Gradual reappearance of post-hibernation circadian rhythmicity correlates with numbers of vasopressin-containing neurons in the suprachiasmatic nuclei of European ground squirrels.
European ground squirrels (Spermophilus citellus) in outside enclosures show suppressed circadian rhythmicity in body temperature patterns during the first days of euthermia after hibernation. This may reflect either gradual reappearance of circadian rhythmicity following suppressed functioning of the circadian system during hibernation, or it may reflect transient days during re-entrainment of the circadian system which, during hibernation, has drifted out of phase with the environmental light-dark cycle. Here we report that animals kept under continuous dim light conditions also showed absence of circadian rhythmicity in activity and body temperature in the first 5-15 days after hibernation. After post-hibernation arrhythmicity, spontaneous circadian rhythms re-appeared gradually and increased daily body temperature range. Numbers of arginine-vasopressin immunoreactive neurons in the suprachiasmatic nuclei correlated positively with individual circadian rhythmicity and increased gradually over time after hibernation. Furthermore, circadian rhythmicity was enhanced rather than suppressed after exposure to a light-dark cycle but not after a single 1-h light pulse (1,700 lux). The results support the view that the functioning of the circadian system in the European ground squirrel is suppressed during hibernation at low temperatures and that it requires several days of euthermia to resume its summer function.


Chromosomally abnormal clones and nonrandom telomeric translocations in cardiac myxomas.
Cardiac myxomas from eight patients were examined cytogenetically in short-term cultures. Cultures could not be established in two of the eight cases. Chromosomally abnormal clones occurred in two of the myxomas; their karyotypes were 45,X,-Y,+7,-18 and 45,X,-Y. In three other myxomas, we found a rare kind of telomere-to-telomere translocation between chromosomes. The telomeres predominantly involved in these three tumors were the 2qter (the end of the long arm of chromosome 2), the 12pter (the end of the short arm of chromosome 12), and Yqter (the end of the long arm of the Y chromosome), respectively. In one other myxoma, 20% of the cells were tetraploid. These findings support the concept that myxomas are neoplastic; those with an abnormal clone may even have malignant potential. The unusual telomere-to-telomere translocations were not observed in a clonal pattern. They may represent a specific type of chromosomal instability associated with a defect in repair or replication of telomeric DNA.


Blib is a multi-module simulation platform for genetics studies and intelligent breeding.
Simulation is an efficient approach for the investigation of theoretical and applied issues in population and quantitative genetics, and animal and plant breeding. In this study, we report a multi-module simulation platform called Blib, that is able to handle more complicated genetic effects and models than existing tools. Two derived data types are first defined in Blib, one to hold the required information on genetic models, and the other one to represent the genetics and breeding populations. A number of subroutines are then developed to perform specific tasks. Four case studies are present as examples to show the applications of Blib, i.e., genetic drift of multiple alleles in randomly mating populations, joint effects of neutral mutation and genetic drift, comparison of mass versus family selection, and choice of testers in hybrid breeding. Blib together with its application modules, has great potential to benefit theoretical genetic studies and intelligent breeding by simulating and predicting outcomes in a large number of scenarios, and identifying the best optimum selection and crossing schemes.


Assessment of Quality of Life, Sexual Quality of Life, and Pain Symptoms in Deep Infiltrating Endometriosis Patients With or Without Associated Adenomyosis and the Influence of a Flexible Extended Combined Oral Contraceptive Regimen: Results of a Prospective, Observational Study.
The quality of life of women with deep infiltrating endometriosis (DIE) is impaired and may improve with combined oral contraceptives (COCs). To compare the overall and sexual quality of life of patients diagnosed with DIE with or without associated adenomyosis (AD) with that of healthy controls and determine the influence of a COC containing 2 mg dienogest/30 μg ethinyl estradiol on these aspects. We enrolled 42 women diagnosed with DIE; 31 diagnosed with DIE + AD by transvaginal ultrasound, and 39 non-AD/DIE controls. All patients were interviewed regarding pain symptoms (dysmenorrhea, dyspareunia, dyschezia, and dysuria), heavy menstrual bleeding using the Pictorial Blood Loss Assessment Chart, quality of life using the Short Form-36 questionnaire (SF-36), and sexual quality of life using the Sexual Quality of Life-Female questionnaire (SQOL-F) and the Brief Profile of Female Sexual Function (B-PFSF) before starting COCs and after 12 months of treatment. There was significant improvement in overall and sexual quality of life after treatment in DIE and DIE + AD patients. Non-AD/DIE controls showed significantly higher scores in the B-PFSF, the SQOL-F and the SF-36 questionnaires (P < .05) at baseline versus the other groups. DIE + AD patients showed poorer quality of sexual life and greater intensity in pain symptoms compared with DIE patients. After 12 months of treatment, there was a significant improvement in overall and sexual quality of life in the DIE and DIE + AD groups, with improvement in sexual quality of life being slightly greater in DIE + AD patients compared with DIE patients. Pain symptoms also decreased in both groups. Patients with DIE + AD showed greater impairment in overall and sexual quality of life compared with patients with isolated DIE which seems to improve with a COC containing 2 mg dienogest/30 μg ethinyl estradiol. Strengths include the long-term follow up, assessment of the impact of two associated conditions, and administration of the same COC in all patients. Limitations include the relatively small sample size, and the fact that we did not assess the effectiveness of a flexible extended COC regimen containing 2 mg dienogest/30 μg ethinyl estradiol since the groups were different at baseline. Patients diagnosed with DIE with or without AD have a decreased quality of life which may improve with a COC containing 2 mg dienogest/30 μg ethinyl estradiol. Further research is needed to confirm our results. Alcalde AM, Martínez-Zamora MÁ, Gracia M, et al. Assessment of Quality of Life, Sexual Quality of Life, and Pain Symptoms in Deep Infiltrating Endometriosis Patients With or Without Associated Adenomyosis and the Influence of a Flexible Extended Combined Oral Contraceptive Regimen: Results of a Prospective, Observational Study. J Sex Med 2022;19:311-318.


Single-cell mass spectrometry.
Owing to recent advances in mass spectrometry (MS), tens to hundreds of proteins, lipids, and small molecules can be measured in single cells. The ability to characterize the molecular heterogeneity of individual cells is necessary to define the full assortment of cell subtypes and identify their function. We review single-cell MS including high-throughput, targeted, mass cytometry-based approaches and antibody-free methods for broad profiling of the proteome and metabolome of single cells. The advantages and disadvantages of different methods are discussed, as well as the challenges and opportunities for further improvements in single-cell MS. These methods is being used in biomedicine in several applications including revealing tumor heterogeneity and high-content drug screening.


Deficits in behavioral initiation and execution processes in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism.
Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to two monkeys led to hypokinesia, tremor, rigidity, adipsia and aphagia. Quantitative assessment of hypokinesia revealed increased reaction time, delayed onset of muscle activity and prolonged movement time in a forelimb reaching task after selective degeneration of the nigrostriatal dopamine (DA) system sparing mesocortical dopamine neurons. The losses of pars compacta cells of substantia nigra, of striatal [3H]mazindol binding and of striatal DA content (more than 90%) quantitatively paralleled the severity of behavioral deficits. Additional monoamine systems were affected with stronger MPTP effects.


In vitro and in vivo investigations on the antiviral activity of a series of mixed-valence rare earth borotungstate heteropoly blues.
A series of mixed-valence rare earth borotungsto-heteropoly blues, K15H2[Ln(BW9W2O39)2].28H2O (Ln2, Ln=La, Ce, Pr, Nd, Sm, Eu, Gd), have been prepared and characterized by IR, UV, XPS, ESR and electrochemistry. The cytotoxicity and antiviral activity of these rare earth borotungstate heteropoly blues were investigated against influenza A(FluVA) strain (A/H1N1/Jingfang/1/91 and A/H3N2/Jingfang/30/95) and influenza virus B(FluVB) (B/Hufang/1/87) in MDCK cells. The results show that K15H2[Pr(BW9W2O39)2].28H2O (Pr2) exhibits the highest antiviral activity against FluVA with EC50 of less than 4.0 microg/ml (A/H1N1/Jingfang/1/91) and 6.0 microg/ml (A/H3N2/Jingfang/30/95), respectively, and has the lowest toxicity with CC50 of more than 480 microg/ml against MDCK cells. Additionally, both K15H2[Pr(BW9W2O39)2].28H2O (Pr2) and K15H2[Eu(BW9W2O39)2].28H2O (Eu2) showed excellent antiviral activities against FluVB by inhibiting FluVB replication at an EC50 of less than 8.0 microg/ml. Furthermore, investigation on in vivo antiviral activity of Pr2 against FluVA(FM1) in mice by giving the dosage either orally (p.o.) or intraperitoneally (i.p.), indicates that Pr2 exhibits higher inhibitory activity than that of positive control, virazole, and that it's more effective when administered by i.p.


Isolation and pharmacological activity of phenylpropanoid esters from Marrubium vulgare.
The isolation and identification of major phenylpropanoid esters from Marrubium vulgare: (+) (E)-caffeoyl-L-malic acid 1, acteoside 2, forsythoside B 3, arenarioside 4, ballotetroside 5, as well as their anti-inflammatory activity are reported for the first time. We evaluated the inhibitory effects of these five compounds on cyclooxygenase (Cox) catalysed prostaglandin biosynthesis activity. Only the glycosidic phenylpropanoid esters showed an inhibitory activity towards the Cox-2 enzyme and three of them: acteoside 2, forsythoside B 3, arenarioside 4, exhibited higher inhibitory potencies on Cox-2 than on Cox-1. These results are of interest, as Cox-2 is mainly associated with inflammation and the Cox-1 inhibition with adverse side effects often observed with non-steroidal anti-inflammatory drugs. The occurrence of these phenylpropanoid esters could also explain some other pharmacological properties of M. vulgare.


Mycoflora and mycotoxins of peanut (Arachis hypogaea L.) seeds in Egypt. 1--Sugar fungi and natural occurrence of mycotoxins.
Sixty-four species and 2 varieties which belong to nineteen genera of fungi were identified from 40 peanut seed samples collected from different places in Egypt by using a dilution-plate method on glucose-Czapek's medium. The most frequent genera were Aspergillus (21 species & 2 varieties), Penicillium (16 species) and Fusarium (6 species). A. flavus, A. fumigatus, A. niger, P. chrysogenum and F. oxysporum were the most common fungal species. Forty seven percent of the samples proved to be toxic to brine shrimp (Artemia salina) larvae. Thin-layer chromatographic analysis revealed that peanuts were contaminated by aflatoxins (11 samples), trichothecene-toxins (10 samples), zearalenone (one sample) and citrinin (one sample). We believe that this is the first report of the natural occurrence of zearalenone and trichothecene-toxins in peanuts.


Quantitative aspects of responses in trigeminal relay neurones and interneurones following mechanical stimulation of sinus hairs and skin in the cat.
1. Stimulus-response relationships in discharges of trigeminal relay- and interneurones were investigated in the barbiturate anaesthetized cat using controlled sinus hair or skin displacements.2. In comparison with discharges in slowly adapting primary afferent fibres the responses in all higher order neurones were considerably reduced in firing rate and often revealed modifications suggesting the interaction of mechanisms actively modulating the afferent input.3. In relay neurones with or without a tonic discharge component the ;dynamic on' response during a trapezoidal displacement of sinus hairs was found to be determined entirely or predominantly by the movement velocity and to be independent of the deflexion angle of a stimulus. In contrast, the static response in tonic relay neurones was determined by both the movement velocity and the displacement amplitude.4. Spatial summation of afferent input caused either only quantitative changes in the responses of relay neurones leaving the general discharge properties unaltered or caused both qualitative and quantitative changes in the responses.5. Interneurones consisted of two functional groups. In about 25% of them the responses were not or only slightly dependent on the intensity of the applied stimulus, often burstlike and of an all or nothing character. In the second group of interneurones the responses showed a quantitative dependence on the applied stimuli. In this group of interneurones responses often increased with the spatial extension of the peripheral stimulus revealing spatial summation of the afferent input.


Pyruvate dehydrogenase E1 alpha subunit genes in the mouse: mapping and comparison with human homologs.
Two gene loci for the E1 alpha subunit of the pyruvate dehydrogenase (PDH) complex have been mapped in the mouse by in situ hybridization. One locus maps to the X chromosome in the region F3-F4, the other to chromosome 19, in band B close to the centromere. This arrangement is exactly comparable to the situation in man where there is an X-linked PDH E1 alpha locus and an autosomal locus on chromosome 4. Comparison of the regional localization of the human and mouse X-linked PDH E1 alpha genes provides further information concerning sites of rearrangement of segments of the X chromosome during mammalian evolution. The human autosomal PDH E1 alpha gene is a "processed" gene, which lacks the introns that are present in the X-linked gene. It codes for a testis-specific E1 alpha subunit that is only expressed after the onset of spermatogenesis. The comparative mapping results in the mouse suggest that the genetic organization and pattern of expression of the two PDH E1 alpha genes is the same in the two species.


IMP3 Predicts Invasion and Prognosis in Human Lung Adenocarcinoma.
Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein associated with several aggressive and advanced cancers. Whether IMP3 can predict invasion, and prognosis in patients with human lung adenocarcinoma (LAC) remains unclear. Ninety-five LAC and 75 non-tumor lung tissue samples were included in a tissue microarray. IMP3 expression was assessed by immunohistochemical examination. Correlation between IMP3 expression levels, clinicopathological characteristics, and overall prognosis was evaluated. In a separate in vitro study, RNA interference method was applied for knockdown of IMP3 gene in human LAC cell lines. Invasive potential of LAC cells was then evaluated by transwell migration assay. IMP3 immunoreactivity was observed in 39 out of 95 (41.1 %) LAC patients, but not in non-tumor lung tissues. IMP3 expression levels were closely associated with histological grade (P = 0.037), TNM stage (P = 0.034), and lymph node metastasis (P = 0.011). Patients presenting with positive IMP3 expression (P = 0.000), an advanced TNM stage (P = 0.000), and lymph node metastasis (P = 0.001) had a worse overall survival, compared to those lacking these characteristics. Both IMP3 expression (hazard ratio [HR], 2.310; 95 % confidence interval [CI] 1.192-4.476; P = 0.013) and TNM stage (HR 2.338; 95 % CI 1.393-3.925; P = 0.001) were independent predictors of poor prognosis. The invasive potential of LAC cells was significantly inhibited by IMP3 knockdown. IMP3 appears to play an important role in tumor invasion in patients with LAC and may serve as a useful prognostic biomarker in these patients.


Evaluation of different substrates to support the growth of Typha latifolia in constructed wetlands treating tannery wastewater over long-term operation.
The aim of this study was to investigate the performance of horizontal subsurface flow constructed wetlands planted with Typha latifolia treating tannery wastewater under long-term operation. Two expanded clay aggregates (Filtralite MR3-8-FMR and Filtralite NR3-8-FNR) and a fine gravel-FG were used as substrate for the constructed wetland units plus one unit with FMR was left as an unvegetated control. The systems were subject to three hydraulic loadings, 18, 8 and 6cmd(-1), and to periods of interruption in the feed. The relationship between the substrate, plant development and removal efficiency, especially of organic matter, was investigated. Organic loadings up to 1800kg BOD(5)ha(-1)d(-1) and 3849kg COD ha(-1)d(-1) were applied leading to mass removals of up to 652kg BOD(5)ha(-1)d(-1) and 1869kg COD ha(-1)d(-1), respectively. The three different substrates were adequate for the establishment of T. latifolia, although the clay aggregates allowed for higher plant propagation levels. The units with FNR and FMR achieved significantly higher COD and BOD5 removal when compared to the FG and to the unplanted units. The systems proved to be tolerant to high organic loadings and to interruptions in feed suggesting this technology as a viable option for the biological treatment of tannery wastewater.


MAPK/ERK and JNK pathways regulate lipid synthesis and cell growth of Chlamydomonas reinhardtii under osmotic stress, respectively.
Microalgae have great potential for the production of biofuels due to the ability of the organism to accumulate large quantities of storage lipids under stress conditions. Mitogen activated protein kinase (MAPK) signaling cascades are widely recognized for their role in stress response signal transduction in eukaryotes. To assess the correlation between MAPK activation and lipid productivity, Chlamydomonas reinhardtii was studied under various concentrations of NaCl. The results demonstrated that C. reinhardtii exhibits elevated levels of extracellular-signal regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) activities after undergoing osmotic stress, as well as an increase in cellular lipid content. To establish a more direct causal link between both kinases and lipid productivity, C. reinhardtii was subjected to biochemically induced regulation of ERK and JNK pathways. Activating the MEK-ERK pathway via C6 ceramide treatment increased ERK activation and lipid production simultaneously, while PD98059 mediated inhibition of the pathway yielded opposite results. Interestingly, suppression of the JNK pathway with SP600125 resulted in a substantial decrease in cell viability under osmotic stress. These results suggest that ERK and JNK MAP kinases have important roles in microalgal lipid accumulation and cell growth under osmotic stress, respectively.


[Quantitative evaluation of knee joint effusions with high resolution real-time sonography].
In three human cadaver specimens an intraarticular effusion of the knee was simulated by injecting sodium chloride in 10 ml portions. The sonographic appearance and quantification as well as the location of the fluid were evaluated. Effusions of the knee joint are a principal sign for many diseases. Their sonographic evaluation is easy and provides valuable clinical information.


Factors affecting renal scarring in posterior urethral valves.
To retrospectively review the occurrence of renal scarring in patients with posterior urethral valves (PUV), and correlate it with various causative factors. The records of 52 patients treated for PUV by the authors were reviewed. Patients with vesico-ureteric reflex (VUR) dysplasia syndrome were excluded from the study. The patients were divided into group I (no renal scarring, n=18) and group II (renal scars present, n=34) based on dimercapto-succinic acid scans. The mode of treatment, presence/absence of breakthrough urinary tract infections (UTI), presence/absence of history of nocturnal/diurnal incontinence, presence/absence of VUR, stable postoperative serum creatinine, rate of drainage of ureters on diethylene triamine penta acetic acid (DTPA) scans and management of bladder dysfunction, if any, were noted. The presence or absence of renal scarring was statistically correlated with occurrence of any of the above factors. Primary valve fulguration was performed in 41 patients and 11 patients had an initial vesicostomy. The median follow up was 3.5 years (range 1.5-15 years). Renal scarring was present in either kidney in 34 patients (bilateral 14, unilateral 20). The mode of initial treatment did not affect the incidence or rate of scarring. The preoperative and postoperative serum creatinine at the end of 1 year did not differ between the two groups. Presence/severity of VUR did not affect the pattern of renal scarring. A highly significant correlation between the occurrence of renal scarring and presence of diurnal incontinence (P< or =0.007, odds ratio=4.5) and breakthrough UTI (P< or =0.002, odds ratio=7.0) was observed. There was also correlation with slow drainage in the ureters on a DTPA scan (P< or =0.0005). Detrusor instability and low compliance on urodynamic assessment did not affect occurrence in the limited number of patients studied. The rate of somatic growth in both groups was retarded as compared to normal healthy counterparts. Breakthrough UTI, diurnal incontinence and poor drainage of ureters on DTPA are associated with a higher incidence of renal scarring. Mode of initial treatment, presence or absence of VUR, and bladder abnormalities do not affect renal scarring in the short term.


Mechanical and Durability Performance Improvement of Natural Hydraulic Lime-Based Mortars by Lithium Silicate Solution.
Natural hydraulic lime (NHL) as a building material has been widely used to restore the historic structure. However, the slow growth rate of strength and durability limits its engineering application. In this work, the NHL-based mortars were pretreated by lithium silicate (LS) solution impregnation and surface spraying. The results show that the compressive strength, surface hardness, and freeze-thaw cycle (FTC) resistance of NHL-based mortar were greatly improved after LS pretreatment. Specifically, the compressive strengths of the sample increased by about 32.7-52.0%. LS was sprayed on the sample's surface (about 0.2 kg/m2) and the surface hardness increased by up to 10 grades. Compared with the control samples, the weight loss of treated samples decreased by about 31.6-43.8%. A rehydration process to generate the hydrated calcium silicate gel (C-S-H) was observed between calcium hydroxide (CH) and LS, which can decrease the sample's porosity and form a silicate coating on the surface. With an increase in the concentration of LS, the macropores (50-10,000 nm) content decreased, while the mesopores (10-50 nm) and nanopores (less than 10 nm) increased. This work reveals that the LS pretreatment provides a potential route to improve NHL-based mortar's mechanical properties and durability.


Pediatric Extracorporeal Membrane Oxygenation Transport by EC-145 With a Custom-Built Sled.
Indications for the use of extracorporeal membrane oxygenation (ECMO) in pediatrics has expanded beyond the initial historic treatment of neonates with respiratory failure. Patients with severe refractory cardiopulmonary failure may benefit from ECMO support until the primary insult has subsided or been treated. More recently, ECMO has been used by some centers as a bridge to transplant for irreversible organ failure. Nationwide Children's Hospital is a referral center that supports the use of ECMO as a bridge to transplant and is able to provide transport services for ECMO patients referred for transplant evaluation. In this report, we describe our design of a unique, custom-built sled designed specifically for the EC-145 helicopter to transport pediatric ECMO patients to our institution. This report is the first, to our knowledge, to describe the safe and successful transport of a pediatric ECMO patient in an EC-145 helicopter.


Preparing for a future COVID-19 wave: insights and limitations from a data-driven evaluation of non-pharmaceutical interventions in Germany.
To contain the COVID-19 pandemic, governments introduced strict Non-Pharmaceutical Interventions (NPI) that restricted movement, public gatherings, national and international travel, and shut down large parts of the economy. Yet, the impact of the enforcement and subsequent loosening of these policies on the spread of COVID-19 is not well understood. Accordingly, we measure the impact of NPIs on mitigating disease spread by exploiting the spatio-temporal variations in policy measures across the 16 states of Germany. While this quasi-experiment does not allow for causal identification, each policy's effect on reducing disease spread provides meaningful insights. We adapt the Susceptible-Exposed-Infected-Recovered model for disease propagation to include data on daily confirmed cases, interstate movement, and social distancing. By combining the model with measures of policy contributions on mobility reduction, we forecast scenarios for relaxing various types of NPIs. Our model finds that in Germany policies that mandated contact restrictions (e.g., movement in public space limited to two persons or people co-living), closure of educational institutions (e.g., schools), and retail outlet closures are associated with the sharpest drops in movement within and across states. Contact restrictions appear to be most effective at lowering COVID-19 cases, while border closures appear to have only minimal effects at mitigating the spread of the disease, even though cross-border travel might have played a role in seeding the disease in the population. We believe that a deeper understanding of the policy effects on mitigating the spread of COVID-19 allows a more accurate forecast of disease spread when NPIs are partially loosened and gives policymakers better data for making informed decisions.


Effect of postoperative subconjunctival 5-fluorouracil injections on the surgical outcome of trabeculectomy in the Japanese.
A controlled study was carried out to evaluate the effect of postoperative subconjunctival 5-fluorouracil (5-FU) injections on the surgical outcomes of trabeculectomy in the Japanese (a total of 196 eyes in 157 patients). The eyes that had undergone trabeculectomy with postoperative 5-FU (5-FU group) included 36 eyes with primary open-angle glaucoma (POAG) and 17 with secondary glaucoma (SG) undergoing their first or second trabeculectomy. There were also 34 eyes with refractory glaucoma. The eyes that had had trabeculectomy without postoperative 5-FU (control group) included 46 POAG and 31 SG eyes undergoing their first or second trabeculectomy and 24 refractory glaucoma eyes. The surgical techniques and postoperative care were virtually identical between the two groups, except that the control group did not receive 5-FU. The results were analyzed by means of a life table method and a postoperative intraocular pressure (IOP) level equal to or less than 20 mmHg was adopted as the criterion for successful IOP control. In the 5-FU group, the success probability (%) at the 3-year follow-up was 93.9 +/- 4.2 (SE) for POAG eyes, 93.8 +/- 6.1 for SG eyes, and 86.7 +/- 5.6 for refractory glaucoma eyes. In the control group, it was 55.0 +/- 7.9, 37.2 +/- 13.5, and 16.1 +/- 7.4, respectively. The difference in success probability between the 5-FU and control groups was highly significant (P less than 0.001 or 0.01). In the POAG and SG eyes, the mean postoperative IOP was significantly lower in the 5-FU group than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)


A Randomized, Double-blind, Phase II Trial of PSA-TRICOM (PROSTVAC) in Patients with Localized Prostate Cancer: The Immunotherapy to Prevent Progression on Active Surveillance Study.
The Immunotherapy to Prevent Progression on Active Surveillance Study is the first trial of immunotherapy for localized prostate cancer. We randomized active surveillance patients to PSA-TRICOM (PROSTVAC) or placebo for 5mo. Final results will be available in 2019.


First-in-human phase I/Ib study of QL1706 (PSB205), a bifunctional PD1/CTLA4 dual blocker, in patients with advanced solid tumors.
QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. We report results from a phase I/Ib study of QL1706 in patients with advanced solid tumors who failed standard therapies. In the phase I study, QL1706 was administered intravenously once every 3 weeks at one of five doses ranging from 0.3 to 10 mg/kg, and the maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of QL1706 were investigated. In the phase Ib study, QL1706 was administered at the RP2D intravenously every 3 weeks, and the preliminary efficacies in non-small cell lung cancer (NSCLC), nasopharyngeal carcinoma (NPC), cervical cancer (CC), and other solid tumors were evaluated. Between March 2020 and July 2021, 518 patients with advanced solid tumors were enrolled (phase I, n = 99; phase Ib, n = 419). For all patients, the three most common treatment-related adverse events (TRAEs) were rash (19.7%), hypothyroidism (13.5%), and pruritus (13.3%). The TRAEs and immune-related adverse events (irAEs) of grade ≥ 3 occurred in 16.0% and 8.1% of patients, respectively. In phase I, 2 of 6 patients in the 10mg/kg group experienced dose-limiting toxicities (DLTs) (grade 3 thrombocytopenia and grade 4 immune-mediated nephritis), so the maximum tolerated dose (MTD) was reached at 10 mg/kg. The RP2D was determined to be 5 mg/kg based on comprehensive analysis of tolerability, PK/PD, and efficacy. For all patients who received QL1706 at the RP2D, the objective response rate (ORR) and median duration of response were 16.9% (79/468) and 11.7 months (8.3-not reached [NR]), respectively; and the ORRs were 14.0% (17/121) in NSCLC, 24.5% (27/110) in NPC, 27.3% (15/55) in CC, 7.4% (2/27) in colorectal cancer, 23.1% (6/26) in small cell lung cancer. For immunotherapy-naive patients, QL1706 exhibited promising antitumor activities, especially in NSCLC, NPC, and CC, with ORRs of 24.2%, 38.7%, and 28.3%, respectively. QL1706 was well tolerated and demonstrated promising antitumor activity in solid tumors, especially in NSCLC, NPC, and CC patients. It is currently being evaluated in randomized phase II (NCT05576272, NCT05179317) and phase III (NCT05446883, NCT05487391) trials. Trial Registration ClinicalTrials.gov Identifier: NCT04296994 and NCT05171790.


Effects of didanosine formulations on the pharmacokinetics of amprenavir.
To determine the effects of concurrent, single doses of didanosine (both buffered and encapsulated enteric-coated bead formulations) on amprenavir steady-state pharmacokinetics, and to determine the effect of staggered dosing of the buffered formulation. Two-period, single-sequence, prospective, open-label drug interaction study with a 10-day washout interval. Clinical research unit. Sixteen healthy volunteers without human immunodeficiency virus infection. Amprenavir 600 mg twice/day was given for the first 4 days of each treatment period, with 12-hour pharmacokinetic evaluations conducted on the last 2 days of each period. Amprenavir was administered according to the following sequential treatments (all fasting): amprenavir alone, concurrent with buffered didanosine, 1 hour before buffered didanosine, and concurrent with the encapsulated enteric-coated bead formulation of didanosine. Plasma was collected 0, 1, 2, 3, 4, 6, 8, and 12 hours after dosing and assayed for amprenavir by using high-performance liquid chromatography. Noncompartmental pharmacokinetic parameters were determined. Geometric mean ratios for each treatment relative to amprenavir alone were determined and reported with 90% confidence intervals (CIs). No significant trends were noted in predose concentrations measured during either period. Area under the concentration-time curve during one 12-hour dosing interval (AUC12) was found to be bioequivalent for all treatments. Peak drug concentration (Cmax) was reduced by 15% on average with concurrent administration of buffered didanosine, and bioequivalence was not demonstrated for this parameter. For concurrent enteric-coated didanosine, geometric mean ratios for Cmax and AUC12 were 0.93 and 0.94, respectively. For buffered didanosine given 1 hour after amprenavir, geometric mean ratios were 1.06 and 1.10 for the same parameters, respectively. No differences were observed in 12-hour concentration (C12) with concurrent administration of buffered or enteric-coated didanosine. Amprenavir AUC12 and C12 are not significantly affected by concurrent administration of the buffered or enteric-coated formulations of didanosine. Therefore, amprenavir may be administered concurrently with either the buffered or the encapsulated enteric-coated bead formulation of didanosine in the fasting state.


Feasibility of continuous non-invasive finger blood pressure monitoring in adult patients admitted to an intensive care unit: A retrospective cohort study.
Arterial catheters are often used for blood pressure monitoring in the intensive care unit (ICU), but they can cause complications. Non-invasive continuous finger blood pressure monitors could serve as an alternative. However, failure to obtain finger blood pressure signals is reported in up to 12% of ICU patients. Our primary objective was to identify the success rate of finger blood pressure monitoring in ICU patients. Secondary objectives were to assess whether patient admission characteristics could be used to identify patients unsuitable for non-invasive blood pressure monitoring and to determine the quality of non-invasive blood pressure waveforms. Retrospective observational study conducted in a cohort of 499 ICU patients. When available, the signal quality of the first hour of finger measurement was determined using an open-source waveform algorithm. Finger blood pressure signals were obtained in 94% of patients. These patients had a high quality blood pressure waveform for 84% of the measurement time. Patients without a finger blood pressure signal significantly more frequently had a history of kidney and vascular disease, were more often treated with inotropic agents, had lower hemoglobin levels, and had higher arterial lactate levels. Finger blood pressure signals were obtained in nearly all ICU patients. Significant differences in baseline characteristics between patients with and without finger blood pressure signals were found, but they were not clinically relevant. The characteristics studied could therefore not be used to identify patients unsuitable for finger blood pressure monitoring.


A case of craniocleidal dysostosis presenting with vascular complications.
A case of craniocleidal dysostosis was presented. In spite of the skeletal abnormalities present, the disease was not diagnosed until the patient, a married woman of 63, developed ischaemia of her right upper limb, followed by cerebral symptoms. An arch aortogram demonstrated an occlusion of the first part of the right subclavian artery involving the origin of the vertebral artery and a post-stenotic dilatation of the left subclavian artery due to costoclavicular compression. Such vascular abnormalities have not been previously described in this condition.


Effects of hepatitis C virus coinfection on survival in veterans with HIV treated with highly active antiretroviral therapy.
With highly active antiretroviral therapy (HAART) available for patients with HIV, hepatitis C virus (HCV) infection has emerged as a potentially important cause of mortality in coinfected patients. Several studies have investigated the effect of coinfection on mortality, with conflicting results. The study cohort consisted of HIV-infected veterans on HAART receiving care at US Department of Veterans Affairs facilities. Inclusion was based on first HAART prescription between January 1997 and February 2003, HCV antibody test result, and baseline CD4 and HIV viral load results within 1 year of starting HAART. We fitted Cox proportional hazards models to study the effect of HCV serostatus on survival time from HAART initiation, controlling for patient demographic and clinical characteristics, facility characteristics, HAART exposure, HAART response, and HCV treatment. Of 12,216 patients in the study cohort, 38% were HCV-seropositive. During an observation time averaging 3.5 years, 2087 patients died. The adjusted hazard ratio for HCV-seropositive patients was 1.56 (95% confidence interval [CI]: 1.42-1.70; P<0.0001) without a HAART exposure measure and 1.38 (95% CI: 1.26-1.51; P<0.0001) with the measure. We obtained similar results in analyses also controlling for HAART response. HCV seropositivity was independently associated with increased risk of death in a large cohort of HAART-treated HIV-infected veterans. Given the success of HAART in extending the lives of HIV patients, HCV has become an important predictor of their mortality.


The REC domain mediated dimerization is critical for FleQ from Pseudomonas aeruginosa to function as a c-di-GMP receptor and flagella gene regulator.
FleQ is an AAA+ ATPase enhancer-binding protein that regulates both flagella and biofilm formation in the opportunistic pathogen Pseudomonas aeruginosa. FleQ belongs to the NtrC subfamily of response regulators, but lacks the corresponding aspartic acid for phosphorylation in the REC domain (FleQ(R), also named FleQ domain). Here, we show that the atypical REC domain of FleQ is essential for the function of FleQ. Crystal structure of FleQ(R) at 2.3Å reveals that the structure of FleQ(R) is significantly different from the REC domain of NtrC1 which regulates gene expression in a phosphorylation dependent manner. FleQ(R) forms a novel active dimer (transverse dimer), and mediates the dimerization of full-length FleQ in an unusual manner. Point mutations that affect the dimerization of FleQ lead to loss of function of the protein. Moreover, a c-di-GMP binding site deviating from the previous reported one is identified through structure analysis and point mutations.


Sequence variability of the tetranucleotide repeat of the human beta-actin related pseudogene H-beta-Ac-psi-2 (ACTBP2) locus.
Sequence analysis of polymerase chain reaction (PCR) amplified products from the presumed tetranucleotide repeat at the human beta-actin related pseudogene H-beta-Ac-psi-2 (ACTBP2) locus shows far greater variability in both PCR product length and sequence than has been previously reported. Alleles differing in size by 1 bp exist, and accurate sizing is required if the locus is to be used to its full potential.


Current concepts in the management of carotid body tumours.
To review the current management of carotid body tumours and examine our own experience at the Singapore General Hospital. Retrospective review. Case note review of patients treated by the Department of Otolaryngology Head and Neck Surgery, Singapore General Hospital over a period of nine years from January 1999 to December 2007. There were a total of ten patients. Eight patients underwent surgery with no mortality or major surgical morbidity. Mean follow-up was 3 years and 5 months with no evidence of recurrence. One patient had bilateral tumours and is under surveillance. The last patient had inoperable disease and received radiotherapy. Our series has shown that carotid body tumours can be safely removed surgically. If the internal carotid artery needs to be resected, we prefer the use of a Pruitt-Inahara shunt. Radiotherapy is reserved for large inoperable cases or patients not fit for surgery.


Laparoscopic living donor hepatectomy for liver transplantation in children.
Because cadaveric organ donors are in short supply, living donors are increasingly being used in transplantations. We have developed a safe and reproducible method for laparoscopic liver resection. Left hepatic lobectomy (resection of segments 2 and 3) was done by laparoscopy in one woman aged 27 years and one man aged 31 years. The grafts were prepared under laparoscopy, without any vascular clamping, and were externalised through a suprapubic Pfannenstiel incision. Both grafts were transplanted conventionally to the patients' respective sons, who were both aged 1 year and had biliary atresia. Donor operations lasted 7 h for the woman and 6 h for the man, and warm ischaemia times were 4 and 10 min, respectively. Blood loss was 150 and 450 mL, respectively, and no transfusions were required. Neither patient had complications during or after surgery; and hospital stay was 7 and 5 days, respectively. Both recipients are alive and have excellent graft function. We have shown the feasibility of laparoscopic living donor hepatectomy from parent to child. If the safety and feasibility of this procedure can be shown in larger series, laparoscopic donor left lobectomy could become a new option for paediatric living donor liver transplantation.


Blur: a sufficient accommodative stimulus.
Experiments under a variety of open and closed loop feedback configurations demonstrate that accommodative responses to target blur are equivalent to those to defocus blur; this supports blur as the 'sufficient' neurological stimulus to accommodations. The hunting action of accommodation compensates for the even error aspect of blur and also adaptively minimizes any close loop error components while finally accepting open loop components.


Detection of Psychrophilic Clostridium spp. in Fecal Samples from Cattle of Different Ages Sampled at the Slaughterhouse Level.
Clostridium estertheticum and C. estertheticum-like spp. are obligate anaerobic psychrophiles causing "blown pack" spoilage of chilled vacuum-packed meat. The present study aimed at detecting and isolating these spoilage bacteria in fecal samples of cattle of different ages at the slaughterhouse level. One hundred two swab fecal samples were obtained and enriched anaerobically in prereduced peptone-yeast-glucose-starch (PYGS) medium for 3 weeks at 4°C and then screened for C. estertheticum and C. estertheticum-like spp. by using a 16S rRNA gene-based real-time PCR (RT-PCR) assay. The RT-PCR-positive samples were further enriched for 3 weeks in prereduced PYGS medium and then subjected to an ethanol (50%, v/v) and lysozyme (4 mg/mL) treatment. Isolation was carried out anaerobically on Columbia agar with 5% defibrinated sheep blood at 4°C for 3 weeks. Isolated strains were identified morphologically and by the 16S rRNA gene. Forty (39%) of 102 samples were RT-PCR positive. The frequency of positive samples was the following: 9 (45%) of 20 in calves (aged ≤160 days), 23 (43%) of 54 in young cattle (aged 161 to 1,000 days), and 8 (29%) of 28 in cows or bulls (aged >1,000 days). Six strains were isolated from 6 of 40 RT-PCR-positive samples. Of these, five were from the calves (n = 1) and young cattle (n = 4). The six isolates were identified as C. estertheticum (n = 1), Clostridium frigoriphilum (n = 1), and C. estertheticum-like spp. (n = 4). The present findings confirm that feces of cattle are an important source of psychrophilic Clostridium spp. The fecal carriage among livestock animals at slaughter is strongly correlated with the risk of carcass contamination. Therefore, the maintenance of slaughter hygiene is of central importance.


Engaging Stakeholders and Patient Partners.
Recent advances in engagement of stakeholders and patient partners in clinical research have bridged the disconnect between researchers and stakeholders, resulting in improved research goals with relevant outcomes, increased clinical trial enrollment, and improved communication of research results. This article focuses on the mechanisms, challenges, and benefits of patient and stakeholder engagement, with strategies for improvement. The 3 stages of clinical research and key iterative steps to create a reciprocal relationship are presented. Despite recent advances in stakeholder engagement, additional investigation and improved reporting of methods will facilitate strong reciprocal relationships between researchers and stakeholders.


Effects of mercury on behavior and performance of northern two-lined salamanders (Eurycea bislineata).
Mercury (Hg) causes a range of deleterious effects in wildlife, but little is known about its effects on amphibians. Our objective was to determine whether Hg affects performance and behavior in two-lined salamanders (Eurycea bislineata). We collected salamanders from Hg-contaminated and reference sites and assessed speed, responsiveness, and prey capture ability. Mercury concentrations were >17× higher in salamanders from the contaminated sites and were among the highest documented in amphibians. In the first, but not in the second, locomotion trial, we found a significant effect of Hg on speed and responsiveness. In the prey capture experiment, reference salamanders ate approximately twice as many prey items as the contaminated salamanders. Together, our results suggest that sublethal Hg concentrations may negatively affect salamanders by reducing their ability to successfully execute tasks critical to survival. Future work is warranted to determine whether Hg has other sublethal effects on salamanders and whether other amphibians are similarly affected.


Nailing distal tibial fractures: does entry technique affect distal alignment?
In treating distal third tibial fractures, restoration of the axial alignment and therefore accurate reduction of the distal fragment minimise the risk of tibiotalar joint malalignment. The aim of this study is to investigate whether there was a difference in accuracy of reduction and axial alignment, when nailing distal third tibial fractures using either the suprapatellar or the infrapatellar tibial nailing entry technique. This retrospective cohort study compared alignment of intramedullary nails performed for distal third tibial fractures between 2015 and 2018 through the suprapatellar and infrapatellar approach at a UK Level 1 trauma centre. It compared a consecutive series of 74 suprapatellar nails and 51 infrapatellar nails, with radiographic assessment of tibial alignment in the antero-posterior and sagittal planes. It included inter- and intra-observer analyses of radiographic measurements. In the coronal plane, mean malalignment in the suprapatellar technique group was 2.8 ± 0.7° and 4.7 ± 0.9° in the infrapatellar technique group (P < 0.01). In the sagittal plane, mean malalignment in the suprapatellar technique group was 4.0 ± 0.8° and 3.5 ± 0.9° in the infrapatellar technique group (P = 0.42). Intra- and inter-observer analysis showed strongly positive correlations between observers. We suggest that the suprapatellar technique may improve coronal plane alignment when intramedullary nailing distal tibial fractures. There was no significant difference in alignment in the sagittal plane. We conclude that the suprapatellar technique may be superior in preventing malalignment when treating distal third tibial fractures, potentially improving clinical outcome.


An experimental manipulation of the intensity of interspecific competition: effects on a small marsupial.
An investigation was made of the effects of reducing and enhancing the intensity of competition on a small marsupial, Antechinus stuartii, from a larger and competitively dominant congener, A. swainsonii. Populations of these species were monitored in two study areas (one control, one experimental) in forest near Canberra, Australia, between February and July in 1980 and 1981. In the experimental study area in 1980 I reduced the numbers of A. swainsonii relative to A. stuartii (thus reducing the intensity of interspecific competition), but in 1981 I augmented the numbers of A. swainsonii (thus increasing the intensity of competition). No manipulations were made in the control study area, and the numbers of both species remained similar there in both years. When the intensity of interspecific competition was reduced, the A. stuartii population increased in size. Increases occurred also in individual movements, home range areas, diurnal activity and in the proportion of large terrestrial prey (larvae, Amphipoda) in the diet. An increase in use of structurally complex forest floor habitats also coincided with decreased arboreal activity. In contrast, when the intensity of competition was enhanced, most of these population and resource shifts were reversed. These findings suggest that reduction in the intensity of interspecific competition allows A. stuartii access to terrestrial sources of food favoured by A. swainsonii, whereas enhancement leads to exclusion of A. stuartii from the forest floor. Competition occurs by interference. This may result in fixed per capita competitive effects of A. swainsonii on A. stuartii, and account for the observed changes in a very broad range of population and resource parameters.


Chemotherapy-induced painful acral erythema in childhood: Burgdorf's reaction.
Painful acral erythema as a reaction to intensive chemotherapy has been increasingly recognized since 1982. It has not been reported in the pediatric literature. We report its occurrence in a 3-year-old boy who had received intensive chemotherapy for acute lymphoblastic leukemia.


Some neighbors are more interfering: Asymmetric priming by stroke neighbors in Chinese character recognition.
Chinese is a visually complex logographic script that consists of square-shaped characters, with each character composed of strokes. Previous masked priming studies using single-character Chinese stroke neighbors (i.e., visually similar characters differing in only one or two strokes, e.g., /) have shown facilitatory or inhibitory priming effects. We tested whether the mixed pattern of stroke neighbor priming might be an instance of asymmetry in priming that has been observed previously with Japanese kana and Latin alphabets. Specifically, a prime lacking a stroke (or line segment) that is present in the target speeds up the recognition of its stroke neighbor almost as much as the identity prime (e.g., - = -), but not the converse (e.g., - >> -). Two experiments, one using a character match task and the second using lexical decision, showed a robust asymmetry in priming by stroke neighbors. The results suggest that the early letter identification process is similar across script types, as anticipated by the Noisy Channel model, which regards the first stage of visual word recognition as a language-universal perceptual process.


Link-specific adaptation in the luminance and chromatic channels.
We present evidence that adaptation occurs in the separate links that connect the receptors to the luminance and the chromatic channels. The relative effectiveness of the L and M cone inputs to the luminance and red/green chromatic channels was determined by using, respectively, heterochromatic flicker photometry and a cancellation technique which maintained a pure yellow. The findings provide evidence for a link-specific adaptation model, wherein one receptor system provides two separate links to the luminance and chromatic channels and the outputs of an individual cone to these two postreceptoral channels can be separately attenuated or weighted at each of these links by colored adapting lights. One line of evidence for link-specific adaptation is that colored adapting fields selectively suppress L and M cone inputs to the red/green chromatic channel by a smaller factor than the luminance channel. A second line of evidence is that there is not only a magnitude difference but also a dynamic difference between adaptive processes operating in the luminance and chromatic channels: the luminance channel has a faster gain change and recovery from adaptation than does the chromatic channel. The results, together with other evidence, make it plausible that an important component of light adaptation in cone vision occurs at the cone-bipolar synapse.


Study on activation mechanism and cleavage sites of recombinant butelase-1 zymogen derived from Clitoria ternatea.
Asparagine endopeptidases (AEPs) were synthesized as a zymogen and were known to undergo pH-dependent autoproteolytic activation using their endopeptidase activity. Butelase-1, one of the few AEPs with ligation activity, can also be synthesized as a zymogen and activated at acidic pH in vitro, but the detailed activation process and potential activation sites of its zymogen are not fully understood. In this study, recombinant butelase-1 exhibited high ligation activity and ineffective endopeptidase activity, and its activities were strictly pH-dependent. The endopeptidase activity caused the activation of butelase-1 zymogen at acidic pH, which was autocatalytic, required sequential removal of C- and N-terminal pro-peptides, and was a bimolecular reaction. The pro-peptides were critical to the stability of butelase-1. Once the pro-peptides left the active domain, butelase-1 was quickly inactivated at pH 7.0. Based on the LC-MS/MS sequencing of activation products, Asp319 and Asn322 were identified as potential C-terminal pro-region hydrolysis sites of the butelase-1 zymogen, which was validated by site-directed mutagenesis. Our results provided a reasonable explanation for the self-activation of butelase-1 zymogen in vitro and provided supplementary information for the activation of AEP ligase zymogen.


Bayesian inference for parameter estimation in lactoferrin-mediated iron transport across blood-brain barrier.
In neurodegenerative diseases such as Alzheimer's and Parkinson's, excessive irons as well as lactoferrin (Lf), but not transferrin (Tf), have been found in and around the affected regions of the brain. These evidences suggest that lactoferrin plays a critical role during neurodegenerative diseases, although Lf-mediated iron transport across blood-brain barrier (BBB) is negligible compared to that of transferrin in normal condition. However, the kinetics of lactoferrins and lactoferrin-mediated iron transport are still unknown. To determine the kinetic rate constants of lactoferrin-mediated iron transport through BBB, a mass-action based ordinary differential equation model has been presented. A Bayesian framework is developed to estimate the kinetic rate parameters from posterior probability density functions. The iron transport across BBB is studied by considering both Lf- and Tf-mediated pathways for both normal and pathologic conditions. Using the point estimates of kinetic parameters, our model can effectively reproduce the experimental data of iron transport through BBB endothelial cells. The robustness of the model and parameter estimation process are further verified by perturbation of kinetic parameters. Our results show that surge in high-affinity receptor density increases lactoferrin as well as iron in the brain. Due to the lack of a feedback loop such as iron regulatory proteins (IRPs) for lactoferrin, iron can transport to the brain continuously, which might increase brain iron to pathological levels and can contribute to neurodegeneration. This study provides an improved understanding of presence of lactoferrin and iron in the brain during neurodegenerative diseases.


Difficulties in Addressing Artificial Hydration and Nutrition Therapy for Terminal Cancer Patients: What to do if Patients/Families' Wishes Differ From the Medically Appropriate Treatment Plans?
Artificial hydration and nutrition therapy (AHNT) initiated by patients/families sometimes differs from medically appropriate treatment plans. We aimed to identify the causes of these differences and examine the ensuing responses and outcomes. Of 133 adult cancer patients receiving end-of-life care in the last 2 years, these discrepancies occurred in 41 patients. We retrospectively examined the following issues: (1) The reason why these discrepancies occurred. (2) Based on the causes identified in (1), the following actions were taken: 1) If the consent to change to medically appropriate AHNT was obtained, physical findings using Japan Palliative Oncology Study (JPOS) group and Edmonton Symptom Assessment System (ESAS) were compared before and 1 week after the intervention. 2) If consent was not obtained, time-limited trial (TLT) was conducted, and these results were compared. (3) The communication between patients/families and medical professionals was compared using Support Team Assessment Schedule. (1) Causes: a) the lack of understanding of the disease condition in 26 cases and b) faulty expectation of AHNT in 15 cases. (2) In 30 cases of 1) (20 of a) and 10 of b)) and 11 of 2) in which TLT was performed, JPOS and ESAS improved significantly. (3) The communication above was improved significantly in 1) and 2) (P = .0027 and .0039, respectively). Providing medically appropriate AHNT with the consent of patients/families is expected to not only alleviate distressing symptoms but also improve the communication between patients/families and medical professionals, as well as improve the quality of palliative care.


Chalcogenide Perovskites and Perovskite-Based Chalcohalide as Photoabsorbers: A Study of Their Properties, and Potential Photovoltaic Applications.
In 2015, a class of unconventional semiconductors, Chalcogenide perovskites, remained projected as possible solar cell materials. The MAPbI3 hybrid lead iodide perovskite has been considered the best so far, and due to its toxicity, the search for potential alternatives was important. As a result, chalcogenide perovskites and perovskite-based chalcohalide have recently been considered options and potential thin-film light absorbers for photovoltaic applications. For the synthesis of novel hybrid perovskites, dimensionality tailoring and compositional substitution methods have been used widely. The study focuses on the optoelectronic properties of chalcogenide perovskites and perovskite-based chalcohalide as possibilities for future photovoltaic applications.


Retinal separation, retinotomy, and macular relocation: I. Experimental studies in the rabbit eye.
An animal model in the rabbit eye was utilized to study mobilization and relocation of the fovea as a potentially beneficial surgical approach to age-related macular disease. After lentectomy and vitrectomy, the retina was completely separated from the pigment epithelium by means of infusion into the subretinal space. A 360 degrees peripheral retinotomy was performed. The retina was rotated up to 60 degrees around the optic nerve as axis and reattached. Scanning and transmission electron microscopy revealed the relative intactness of outer segments and pigment epithelium after this procedure, both acutely and 3 days following reattachment.


Activation of antigen-specific cytotoxic T lymphocytes by beta 2-microglobulin or TAP1 gene disruption and the introduction of recipient-matched MHC class I gene in allogeneic embryonic stem cell-derived dendritic cells.
A method for the genetic modification of dendritic cells (DC) was previously established based on the in vitro differentiation of embryonic stem (ES) cells to DC (ES-DC). The unavailability of human ES cells genetically identical to the patients will be a problem in the future clinical application of this technology. This study attempted to establish a strategy to overcome this issue. The TAP1 or beta(2)-microglobulin (beta(2)m) gene was disrupted in 129 (H-2(b))-derived ES cells and then expression vectors for the H-2K(d) or beta(2)m-linked form of K(d) (beta2m-K(d)) were introduced, thus resulting in two types of genetically engineered ES-DC, TAP1(-/-)/K(d) ES-DC and beta(2)m(-/-)/beta(2)m-K(d) ES-DC. As intended, both of the transfectant ES-DC expressed K(d) but not the intrinsic H-2(b) haplotype-derived MHC class I. Beta(2)m(-/-)/beta(2)m-K(d) and TAP1(-/-)/K(d) ES-DC were not recognized by pre-activated H-2(b)-reactive CTL and did not prime H-2(b) reactive CTL in vitro or in vivo. Beta(2)m(-/-)/beta(2)m-K(d) ES-DC and TAP1(-/-)/K(d) ES-DC had a survival advantage in comparison to beta(2)m(+/-)/beta(2)m-K(d) ES-DC and TAP1(+/+)/K(d) ES-DC, when transferred into BALB/c mice. K(d)-restricted RSV-M2-derived peptide-loaded ES-DC could prime the epitope-specific CTL upon injection into the BALB/c mice, irrespective of the cell surface expression of intrinsic H-2(b) haplotype-encoded MHC class I. Beta(2)m(-/-)/beta(2)m-K(d) ES-DC were significantly more efficient in eliciting immunity against RSV M2 protein-expressing tumor cells than beta(2)m(+/-)/beta(2)m-K(d) ES-DC. The modification of the beta(2)m or TAP gene may therefore be an effective strategy to resolve the problem of HLA class I allele mismatch between human ES or induced pluripotent stem cells and the recipients to be treated.


Role of the Gp16 lytic transglycosylase motif in bacteriophage T7 virions at the initiation of infection.
The predicted catalytic glutamate residue for transglycosylase activity of bacteriophage T7 gp16 is not essential for phage growth, but is shown to be beneficial during infection of Escherichia coli cells grown to high cell density, conditions in which murein is more highly cross-linked. In the absence of the putative transglycosylase, internalization of the phage genome is significantly delayed during infection. The lytic transglycosylase motif of gp16 is essential for phage growth at temperatures below 20 degrees C, indicating that these growth conditions also lead to increased cross-linking of peptidoglycan. Overexpression of sltY, E. coli soluble lytic transglycosylase, partially complements the defect in infection of mutant phage particles, allowing them to infect at higher efficiencies. Conversely, an sltY deletion increases the latent period of wild-type phage.


Demonstration of cerebellar atrophy in neuroacanthocytosis of 2 siblings.
Neuroacanthocytosis is a rare hereditary disorder characterized by involuntary choreiform movements and erythrocytic acanthocytosis in the peripheral blood. Clinical manifestations of this disorder resemble those of Huntington disease (HD). Neuroimaging features of neuroacanthocytosis are atrophy and signal intensity change of the striata on MR imaging, as in HD. We report herein the cases of 2 siblings with neuroacanthocytosis showing cerebellar atrophy as well as atrophy and signal intensity changes of striata.


Impact of 123I-Ioflupane SPECT in Patient Management: Essential Tremor.
The usefulness of I-ioflupane imaging for detecting loss of functional dopaminergic neuron terminals in the striatum of patients with clinically uncertain parkinsonian syndromes is well known, especially to differentiate essential tremor from parkinsonisms. Here we present a case of a patient suspected of essential tremor but not responding to standard therapy, in which the results of DaTscan were fundamental to set up an alternative therapeutic approach.


Extraction methodology of lignin from biomass waste influences the quality of bio-oil obtained by solvothermal depolymerization process.
Lignin from sugarcane bagasse was extracted using three different methods such as Alkaline, Ethanosolv, and Hydrotropic extraction and the effect of each method on yield and quality of bio-oil obtained when the lignin was depolymerized through solvothermal liquefaction was studied using ethanol as solvent. The maximum lignin yield was obtained in the hydrotropic extraction method when Sodium Xylene Sulfonate was used as the hydrotropic solvent at a concentration of 1.43 M and a temperature of 90 °C. Hydrothermal experiments were performed at temperature of 250 °C with a residence time of 30 min and lignin to ethanol ratio of 1:200 g/mL respectively. Among the methods used, the Ethanosolv lignin showed the highest extent of depolymerization (86.7%) to yield bio-oil at 250 °C with reduced biochar formation at lignin to solvent ratio of 1:200. Biochar obtained was used in adsorption studies of Cadmium (Cd), Lead (Pb), Nickel (Ni), and Zinc (Zn) and results showed that more than 85% removal of all the metals under lower concentration levels.


Expression of T-Cell Exhaustion Molecules and Human Endogenous Retroviruses as Predictive Biomarkers for Response to Nivolumab in Metastatic Clear Cell Renal Cell Carcinoma.
We sought to validate levels of CD8+ tumor-infiltrating cells (TIC) expressing PD-1 but not TIM-3 and LAG-3 (IF biomarker; Pignon and colleagues, 2019) and to investigate human endogenous retroviruses (hERV) as predictors of response to anti-PD-1 in a randomized trial of nivolumab (nivo) versus everolimus (evero) in patients with metastatic clear cell renal cell carcinoma (mccRCC; CheckMate-025). Tumor tissues (nivo: n = 116, evero: n = 107) were analyzed by multiparametric immunofluorescence (IF) and qRT-PCR. Genomic/transcriptomic analyses were performed in a subset of samples. Clinical endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and durable response rate (DRR, defined as complete response or partial response with a PFS ≥ 12 months). In the nivo (but not evero) arm, patients with high-IF biomarker density (24/116, 20.7%) had higher ORR (45.8% vs. 19.6%, P = 0.01) and DRR (33.3% vs. 14.1%, P = 0.03) and longer median PFS (9.6 vs. 3.7 months, P = 0.03) than patients with low-IF biomarker. By RNA sequencing, several inflammatory pathways (q < 0.1) and immune-related gene signature scores (q < 0.05) were enriched in the high-IF biomarker group. When combined with the IF biomarker, tumor cell (TC) PD-L1 expression (≥1%) further separated clinical outcomes in the nivo arm. ERVE-4 expression was associated with increased DRR and longer PFS in nivo-treated patients. High levels of CD8+ TIC expressing PD-1 but not TIM-3 and LAG-3 and ERVE-4 expression predicted response to nivo (but not to evero) in patients with mccRCC. Combination of the IF biomarker with TC PD-L1 improved its predictive value, confirming our previous findings.


Semi-manual mastoidectomy assisted by human-robot collaborative control - A temporal bone replica study.
To develop an otological robot that can protect important organs from being injured. We developed a five degree-of-freedom robot for otological surgery. Unlike the other robots that were reported previously, our robot does not replace surgeon's procedures, but instead utilizes human-robot collaborative control. The robot basically releases all of the actuators so that the surgeon can manipulate the drill within the robot's working area with minimal restriction. When the drill reaches a forbidden area, the surgeon feels as if the drill hits a wall. When an engineer performed mastoidectomy using the robot for assistance, the facial nerve in the segmented region was always protected with a more than 2.5mm margin, which was almost the same as the pre-set safety margin of 3mm. Semi-manual drilling using human-robot collaborative control was feasible, and may hold a realistic prospect of clinical use in the near future.


The magnetic field of cortical current sources: the application of a spatial filtering model to the forward and inverse problems.
We extend our theoretical model based on spatial filtering to determine the ability of a SQUID magnetometer to resolve 2 localized current sources in the brain. We find that in order to resolve 2 separated but coaxial cortical sources, the source-to-pickup coil distance must be comparable to the distance between the 2 sources. The size of the current sources affects the resolving power of a magnetometer, but an anisotropy of 3 in the cortical tissue does not produce a significant effect. The model also provides a solution of the inverse calculation, either to reconstruct the original current source distribution from the measured magnetic field, or to continue the field at the magnetometer inward towards the sources. Both the inverse and inward calculations are limited by the fact that the inverse filter function serves as a high-pass filter, which leads to instabilities at high spatial frequencies, particularly in the presence of noise. The instabilities can be minimized by choosing an appropriate window to attenuate the noise, but this in turn reduces the spatial resolution.


An application of a mixed-effects location scale model for analysis of Ecological Momentary Assessment (EMA) data.
For longitudinal data, mixed models include random subject effects to indicate how subjects influence their responses over repeated assessments. The error variance and the variance of the random effects are usually considered to be homogeneous. These variance terms characterize the within-subjects (i.e., error variance) and between-subjects (i.e., random-effects variance) variation in the data. In studies using ecological momentary assessment (EMA), up to 30 or 40 observations are often obtained for each subject, and interest frequently centers around changes in the variances, both within and between subjects. In this article, we focus on an adolescent smoking study using EMA where interest is on characterizing changes in mood variation. We describe how covariates can influence the mood variances, and also extend the standard mixed model by adding a subject-level random effect to the within-subject variance specification. This permits subjects to have influence on the mean, or location, and variability, or (square of the) scale, of their mood responses. Additionally, we allow the location and scale random effects to be correlated. These mixed-effects location scale models have useful applications in many research areas where interest centers on the joint modeling of the mean and variance structure.


The Opioid Epidemic in the United States: Where Do Patients Requiring Elective Arthroplasty Stand?
Over the past decade, awareness about opioid abuse in the general community and among prescribers has increased. This study evaluated how opioid prescribing patterns before and after total hip arthroplasty (THA) and total knee arthroplasty (TKA) may have changed during a recent 5-year period. The Truven Health MarketScan database were queried for patients who underwent elective THA and TKA for primary osteoarthritis between 2013 and 2017. The trend analysis evaluated for changes in opioid prescriptions and multivariate regression identified predictors for chronic postoperative opioid use. Data were available for 27,908 THA patients and 47,220 TKA patients. The proportion of opioid naïve patients before THA or TKA increased significantly (P < 0.001). Median oral morphine equivalents prescribed during the first postoperative year after THA or TKA decreased significantly (P < 0.001). The proportion of patients with chronic postoperative opioid use also decreased for TKA patients (P < 0.001). A notable, downward trend was seen in the proportion of patients who received opioids before elective arthroplasty, in the amount of opioid prescribed after surgery, and in TKA patients, the frequency of chronic opioid use after surgery. These findings reflect the effectiveness of efforts to combat the opioid epidemic after elective arthroplasty surgery.


Efficient synthesis and evaluation of bimodal ligand NETA.
The efficient and short synthetic route to the structurally novel bimodal ligand NETA for antibody-targeted radiation therapy (radioimmunotherapy, RIT) of cancer was developed. The structure of NETA was determined by X-ray crystallography. The arsenazo-based UV spectroscopic complexation kinetics data suggest that NETA is a promising chelator for use in RIT applications of (212)Bi, (213)Bi, and (177)Lu.


Effect of muscle activation scheme in human head-neck model on estimating cervical spine ligament strain from military volunteer frontal impact data.
Cervical spine (c-spine) injuries are a common injury during automobile crashes. The objective of this study is to verify an existing head-neck (HN) finite element model with military volunteer frontal impact kinematics by varying the muscle activation scheme from previous literature. Proper muscle activation will allow for accurate percent elongation (strain) of the c-spine ligaments and will serve to establish ligamentous response during non-injury frontal impacts. Previous human research volunteer (HRV) frontal impact sled tests reported kinematic data that served as the input for HN model simulation. Peak sled acceleration (PSA) was varied between 10G and 30G for HRVs. Muscle activation was shifted to begin at 0 ms at start of impact to allow for proper muscle contraction in the HN model. Then, extensor muscle activation magnitude was varied between 20 and 100% to determine the proper activation necessary to match kinematic outputs from the model with experimental results. The model was validated against 10G test recorded response. Ligament strain was measured from multiple ligaments along the c-spine once the model was verified. The 40% activated extensor muscle scheme was deemed the most biofidelic, with CORA scores of 0.743 and 0.686 for head X linear acceleration and angular Y acceleration for 10G pulse. All PSA groups scored well with this muscle activation. Most ligaments were buffered well by the active simulation, with only the interspinous ligament nearing physiologic injury. With the HN model verified against additional kinematic data, simulations with higher accelerations to predict areas of injury in real life crash scenarios are possible.


Role of retention of the condylar cartilage in open treatment of intracapsular condylar fractures in growing goats: three-dimensional computed tomographic analysis.
Our aim was to investigate the role of retention of the condylar cartilage in open reduction and internal fixation (ORIF) of intracapsular condylar fractures (ICFs) in growing goats by three-dimensional computed tomographic (CT) analysis. Twelve goats 6 months old were randomly divided into three groups. ICFs were created bilaterally in mandibular condyles and treated with ORIF. On the one side (n=4) the condylar cartilage was removed, and on the other side (n=4) it was retained. Condyles in the control group (n=4) were untouched. CT scans were taken immediately postoperatively, and 3 and 6 months later. The heights of the rami among the three groups were compared, There were significant reductions in the height of rami in the group from which the cartilage had been removed 3 and 6 months postoperatively compared with controls, but no significant differences between control group and the group in which it had been retained. We conclude that retaining condylar cartilage in the ORIF for ICF of growing goats has no harmful effect on condylar growth, but removal can limit growth.


Somatostatin content and release measured in cerebral biopsies from demented patients.
Somatostatin-like immunoreactivity (SLIR) has been assayed in frontal and temporal cortex obtained at diagnostic craniotomy and post-mortem from patients with histologically verified Alzheimer's disease. SLIR content was not significantly different from controls in the frontal and temporal lobes, except in the temporal cortex post-mortem. The K+-stimulated release of endogenous SLIR from tissue prisms ('mini-slices') prepared from neocortex obtained at diagnostic craniotomy from Alzheimer patients was not below the control values. Indices of cholinergic varicosities in similar samples from the frontal and temporal lobes are reduced; accordingly, somatostatin does not seem to be as prominently involved in these regions. Patients with Alzheimer's disease underwent neuropsychological assessment shortly before sampling the temporal lobe. Scores for WAIS full scale and the verbal subscale and the Token Test (measure of language comprehension) significantly correlated with the SLIR content; mean values (fmole/mg protein) were 817, 1468 and 1363 for aphasic and non-aphasic Alzheimer patients and controls, respectively. Ventricular fluid obtained from Alzheimer patients during surgery, did not have a significantly different SLIR content compared to controls. SLIR contents of ventricular fluid and neocortex from demented patients, without any specific histological changes in the sample obtained at diagnostic craniotomy, were also not significantly different from controls. Previously, we have shown that these demented patients, as well as those with histologically verified Alzheimer's disease, have a reduced SLIR content of lumbar fluid so it seems that somatostatin neurones located outside the frontal and temporal lobes are affected relatively early in the disease process.


Characteristics and Management of Patients with Refractory or Unexplained Chronic Cough in Outpatient Hospital Clinics in Spain: A Retrospective Multicenter Study.
Chronic cough (cough that persists for ≥ 8 weeks) can cause a range of physical symptoms and psychosocial effects that significantly impair patients' quality of life. Refractory chronic cough (RCC) and unexplained chronic cough (UCC) are challenging to diagnose and manage, with substantial economic implications for healthcare systems. This retrospective multicenter non-interventional study aimed to characterize the profile and health resource consumption of patients with RCC or UCC who attended outpatient clinics at Spanish hospitals. Data were collected from medical records of patients with RCC or UCC for up to 3 years before study inclusion. The patient cohort (n = 196) was representative of the chronic cough population (77.6% female, mean age 58.5 years). Two-thirds of patients (n = 126) had RCC. The most frequently visited doctors were pulmonologists (93.4% of patients) and primary care physicians (78.6%), with a mean of 5 visits per patient over three years' observation. The most common diagnostic tests were chest x-ray (83.7%) and spirometry with bronchodilation (77.0%). The most commonly prescribed treatments were proton pump inhibitors (79.6%) and respiratory medications (87.8%). Antibiotics were prescribed empirically to 56 (28.6%) patients. Differences between RCC or UCC groups related mainly to approaches used to manage cough-associated conditions (gastroesophageal reflux disease, asthma) in patients with RCC. RCC and UCC are responsible for high health resource utilization in Spanish hospitals. Specific treatments targeting the pathological processes driving chronic cough may provide opportunities to reduce the associated burden for patients and healthcare systems.


MicroRNA-125b expression and intrahepatic metastasis are predictors for early recurrence after hepatocellular carcinoma resection.
Early hepatocellular carcinoma (HCC) recurrence after curative resection is a known poor prognostic factor. We aimed to identify microRNAs associated with recurrence after curative HCC resection. To identify risk factors for early recurrence and metastasis, 694 patients who underwent primary curative HCC resection were analyzed. We evaluated microRNA expression in cancerous and non-cancerous tissues by microarray and quantitative PCR analyses using 16 HCC samples. We defined patients who had a recurrence within 1 year of resection as the early recurrence (ER) group, patients who had a recurrence within 1-5 years as the late recurrence (LR) group, and patients who did not recur during the 5-year observation period as the no recurrence (NR) group. We examined the relationship between microRNA expression and clinical features. Multivariate analysis revealed that α-fetoprotein >31 ng/mL, tumor size >4 cm, and intrahepatic metastasis (IM) were significant factors. Afterwards, microarray analyses revealed that microRNA (miR)-125b-5p and miR-148a-3p were significantly downregulated in recurrent cases. The ratio of miR-125b-5p expression in cancerous versus non-cancerous tissue (miR-125b ratio), but not miR-148a-3p, was significantly lower in the ER group. Early recurrence was associated with reduced overall survival compared with the LR and NR group. The miR-125b ratio was significantly lower in the ER group than in the LR and NR groups. Multivariate analysis showed that a low miR-125b ratio and IM were independently associated with ER and disease-free survival. Assessing tissue miR-125b-5p expression and IM is useful for stratifying patients at risk of early HCC recurrence after curative resection.


Exposure assessment to bisphenol A (BPA) in Portuguese children by human biomonitoring.
Exposure to bisphenol A (BPA) is known to be widespread and available data suggests that BPA can act as an endocrine disruptor. Diet is generally regarded as the dominant BPA exposure source, namely through leaching to food from packaging materials. The aim of this study was to evaluate the exposure of 110 Portuguese children (4-18 years old), divided in two groups: the regular diet group (n = 43) comprised healthy normal weight/underweight children with no dietary control; the healthy diet group (n = 67) comprised children diagnosed for obesity/overweight (without other known associated diseases) that were set on a healthy diet for weight control. First morning urine samples were collected and total urinary BPA was analyzed after enzymatic hydrolysis via on-line HPLC-MS/MS with isotope dilution quantification. Virtually, all the children were exposed to BPA, with 91% of the samples above the LOQ (limit of quantification) of 0.1 μg/L. The median (95th percentile) urinary BPA levels for non-normalized and creatinine-corrected values were 1.89 μg/L (16.0) and 1.92 μg/g creatinine (14.4), respectively. BPA levels in the regular diet group were higher than in the healthy diet group, but differences were not significant. Calculated daily BPA intakes, however, were significantly higher in children of the regular diet group than in children of healthy diet group. Median (95th percentile) daily intakes amounted to 41.6 (467) ng/kg body weight/day in the regular diet group, and 23.2 (197) ng/kg body weight/day in the healthy diet group. Multiple logistic regression analysis revealed that children in the healthy diet group had 33% lower intakes than children in the regular diet group (OR 0.67; 95% CI 0.51-0.89). For both groups, however, urinary BPA levels and daily BPA intakes were within the range reported for other children's populations and were well below health guidance values such as the European Food Safety Authority (EFSA) temporary tolerable daily intake (t-TDI) of 4 μg/kg body weight/day. In addition, lower daily BPA intakes were more likely linked with the inherent dietary approach rather than with high BMI or obesity.


Pattern of birth in restrictive and bulimic eating disorders.
To determine whether different eating disorders are associated with being born at different points in the year. Based on previous research, it was hypothesised that being born during warm months (June-August) is likely to be associated with restrictive anorexia, rather than bulimic disorders (bulimia nervosa, binge-purge anorexia). Case notes from 105 eating-disordered women were used to yield dates of birth and diagnosis. Associations were calculated between diagnostic group and birth period (month, quarter of year, high-risk quarter). Restrictive anorexics were significantly more likely than the bulimics (42.6% vs. 24.1%) to be born during the warmest quarter (June-August) than during the remainder of the year. This preliminary study suggests that being born during warmer periods may form a small risk factor for the development of a restrictive eating disorder. Further research is suggested to test and extend the hypothesis.


In-Vitro Study of Urokinase Thrombolysis Following Stereotactic Aspiration of Intracerebral Hematoma.
A consensus regarding the ideal regimen for urokinase (UK) thrombolysis subsequent to stereotactic spontaneous intracerebral hemorrhage aspiration has yet to be established. The purpose of this study is to evaluate the efficacy of UK thrombolysis relative to when the regimen is changed. Venous blood from 30 heathy volunteers was obtained for this in-vitro study. Various concentrations of UK solution were added to microcentrifuge tubes containing the clotted blood. The efficacy of UK thrombolysis was identified by checking the weight of lysed hematoma following various time intervals with different concentrations of UK solution. Group one, the "3×4" group involved four administrations every 3 hours over 12 hours, and group two, the "6×2" group involved two administrations every 6 hours over 12 hours. More hematoma was lysed in the 3×4 group than the 6×2 group across all concentration levels (however, the differences were only significant between groups at the 500 and 1000 IU concentration levels, p<0.05). There were no significant differences of lysed hematoma among the various UK solution concentrations within groups. This study suggests that frequent administrations of UK thrombolysis may result in a greater degree of lysed hematoma in comparison to a higher concentration of UK.


[Funding in 2012 for Division of Microbiology by National Natural Science Foundation of China].
We provide here an overview of proposals applied and projects funded by the division of microbiology, department of life sciences, National Natural Science Foundation of China in 2012. We analyzed the traits and problems in different sub-disciplines, and illustrated the stimulating policy for future funding. This overview provides reference for Chinese researchers to apply relevant funding for projects in microbiology.


The future of oral pathology practice.
Oral and maxillofacial pathology (OMP) may be viewed as a specialty of dentistry, which addresses the diagnosis and treatment of diseases of the oral and perioral regions. Consensus definitions may be found in the accreditation standards for OMP as published by the American Dental Association, and in the Constitution and Bylaws of the American Academy of Oral and Maxillofacial Pathology (AAOMP). These sources describe roles for OMP in laboratory diagnosis (histopathology), and clinical practice. Eversole recognizes these divisions of OMP in his discussion of evidence-based practice, noting that oral medicine shares with OMP responsibilities in the care of patients with oral disease. Broadly viewed, all clinical disciplines and specialties of dentistry provide services in disease diagnosis and treatment. However, Eversole makes a distinction between the diagnostic and treatment services provided throughout dentistry, and those offered by OMP, excluding from OMP those primarily focused on dental caries, diseases of the periodontium, missing teeth and tooth structure, and dental misalignment. The focus of this essay addresses the future of OMP practice.


Solid character of membrane ceramides: a surface rheology study of their mixtures with sphingomyelin.
The compression and shear viscoelasticities of egg-ceramide and its mixtures with sphingomyelin were investigated using oscillatory surface rheology performed on Langmuir monolayers. We found high values for the compression and shear moduli for ceramide, compatible with a solid-state membrane, and extremely high surface viscosities when compared to typical fluid lipids. A fluidlike rheological behavior was found for sphingomyelin. Lateral mobilities, measured from particle tracking experiments, were correlated with the monolayer viscosities through the usual hydrodynamic relationships. In conclusion, ceramide increases the solid character of sphingomyelin-based membranes and decreases their fluidity, thus drastically decreasing the lateral mobilities of embedded objects. This mechanical behavior may involve important physiological consequences in biological membranes containing ceramides.


Folate transport in Lactobacillus salivarius. Characterization of the transport mechanism and purification and properties of the binding component.
Lactobacillus salivarius cells contain an inducible transport system for folate. Influx via this system is time- and temperature-dependent, requires glucose and glutamine for optimum activity, and is half-maximal at folate concentrations in the nanomolar range. The folate internalized after 30 min at 30 degrees C is not released from the cells by excess extracellular folate and is recovered in cell extracts primarily in metabolized forms. A membrane-associated folate-binding protein is also present in cells that have been induced to transport folate. This binding protein constitutes 1% of total cellular protein, exhibits a high affinity for folate (KD = 0.40 nM), and requires divalent cations for optimum binding activity. Folate binds rapidly to this protein, while the exchange of bound substrate with folate added subsequently is relatively slow and dependent on the metabolic state of the cell. The transport rate per binding site is 0.05/min at 30 degrees C. A comparison of substrate specificity showed that folate binding and transport are both inhibited to the same extent by several different folate compounds, and a parallel irreversible inhibition of both processes is observed by prior treatment of the cells with a carbodiimide-activated derivative of folic acid. Binding protein labeled covalently with [3H]folate and solubilized with Triton X-100 was purified by a fractionation procedure involving absorption and elution from microgranular silica and molecular sieve chromatography. The isolated protein appeared homogeneous by gel electrophoresis and had an apparent molecular weight of 21,000. Monoclonal antibodies to the folate transport protein of Lactobacillus casei showed a high degree of cross-reactivity to the isolated binding protein from L. salivarius, indicating that these proteins share common epitopes. These results suggest that folate uptake by L. salivarius proceeds via an abundant membrane-associated binding protein which facilitates the movement of folate across the membrane as an electroneutral complex with cations. The substrate then slowly dissociates from internalized binding sites and is metabolized sequentially to coenzyme forms and then to membrane-impermeable folylpolyglutamates.


Determination of morphine in the plasma of addicts in using Zeolite Y extraction following high-performance liquid chromatography.
The measurement of morphine in biological samples has become a routine in many clinical and forensic toxicology laboratories. A high-performance liquid chromatography (HPLC) method was developed for the determination of morphine in plasma. Samples were extracted using Zeolite Y column followed by reversed phase HPLC with fluorescence detection. This method was based on an ex-calibration procedure and was linear between 20 and 200 ng/ml of morphine. Blood from 10 male opiate addicts were obtained from Rosbeh Hospital. All of the male smoked opiate (heroin, opium) and cigarettes. The mean total level 5 h after the last abuse was 152.4 ng/ml and 37.6 ng/ml at 10-15 h. The method was reliable for morphine determination in blood even after 5 half-lives after the last abuse. This method is simple and rapid and may be useful for routine monitoring of plasma morphine concentration.


Imaging of lymphadenopathy in the neck.
Imaging is playing a major role in the assessment of cervical lymphadenopathy. In infectious disease, the assessment of abscess formation and the relation of the abscess to surrounding vital structures is crucial for its management. In head and neck malignancies, imaging can be helpful for staging. Imaging of the neck for the assessment of nodal metastases can be used to detect occult metastases or to assess operability of palpable metastases. The detection of small occult metastases has limitations, as micrometastases cannot be depicted; however, imaging can fulfill a role in diminishing the risk of occult metastases, and thus influence management. For this purpose a very sensitive technique is necessary. The currently used radiological criteria are not sensitive enough to accomplish enough reduction of the risk of occult metastases; therefore, more sensitive CT and MRI criteria, but especially ultrasound-guided aspiration, should be employed to assess the clinically negative neck.


[Factors associated with the practice of exclusive breastfeeding among mothers of children aged 6 to 12 months in Kaolack (Senegal)].
the World Health Organization (WHO) recommends immediate and exclusive breastfeeding in order to reduce malnutrition and neonatal mortality. The purpose of this study was to determine the prevalence of exclusive breastfeeding (EBF) and to identify its associated factors among mothers of children aged 6 to 12 months in Kaolack. we conducted a cross-sectional descriptive and analytical study. The study was conducted from July 8th, 2020 to February 8th, 2021. Multivariate analysis was performed using the logistic regression model. The target population consisted of mothers of children aged 6 to 12 months residing in the city of Kaolack and met during vaccination sessions. a total of 400 women were enrolled in the study. Among them, 51.8% practiced EBF according to the WHO recommendations. The average age of mothers was 27.42 years; 56.3% were housewives and 82.7% have done at least 4 antenatal care (ANC). Logistic regression showed an association between EBF and the following factors: age < 25 years (OR=2.03 CI 95% [1.23-3.36]), receiving advice on EBF during ANCs (OR=2.92 CI 95% [1.70-5.01]), receiving advice on EBF during postnatal care (PNC) (OR=4.33 CI 95% [2.51-7.45]), the permanent presence of mother with her baby (OR=3.97 CI 95% [1.99-7.91]), and a good knowledge of EBF (OR=4.54 CI 95% [1.96-10.51]). these modifiable factors can help improve the practice of EBF in the city of Kaolack.


The bivalve Glycymeris pilosa as a multidecadal environmental archive for the Adriatic and Mediterranean Seas.
We evaluated the potential of Glycymeris pilosa as an environmental indicator for the Mediterranean region by applying sclerochronological techniques on a sample set collected from Pašman Channel in the middle Adriatic Sea. Maximal longevity of analyzed shells was 69 years. Growth increments in acetate peels of the hinge region had clear boundaries, and there was a strongly synchronous signal in growth-increment width among individuals. The final, replicated chronology spanned 1969 to 2013. Shell growth negatively correlated with local summer sea temperatures and positively with November precipitation. High correlation between shell growth and circulation patterns in the northern Ionian was also observed, with slower growth occurring during cyclonic regimes. Given its broad distribution in the region and the ability to crossdate, generate annually-resolved chronologies, and of a length that substantially overlaps with observational records, G. pilosa has considerable potential to test hypotheses relating to environmental variability and biological response in the Mediterranean.


Have you M.E.T. the future of better patient safety?
A new approach to inpatient safety, medical emergency teams (METs), are taking hold in hospitals around the world. Learn how they improve safety by stepping into crises before they become "codes".


Forerunners of REM sleep.
The development of sleep research can be divided into two main periods. The first one was initiated in 1863 by the first systematic measurement of the depth of sleep, the second in 1953 by the discovery of recurrent episodes of rapid eye movements in sleep. The main methodological procedure in the first of these two periods was the measurement of a single physiological variable, while beginning with long-term measurements of the electroencephalogram (EEG) in sleep, multi-channel, polygraphic recording became the method of choice for sleep studies. Although rhythmic changes in the ultradian frequency range of one to 2 h were observed early in many variables during sleep (movements, autonomic functions, penile erections), the recognition of the existence of two different states of sleep (rapid eye movement (REM) and non-rapid eye movement (NREM sleep)) was contingent upon a 'synthetic' view, which focus on the coalescence of multiple variables. The dual concept of sleep organization evolved stepwise in parallel to the rapid growth of neurophysiological knowledge and techniques in the first half of the 20th century, culminating in the discovery of REM sleep.


Identifying Common Molecular Mechanisms in Experimental and Human Acute Kidney Injury.
Acute kidney injury (AKI) is a highly prevalent, heterogeneous syndrome, associated with increased short- and long-term mortality. A multitude of different factors cause AKI including ischemia, sepsis, nephrotoxic drugs, and urinary tract obstruction. Upon injury, the kidney initiates an intrinsic repair program that can result in adaptive repair with regeneration of damaged nephrons and functional recovery of epithelial activity, or maladaptive repair and persistence of damaged epithelial cells with a characteristic proinflammatory, profibrotic molecular signature. Maladaptive repair is linked to disease progression from AKI to chronic kidney disease. Despite extensive efforts, no therapeutic strategies provide consistent benefit to AKI patients. Since kidney biopsies are rarely performed in the acute injury phase in humans, most of our understanding of AKI pathophysiology is derived from preclinical AKI models. This raises the question of how well experimental models of AKI reflect the molecular and cellular mechanisms underlying human AKI? Here, we provide a brief overview of available AKI models, discuss their strengths and limitations, and consider important aspects of the AKI response in mice and humans, with a particular focus on the role of proximal tubule cells in adaptive and maladaptive repair.


The assay of soil carbon with naturally occurring cosmic ray neutrons.
The detection of gamma rays induced in soil by naturally occurring cosmic ray neutrons is explored with the Geant4 Simulation Toolkit to monitor carbon sequestration in soil. The simulated soil is a uniform mixture of minerals, air, water, and soil organic carbon. As the soil organic carbon increases from 0% to 15% by volume, the mineral matter decreases, and gamma ray counts from mineral-related isotopes decrease. Characteristic gamma ray energies from a variety of elements are collected near the surface with a germanium detector. Of these, the 2.224 MeV gamma ray from hydrogen is sensitive to changes in soil organic carbon as low as 0.12% after counting for the equivalent of 3.45 days. Counting longer is recommended to reduce the sensitivity of the primary 4.438 MeV gamma ray from carbon below its current value of 2.81% in the simulation.