 97 patients treated with epirubicin and 124 treated with miriplatin were analyzed. The percentage of patients showing TE-4 was 46.8% in the miriplatin-TACE group, being significantly higher than that in the epirubicin-TACE group (33.0%). The cumulative local recurrence rates at 18 months were 71.2% in the miriplatin-TACE group and 43.1% in the epirubicin-TACE group; multivariate analysis revealed higher local tumor recurrence rates in the miriplatin-TACE group than in the epirubicin-TACE group. For HCC patients, although miriplatin-TACE was superior to epirubicin-TACE in the short term, it proved inferior to the latter in the long term. The merits of TACE using miriplatin should be further investigated, because adverse effects appear to be minimal after miriplatin administration.


Pathologic comparison of asymmetric or sulcus fixation of 3-piece intraocular lenses with square versus round anterior optic edges.
To evaluate the pathologic findings of 3-piece intraocular lenses (IOLs) with asymmetric or sulcus fixation in pseudophakic cadaver eyes, comparing IOLs with square or round edges on the anterior optic surface. Comparative case series with pathology. A total of 661 pseudophakic cadaver eyes, obtained from eye banks within the United States, implanted with different IOLs. Anterior segment scanning of whole eyes with a high-frequency ultrasound system or high-resolution anterior segment magnetic resonance imaging followed by gross examination. Selected eyes were processed for complete histopathologic analysis. Findings from imaging, gross, and histopathologic evaluation that could be related to out-of-the-bag fixation of the lenses. Of 661 pseudophakic cadaver eyes obtained, 13 had 3-piece hydrophobic acrylic IOLs with anterior and posterior square optic edges, and 14 had 3-piece lenses with anterior round edges (13 silicone lenses and 1 hydrophobic acrylic lens) without symmetric in-the-bag fixation. These 27 selected eyes were processed for complete histopathologic analysis. Gross findings in both groups were composed of IOL decentration and tilt, pigmentary dispersion within the anterior segment and on the IOL surface, and iris transillumination defects. Histopathology of the 14 eyes with 3-piece IOLs with round anterior optic edges showed mild focal disruption of the iris pigmented layer and loop protrusion/erosion in the ciliary sulcus. Additional changes observed in the 13 eyes with square anterior optic edge IOLs included iris changes, such as vacuolization, disruption and loss of the pigmented epithelial layers, iris thinning and atrophy, synechiae, and pigmentary dispersion within the trabecular meshwork. One eye also exhibited initial signs of optic nerve disc cupping. In this series, pathologic findings were more severe in eyes implanted with 3-piece IOLs with square anterior optic edges, suggesting that IOLs with round anterior edges are more suitable for sulcus fixation. Proprietary or commercial disclosure may be found after the references.


Role of endogenous endothelin peptides in intestinal ischemia-reperfusion injury in rats.
In this study, the effects of BQ123 (an ET(A) receptor antagonist), bosentan (a nonselective ET(A)-ET(B) antagonist), and phosphoramidon (an endothelin converting enzyme inhibitor) were investigated on intestinal mucosal lesion formation and changes in tissue PGE2 and LTC4 levels due to intestinal ischemia-reperfusion (I/R) injury in rats. Following 30 min of ischemia, the substances were given via the inferior caval vein, and 10 min later the intestine was subjected to reperfusion for 30 min. The intestinal specimens were evaluated both microscopically and the tissue PGE2 and LTC4 levels were obtained for each group. The histopathologic examination revealed a significant reduction in tissue injury in both BQ123 and phosphoramidon pretreated groups compared with the control group. Bosentan, on the contrary, did not decrease the injury. The pharmacologic examination revealed a significant reduction of PGE2-like activity in both BQ123 and phosphoramidon pretreated groups, compared with the control group, while LTC4-like activity remained unchanged except for an increase in the bosentan pretreated group.


The Role of Prehabilitation in Modern Esophagogastric Cancer Surgery: A Comprehensive Review.
Esophagogastric cancer is among the most common malignancies worldwide. Surgery with or without neoadjuvant therapy is the only potentially curative treatment option. Although esophagogastric resections remain associated with major surgical trauma and significant postoperative morbidity. Prehabilitation has emerged as a novel strategy to improve clinical outcomes by optimizing physical and psychological status before major surgery through exercise and nutritional and psychological interventions. Current prehabilitation programs may be unimodal, including only one intervention, or multimodal, combining the benefits of different types of interventions. However, it still is an investigational treatment option mostly limited to clinical trials. In this comprehensive review, we summarize the current evidence for the role of prehabilitation in modern esophagogastric cancer surgery. The available studies are very heterogeneous in design, type of interventions, and measured outcomes. Yet, all of them confirm at least some positive effects of prehabilitation in terms of improved physical performance, nutritional status, quality of life, or even reduced postoperative morbidity. However, the optimal interventions for prehabilitation remain unclear; thus, they cannot be standardized and widely adopted. Future studies on multimodal prehabilitation are necessary to develop optimal programs for patients with esophagogastric cancer.


Nuclear phosphoinositides: location, regulation and function.
Lipid signalling in human disease is an important field of investigation and stems from the fact that phosphoinositide signalling has been implicated in the control of nearly all the important cellular pathways including metabolism, cell cycle control, membrane trafficking, apoptosis and neuronal conduction. A distinct nuclear inositide signalling metabolism has been identified, thus defining a new role for inositides in the nucleus, which are now considered essential co-factors for several nuclear processes, including DNA repair, transcription regulation, and RNA dynamics. Deregulation of phoshoinositide metabolism within the nuclear compartment may contribute to disease progression in several disorders, such as chronic inflammation, cancer, metabolic, and degenerative syndromes. In order to utilize these very druggable pathways for human benefit there is a need to identify how nuclear inositides are regulated specifically within this compartment and what downstream nuclear effectors process and integrate inositide signalling cascades in order to specifically control nuclear function. Here we describe some of the facets of nuclear inositide metabolism with a focus on their relationship to cell cycle control and differentiation.


Effect of formalin in early stages of the freshwater neotropical catfish, Lophiosilurus alexandri.
The objective of this study was to evaluate the acute toxicity of formalin and its level of therapeutic safety in early stages of Lophiosilurus alexandri. Experiment 1, larvae 7 days after hatching (DAH) were exposed to 43.2, 86.4, 172.8, 345.6, 691.2, 1404.0 mg/L of formalin. Experiment 2, juveniles with 22 DAH exposed to 54, 108, 216, 432, 648 mg/L. Experiment 3, 45 DAH exposed to 86.4, 172.8, 345.6, 691.2, 1036.8 mg/L. The experiments had a control without addition of formalin and all were carried out in duplicate. The LC50-12 h were: Experiment 1 = 108.86 mg/L; 2: 152.74 mg/L; 3: 244.38 mg/L of formalin. The respective safety levels were: Experiment 1 = 66.22 mg/L (1 h), 10.89 mg/L (12 h); 2 = 49.17 mg/L (2 h), 15.27 mg/L (12 h); 3 = 68.89 mg/L (2 h), 24.44 mg/L (12 h). The results showed that the developmental stage influenced the sensitivity of animals to formalin.


Understanding quantitative genetic variation.
Until recently, it was impracticable to identify the genes that are responsible for variation in continuous traits, or to directly observe the effects of their different alleles. Now, the abundance of genetic markers has made it possible to identify quantitative trait loci (QTL)--the regions of a chromosome or, ideally, individual sequence variants that are responsible for trait variation. What kind of QTL do we expect to find and what can our observations of QTL tell us about how organisms evolve? The key to understanding the evolutionary significance of QTL is to understand the nature of inherited variation, not in the immediate mechanistic sense of how genes influence phenotype, but, rather, to know what evolutionary forces maintain genetic variability.


Facilitators, Barriers, and Best Practices for In-Person and Telehealth Lactation Support During the COVID-19 Pandemic.
To explore the perspectives of lactation support providers delivering breastfeeding education via in-person and telehealth consultations and assess the impact of COVID-19 on the provision of breastfeeding education. Qualitative descriptive study using purposive sampling. Massachusetts-based lactation support providers who provided in-person and/or telehealth consultations in various practice settings (e.g., inpatient; outpatient; private practice; and the Special Supplemental Nutrition Program for Women, Infants, and Children). Fourteen Massachusetts-based lactation support providers, ages 36 to 68 years. Participants completed an online demographic and employment characteristics survey and virtual key informant interviews, from which six main themes were defined. The six main themes included Common Questions Asked by Clients, Prenatal and Postpartum Consultation Topics, Facilitators for Telehealth Versus In-Person Consultations, Barriers for Telehealth Versus In-Person Consultations, Best Practices, and COVID-19 Adaptations. From participant interviews, common subthemes emerged. The primary adaptation due to COVID-19 was shifting to telehealth. Content in lactation consultations was similar via in-person and telehealth sessions. Typical content areas included breast pumping and mother's milk supply. A notable difference was the lack of physical examinations for women and newborns in telehealth sessions. Scheduling flexibility was a key facilitator of telehealth consultations, whereas the inability to provide hands-on assistance and chaotic home environments were common barriers. In-person facilitators included weighing newborns to assess feeding success and insurance billing coverage, whereas unsupportive family members were noted as a barrier. Diversity, equity, and inclusion-related barriers (e.g., language barriers, lack of reflective diversity, lack of stable Internet access) were observed in both settings. Best practices for in-person and telehealth consultations included meeting mothers where they are and focusing on mothers' goals. Practice adaptations adopted during the pandemic and best practice recommendations may be useful for lactation support providers and other health care professionals caring for breastfeeding dyads.


Catatonia and mania in patient with AIDS: treatment with lorazepam and risperidone.
A 30-year-old woman presented with psychiatric symptoms and was found to be HIV positive prior to admission to the hospital. We present the first case report of catatonia and mania in an HIV-positive subject unrelated to infectious processes. The catatonic symptoms were alleviated by intravenous lorazepam, and manic symptoms were adequately treated with risperidone. Clinicians need to be aware that HIV infection should be considered in all patients with new-onset mania alternating with catatonia or in those with HIV risk factors.


Increased intra-articular concentration of bradykinin in the temporomandibular joint changes the sensitivity of muscle spindles in dorsal neck muscles in the cat.
The aim of the present study was to investigate to what extent activation of bradykinin-sensitive nerve endings of the temporomandibular joint (TMJ) might induce changes in the muscle spindles output from neck muscles through reflex effects on cervical fusimotor neurones. To this end, 26 muscle spindle afferents (MSAs) emanating from the trapezius and splenius muscles of the anaesthetised cat (alpha-chloralose, initial dosage 60 mg/kg) were recorded during injection of Bradykinin (BK) (12.5-50 microg/ml) in the ipsilateral TMJ. Fifteen (58%) MSAs exhibited statistically significant fusimotor effects to injection of BK into the TMJ. Of the 15, ten MSAs showed a response related to activation of static fusimotor neurones, three MSAs showed a response related to an activation of both static and dynamic fusimotor neurones and two MSAs showed a inhibition of both static and dynamic fusimotor neurones. The control experiments suggests that the effects observed were due to activation of BK sensitive nerve endings in the TMJ. It seems possible that the reflex connections between TMJ nociceptors and the fusimotor-muscle spindle system of dorsal neck muscles might be involved in the pathophysiological mechanisms responsible for the sensory-motor disturbances in the neck region often found on patients with temporomandibular disorders.


Integration of seawater and grey water reuse to maximize alternative water resource for coastal areas: the case of the Hong Kong International Airport.
Development, population growth and climate change have pressurized water stress in the world. Being an urbanized coastal city, Hong Kong has adopted a dual water supply system since the 1950s for seawater toilet flushing for 80% of its 7 million inhabitants. Despite its success in saving 750,000 m(3)/day of freshwater, the saline sewage (consisting of about 20-30% of seawater) appears to have sacrificed the urban water cycle in terms of wastewater reuse and recycling. Can seawater toilet flushing be applied without affecting the urban water cycle with respect to sustainable water resource management? To address this issue, we examined the entire urban water cycle and developed an innovative water resource management system by integrating freshwater, seawater and reclaimed grey water into a sustainable, low-freshwater demand, low-energy consumption, and low-cost triple water supply (TWS) system. The applicability of this novel system has been demonstrated at the Hong Kong International Airport which reduced 52% of its freshwater demand.


The effects of melanocortins and electrical fields on neuronal growth.
The effects of the neuropeptide molecules, adrenocorticotrophic hormone or alpha-melanocyte stimulating hormone, on various parameters of in vitro nerve growth, have been studied in the presence and absence of a small applied electric field. Striking effects on rates of nerve growth occurred. Selected concentrations of either substance alone, produced a three- to fourfold increase in nerve growth rate; other concentrations were inhibitory. The applied electric field alone increased rates of growth threefold. Further augmented rates of growth were seen when either neuropeptide was present simultaneously with an applied field. Under these latter conditions, galvanotropic (cathodal) orientation persisted, while nerve branching was suppressed. Given the clinical interest in melanocortin-stimulated nerve regeneration, perhaps a combined electrical and neuropeptide approach would be warranted.


Glycogen metabolism in rat ependymal primary cultures: regulation by serotonin.
Ependymal primary cultures are a model for studying ependymal energy metabolism. Intracellular glycogen is built up in the cultures dependent on culture age and the presence of glucose and glutamate. This energy store is mobilized upon glucose withdrawal, stimulation with isoproterenol, forskolin or serotonin and after uncoupling of oxidative phosphorylation from ATP production. Serotonin regulates ependymal glycogen metabolism predominantly via 5-HT receptor (5-HTR) 7, which elicits an increase in the level of ependymal cyclic AMP. Although the most abundant mRNAs for serotonin receptors are those of 5-HTR 2B and 5-HTR 3A, ependymal cells in primary culture do not respond to serotonin with an increase in their concentration of cytosolic calcium ions. The mRNAs of 5-HTRs 1A, 6, 1B, 5B, 7, 1/2C and 5A are also detectable in order of decreasing abundance. The mRNAs for 5-HTRs 1D, 1F, 3B and 4 are absent from the cultured cells. The ability of serotonin to mobilize ependymal glycogen depends on the culture age and the time allowed for glycogen buildup. During glycogen buildup time, glutamate is consumed by the cells. An increased ability of 5-HT to mobilize ependymal glycogen stores is noticed after the depletion of glutamate from the glycogen buildup medium. In ependymal primary cultures, cilia are colocalized with glycogen phosphorylase isozyme BB, while the MM isoform is not expressed. It is known from the literature that an increase in the concentration of cytosolic cAMP in ependymal cells leads to a decrease in ciliary beat frequency. Therefore, the present data point towards a function for ependymal glycogen other than supplying energy for the movement of cilia.


A microtechnique for quantification of detergent-solubilized muscarinic and nicotinic acetylcholine receptors using a semi-automated cell harvestor.
A specific method for the rapid assay of muscarinic acetylcholine receptors (mAChR), either detergent-solubilized or in neuroblastoma cells, is described. This method is also applicable to the assay of nicotinic acetylcholine receptors. The procedure employs a cell harvestor and microtiter plates, and has the advantage of requiring small quantities of radioligand, microgram quantities of detergent-solubilized cholinergic receptor or less cells. The binding parameters such as the equilibrium dissociation constants (Kd) of mAChR and nicotinic acetylcholine receptor (nAChR) and inhibition constants (Ki) for antagonists determined by the present method are in excellent agreement with values determined by other methods. This assay procedure for mAChR and nAChR should facilitate the rapid screening of cholinergic agonists/antagonists and also the further purification and characterization of mAChR.