Efficient MIR crosstalk reduction based on silicon-on-calcium fluoride platform with Ge/Si strip arrays.
Reduction of the crosstalk (CT) between contiguous photonic components is still a big challenge in fabricating high packing density photonic integrated circuits (PICs). Few techniques to accomplish that goal have been offered in recent years but all in the near-IR region. In this paper, we report a design for realizing a highly efficient CT reduction in the MIR regime, for the first time to the best of our knowledge. The reported structure is based on the silicon-on-calcium-fluoride (SOCF) platform with uniform Ge/Si strip arrays. Using Ge strips shows better CT reduction and longer coupling length (Lc) than the conventional Si based devices over a wide bandwidth in the MIR region. The effect of adding a different number of Ge and Si strips with different dimensions between two adjacent Si waveguides on the Lc and hence on the CT is analyzed using both full vectorial finite element method and 3D finite difference time domain method. An increase in the Lc by 4 orders of magnitude and 6.5 times are obtained using Ge and Si strips, respectively, compared to strips-free Si waveguides. Consequently, crosstalk suppression of - 35 dB and - 10 dB for the Ge and Si strips, respectively, is shown. The proposed structure is beneficial for high packing density nanophotonic devices in the MIR regime, such as switches, modulators, splitters, and wavelength division (de)multiplexers, which are important for MIR communication integrated circuits, spectrometers, and sensors.


The effects of naltrexone, an opioid receptor antagonist, on plasma LH levels in common carp (Cyprinus carpio L.).
Naltrexone-an opioid receptor antagonist, was administered intraperitoneally to sexually mature male and female common carp in the prespawning period, in order to investigate its effects on spontaneous or sGnRH-A-stimulated LH secretion. Naltrexone and sGnRH-A were injected at the same time. The possible involvement of a dopaminergic system in this process was studied in males pre-treated with pimozide (a dopamine receptor antagonist) 12 h before naltrexone and/or sGnRH-A administration. Blood samples for the analysis of carp LH concentrations were taken just before the injections and then after the injections, serial sampling during 24 h was performed. In male carp, naltrexone (500 or 5000 microg kg(-1)) decreased spontaneous LH release, but there were no effects of naltrexone on sGnRH-A-stimulated LH secretion. In males pre-treated with pimozide, a similar response to naltrexone injection (500 microg kg(-1)) as in pirnozide non-treated fish, was observed. The highest dose of naltrexone, 5000 microg kg(-1), significantly stimulated LH release, in response to sGnRH-A administration in pimozide pre-treated males. In female carp, contrary to males, naltrexone at a dose of 500 microg kg(-1), caused significant stimulation of spontaneous LH release. These data indicate that endogenous opioid peptides modify LH secretion in sexually mature carp. In males, they stimulate LH secretion, acting rather on the hypothalamic GnRH system and in females, opioids inhibit LH release by the influence on the dopaminergic system.


Morphological Characteristics of the Action of Cationic Peptide Warnerin on Regeneration of the Connective Tissue around Implanted Teflon Catheters in Mice under Conditions of Immunosuppression.
Warnerin pretreatment of catheter segments subcutaneously implanted to mice under conditions of immunosuppression led to a significant increase in the number of neutrophils in the surrounding tissues on day 1; the number of fibroblasts tended to decrease by day 3. Immunohistochemical study showed the presence of T and B lymphocytes on day 3, but no positive reactions to vimentin and CD34 were observed during the first 2 days. These changes suggest that warnerin reduced the intensity of regeneration processes in tissues around the implant, which can be used for suppression of fibrosis.


[End-of-life care as a statistic: can quality really be expressed in numbers?].
Quantitative measurement of the quality of end-of-life-care is problematic. While it is easy to define the problem, it is far harder to assess the value of the outcome.


[Pathomimia and plastic surgery, a case report].
Pathomimia is defined as a dummy pathology self-induced deliberately and is neither associated with mental confusion nor disturbance of consciousness. This article reports a case of pathomimia in plastic surgery. One of our patients had intentionally injected physiological saline solution into her breast implants in order to increase their volume. Implants removal was necessary because of severe local inflammatory signs. Psychiatric assessment revealed body dysmorphic disorder (BDD) developed on an hysterical personality, which explained the self-induced injuries. This nosologic entity must be promptly identified because it's diagnosis remains problematic and a multidisciplinary medical management is essential.


Evaluation of iron deficiency as a nutritional adaptation to infectious disease: an evolutionary medicine perspective.
An evolutionary perspective suggests that iron deficiency may have opposing effects on infectious disease risk, decreasing susceptibility by restricting iron availability to pathogens, and increasing susceptibility by compromising cellular immunocompetence. In some environments, the trade-off between these effects may result in optimal iron intake that is inadequate to fully meet body iron needs. Thus, it has been suggested that moderate iron deficiency may protect against acute infection, and may represent a nutritional adaptation to endemic infectious disease stress. To test this assertion, we examined the association between infection, reflected by C-reactive protein, a biomarker of inflammation, and iron status, reflected by transferrin receptor (TfR) and zinc protoporphyrin to heme ratio (ZPP:H), among school-age Kenyan children, and evaluated the hypothesis that moderate iron deficiency is associated with lower odds of infectious disease. TfR > 5.0 mg/l, with sensitivity and specificity for iron deficiency (ZPP:H > 80 micromol/mol) of 0.807 and 0.815, was selected as the TfR definition of iron deficiency. Controlling for age and triceps skinfold thickness (TSF), the odds ratio (OR) for acute viral or bacterial infection associated with iron deficiency (compared to normal/replete) was 0.50 (P = 0.11). Controlling for age and TSF, the OR for infection associated with an unequivocally iron replete state (compared to all others) was 2.9 (P = 0.01). We conclude that iron deficiency may protect against acute infection in children.


The hybrid procedure of thoracoscopic and hand-assisted laparoscopic resection of an esophageal gastrointestinal stromal tumor: A case report.
Esophageal gastrointestinal stromal tumors (E-GIST) are very rare tumors, and there is no consensus regarding the optimal surgical approach for E-GISTs. Here, we report a case of a large E-GIST that was resected via video-assisted thoracoscopic surgery (VATS) and hand-assisted laparoscopic surgery (HALS). When examining for comorbidities of myasthenia gravis using computed tomography, a 7-cm-sized tumor was detected in the lower esophagus of a 68-year-old woman. Further examination revealed the tumor to be an E-GIST with high malignant potential, and thus, esophagectomy was performed. The hybrid procedure for VATS and HALS techniques was safe and minimally invasive for this E-GIST that required esophagectomy. Thus, esophagectomy with VATS and HALS is thought to be a reasonable surgical option for resecting large E-GISTs, for which enucleation is not recommended.


Comparison of nasotracheal versus orotracheal intubation for sedation, assisted spontaneous breathing, mobilization, and outcome in critically ill patients: an exploratory retrospective analysis.
Nasotracheal intubation (NTI) may be used for long term ventilation in critically ill patients. Although tracheostomy is often favored, NTI may exhibit potential benefits. Compared to orotracheal intubation (OTI), patients receiving NTI may require less sedation and thus be more alert and with less episodes of depression of respiratory drive. We aimed to study the association of NTI versus OTI with sedation, assisted breathing, mobilization, and outcome in an exploratory analysis. Retrospective data on patients intubated in the intensive care unit (ICU) and ventilated for > 48 h were retrieved from electronic records for up to ten days after intubation. Outcome measures were a Richmond Agitation and Sedation Scale (RASS) of 0 or - 1, sedatives, vasopressors, assisted breathing, mobilization on the ICU mobility scale (ICU-MS), and outcome. From January 2018 to December 2020, 988 patients received OTI and 221 NTI. On day 1-3, a RASS of 0 or - 1 was attained in OTI for 4.0 ± 6.1 h/d versus 9.4 ± 8.4 h/d in NTI, p < 0.001. Propofol, sufentanil, and norepinephrine were required less frequently in NTI and doses were lower. The NTI group showed a higher proportion of spontaneous breathing from day 1 to 7 (day 1-6: p < 0.001, day 7: p = 0.002). ICU-MS scores were higher in the NTI group (d1-d9: p < 0.001, d10: p = 0.012). OTI was an independent predictor for mortality (odds ratio 1.602, 95% confidence interval 1.132-2.268, p = 0.008). No difference in the rate of tracheostomy was found. NTI was associated with less sedation, more spontaneous breathing, and a higher degree of mobilization during physiotherapy. OTI was identified as an independent predictor for mortality. Due to these findings a new prospective evaluation of NTI versus OTI should be conducted to study risks and benefits in current critical care medicine.


In vitro studies of changes in human endothelial cell functions under the effect of imiquimod.
Imiquimod (1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine) is an active immunomodulator with antiviral effects. In addition to its stimulatory effect on cell-mediated immunity, in vivo studies have detected its antiviral and antiangiogenic effects. Possible direct effect of imiquimod on endothelial cells remains not studied. We have shown that imiquimod inhibited proliferation and migration of human endothelial cells (EA.hy 926 strain) in vitro and induced apoptosis (but not necrosis) of endothelial cells and production of IL-6 cytokine. These results suggest that imiquimod inhibits angiogenesis via direct modulation of endothelial cell function.


Characterising Biosecurity Initiatives Globally to Support the Development of a Progressive Management Pathway for Terrestrial Animals: A Scoping Review.
While biosecurity is of increasing importance globally, there is still limited evidence of the factors or elements that support the progressive and sustainable scaling up of biosecurity along the value chains from the local to the global level. To gain insight into the current body of literature on biosecurity, a mixed-methods approach was used based on a scoping literature review and an online survey with subject matter experts. Six databases were searched for published literature, and textual information from titles and abstracts of all included records (n = 266) were analysed through inductive content analysis to build biosecurity-relevant categories and identify strengths, weaknesses, opportunities, and threats (SWOT) of existing biosecurity systems or initiatives (such as projects or programs). Most records focused on initiatives in high-income countries, traditional livestock species (pigs, poultry, and large ruminants), and the production stage and had a disease-specific focus. No records described a comprehensive or global framework to progressively scale up biosecurity. Overall, the findings highlight the need for initiatives such as the FAO Progressive Management Pathway for Terrestrial Animal Biosecurity (FAO-PMP-TAB), which is a stepwise approach for strengthening biosecurity management along value chains to enhance the health, resilience, and sustainability of animal sectors. The findings highlight important elements and provide recommendations useful for developing approaches or a global framework to progressively improve biosecurity management.


Extracellular vesicles produced by the protozoan parasite Trichomonas vaginalis contain a preferential cargo of tRNA-derived small RNAs.
Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis, the most prevalent non-viral sexually transmitted infection worldwide. Trichomonas vaginalis releases extracellular vesicles that play a role in parasite:parasite and parasite:host interactions. The aim of this study was to characterise the RNA cargo of these vesicles. Trichomonas vaginalis extracellular vesicles were found to encapsulate a cargo of RNAs of small size. RNA-seq analysis showed that tRNA-derived small RNAs, mostly 5' tRNA halves, are the main type of small RNA in these vesicles. The tRNA-derived small RNAs in T. vaginalis extracellular vesicles were shown to be derived from the specific processing of tRNAs within cells. The specificity of this RNA cargo in T. vaginalis extracellular vesicles suggests a preference for packaging. The RNA cargo of T. vaginalis was shown to be rapidly internalised by human cells via lipid raft-dependent endocytosis. The potential role of these tsRNAs - an emerging class of small RNAs with regulatory functions - on altering host cellular responses requires further examination, suggesting a new mode of parasite:host communication.


In vivo binding of [18F]GBR 13119 to the brain dopamine uptake system.
Regional rat brain uptake of [18F]GBR 13119, a high specific activity, positron-emitter labeled derivative of the potent dopamine uptake antagonist GBR 12935, is reported. Striatum to cerebellum ratios of 3 are obtained at 90 minutes post injection. Specific binding in striatum can be blocked by pretreatment with dopamine uptake system antagonists (mazindol, nomifensine) but not with receptor antagonists (spiperone, flupenthixol). [18F]GBR 13119 is proposed as a new positron-emitting radioligand for in vivo PET studies of the pre-synaptic dopamine uptake system.


Ketanserin antagonises the anorectic effect of DL-fenfluramine in the rat.
To determine the role played by 5-HT2 receptors in the anorectic action of DL-fenfluramine, the ability of the selective 5-HT2 receptor antagonist ketanserin to block the reduction in food intake produced by this drug was investigated in non-deprived rats. Ketanserin (1 and 2.5 mg/kg i.p.) produced a dose-dependent antagonism of the anorectic effect of DL-fenfluramine (3 mg/kg i.p.). Prazosin (1 mg/kg i.p.) did not antagonise this effect. It is concluded that the anorectic actions of DL-fenfluramine are mediated via 5-HT2 receptors.


PCDDs, PCDFs, and PCBs concentrations in breast milk from two areas in Korea: body burden of mothers and implications for feeding infants.
We determined breast milk concentration of polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs) in 24 mothers living in Korea, and assessed the maternal body burden based on PCDDs/PCDFs and PCBs concentrations in breast milk and an infant intake rate through breast-feeding based on their concentration in breast milk. PCDDs/PCDFs and PCBs levels in breast milk from primipara mothers were found to be higher than those from multipara mothers. For total PCDDs/PCDFs TEQ level, 2,3,4,7,8-PeCDD was the predominant congener, and the proportion of 2,3,7,8-TCDD was less than 3% of total PCDDs/PCDFs TEQ level. For PCBs TEQ level, PCB-126 was the predominant congener. Maternal body burden levels of PCDDs/PCDFs and PCBs based on their concentrations in breast milk were 268-622 TEQ ng. The daily dioxin intakes of mothers were predicted to be 0.78-2.18 TEQ pg/kg/day for PCDDs/PCDFs and 0.34-0.66 TEQ pg/kg/ day for PCBs. For the first year, the body burden of an infant was predicted to be 212 TEQ ng and the daily intake of an infant was predicted to be 85 TEQ pg/kg/day, assuming the mean dioxin-related compounds concentration (27.54 TEQ pg/g fat).


β-Estradiol inhibits melatonin synthesis and melatonin receptor expression in sheep granulosa cells.
Melatonin, an important regulator of mammalian reproduction, is mainly produced in the pineal gland, and granulosa cells (GCs), the main mammalian ovarian secretory cells, synthesize melatonin and express melatonin receptors (MRs) MT1 and MT2. However, studies on melatonin regulation in GCs are lacking in sheep. In this study, we explored the effects of β-estradiol (E2) on melatonin production and MR expression in GCs. We cultured sheep GCs to analyze the expression of the melatonin rate-limiting enzymes AANAT and HIOMT and the effects of E2 on AANAT, HIOMT, and MR expression and melatonin synthesis. To determine whether estrogen receptors (ERs) mediated E2 action on melatonin secretion and MR expression, we assessed ERA and ERB expression in GCs and observed whether ER antagonists counterbalanced the effects of E2. GCs expressed AANAT and HIOMT mRNA, indicating that they transformed exogenous serotonin into melatonin. E2 inhibited melatonin production by downregulating AANAT, HIOMT, and MRs. GCs expressed ERA and ERB; ERA/ERB inhibitors abolished E2-mediated inhibition of melatonin secretion and MR expression. PHTPP upregulated melatonin secretion and MT1 expression in E2-treated GCs, but did not significantly affect AANAT and MT2 expression. In conclusion, melatonin secretion in GCs was inhibited by E2 through an ERA- and ERB-mediated process.


Development of stable influenza vaccine powder formulations: challenges and possibilities.
Influenza vaccination represents the cornerstone of influenza prevention. However, today all influenza vaccines are formulated as liquids that are unstable at ambient temperatures and have to be stored and distributed under refrigeration. In order to stabilize influenza vaccines, they can be brought into the dry state using suitable excipients, stabilizers and drying processes. The resulting stable influenza vaccine powder is independent of cold-chain facilities. This can be attractive for the integration of the vaccine logistics with general drug distribution in Western as well as developing countries. In addition, a stockpile of stable vaccine formulations of potential vaccines against pandemic viruses can provide an immediate availability and simple distribution of vaccine in a pandemic outbreak. Finally, in the development of new needle-free dosage forms, dry and stable influenza vaccine powder formulations can facilitate new or improved targeting strategies for the vaccine compound. This review represents the current status of dry stable inactivated influenza vaccine development. Attention is given to the different influenza vaccine types (i.e. whole inactivated virus, split, subunit or virosomal vaccine), the rationale and need for stabilized influenza vaccines, drying methods by which influenza vaccines can be stabilized (i.e. lyophilization, spray drying, spray-freeze drying, vacuum drying or supercritical fluid drying), the current status of dry influenza vaccine development and the challenges for ultimate market introduction of a stable and effective dry-powder influenza vaccine.


Studies on the mechanism of suppression of experimental allergic encephalomyelitis induced by myelin basic protein-cell conjugates.
The mechanism of suppression of experimental allergic encephalomyelitis (EAE) induced in Lewis rats by pretreatment with myelin basic protein (MBP) coupled to syngeneic spleen leukocytes (SL) was examined. Studies on the kinetics of the tolerance induction showed that pretreatment with MBP-SL suppressed EAE if given 7 but not 3 days before the disease-inducing injection of MBP in Freund's complete adjuvant. Treatment with cyclophosphamide 48 hr before administration of MBP-SL completely abolished the suppression of EAE. Transfer of lymph node and spleen cells from MBP-syngeneic erythrocyte conjugate (MBP-RBC) but not MBP-SL-pretreated rats resulted in suppression of disease in recipients subsequently given a disease-inducing injection of MBP. Administration of MBP coupled to SL from the histocompatible rat strain F344 resulted in suppression of the MBP-induced proliferative response of spleen cells from Lewis rats which had been given a disease-inducing injection of MBP. Taken together these results are consistent with the suppression of EAE induced by MBP-SL being mediated by suppressor T cells.


The level of proinflammatory cytokines: interleukins 12, 23, 17 and tumor necrosis factor α in patients with metabolic syndrome accompanying severe psoriasis and psoriatic arthritis.
The incidence of metabolic syndrome is estimated at 15-24% in the general population and at 30-50% in patients with psoriasis. A probable cause of the described correlation is a constant release in chronic dermatosis of proinflammatory cytokines and their influence on individual systems and organs. Assessment of the concentration of the proinflammatory cytokines (IL-12, IL-23, IL-17 and TNF-α) in blood serum and their correlation with the intensity of skin lesions, the presence of psoriatic arthritis and the risk of development of obesity and metabolic syndrome. The concentrations of subunit p70 IL-12, IL-17 and IL-23, and TNF-α in subjects with psoriasis and metabolic syndrome were determined. The level of the studied cytokines, IL-17, IL-23 and TNF-α was higher in patients diagnosed with psoriasis. Higher levels of IL-17, IL-23 and TNF-α were observed in patients with metabolic syndrome accompanying psoriasis. A higher level of IL-17 and IL-23 was found in sera of patients with psoriatic arthritis in comparison to normal psoriasis. In the study, a higher level of IL-17 and IL-23 was also shown in patients with psoriatic arthritis in comparison to patients with normal psoriasis. The effectiveness of anti-IL12/23 drugs in psoriatic arthritis is a confirmation of the obtained results of the studies. Additionally, the increased level of IL-17, both in patients with metabolic syndrome and with psoriasis, could indirectly indicate an increased cardiovascular risk in patients with affected joints in comparison to psoriasis affecting only the skin.


Distal basilar artery aneurysms: conditions for safe and secure clipping.
In general, vertebro-basilar aneurysms are good indications for endovascular treatment. However, basilar artery (BA) bifurcation aneurysms, BA-superior cerebellar artery (SCA) aneurysms, and sometimes mid-basilar aneurysms are also good indications for clipping. In this paper, conditions for safe and secure clipping for distal basilar aneurysms are discussed.There are several tips for the clipping of distal BA aneurysms. Among them, the following are very important: patency of the perforators, posterior cerebral artery (P1), and SCA must always be maintained. Several modalities including micro-Doppler ultrasonography and indocyanine green video-angiography (ICGVA) should be used to confirm the patency of these vessels. Each confirmation of patency of the vessels after clipping must be compared to those from before the clipping. Intra-operative digital subtraction angiography (DSA) is needed for large or giant aneurysms.


Plasma isoprostanoids assessment as Alzheimer's disease progression biomarkers.
Alzheimer's Disease (AD) is the most common neurodegenerative disease worldwide. So, there is a need to identify AD early diagnosis and monitoring biomarkers in blood samples. The aim of this study was to analyse the utility of lipid peroxidation biomarkers in AD progression evaluation. Participants (n = 19) were diagnosed with AD at early stages (Time 0, T0), and they were re-evaluated 2 years later (Time 1, T1). Plasma biomarkers from AD patients were determined at both times. Some analytes, such as dihomo-isoprostanes (17-epi-17-F2t-dihomo-IsoP, 17-F2t-dihomo-IsoP, Ent-7(RS)-7-F2t-dihomo-IsoP), and neuroprostanes (10-epi-10-F4t-NeuroP) showed very high probability of showing an increasing trend over time. Baseline values allowed to develop an affordable preliminary regression model to predict long-term cognitive status. So, some lipid peroxidation biomarkers would deserve consideration as useful progression AD biomarkers. The developed prediction model would constitute an important minimally invasive approach in AD personalized prognosis and perhaps could have some interest also in experimental treatments evaluation.


Are the dorsal noradrenergic bundle projections from the locus coeruleus important for neocortical or hippocampal activation?
Three different methods were used to examine the importance of the dorsal noradrenergic bundle projections from the locus coeruleus (LC) in activation of the neocortex and hippocampus in freely moving rats. (1) After cerebral norepinephrine (NE) was depleted by systemic neonatal injections of 6-hydroxydopamine (6-OHDA) both atropine-resistant and atropine-sensitive forms of hippocampal rhythmical slow activity (RSA; theta) and neocortical low voltage fast activity (LVFA) remained intact. Compared to controls the adult rats treated with 6-OHDA in infancy reared less in a 24 h time sample of behavior and ran less in running wheels. (2) Brain dopamine and NE were also depleted by systemic injections of alpha-methyl-p-tyrosine. Following this treatment rats were very inactive behaviorally. However, normal activation of the hippocampus and neocortex was still present. (3) In normal rats, electrical stimulation of the LC was relatively ineffective, compared to stimulation of nucleus reticularis pontis caudalis, in producing behavioral changes (especially locomotion) or either atropine-resistant or atropine-sensitive hippocampal RSA or neocortical LVFA. It is concluded that the locus coeruleus is not important for cerebral activation, and that mechanisms for cerebral activation are probably diffusely represented in the reticular core. The data also show that when attempting to assess the effect of experimental manipulations on brain activity it is essential to control for the possible effects of changes in behavior.


Evaluation of workplace infection prevention and control measures for COVID-19: A prospective cohort study in Japan.
Encouraging the implementation of infection prevention and control (IPC) measures has been necessary to prevent workplace infections caused by the coronavirus disease 2019 (COVID-19). However, the effectiveness of these measures in reducing infections has not been thoroughly evaluated. We evaluated employees' COVID-19 infection rates in relation to the implementation of IPC measures at their workplaces to identify effective workplace measures. This prospective cohort study was conducted between December 2020 and December 2021 using Internet-based self-assessment questionnaires, with 11,982 participants included from the baseline. To estimate whether implementing workplace IPC measures was associated with COVID-19 incidence rates among participants, we estimated multivariate-adjusted relative risk (RR) using a log-binomial model. After adjusting for sex, age, education, household members, occupation-related factors, and personal preventive behaviors, requesting ill employees to refrain from going to work showed significantly lower COVID-19 infection rates than not requesting it (RR: 0.56, 95% CI: 0.34-0.91, p = 0.019). Employees restricted from reporting to work when ill had significantly lower COVID-19 infection rates than those who did not follow this measure. The results indicated that not coming to work when ill was effective in reducing COVID-19 infections at the workplace. We suggest that companies proactively adopt this policy and encourage their employees to comply with it.


Surgical Correction of Pelvic Organ Prolapse Has No Effect on Renal Function.
The aims of the study were to determine whether symptomatic pelvic organ prolapse (POP) is a cause of subclinical renal impairment by characterizing baseline renal function in women undergoing surgical correction for POP and to assess the effect of surgical POP repair on estimated glomerular filtration rate (eGFR) postoperatively. A prospective cohort study was designed to evaluate women undergoing surgical repair for at least stage II anterior or apical POP at a single institution. Data collected included preoperative serum creatinine values, patient demographics, and clinical risk factors for renal impairment. Postoperative serum creatinine values were obtained at routine 4- to 6-week follow-up. At that time, patients were evaluated for objective and subjective surgical success and surveyed on postoperative nonsteroidal anti-inflammatory drug use. Preoperative eGFRs were calculated and compared with postoperative values. Appropriate statistical tests were performed. A total of 25 participants were recruited between August 2019 and March 2020. The median age was 70 years (interquartile range, 62-73 years). One participant (4%) reported a history of stage III chronic kidney disease preoperatively. At a median follow-up of 40 days (interquartile range, 34-49 days), no prolapse was recorded past the level of the hymen. There was no difference between preoperative and postoperative eGFR (median preoperative, 81 vs 76 mL/min per 1.73 m2, P = 0.3). Higher POP stage was not associated with significant changes in postoperative eGFR (P = 0.09). Surgical POP repair is not associated with any change in eGFR. It is unlikely that untreated POP causes subclinical renal impairment in the vast majority of women.


Exclusive Primary Lesion of Oral Leishmaniasis with Immunohistochemical Diagnosis.
A case of oral leishmaniasis without cutaneous involvement affecting the upper alveolar ridge mucosa/gingiva and the hard palate is reported in a 41-year-old Brazilian man. Microscopic examination disclosed scarce amastigotes and the definitive diagnosis was facilitated by immunohistochemical analysis. The clinical presentation of this lesion is unusual and underlies the importance of considering leishmaniasis in the differential diagnosis of oral lesions, especially in endemic areas. A literature review of the cases of mucosal leishmaniasis with exclusive primary lesions of the oral mucosa was also performed.


Recognition of emotion from body language among patients with unipolar depression.
Major depression may be associated with abnormal perception of emotions and impairment in social adaptation. Emotion recognition from body language and its possible implications to social adjustment have not been examined in patients with depression. Three groups of participants (51 with depression; 68 with history of depression in remission; and 69 never depressed healthy volunteers) were compared on static and dynamic tasks of emotion recognition from body language. Psychosocial adjustment was assessed using the Social Adjustment Scale Self-Report (SAS-SR). Participants with current depression showed reduced recognition accuracy for happy stimuli across tasks relative to remission and comparison participants. Participants with depression tended to show poorer psychosocial adaptation relative to remission and comparison groups. Correlations between perception accuracy of happiness and scores on the SAS-SR were largely not significant. These results indicate that depression is associated with reduced ability to appraise positive stimuli of emotional body language but emotion recognition performance is not tied to social adjustment. These alterations do not appear to be present in participants in remission suggesting state-like qualities.


DNA aneuploidy identifies a subset of Luminal subtype breast carcinoma patients with worse clinical outcome.
In breast carcinoma (BC), the relationship between the ploidy pattern and molecular subtyping is still unknown. We aim to investigate the prognostic impact of DNA ploidy within molecular subtypes of a large cohort of BC patients. The series involved 520 BC patients with no neoadjuvant therapy and a median follow-up of 115.5 months. Immunohistochemical assessment of hormonal receptors, ERBB2 (HER2) status and Ki67 proliferative activity was the basis of the surrogate molecular subtyping. Ploidy was evaluated by DNA flow cytometry in fresh/frozen tumour samples. Kaplan-Meier (K-M) survival estimation was used for prognostic statistical analysis. Luminal A subtype had the lowest prevalence of disease recurrences (23.6 %) and deaths from disease (18.3 %), while Luminal B (42.2 %/37.9 %), Triple-negative (46.4 %/40.6 %), and HER2-positive (55.9 %/50.0 %) subtypes had the highest. The Triple-positive subtype shows an intermediate/low frequency of adverse events (29.4 % of disease recurrences and 17.6 % of deaths from disease). Luminal A tumours were mostly diploid (55.3 %), while Triple-negative and HER2-positive tumours showed a high incidence of aneuploidy (82.6 % and 88.2 %, respectively). Luminal B and Triple-positive tumours had an intermediate percentage of aneuploidy (63.8 % and 70.6 %, respectively). K-M survival curves showed that DNA aneuploidy is significantly associated with shorter disease-free survival and overall survival in Luminal A and Luminal B molecular subtypes. DNA aneuploidy identifies a subset of Luminal BC patients with worse clinical outcome, potentially eligible for more aggressive adjuvant therapy.


The effective and specific isolation of antibodies from human serum by using thiophilic paramagnetic polymer beads.
A rapid and effective method to specifically isolate immunoglobulin G (IgG) from human serum by thiophilic paramagnetic polymer beads was developed. The thiophilic paramagnetic beads were synthesized with vinyl acetate and divinylbenzene by microsuspension polymerization in the presence of magnetite nanoparticles. Divinylsulfone and 2-mercapto-benzothiazole were subsequently used to modify the surface of these beads, resulting in thiophilic particles that exhibited a high specificity to the antibodies in serum at low salt concentration. The adsorbed IgG was eluted by 0.8M KCl and 72% of the IgG in the serum was recovered. The purity of the isolated IgG reached 98.4% and the bioactivity was fully maintained (>99%). The high efficiency, mild conditions and simplicity make this technology suitable for the economic purification of antibodies in a large scale.


Novel 5-substituted, 2,4-diaminofuro[2,3-d]pyrimidines as multireceptor tyrosine kinase and dihydrofolate reductase inhibitors with antiangiogenic and antitumor activity.
Recent evidence suggests that combination therapy of cancer with receptor tyrosine kinase (RTK) inhibitors, which are usually cytostatic, with conventional chemotherapeutic agents, which are usually cytotoxic, provide an improved treatment option. We have designed, synthesized, and evaluated a series of novel 2,4-diamino-5-substituted furo[2,3-d]pyrimidines with RTK and dihydrofolate reductase (DHFR) inhibitory activity in single molecules, as potential cytostatic and cytotoxic agents with antitumor activity. These compounds were synthesized from 2,4-diamino-5-chloromethyl furo[2,3-d]pyrimidine and aryl methyl ketones using the Wittig reaction to afford the C-8-C-9 unsaturated analogs followed by catalytic reduction to the corresponding saturated compounds. The saturated and unsaturated C-8-C-9 bridged compounds were evaluated as inhibitors of vascular endothelial growth factor receptor (VEGFR-2, Flk, KDR), epidermal growth factor receptor, and platelet-derived growth factor receptor-beta (PDGFR-beta). Selected analogs were also evaluated as antiangiogenic agents in the chicken embryo chorioallantoic membrane (CAM) assay. The compounds were also evaluated as inhibitors of human (h) DHFR and Toxoplasma gondii (tg) DHFR. In each evaluation, a known standard compound was used as a comparison. Of the compounds evaluated, compound 32 was as potent as the standard compounds against VEGFR-2 and PDGFR-beta, showing dual inhibitory activity against RTK. This analog was also highly effective in the CAM assay. A second analog 18 also demonstrated dual VEGFR-2 and PDGFR-beta inhibitory activity as well as potent antiangiogenic activity in the CAM assay. Four additional analogs were also effective against PDGFR-beta and in the CAM assay. An unsaturated C-8-C-9 moiety was necessary for RTK inhibitory activity. Compound 32 also showed inhibitory activity against hDHFR and tgDHFR, illustrating the multitarget inhibitory potential of these analogs. The biological activity of these analogs also suggests the necessity of an unsaturated C-8-C-9 bridge for dual RTK and DHFR inhibitory activity. Compounds 18 and 32 were also evaluated in a B16 melanoma mouse model and were found to be more active as antitumor agents than methotrexate. In addition, both 18 and 32 were also active in decreasing lung metastases in a mouse model of B16 melanomas.


Impaired cerebral autoregulation in Fabry disease: A case-control study.
Cerebral small vessel disease is a common manifestation among patients with Fabry disease (FD). As a biomarker of cerebral small vessel disease, the prevalence of impaired cerebral autoregulation as assessed by transcranial Doppler (TCD) ultrasonography was evaluated in FD patients and healthy controls. TCD was performed to assess pulsatility index (PI) and vasomotor reactivity expressed by breath-holding index (BHI) for the middle cerebral arteries of included FD patients and healthy controls. Prevalence of increased PI (>1.2) and decreased BHI (<0.69) and ultrasound indices of cerebral autoregulation were compared in FD patients and controls. The potential association of ultrasound indices of impaired cerebral autoregulation with white matter lesions and leukoencephalopathy on brain MRI in FD patients was also evaluated. Demographics and vascular risk factors were similar in 23 FD patients (43% women, mean age: 51 ± 13 years) and 46 healthy controls (43% women, mean age: 51 ± 13 years). The prevalence of increased PI (39%; 95% confidence interval [CI]: 20%-61%), decreased BHI (39%; 95% CI: 20%-61%), and the combination of increased PI and/or decreased BHI (61%; 95% CI: 39%-80%) was significantly (p < .001) higher in FD patients compared to healthy controls (2% [95% CI: 0.1%-12%], 2% [95% CI: 0.1%-12%], and 4% [95% CI: 0.1%-15%], respectively). However, indices of abnormal cerebral autoregulation were not associated independently with white matter hyperintensities and presented a low-to-moderate predictive ability for the discrimination of FD patients with and without white matter hyperintensities. Impaired cerebral autoregulation as assessed by TCD appears to be highly more prevalent among FD patients compared to healthy controls.


Distinctive Patterns of CTNNB1 (β-Catenin) Alterations in Salivary Gland Basal Cell Adenoma and Basal Cell Adenocarcinoma.
Salivary gland basaloid neoplasms are diagnostically challenging. Limited publications report that some basal cell adenomas harbor CTNNB1 mutations, and nuclear β-catenin expression is prevalent. We evaluated β-catenin expression in basal cell adenomas and adenocarcinomas in comparison with salivary tumors in the differential diagnosis and performed targeted genetic analysis on a subset of cases. β-catenin immunohistochemistry was performed on formalin-fixed, paraffin-embedded whole sections from 73 tumors. Nuclear staining was scored semiquantitatively by extent and intensity. DNA was extracted from 6 formalin-fixed, paraffin-embedded samples (5 basal cell adenomas, 1 basal cell adenocarcinoma) for next-generation sequencing. Nuclear β-catenin staining was present in 18/22 (82%) basal cell adenomas; most were diffuse and strong and predominant in the basal component. Two of 3 basal cell adenocarcinomas were positive (1 moderate focal; 1 moderate multifocal). All adenoid cystic carcinomas (0/20) and pleomorphic adenomas (0/20) were negative; 2/8 epithelial-myoepithelial carcinomas showed focal nuclear staining. Most β-catenin-negative tumors showed diffuse membranous staining in the absence of nuclear staining. Four of 5 basal cell adenomas had exon 3 CTNNB1 mutations, all c.104T>C (p.I35T). Basal cell adenocarcinoma showed a more complex genomic profile, with activating mutations in PIK3CA, biallelic inactivation of NFKBIA, focal CYLD deletion, and without CTNNB1 mutation despite focal β-catenin expression. Nuclear β-catenin expression has moderate sensitivity (82%) for basal cell adenoma but high specificity (96%) in comparison with its morphologic mimics. CTNNB1 mutation was confirmed in most basal cell adenomas tested, and findings in basal cell adenocarcinoma suggest possible tumorigenic mechanisms, including alterations in PI3K and NF-κB pathways and transcriptional regulation.


Effect of common antivertiginous agents on the high velocity vestibulo-ocular reflex.
It has long been suggested that antivertiginous medications exert their symptomatic effect through inhibition of the vestibulo-ocular reflex (VOR). We tested this hypothesis by directly measuring the VOR after administration of three agents from different substance classes: an antihistamine, a benzodiazepine and a calcium channel antagonist. The gain and the variability of the high velocity VOR was assessed using video head impulses (vHIT) under the following conditions: baseline, after dimenhydrinate, after diazepam and after cinnarizine. We found that all three medications did not change any VOR gain or variability parameter: At 60ms, the gain was 0.95 at baseline, 0.99 under dimenhydrinate, 0.99 under diazepam and 0.96 under cinnarizine. The gain variability across repetitive head impulses remained also uninfluenced. The human high frequency VOR remains robust to pharmacological perturbations at common clinical doses and the assumption that symptomatic vertigo relief is achieved merely through impairment of the VOR requires re-examination. Alternative mechanisms of pharmacological action might be operant, such as the modulation of vestibulo-cortical pathways, a differential effect on the low frequency VOR and an altered sensitivity to drugs in acute unilateral vestibulopathy.


Diskogenic Reactivation of Herpes Zoster.
Varicella zoster virus remains dormant in the dorsal root ganglia after childhood exposure to chickenpox. Its reactivation results in herpes zoster, otherwise known as shingles, which is a painful vesicular rash in a dermatomal distribution. We present a case of foraminal disk extrusion that resulted in radicular pain in a dermatomal distribution. The resultant inflammatory response around the dorsal root ganglion triggered an episode of shingles, which elegantly highlights the pathophysiology of this condition at a gross anatomic level.


Older adults recruit dorsomedial prefrontal cortex to decrease negativity during retrieval of emotionally complex real-world events.
Recent research from our lab has highlighted a prefrontally-mediated control mechanism that decreases the subjective richness of negative episodic events during older adults' episodic memory retrieval. The current study examined whether such a mechanism was also engaged during retrieval of real-world negative events. In a scanned autobiographical memory task, 56 participants (ages 18-83) were presented with images associated with the 2013 Boston Marathon Bombings. Images fell into three categories: primarily positive, primarily negative, and mixed-valence. Participants retrieved a personal memory associated with each image, elaborated on that memory in as much detail as possible, and rated memory positivity and memory negativity. Unlike in recent episodic memory studies, young and older adults did not differ in how prefrontal regions contributed to retrieval of autobiographical memories associated with primarily negative images. However, there was an age-related reversal in the role of dorsomedial prefrontal recruitment during retrieval of autobiographical memories associated with mixed-valence images: Activity was associated with increased negativity ratings in young adults and decreased negativity in older adults. These findings are the first evidence that older adults engage a prefrontally-mediated mechanism at the time of retrieval to reduce the negativity of memories for real-world emotional events, and further suggest that they may only do so in the case of emotional ambiguity. Such a mechanism could have important implications for understanding how older adults may respond to and evaluate negative events in their daily lives.


Nutrition-related health promotion through an after-school project: the responses of children and their families.
UK health policy is concerned with emphasising nutritional status as a factor in the relationship of social inequalities to health outcomes. This paper examines pupil and parent responses to an after-school 'Food Club' designed to promote food preparation skills and healthier food choices amongst 12-13 year olds in low-income areas in North East England. The rationale for the intervention was a series of distinct but connected premises: food preparation skills are essential to inexpensive healthier eating; practical cooking skills are given limited emphasis in the secondary school curriculum; children have some choice over what they eat and may serve as a conduit of influence within the family. The qualitative investigation used group discussions and individual interviews with participating pupils and their parents. Most participating pupils enjoyed the practical emphasis upon food preparation, believed their skills developed, and were aware of the underlying message about healthier eating, but only made limited changes to their diet. Interviews with parents showed most to be positive about their child's involvement in such a club, though they varied in their attitude to its underlying message. There was some evidence of children being more involved in cooking at home and making some specific requests about food, but little to suggest they were influencing family food consumption. The findings suggest that an extra-curricular Food Club is an appropriate and feasible approach to developing food preparation skills with pupils in this age group. These findings raise questions about children's opportunities to exercise food preparation skills and make food choices within families, and the extent to which barriers to dietary change may be lowered through educational initiatives directed at pupils.


Clinical Nurse Specialist Practice: Impact on Improving Sedation Practice in Critical Care.
Prolonged mechanical ventilation results from deeper levels of sedation. This may lead to impaired respiratory muscle functioning that develops into pneumonia, increases antibiotic use, increases delirium risk, and increases length of hospitalization. A trauma and surgical intensive care unit interdisciplinary team conducted a quality improvement project to lighten sedation levels and shorten mechanical ventilation time. The project included multimodal elements to improve sedation practice. Standardizing the spontaneous awakening trial algorithm, creation of electronic health record tools, integration of sedation practices into daily rounds, and focused education for nursing were implemented in April 2021 through October 2021. A reduction of median hours spent on mechanical ventilation was achieved. Mechanical ventilation hours decreased from 77 to 70. Richmond Agitation Sedation Scale levels improved from a median of -2 to -1, and daily spontaneous awakening trials increased from 10% to 27% completed. The quality improvement project demonstrated that, with increased daily spontaneous awakening trials and lighter sedation levels, the time patients spent on mechanical ventilation was shortened. There was no increase to self-extubation with lighter sedations levels. Shorter time on mechanical ventilation can reduce patient harm risks.


Visualization of sinus venosus atrial septal defect by transesophageal echocardiography.
Atrial septal defect (ASD) is usually suspected clinically but requires a confirmative diagnostic procedure before surgical repair. Two-dimensional and Doppler echocardiography have high sensitivity and specificity for ASD, but the sensitivity of echocardiography is not as high in detecting sinus venosus ASD as it is in ostium primum or secundum defect because of the difficulty in visualizing the sinus venosus area from the subcostal window. For the posteriorly located cardiac structures, including the atrial septum, visualization is superior by transesophageal echocardiography. We describe a case in which sinus venosus ASD was not visualized by conventional transthoracic echocardiography but was diagnosed confidently by transesophageal echocardiography.


Postpartum depressive symptoms and its association to daytime sleepiness and restless legs during pregnancy.
Postpartum depression is a common condition, which consequences might be harmful for both mother and child. Since sleep and depression are closely related it is possible that women who suffer from sleep related problems during pregnancy are more likely to develop depression in the postpartum period. This study aims to investigate the possible association between depressive symptoms in the postpartum period and sleep related problems during pregnancy. In this study 293 women in the last trimester of pregnancy answered a questionnaire about symptoms of restless legs, snoring and daytime sleepiness. They also completed the Epworth Sleepiness Scale (ESS). The same women were screened for depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) four to ten weeks after giving birth. Additional information about social data, pregnancy and delivery was received from the medical charts. Women with postpartum depressive symptoms had higher prevalence of excessive daytime sleepiness defined as ESS score ≥10 (OR 3.84, CI 1.57-9.39), and restless legs syndrome (OR 2.837 CI 1.18-6.84) in last trimester of pregnancy, when adjusted for socio-demographic factors and obstetric risk factors. No association was found between postpartum depressive symptoms and snoring. Depressive symptoms after childbirth are preceded by sleep related problems such as daytime sleepiness and restless legs, already during pregnancy. The results from Epworth Sleepiness Scale and a questionnaire concerning Restless Legs Syndrome completed during pregnancy might be a valuable contribution for detecting women at risk for postpartum depression, enabling preventive interventions.


Diffusion kurtosis imaging and arterial spin labeling for the noninvasive evaluation of persistent post-contrast acute kidney injury.
We investigated whether diffusion kurtosis imaging (DKI) and arterial spin labeling (ASL) facilitated the assessment of serial alterations in persistent post-contrast acute kidney injury (PC-AKI). We randomly divided 24 rats into four PC-AKI groups (days 1, 3, 7, and 13, n = 6/group), with an additional six control animals. We conducted functional magnetic resonance imaging (MRI), diffusion kurtosis imaging (DKI), and arterial spin-labeling (ASL) analyses. Mean kurtosis (MK), axial kurtosis (Ka), mean diffusivity (MD), fractional anisotropy (FA), radial kurtosis (Kr), and renal blood flow (RBF) maps were normalized to baseline (prior to contrast injection) to calculate adjusted △RBF, △MK, △Ka, △MD, △FA, and △Kr values. We also investigated urinary neutrophil gelatinase associated lipocalin (NGAL), serum cystatin C (CysC), aquaporin-2 (AQP2), hypoxia-inducible factor-1 (HIF-1α), and histological indices. In the inner stripe of the outer medulla, when compared with controls, decreased △FA and △MD levels were observed on days 1, 3, and 7, and a distinct elevation in △MK and △Kr on days 1-13, and a persistent decrease in △RBF on days 1-13, and a prominent increase in △Ka on days 7 and 13 in PC-AKI animals (all p < 0.05). △Ka and △MK were positively correlated with AQP-2 (r = 0.8086, p < 0.0001 and r = 0.7314, p < 0.0001, respectively), and △RBF was highly correlated with HIF-1α (r = -0.7592, p < 0.0001). Moreover, both CysC and NGAL were significantly elevated in PC-AKI animals when compared with controls from days 1-13 (all p < 0.05). Renal histological data indicated severe tubular and glomerular injury at days 1-13 in all PC-AKI groups. ASL and DKI may be noninvasively and longitudinally used to detect PC-AKI and predict further outcomes.


Electron microscopical and histochemical studies of outer hair cells in normal rabbits.
The outer hair cells of the rabbit were electron microscopically and histochemically investigated. The results clearly showed that the outer hair cells of the rabbit have no agglomeration of mitochondria in its infranuclear region. This anatomical fact means that the functional mechanism in the outer hair cells of the rabbit may be substantially different from that of other animals which have agglomeration of mitochondria. From the results of the histochemical study, it is reasonably supposed that the anaerobic energy metabolism may ordinarily play the leading part in sustaining the cellular functions in the infranuclear region of the outer hair cells of the rabbit.


Too Tall for the DXA Scan? Contributions of the Feet and Head to Overall Body Composition.
Accurate assessment of total body composition in tall (>1.96m) individuals using dual energy x-ray absorptiometry (DXA) scans is problematic due to current height restrictions of the scan table. The aim of this investigation was to quantify absolute and relative contributions of fat, bone and lean mass, of the feet and head regions, to whole-body composition DXA scan totals. Whole-body DXA scans were performed in collegiate athletes. Athlete DXA scans were included in data analyses if the entire body fit within the confines of scan table area. The feet region of interest (ROI) was delineated at the ankle joint mortise, marked superiorly by the inferior margin of the tibial plafond and encompassing all inferior anatomical structures. The head region was calculated by the DXA scan software. Both absolute (kg) and relative (feet/whole-body x 100 = feet mass %) contributions to body composition were calculated. Data presented as mean±SD. 132 National Collegiate Athletic Association (NCAA) athletes (85 female) underwent DXA scans which met the inclusion criteria. The feet region represented: 1.9±0.3kg (2.6±0.3%) of total mass; 0.4±0.3kg (2.6±0.5%) of fat mass; 1.3±0.3kg (2.5±0.3%) of lean mass; and 0.14±0.0kg (5.4±0.6%) of bone mineral content (BMC). The head region represented: 4.8±0.5kg (6.9±0.8%) of total mass; 1.2±0.2kg (8.2±3.0%) of fat mass; 3.2±0.5kg (6.1±0.9%) of lean mass; and 0.48±0.07kg (18.7±2.7%) of BMC. Significant negative relationships were found between head% versus whole-body BMC (r=-0.54;p < 0.0001), lean mass (r=-0.57;p<0.0001), and fat mass (r=-0.81;p<0.0001) and between feet% versus fat mass (r=-0.68;p<0.0001). A significant positive relationship was noted between feet% versus whole-body BMC (r=0.18;p=0.04) but not versus lean mass (r=0.15;p=0.09). Removing the feet from whole-body composition analyses reduces lean, fat and bone mass compartment totals by 3%-5%. Removing the head region reduces body composition compartments by 6%-19%, from whole-body DXA scan totals.


Differentiation of Boettcher's cells during postnatal development of rat cochlea.
Contrary to the highly specialized epithelial cells of the mammalian auditory organ, little is known about the surrounding cells and, in particular, Boettcher's cells (BC). Our morphological studies show that, in rats, these cells began their differentiation around postnatal day 8 (P8) reaching maturity around P20, when they are completely covered by Hensen's and Claudius' cells. Tight junctions were noted near the apex of BC, providing that they were in direct contact with the endolymphatic space, between approximately P8 and P16. We observed gap junctions between BC and adjacent cells before the end of the covering process suggesting the additional involvement of BC in potassium recycling into the endolymph. Adherens junctions were also seen between BC throughout their maturation. Importantly, we noticed cytoplasmic secretory granules and an accumulated material, probably a secretion, in the intercellular space, between P8 and P25. These results indicate that BC could basally take part in the secretion of the extracellular matrix of the basilar membrane. Finally, we show that the basolateral interdigitations of BC are longer and more tighlty grouped at maturity and harbour urea transporters as early as P18. Our observations thus support the view that BC perform several functions.


[Clinical evaluation of SM-4300 against bacterial infections in the field of internal medicine].
A new drug of human intact immunoglobulin, SM-4300 was applied to the acute respiratory infections in the field of internal medicine. SM-4300 was administered intravenously for 1 or 3 days at a daily dose of 2.5 g to 4 patients suffering from respiratory infections. We have obtained the results as follows. Clinical effects of SM-4300 were good in 2 cases, fair in 1 case, unknown in 1 case, and no side effects were observed.


Long-term follow-up of patients after gamma intracoronary brachytherapy failure (from GAMMA-I, GAMMA-II, and SCRIPPS-III).
We report the long-term outcome of 225 patients who failed gamma-brachytherapy for in-stent restenosis. Total adverse events, target vessel revascularization, and myocardial infarction were higher after repeat percutaneous coronary intervention versus coronary artery bypass grafting. Therefore, coronary artery bypass grafting may be the preferable first-line therapy in these patients until other therapies (i.e., drug-eluting stents) are available. Shorter time from brachytherapy to radiation failure and late thrombosis after brachytherapy were independent predictors of adverse events.


Allele and genotype frequencies of CYP2C9 in a Korean population.
To determine the frequencies of the variant alleles and the genotypes of CYP2C9 in a Korean population. Three hundred and fifty-eight healthy Korean subjects were studied. CYP2C9 alleles were detected by polymerase chain reaction-restriction fragment length polymorphism assays and direct sequencing assays. The allele frequencies were 0.934 for CYP2C9*1, 0.060 for CYP2C9*3 and 0.006 for CYP2C9*13. The CYP2C9*2,*4,*5 and *11 alleles were not detected. The frequencies of the CYP2C9*1/*1, *1/*3 and *1/*13 genotypes were 0.869, 0.120 and 0.011, respectively. The frequency of the CYP2C9*3 allele in the Korean population studied was significantly higher than reported elsewhere, and a novel allele, CYP2C9*13, was found at a frequency of 0.006 (95% confidence interval 0, 0.012). Only three genotypes of CYP2C9, CYP2C9*1/*1,*1/*3 and *1/*13 were observed in this Korean population.


The 2022 summer marine heatwaves and coral bleaching in China's Greater Bay Area.
From July to August 2022, scleractinian coral communities in China's Greater Bay Area (GBA) in the northern South China Sea (nSCS) experienced an unprecedented bleaching event, despite the fact that coral communities in this area are often considered coral thermal refugia due to their high latitude distribution. Field surveys of six sites covering three main coral distribution areas of the GBA revealed that coral bleaching occurred at all sites. Bleaching was more severe in shallow water (1-3 m) than in deep water (4-6 m), as indicated by both percent bleached cover (51.80 ± 10.04% vs. 7.09 ± 7.37%) and bleached colonies (45.86 ± 11.22% vs. 6.58 ± 6.53%). Coral genera Acropora, Favites, Montipora, Platygyra, Pocillopora, and Porites showed high susceptibility to bleaching, and Acropora and Pocillopora suffered high post-bleaching mortality. In the three areas surveyed, analysis of oceanographic data detected marine heatwaves (MHWs) during the summer, with mean intensities between 1.62 and 1.97 °C and durations between 5 and 22 days. These MHWs were primarily driven by increased shortwave radiation due to strong western Pacific Subtropical High (WPSH), combined with reduced mixing between the surface and deep upwelling waters due to reduced wind speed. Comparing with histological oceanographic data showed that the 2022 MHWs were unprecedented, and there was a significant increase in the frequency, intensity, and total days of MHWs during 1982-2022. Furthermore, the heterogeneous distribution of summer MHW characteristics indicates that the coastal upwelling may modulate the spatial distribution of summer MHWs in nSCS through its cooling effect. Overall, our study indicates that MHWs may have affected the structure of the subtropical coral communities in the nSCS, and impaired their potential as thermal refugia.


Calcium movement in vivo and in vitro in secretory-stage enamel of rat incisors.
The lower incisors of young rats were dissected, immersed in physiological saline containing 45Ca under various conditions, and processed for autoradiography. The data were compared with those from in vivo 45Ca autoradiography. In secretory-stage enamel, wiped free of the enamel organ and immediately immersed in radioactive saline, there was intense labelling in the surface layers. The labelled area expanded only gradually into the deeper layers at a rate similar to that observed in vivo. Labelling in the enamel was similar in pattern but much weaker in intensity when the incisor was identically treated in vitro with the enamel organ attached. Glutaraldehyde pretreatment of the exposed enamel abolished expansion of the labelled area, whereas a hypochlorite pretreatment allowed a rapid diffusion of the isotope into the deeper layers of the secretory-stage enamel. The findings confirm the role of the enamel organ as a diffusion barrier to the penetration of calcium from the extracellular fluid to the secretory-stage enamel, and suggest an intimate correlation between physicochemical properties of the organic enamel matrix and the rate of surface-to-interior diffusion of calcium within the secretory-stage enamel of rat incisors.


Philanthropy in Public Libraries: Its Impact on Community Well-Being Missions.
Public libraries support community well-being missions related to access to information, knowledge creation, public service programming and social cohesion. Interviews in this study were designed to discover whether philanthropy in the form of giving positively impact their ability to deliver these missions. Four public library directors in Mississippi were selected for this study because the state reports low community well-being measures and high charitable giving. Findings suggest that philanthropy is a fundamental partner in community well-being missions for these libraries even though, as a sector, public libraries measure low in philanthropic support.


Seed abortion in wind-dispersed pods of Dalbergia sissoo: maternal regulation or sibling rivalry?
Dalbergia sissoo, a wind-dispersed tropical tree, shows a positively skewed distribution of seeds per pod. This is attributed to the enhanced dispersal advantage of few-seeded pods due to their reduced wing loading (ratio of weight to pod surface area) and low settling velocity. The proximate mechanisms causing the positively skewed distribution were investigated. The distribution could not be attributed to the distribution pattern of ovule number per ovary, pollen grain limitation, lack of ovule fertilization, or post-fertilization elimination of many-seeded pods. Rather, it was caused by the post-fertilization abortion of seeds within a pod 2 weeks after fertilization. This intra-pod seed abortion (IPSA) is due to a dominance hierarchy of fertilized ovules from the distal (near stigma) to the basal end, generated by the temporal differences in fertilization. The dominant developing seeds at the distal end cause the abortion of others through the production and diffusion of an aborting agent. When the dominance hierarchy of the siblings is not intense, pods are formed with more than one seed. We argue that the positively skewed distribution of seeds per pod is not due to maternal regulation but is a result of sibling rivalry. We propose that this sibling rivalry is generated by genetic differences in pollen grain fitness and disucss the results in the context of parent-offspring conflict.


A persistent defect in the blood-brain barrier after ventral funiculus lesion in adult cats: implications for CNS regeneration?
Previous studies have shown that, in adult cats, spinal motoneurons are able to regenerate their axons after lesions in the ventral funiculus of the spinal cord. These axons regrow through a scar tissue composed of glial processes and connective tissue elements before they enter the denervated ventral root. In the present study the integrity of the blood-brain barrier (BBB) in the lesion area was assessed by i.v. injections of horseradish peroxidase (HRP), 3 weeks to 7 months postoperatively. The lesion area in the lumbosacral spinal cord was compared with the intact cervical spinal cord and the area postrema in the light and electron microscope. The results show that the BBB fails after a ventral funiculus lesion. The BBB was not restored during the examined period. The leakage of HRP appears to be the result of a transendothelial vesicular transport. In addition, it was observed that the blood vessels in the lesion area were surrounded by wide and irregular perivascular spaces with broken outer basal laminae. Other studies on traumatic defects in the BBB have indicated that the barrier is reorganized within 4 weeks after the lesion. The possibility that a prolonged defect in the BBB after a ventral spinal cord lesion might be linked with the survival of axonal sprouts is discussed.


Patterns of gas exchange and organic acid oscillations in tropical trees of the genus Clusia.
Gas exchange patterns and nocturnal acid accumulation were examined in four species of Clusia under simulated field conditions in the laboratory. Clusia alata and C. major had midday stomatal closure, substantial net CO2 exchange ([Formula: see text]) during the night, and the highest water use efficiency (WUE). C. venosa showed a pattern similar to a C3 plant, with nighttime stomatal closure, while C. minor maintained positive [Formula: see text] continuously throughout a 24-h period. However, large changes in titratable acidity, which closely matched changes in citrate and malate levels, indicated that Crassulacean acid metabolism (CAM) is active in all four species. C. venosa showed dawn-dusk oscillations in titratable acidity that were higher than the values reported for other C3-CAM intermediates, while the nighttime acid accumulation of 998 mol m-3 observed in C. major is unsurpassed by any other CAM plant. Moreover, the dawn-dusk changes in citrate levels of over 65 mol m-3 in C. alata and C. minor, and over 120 mol m-3 in C. major, are 3-6 times higher than values reported for other CAM plants. Although these oscillations in citrate levels were quite large, and the nighttime dark respiration rates were high, the O2 budget analysis suggestes that only part of the reducing power generated by the synthesis of citric acid enters the respiratory chain. Dawn-dusk changes in malate levels were just over 50 mol m-3 for C. venosa but over 300 mol m-3 for C. major. Between 28% (C. major) and 89% (C. venosa) of the malate accumulated during the night was derived from recycled respiratory CO2. These daily changes in malate and citrate levels also contributed significantly to changes in leaf sap osmolality. This variability in CO2 uptake patterns, the recycling of nighttime respiratory CO2, and the high WUE may have contributed to the successful invasion of Clusia into a wide range of habitats in the tropics.


Development of a modified QuEChERS method for the determination of veterinary antibiotics in swine manure by liquid chromatography tandem mass spectrometry.
A QuEChERS (quick, easy, cheap, effective, rugged and safe) based methodology was developed for the rapid, simultaneous quantification and identification of 26 veterinary drugs in swine manure by liquid chromatography tandem mass spectrometry. The selected antibiotics included tetracyclines, sulfonamides, macrolides, fluoroquinolones, lincosamides and pleuromutilins. This is the first study to determine pleuromutilin levels in manure. The QuEChERS process involved two simple steps. First, sample extraction with methanol: acetonitrile: 0.1M EDTA-McIlvaine buffer followed by phase separation with MgSO4: NaCl addition. The supernatant was then extracted and cleaned by dispersive solid-phase extraction using a primary-secondary amine (PSA) and octadecylsilane (C18) support. The proposed method provides a linearity in the range of 1-500ngmL-1 and linear regression coefficients (r) were greater than 0.996. MDL and MQL ranged between 0.01-1.86μgkg(-1) and 0.05-5.91μgkg(-1), respectively. Recoveries ranged from 61.39 to 105.65% with the exception of sulfaquinoxaline (55.7-56.8%) and valnemulin (33.7-37.7%). This method resulted in good precision (repeatability and reproducibility) and relative standard deviations less than 17% within the same day, and lower than 20% between days. The method was then applied to study the swine manure samples collected from Guangdong, China. Chlortetracycline, tetracycline, doxycycline, sulfadimidine and tilmicosin were detected in all samples indicating high residuals in manure. In fact tilmicosin was detected at 14400μgkg(-1) suggesting that prudent treatment of manure should be conducted to prevent environmental contamination. In conclusion, this workflow can provide a simpler and more cost-effective alternative to conventional methods and is compatible with processing large sample numbers over a short time period.


Large lungworms (Nematoda: Dictyocaulidae) recovered from the European bison may represent a new nematode subspecies.
Although the Dictyocaulus lungworm, the agent of dictyocaulosis, is one of parasitological threats to European bison, its systematic position remains unclear. The aim of the present study was to evaluate the morphological features of the lungworm and the pathological lesions it induces, and to analyse mitochondrial (mt) genetic markers for systematic and molecular epidemiological studies. The morphological findings indicate that Dictyocaulus lungworms of European bison can be distinguished from those of cattle on the basis of differences in buccal capsule wall length, total body length, and spicules length in males, all of which were significantly longer in those of European bison. Nucleotide diversity calculated from pairwise sequence alignments of partial cytochrome c oxidase subunit 1 (cox1), cytochrome B (cytB) and NADH dehydrogenase subunit 5 (nad5) of specimens from cattle and European bison varied from 1.7% for nad5, 2.1% for cytB, to 3.7% for cox1 gene. Thus, among the lungworms of European bison and cattle, nad5 and cytB were the most conserved proteins, whereas cox1 was the most diverse. The mt cytB marker gene may be a suitable candidate for distinguishing between the two genotypes, as nad5 demonstrated the greatest within-genus sequence variation. The lung tissue of infected European bison manifests signs of verminous pneumonia characterized by interstitial pneumonia, bronchitis and bronchiolitis. Therefore, it appears that European bison and cattle are infected with slightly diverged, morphologically-different, genotypes of D. viviparus, indicating they belong to two separate worm populations. We propose, therefore, that the lungworm of European bison should be classified as D. viviparus subsp. bisontis.


The intercalated tendon graft for treatment of extensor pollicis longus tendon rupture.
Twenty-one patients with ruptures of the extensor pollicis longus tendon were treated with a subcutaneously placed free tendon graft. The repair was performed a mean of 6 weeks after rupture, range from 1 to 21 weeks. Data was collected on 19 of these patients, with a mean follow-up of 30 months, range from 6 to 124 months. Near uniform satisfaction was reported. The mean loss of interphalangeal joint extension and flexion and combined metacarpophalangeal-interphalangeal joint motion was 6 degrees, 3 degrees, and 10 degrees, respectively. The mean loss of pinch strength was 7%. All patients were able to elevate their thumbs to the level of the palm. This is a simple, reliable, and effective procedure that avoids the use of an adjacent motor-tendon unit. Muscle contracture appears reversible and this procedure may be used successfully even when treatment has been delayed.


Sleep duration or bedtime? Exploring the relationship between sleep habits and weight status and activity patterns.
To assess the effects of early and late bedtimes and wake up times on use of time and weight status in Australian school-aged children. Observational cross-sectional study involving use of time interviews and pedometers. Free-living Australian adolescents. 2200 9- to 16-year-olds from all states of Australia NA. Bedtimes and wake times were adjusted for age and sex and classified as early or late using median splits. Adolescents were allocated into 4 sleep-wake pattern groups: Early-bed/Early-rise; Early-bed/Late-rise; Late-bed/Early-rise; Late-bed/Late-rise. The groups were compared for use of time (screen time, physical activity, and study-related time), sociodemographic characteristics, and weight status. Adolescents in the Late-bed/Late-rise category experienced 48 min/d more screen time and 27 min less moderate-to-vigorous physical activity (MVPA) (P<0.0001) than adolescents in the Early-bed/Early-rise category, in spite of similar sleep durations. Late-bed/Late-rise adolescents had a higher BMI z-score (0.66 vs. 0.45, P=0.0015). Late-bed/Late-rise adolescents were 1.47 times more likely to be overweight or obese than Early-bed/Early-rise adolescents, 2.16 times more likely to be obese, 1.77 times more likely to have low MVPA, and 2.92 times more likely to have high screen time. Late-bed/Late-rise adolescents were more likely to come from poorer households, to live in major cities, and have fewer siblings. Late bedtimes and late wake up times are associated with an unfavorable activity and weight status profile, independent of age, sex, household income, geographical remoteness, and sleep duration.


Studying tumor growth in Drosophila using the tissue allograft method.
This protocol describes a method to allograft Drosophila larval tissue into adult fly hosts that can be used to assay the tumorigenic potential of mutant tissues. The tissue of interest is dissected, loaded into a fine glass needle and implanted into a host. Upon implantation, nontransformed tissues do not overgrow beyond their normal size, but malignant tumors grow without limit, are invasive and kill the host. By using this method, Drosophila malignant tumors can be transplanted repeatedly, for years, and therefore they can be aged beyond the short life span of flies. Because several hosts can be implanted using different pieces from a single tumor, the method also allows the tumor mass to be increased to facilitate further studies that may require large amounts of tissue (i.e., genomics, proteomics and so on). This method also provides an operational definition of hyperplastic, benign and malignant growth. The injection procedure itself requires only ∼1 d. Tumor development can then be monitored until the death of the implanted hosts.


Role of Mosque Communities in Supporting Muslims with Mental Illness: Results of CBPR-oriented Focus Groups in the Bay Area, California.
Objective The purpose of this study was to explore perspectives of Muslims residing in the Bay Area, California on the role of the mosque community in supporting community members' mental health needs and barriers to mental health care for members who experience mental health challenges. Methods This study employed a CBPR-focused qualitative approach in the form of content analysis of three focus group discussions organized and conducted with the help of a Community Advisory Board made up of members of the Muslim Community Association. Results Two major themes were identified upon examination of the data: services needed in the mosque community and barriers to addressing mental health issues in the mosque community. Specifically, participants reported wanting support groups within the mosque space, mosque-based activities, virtual support, community social workers, and family-oriented services. Barriers reported included community stigma, lack of cultural awareness of race-ethnic minorities within the community, attribution of mental illness to lack of faith or supernatural causes, and specific barriers unique to vulnerable/special subgroups within the community. Conclusion These findings highlight the need for developing mental health-related services and social support initiatives within the mosque space, specifically for those Muslim Americans living in the Bay Area in California. Furthermore, special attention needs to be placed on the barriers to accessing these services as identified by the community members.


High Pin1 expression is associated with tumor progression in colorectal cancer.
Peptidyl prolyl cis-trans isomerase (Pin1) isomerizes only phosphorylated serine or threonine residues preceding proline in certain proteins and affects the protein function. Pin1 interacts with many signaling pathways, including Wnt signaling pathway that is crucial for colorectal tumorigenesis. Pin1 promotes cyclin D1 over-expression directly or through the stabilization of beta-catenin. Pin1 is over-expressed in some cancers such as prostate and breast cancers. This study aimed to determine whether Pin1 plays a role in colorectal tumorigenesis through the upregulation of beta-catenin and cyclin D1. Immunohistochemical analyses were performed on 105 colorectal cancer tissue samples using anti-Pin1, anti-beta-catenin, and anti-cyclin D1 antibodies. We examined the relationships between Pin1 expression and clinicopathological factors, prognosis, and beta-catenin/cyclin D1 expression. High Pin1 expression was observed in 40 cases (38%) and positively correlated with histological type (P=0.0240), depth of invasion (P=0.0051), and staging (P=0.0027) of colorectal tumors. High Pin1 expression was also correlated with the over-expressions of both beta-catenin (P=0.0225) and cyclin D1 (P=0.0137). These results suggest that Pin1 plays an important role in colorectal tumorigenesis, presumably by increasing beta-catenin and cyclin D1 expressions.


Germacranolides from seeds of the endangered Umbelliferae species Rouya polygama.
From the etheral extract of Rouya polygama Coincy seeds (Umbelliferae) six new germacranolides 1-6 were isolated. The structures were elucidated by chemical methods and spectroscopic analysis. Compounds 1 and 4 exhibited activity against Artemia salina larvae.


Magnesium sulfate in emergency department patients with hypertension.
To compare the effect of IV magnesium with other antihypertensives in emergency department (ED) patients with hypertension. ED patients with a systolic BP > 135 mmHg or diastolic BP > 85 were approached for entry into the study. Those granting consent were randomly placed into one of three treatment groups: (1) 1.5 gm IV MgSO(4) (n = 42), (2) a parenteral or oral antihypertensive agent (n = 41), (3) both IV MgSO(4) and an antihypertensive agent (n = 44). Systolic and diastolic blood pressures were measured at entry into the study and at 15, 30, 45, and 60 min after magnesium or other antihypertensive medications were given. The main outcome measure was blood pressure at 60 min, and results were compared using one-way analysis of variance with the post hoc Tukey HSD test. Compared to systolic and diastolic blood pressures at time 0, both were lower at 15, 30, 45, and 60 min in all groups (p < 0.05). No significant difference in systolic or diastolic BP at any time point was observed when response to treatment was compared between the three groups. Intravenous MgSO(4) is as effective as antihypertensives at lowering BP in emergency department patients.


Microcystic meningiomas: radiological characteristics of 16 cases.
As a rare subtype of meningioma, only a few reports deal with radiological characteristics of microcystic meningiomas and the problem remains controversial. The authors have analyzed the radiological findings of a series of microcystic meningiomas with a special focus on magnetic resonance images (MRI) and conventional angiography. Sixteen patients of histologically proven microcystic meningiomas were included. Analysis of preoperative MRI including signal intensity characteristics, enhancement patterns and peritumoural edema were performed and correlated with angiographic and histological findings. Peritumoural edema was graded using edema index (EI) which was defined as the ratio of VE/VT. The tumours were uniformly visualized as a high-signal mass lesion in T2-weighted images and as a low-signal mass lesion in T1-weighted images regardless of tumour vascularity shown by angiography. T2-weighted images revealed that peritumoural brain edema was severe in 11, moderate in 1, mild in 2 and negligible in 2 patients and this was closely related to the co-existence of irregular tumour marginal enhancement. However, other features failed to distinguish these lesions from other subtypes of meningioma. The cases presented demonstrate that characteristic MRI findings suggestive of microcystic meningiomas are; (1) low signal intensity mass in T1- and high signal intensity mass in T2-weighted images; (2) high incidence of peritumoural edema.


Analysis of vertical fluorescence resonance energy transfer from the surface of a small-diameter sphere.
Fluorescence resonance energy transfer (FRET) measurements have been used to analyze fluorophore separations in a number of varying geometries, including small particles and extended surfaces. This study focuses on the geometry created by a donor extended above the surface of a small sphere (radius < R0), where the acceptors are integrated into the sphere surface. The model of this geometry was based on an amphipathic molecule with its lipophilic region integrated into a detergent micelle and its hydrophilic region extending outward from the micelle surface, where the donor fluorophore is attached to the hydrophilic region of the molecule. Based on random acceptor incorporation into the micelle, a Poisson distribution was used to calculate the distribution of acceptor probes across the micelle population. The model converges to RET on a flat surface when the radius of the micelle exceeds 0.8 R0. The model was also used to simulate FRET data showing that the positions of donors above the micelle surface could be uniquely resolved. Experimental verification of the model was achieved in a sulfobetaine palmitate micelle with fluorescein isothiocyanate donors attached to detergent-solubilized lipopolysaccharide (LPS) and lipophilic Fast-DiI acceptors. The use of steady-state analysis allowed resolution of cases in which donors were located at different distances from the surface. Combining steady-state with excited-state lifetime analysis allowed resolution of cases where there was a combination of distances. Given the large number of biomolecules that interact with lipids, this approach may prove generally useful for defining molecular conformation.


Cardiovascular and respiratory effects of beta-endorphin in anesthetized and conscious rats.
This study deals with the effects of beta-endorphin on blood pressure, heart rate, and respiratory frequency in anesthetized and conscious rats after both peripheral and central administration. Intravenous injection of beta-endorphin (40 and 160 micrograms/kg) in urethane-anesthetized rats resulted in a prolonged decrease in blood pressure, which, after the higher dose, was accompanied by bradycardia. In the pentobarbitone-anesthetized animals the same doses of beta-endorphin caused a small rise in blood pressure without affecting heart rate. No effect on respiratory frequency was observed. In urethane-anesthetized rats with hemorrhagic shock intravenous naloxone elicited a small pressor effect. Intracerebroventricular injection (i.c.v.) of beta-endorphin (40 micrograms/rat) in urethane-anesthetized rats resulted in severe respiratory depression and death. With lower doses there was a decrease in all parameters studied without ensuing death. Respiratory depression was even more pronounced in pentobarbitone-anesthetized rats, occurring with much lower doses of the peptide than in the urethane-anesthetized animals. beta-endorphin in the dose of 0.6 micrograms/rat still reduced respiratory frequency as well as heart rate without affecting blood pressure. Naloxone pretreatment antagonized the respiratory depression and death, while the decrease in heart rate was diminished. In conscious rats 10 microgram/rat, i.c.v., of beta-endorphin resulted in a decrease in heart rate and blood pressure without affecting respiratory frequency. It is concluded that beta-endorphin, or related opioid peptides, may be involved in cardiovascular and respiratory regulation. The effects of beta-endorphin, however, are markedly modified by the anesthetic agent used.


Using Simulation for Clinical Practice Hours in Nurse Practitioner Education in The United States: A Systematic Review.
The National Organization for Nurse Practitioner Faculty (NONPF) does not allow simulation to be used in lieu of traditional clinical hours. The NONPF cites a lack of empirical evidence related to learning outcomes with simulation as rationale for its stance. The purpose of this systematic review was to search, extract, appraise, and synthesize research related to the use of simulation in Nurse Practitioner (NP) education in order to answer the two following questions: 1) What research related to simulation in NP education has emerged in the literature between 2010 and April 2015?, and 2) Of the research studies that have emerged, what level of Kirkpatrick's Training Evaluation Model (1994) is evaluated? This review was reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A literature search was completed in PubMed and CINAHL using a combination of medical subject headings, or Mesh terms, as well as keywords to retrieve non-indexed citations. The inclusion criteria for this review were broad in order to disseminate information on future research needed. The review considered studies related to NP education that included any form of simulation intervention, e.g. role-playing and standardized patients. The review considered studies that described original research, but no other design restrictions were imposed. The review was limited to studies published in the English language. The database search strategy yielded 198 citations. These results were narrowed down to 15 studies based on identified inclusion criteria. There is a lack of empirical evidence in the literature to support using simulation in lieu of direct patient care clinical hours in NP education. The evidence in this systematic review affirms NONPF's statement. Five years after the inception of NONPF's position statement, research to support learning outcomes with simulation in nurse practitioner education remains lacking. There is a need to produce rigorous scientific studies in the future in order to provide quantitative support to allow simulation to be counted as clinical hours in NP programs.


The mitochondrial genome sequence of the scorpion Centruroides limpidus (Karsch 1879) (Chelicerata; Arachnida).
The mitochondrial genome of the scorpion Centruroides limpidus (Chelicerata; Arachnida) has been completely sequenced and is 14519 bp long. The genome contains 13 protein-encoding genes, two ribosomal RNA genes, 21 transfer RNA genes and a large non-coding region related to the control region. The overall A+T composition is the lowest among the complete mitochondrial sequences published within the Chelicerata subphylum. Gene order and gene content differ slightly from that of Limulus polyphemus (Chelicerata: Xiphosura): i.e., the lack of the trnD gene, and the translocation-inversion of the trnI gene. Preliminary phylogenetic analysis of some Chelicerata shows that scorpions (C. limpidus and Mesobuthus gibbosus) make a tight cluster with the spiders (Arachnida; Araneae). Our analysis does not support that Scorpiones order is the sister group to all Arachnida Class, since it is closer to Araneae than to Acari orders.


Vitrification negatively affects the Ca2+-releasing and activation potential of mouse oocytes, but vitrified oocytes are potentially useful for diagnostic purposes.
To what extent does vitrification affect the Ca2+-releasing and activation potential of mouse oocytes, which are commonly used to determine the oocyte activation potential of human spermatozoa? The effect of mouse oocyte vitrification on Ca2+ dynamics and developmental competence after oocyte activation was assessed and compared with fresh mouse oocytes. Moreover, the Ca2+ store content of the endoplasmic reticulum was determined at different time points during the vitrification-warming procedure. Finally, the Ca2+ pattern induced by cryoprotectant exposure was determined. After human sperm injection into mouse oocytes, Ca2+ dynamics but not fertilization rates were significantly altered by vitrification warming (P < 0.05). Ca2+ dynamics in response to SrCl2 or ionomycin were also altered by oocyte vitrification. In contrast, activation and blastocyst rates after SrCl2 exposure were not affected (P > 0.05), whereas activation rates after ionomycin exposure were significantly lower in vitrified-warmed oocytes (P < 0.05); blastocyst rates were not affected (P > 0.05). Cryoprotectant exposure was associated with a strong drop in endoplasmic reticulum Ca2+ store content. Oocytes rapidly recovered during warming and recovery in Ca2+-containing media; a threshold area under the curve of Ca2+ dynamics to obtain activation rates above 90% was determined. Vitrified-warmed mouse oocytes display reduced Ca2+-releasing potential upon oocyte activation, caused by cryoprotectant exposure. With adapted classification criteria, these oocytes could be used for diagnosing oocyte activation deficiencies in patients. Evaluating the Ca2+-signalling machinery in vitrified-warmed human oocytes is required.


Control of luciferase synthesis in a newly isolated strain of Photobacterium leiognathi.
In previous studies with luminous bacteria of all different species it has been reported that the synthesis of luciferase is autoinducible: during growth at low cell densities synthesis is effectively repressed while after induction, at higher cell densities, the rate of synthesis of enzyme is up to five times the growth rate. In this paper we report on newly isolated strains of Photobacterium leiognathi which show continued luciferase synthesis irrespective of the cell density. The specific synthesis rate may nevertheless differ from the rate of growth and depends on the luciferase content of the inoculated cells. A ratio of 1 was established for cells having a maximum luciferase content varying to a ratio of about 2 for cells that contained only 1% of the maximum.


Blockade of endothelin ET(A)/ET(B) receptors favors a role for endothelin during acute Trypanosoma cruzi infection in rats.
Endothelin has been implicated in the pathogenesis of experimental and human Chagas' disease (American trypanosomiasis). In the present study, we tested the effect of bosentan, an antagonist of both ET(A) and ET(B) endothelin receptors, on parasitemia, histopathology (heart and diaphragm), heart levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, interferon (IFN)-gamma, CCL2, CCL3 and CCL5, and the serum levels of nitrate/nitrite (NOx). Bosentan treatment was accompanied by a significant increase in parasitemia and tissue parasitism or inflammation. In vehicle-treated rats, Trypanosoma cruzi infection increased the cardiac levels of TNF-alpha, IFN-gamma and IL-10, at day 9 post inoculation, and the TNF-alpha remained elevated until day 13. The infection also caused a significant increase in the cardiac levels of the chemokines CCL2 (9, 13 and 18 days) and CCL3 (13 and 18 days). Bosentan-treatment had no significant effect on the infection-associated increase in IFN-gamma and chemokine concentrations. There was a lower increase in IL-10 at day 9 and this was mirrored by a greater increase of TNF-alpha at day 13, in comparison with vehicle-treated rats. These latter findings correlated well with the enhanced inflammatory process in hearts of bosentan-treated infected rats. Bosentan treatment reduced the infection-associated increase in NOx serum concentration. Altogether, our data suggest that ET action on ET(A) and ET(B) receptors may play a role in the initial control of T. cruzi infection in rats probably by interfering in NO production.


A population-based study on the association between educational length, prostate-specific antigen testing and use of prostate biopsies.
The aim of this study was to determine whether educational length affects prostate-specific antigen (PSA) testing and the time to prostate biopsy for men with raised PSA values. Using register data on all men in Stockholm County in 2013 (n = 1,052,841), the limited-duration point prevalence of PSA testing and time between test and prostate biopsy or repeat testing were analysed. Patterns of follow-up were assessed using Kaplan-Meier product limit estimators and Cox proportional hazard models. Educational length was categorized as short (≤ 9 years), intermediate (10-12 years) or long (≥ 13 years). PSA testing increased with educational length in all age groups. Among men aged 50-69 years, 61% with long and 54% with short education had had a PSA test within the preceding 10 years (p < 0.001). In men with PSA 4-10 ng/ml, 40% [95% confidence interval (CI) 38-41] with long and 27% (95% CI 26-29) with short education underwent a prostate biopsy within 12 months. After adjusting for PSA level and age, educational length was still associated with the chance of having a prostate biopsy in men with PSA 4-10 ng/ml (hazard ratio 1.22, 95% CI 1.12-1.31), but not in men with higher PSA values. PSA testing increased with educational length. Men with long education were more likely to have a prostate biopsy after an increased PSA value below 10 ng/ml than men with short education. These differences may contribute to the worse prostate cancer outcomes observed among men with lower socioeconomic status.


Establishment of fibroblast and myofibroblast phenotypes for use in in vitro co-culture models.
Fibroblasts function to secrete and modify components of the extracellular matrix. During wound healing, fibroblasts migrate to the site of injury and differentiate into contractile myofibroblasts; this differentiation is characterised by an increased contractile capacity. Fully differentiated myofibroblasts can be distinguished from fibroblasts via the higher expression of α-smooth muscle actin as well as a denser cytoskeleton. Impaired wound healing has been characterised by a lack of myofibroblasts; as a result, tissue does not fully regain its strength and function. Under pathological conditions, this may be associated with the effect that a pro-inflammatory microenvironment has on fibroblast and skeletal muscle progenitor cell migration and differentiation. Given their distinct roles in tissue maintenance and repair, the communication between fibroblasts versus myofibroblasts with other cellular mediators of repair is likely to influence cell behaviour and the outcome of wound repair. An in vitro test model is required to investigate this intercellular influence, but the establishment of such a model is hampered by the difficulty in retaining the dedifferentiated fibroblastic phenotype under regular serum-containing cell culture conditions. We present a model that supports the establishment and retention in culture of fibroblast and myofibroblast phenotypes for use in a simple, inexpensive, yet relevant in vitro 2D assay. This model is then applied in a co-culture setting to determine whether the presence of myoblasts affects the ability of fibroblasts versus myofibroblasts to close an in vitro wound. Our results emphasize the importance of considering the impact of paracrine communication between all cells during wound healing.


COVID-19 Treatments: Then and Now.
The coronavirus disease 2019 (COVID-19) pandemic has evolved over the past 3+ years, and strategies to prevent illness and treat infection have changed over time. As COVID-19 transitions from a pandemic to an endemic infection, widespread nonpharmaceutical interventions such as mask mandates and governmental policies requiring social distancing have given way to more selective strategies for risk mitigation. Monoclonal antibody therapies used for disease prevention and treatment lost utility owing to the emergence of resistant viral variants. Oral antiviral medications have become the mainstay of treatment in nonhospitalized individuals, whereas systemic corticosteroids remain the cornerstone of therapy in those requiring supplemental oxygen. Emerging literature also supports the use of additional immune-modulating therapies in select admitted patients. Importantly, the COVID-19 pandemic highlighted both unprecedented research and development of medical interventions while also drawing attention to significant pitfalls in the global response. This review provides a comprehensive update in prevention and management of COVID-19.


Evolutionary rescue via niche construction: Infrequent construction can prevent post-invasion extinction.
A population experiencing habitat loss can avoid extinction by undergoing genetic adaptation-a process known as evolutionary rescue. Here we analytically approximate the probability of evolutionary rescue via a niche-constructing mutation that allows carriers to convert a novel, unfavorable reproductive habitat to a favorable state at a cost to their fecundity. We analyze competition between mutants and non-niche-constructing wild types, who ultimately require the constructed habitats to reproduce. We find that over-exploitation of the constructed habitats by wild types can generate damped oscillations in population size shortly after mutant invasion, thereby decreasing the probability of rescue. Such post-invasion extinction is less probable when construction is infrequent, habitat loss is common, the reproductive environment is large, or the population's carrying capacity is small. Under these conditions, wild types are less likely to encounter the constructed habitats and, consequently, mutants are more likely to fix. These results suggest that, without a mechanism that deters wild type inheritance of the constructed habitats, a population undergoing rescue via niche construction may remain prone to short-timescale extinction despite successful mutant invasion.