An efficient method for measuring the internal parameters of optical cameras based on optical fibres.
In this work, we report an expedient auto-collimating method for self-measuring the internal parameters (IPs) of optical cameras. Several key optical components, including the thin optical fibre (TOF), reflecting prism, and receiver, are introduced into optical cameras. The TOF outgoing end and area-array image receiver are integrated onto the focal-plane assembly of optical cameras. Different wavelengths of light, which are emitted by external sources, are transmitted to the focal plane through optical fibres. Because one optical fibre can transmit different wavelengths of light, the same position on the focal plane can obtain point light sources (PLSs) with different wavelengths. Then, the optical system of the cameras spontaneously transforms the PLSs into auto-collimating lights. The auto-collimating lights are reflected by a two-plane prism, return to the camera optical system, reach the focal plane and are received by the area-array sensor. Finally, the IPs are calculated based on a mathematical model of the imaging relation between fibre light sources and images. The experiment confirms that this method is efficient and has a level of precision of dozens of micrometres for an optical camera with a short focal length and small field of view. Our method is suitable for on-orbit IP measurements for cameras without spatial or temporal limitations.


Non-Hermitian guided modes and exceptional points using loss-free negative-index materials.
We analyze the guided modes in coupled waveguides made of negative-index materials without gain or loss. We show that it supports non-Hermitian phenomenon on the existence of guided mode versus geometric parameters of the structure. The non-Hermitian effect is different from parity-time (P T) symmetry, and can be explained by a simple coupled-mode theory with an anti-P T symmetry. The existence of exceptional points and slow-light effect are discussed. This work highlights the potential of loss-free negative-index materials in the study of non-Hermitian optics.


A fluorometric assay for the measurement of endothelial cell density in vitro.
A fluorometric assay for determining endothelial cell numbers based on the endogenous enzyme acid phosphatase is described. In preliminary studies, three substrates--p-nitrophenyl phosphate, 4-methylumbelliferyl phosphate, and 2'-[2-benzthiazoyl]-6'-hydroxy-benthiazole phosphate (AttoPhos)--were compared with respect to their kinetic, optimum assay conditions, sensitivity, and detection limits. Only AttoPhos was found to have a high degree of sensitivity, reliability, and reproducibility for measuring both high and low cell numbers in the same plate. In subsequent experiments, assay conditions were validated for measuring endothelial cell density in response to basic fibroblast growth factor and fumagillin. Furthermore, the AttoPhos assay revealed a linear correlation between acid phosphatase activity and cell number in many cell types, including BALB/3T3, CHO-K1, A431, MCF7, 2008, SK-OV-3, T47-D, and OVCAR-3. This assay is potentially valuable for use in many in vitro systems in which the quantitation of cell density and proliferation is necessary. The practical advantages of AttoPhos assay for measuring endothelial cell numbers include (1) nonradioactivity, (2) simplicity, (3) economy, (4) speed of assessment of proliferation of large number of samples, and (5) amenability to high-throughput drug screening.


[The treatment of recurrent duodenal ulcers after vagotomy].
The authors report data on reoperation of 36 patients of ulcer disease of the duodenum with a history of surgical intervention using vagotomy. Reoperation was performed for recurrence. The method of duodenal stump suturing and complex prophylaxis of inconsistency of the duodenal stump sutures during the operation and in the postoperative period is described.


Exploring the perspectives of primary care providers on use of the electronic Patient Reported Outcomes tool to support goal-oriented care: a qualitative study.
Digital health technologies can support primary care delivery, but clinical uptake in primary care is limited. This study explores enablers and barriers experienced by primary care providers when adopting new digital health technologies, using the example of the electronic Patient Reported Outcome (ePRO) tool; a mobile application and web portal designed to support goal-oriented care. To better understand implementation drivers and barriers primary care providers' usage behaviours are compared to their perspectives on ePRO utility and fit to support care for patients with complex care needs. This qualitative sub-analysis was part of a larger trial evaluating the use of the ePRO tool in primary care. Qualitative interviews were conducted with providers at the midpoint (i.e. 4.5-6 months after ePRO implementation) and end-point (i.e. 9-12 months after ePRO implementation) of the trial. Interviews explored providers' experiences and perceptions of integrating the tool within their clinical practice. Interview data were analyzed using a hybrid thematic analysis and guided by the Technology Acceptance Model. Data from thirteen providers from three distinct primary care sites were included in the presented study. Three core themes were identified: (1) Perceived usefulness: perceptions of the tool's alignment with providers' typical approach to care, impact and value and fit with existing workflows influenced providers' intention to use the tool and usage behaviour; (2) Behavioural intention: providers had a high or low behavioural intention, and for some, it changed over time; and (3) Improving usage behaviour: enabling external factors and enhancing the tool's perceived ease of use may improve usage behaviour. Multiple refinements/iterations of the ePRO tool (e.g. enhancing the tool's alignment with provider workflows and functions) may be needed to enhance providers' usage behaviour, perceived usefulness and behavioural intention. Enabling external factors, such as organizational and IT support, are also necessary to increase providers' usage behaviour. Lessons from this study advance knowledge of technology implementation in primary care. Clinicaltrials.gov Identified NCT02917954. Registered September 2016, https://www.clinicaltrials.gov/ct2/show/study/NCT02917954.


The influence of naloxone on the C fiber response of dorsal horn neurons and their inhibitory control by raphe magnus stimulation.
In intact rats anesthetized with chloralose, the effects of naloxone were studied on the responses of spinal cord dorsal horn neurons to C fiber stimulation and upon the inhibition induced on these responses by stimulation of the nucleus raphé magnus (NRM). (1) A mean 44% facilitatory effect on responses to C fibers was observed for 12/19 units. (2) A mean 30% reduction of the inhibitory effects of NRM was found for 14/29 units. (3) However there is no clear relationship between these facilitatory effects and the diminution of the efficiency of NRM stimulation. These results demonstrate a facilitatory effect of naloxone upon the transmission of noxious messages at the spinal level and confirm that opiate endogenous substances are implicated in the inhibitory mechanisms activated by stimulation of NRM.


Adverse events related to abiraterone and enzalutamide treatment: analysis of the EudraVigilance database and meta-analysis of registrational phase III studies.
Data from clinical trials do not always provide adequate information to judge the impact of new treatments when used in a real-world setting. The aim of our study was to analyze adverse events (AEs) associated with enzalutamide (ENZ) and abiraterone (ABI) using real-life data from the EudraVigilance (EV) database. The EV database is the system for managing and analyzing information on suspected adverse reactions to medicines, which have been authorized or are being studied in clinical trials in the European Economic Area. We recorded the number of AEs for ABI and ENZ per category and severity from January 2013 to January 2019. In addition, we recorded AEs per age group. A meta-analysis of AEs reported in registrational phase III studies (AFFIRM, PREVAIL, COU-AA) was performed. The number of individual cases identified in EV database was 13,562 for ABI and 40,599 for ENZ. Over 90% of the reported AEs were defined as serious for both drugs. Older patients (>85 years and 65-85 years) treated with ABI or ENZ are at increased risk of cardiac, infectious, metabolic, and respiratory disorders when compared with younger patients (<65). According to registrational phase III studies, the most frequent AEs in patients treated with ABI are hepatobiliary disorders, while the most frequent AEs in patients treated with ENZ are psychiatric and vascular disorders. Several AEs present in the EV database are not reported in the registrational phase III studies. It is important to note that we have no information on the number of patients under treatment in the EV database. The EV database highlights several AEs that are not reported in registrational phase III studies as well as different AEs profiles according to age. Clinicians should consider these data when treating patients with castration-resistant prostate cancer with ABI or ENZ.


Dissecting metal ion-dependent folding and catalysis of a single DNAzyme.
Protein metalloenzymes use various modes for functions for which metal-dependent global conformational change is required in some cases but not in others. In contrast, most ribozymes require a global folding that almost always precedes enzyme reactions. Herein we studied metal-dependent folding and cleavage activity of the 8-17 DNAzyme using single-molecule fluorescence resonance energy transfer. Addition of Zn2+ and Mg2+ induced folding of the DNAzyme into a more compact structure followed by a cleavage reaction, which suggests that the DNAzyme may require metal-dependent global folding for activation. In the presence of Pb2+, however, the cleavage reaction occurred without a precedent folding step, which suggests that the DNAzyme may be prearranged to accept Pb2+ for the activity. Neither ligation reaction of the cleaved substrates nor dynamic changes between folded and unfolded states was observed. These features may contribute to the unusually fast Pb2+-dependent reaction of the DNAzyme. These results suggest that DNAzymes can use all modes of activation that metalloproteins use.


Detection of early allograft dysfunction at 30 min of reperfusion in liver transplantation: An intraoperative diagnostic tool with real time assessment of graft function.
During the anhepatic phase of liver transplantation (LT), fibrinolytic activity increases, since the liver clears tissue plasminogen activator (tPA). We hypothesize that patients who fail to reduce fibrinolytic activity following graft reperfusion will have an increased rate of early allograft dysfunction (EAD). Assessment of fibrinolysis in liver transplant recipients was quantified with thrombelastography (TEG) LY30. Changes in LY30 were assessed after graft reperfusion. The 30-min post-reperfusion LY30 was subtracted from the anhepatic LY30 quantifying fibrinolytic changes (delta-LY30). Seventy-three primary LT patients were included in the analysis. Receiver operating characteristic curve (ROC) analysis identified an inflection point of delta-LY30-5.3% as a risk factor for EAD. EAD occurred in 44% of these patients compared to 5% in high delta-LY30 (p = 0.002). LT recipients that develop hyperfibrinolysis who fail to reduce fibrinolytic activity 30 min after graft reperfusion had an EAD rate 8-fold higher than patients who had a large reduction in LY30 following reperfusion.


Simultaneous production of hydrogen-methane and spatial community succession in an anaerobic baffled reactor treating corn starch processing wastewater.
Corn starch processing wastewater (CSPW) is a high-strength organic wastewater and biological treatment is considered as the dominant process. The present work investigated the effects of pH on the bioenergy production and spatial succession of microbial community in an anaerobic baffled reactor (ABR) treating CSPW. The results showed that above 90.5% of COD removal and above 16.6 L d-1 of methane were achieved at the influent pHs of 8.0 and 7.0 under organic loading rate of 4.0 kg COD·m-3·L-1 condition. Further decreasing the influent pH to 6.0 resulted in the COD removal decreased to 89.7%. Besides, 9.2 L d-1 of hydrogen and 13.0 L d-1 of methane were obtained. There was significant difference in the volatile fatty acids profiles during the variation of pH. Illumina Miseq sequencing showed that Clostridium, Ethanoligenens, Megasphaera, Prevotella and Trichococcus with relative abundance of 2.1%∼28.1% were the dominant hydrogen-producing bacteria in C1. Methanogens (Methanothrix and Methanobacterium) dominated in the last three compartments. Function predicted analysis revealed that the abundance of metabolic-related gene families containing carbohydrate, amino acids and energy in the last three compartments were higher than that in C1. A deduced biodegradation model of CSPW in ABR revealed that the anaerobic sludge in C1 mainly produced hydrogen. Microbial population in C3 was responsible for COD removal and methane production. The redundancy analysis revealed that hydrogen production was highly correlated with some hydrogen-producing bacteria in C1, whereas methane production was positively correlated with microbial group in C2∼ C4.


The effect of solutions of varying branched-chain concentration on the plasma amino acid pattern and metabolism in intensive care patients.
30 intensive care surgical patients were investigated over a period of five days following trauma or major surgery. They were randomised by card into two groups, Group I received an amino acid solution containing 45 per cent branched-chain amino acids (BCAA), and group II an amino acid solution with a 10 per cent content of BCAAs. After 24 hours of infusion, the total amino acid concentration and branched-chain amino acid concentration in the plasma of Group I patients already clearly exceeded the normal range, and continued to increase during the period of study. In Group II these parameters rapidly returned to normal where they remained. Cumulative negative nitrogen balance and nitrogen excretion on each day of investigation were significantly less in Group II. These results indicate that after severe trauma or major surgery amino acid solutions containing high concentrations of BCAAs may be an unphysiological load on the already stressed metabolism, rather than a benefit.


TLR2 and TLR4 serve distinct roles in the host immune response against Mycobacterium bovis BCG.
Toll-like receptor (TLR) proteins mediate cellular activation by microbes and microbial products. To delineate the role of TLR proteins in the development of host immune responses against mycobacteria, wild-type and TLR-deficient mice were infected with nonpathogenic Mycobacterium bovis bacillus Calmette-Guerin (BCG). Two weeks after intraperitoneal challenge with BCG, few bacilli were present in the lungs of wild-type and TLR4(-/-) mice, whereas bacterial loads were tenfold higher in the lungs of infected TLR2(-/-) mice. BCG challenge in vitro strongly induced proinflammatory cytokine secretion by macrophages from wild-type and TLR4(-/-) mice but not by TLR2(-/-) macrophages. In contrast, intracellular uptake, intracellular bacterial growth, and suppression of intracellular bacterial growth in vitro by interferon-gamma (IFN-gamma) were similar in macrophages from all three mouse strains, suggesting that BCG growth in the lungs of TLR2(-/-) mice was a consequence of defective adaptive immunity. Antigenic stimulation of splenocytes from infected wild-type and TLR4(-/-) mice induced T cell proliferation in vitro, whereas T cells from TLR2(-/-) mice failed to proliferate. Unexpectedly, activated CD4(+) T cells from both TLR-deficient mouse strains secreted little IFN-gamma in vitro compared with control T cells. A role for TLR4 in the control of bacterial growth and IFN-gamma production in vivo was observed only when mice were infected with higher numbers of BCG. Thus, TLR2 and TLR4 appear to regulate distinct aspects of the host immune response against BCG.


Caffeic acid recovers ischemia-induced synaptic dysfunction without direct effects on excitatory synaptic transmission and plasticity in mouse hippocampal slices.
Caffeic acid is a polyphenolic compound present in a vast array of dietary components. We previously showed that caffeic acid reduces the burden of brain ischemia joining evidence by others that it can attenuate different brain diseases. However, it is unknown if caffeic acid affects information processing in neuronal networks. Thus, we now used electrophysiological recordings in mouse hippocampal slices to test if caffeic acid directly affected synaptic transmission, plasticity and dysfunction caused by oxygen-glucose deprivation (OGD), an in vitro ischemia model. Caffeic acid (1-10 μM) was devoid of effect on synaptic transmission and paired-pulse facilitation in Schaffer collaterals-CA1 pyramidal synapses. Also, the magnitude of either hippocampal long-term potentiation (LTP) or the subsequent depotentiation were not significantly modified by 10 μM caffeic acid. However, caffeic acid (10 μM) increased the recovery of synaptic transmission upon re-oxygenation following 7 min of OGD. Furthermore, caffeic acid (10 μM) also recovered plasticity after OGD, as heralded by the increased magnitude of LTP after exposure. These findings show that caffeic acid does not directly affect synaptic transmission and plasticity but can indirectly affect other cellular targets to correct synaptic dysfunction. Unraveling the molecular mechanisms of action of caffeic acid may allow the design of hitherto unrecognized novel neuroprotective strategies.


Use of the Ames test in toxicology.
The Salmonella/microsome assay (Ames test) is one of the most widely used short-term tests. Despite the ubiquitous presence of this assay and the large number of chemicals tested, there is still controversy over the value of Salmonella/microsome assay results in risk assessment. Understanding of the properties and performance of the test system is necessary to provide an appropriate answer to this question. Based on both theoretical and empirical considerations, the results of the assay can provide useful information to assist in the development of further studies and as part of the data which can be used in evaluating potential biological effects or projected lack of adverse effects. The value of the Salmonella/microsome assay in performing these functions is considerably enhanced by consideration of all the information which the assay data provide.


Update on antifungal therapy.
Fungal pathogens are becoming increasingly important for human and small animal medicine. This article highlights many standards-of-care and new agents for treatment of these pathogens for small animals and people.


Transport of dissolved gas and its ecological impact after a gas release from deepwater.
Previous models on simulating gas releases in deepwater were not focused on the dissolved component and its impact on water quality. This paper presents a new model developed for simulating the transport/spread of dissolved methane from an underwater release and its impact on dissolved oxygen in ambient water. Methane dissolves into ambient water from gas phase, direct from hydrate phase, and from dissociating hydrates formed earlier. Dissolved methane affects the dissolved oxygen levels in ambient water due to microbial interaction and possible direct absorption of oxygen into methane bubbles. We use new model simulations of Deepspill field experiments to compare with instantaneous profiles which were unpublished until now. The comparisons are very good with a short time lag, but are within the acceptable discrepancy for models for emergency response and contingency planning. Scenario simulations show the effect on dissolved oxygen due to different methane release situations.


Lipoprotein lipids in chronic renal failure and haemodialysis. The influence of etiology and implications for atherogenesis.
Lipoprotein lipid analysis has been carried out in 39 women and 28 men with chronic renal failure on haemodialysis. The results have been analysed in relation to the etiology of the renal disease and compared with those obtained in age- and sex-matched controls and in triglyceride-matched controls. Serum cholesterol was normal or low in glomerulonephritis but was normal in analgesic nephropathy. Serum triglycerides and VLDL lipids were raised uniformly regardless of the etiology of the renal disease. LDL triglyceride and HDL triglyceride were also raised. LDL cholesterol and phospholipid were low in glomerulonephritis but were normal in analgesic nephropathy. HDL cholesterol was reduced in both male and female patients regardless of etiology, statistical significance was not reached for the women. The ratio of esterified to free cholesterol tended to be reduced in all the lipoproteins regardless of sex or etiology but the changes were not significant in all groups. Comparison of the lipid abnormalities with those found in other hyperlipidaemic states suggests that the lipid disorders found in chronic renal failure are probably insufficient to explain the rapid development of vascular disease which has been reported.


Oral tyrosine kinase 2 inhibitor PF-06826647 demonstrates efficacy and an acceptable safety profile in participants with moderate-to-severe plaque psoriasis in a phase 2b, randomized, double-blind, placebo-controlled study.
Psoriasis treatments lack durable efficacy and have inconvenient administration, highlighting the need for new therapies. To evaluate the efficacy and safety of tyrosine kinase 2 inhibitor, PF-06826647, in moderate-to-severe plaque psoriasis. This phase 2b, double-blind study randomized participants to oral, once-daily PF-06826647 (1:1:2:2:2) 50:100:200:400 mg:placebo (16 weeks), then 200 or 400 mg (24 weeks) (NCT03895372). The primary end point was a proportion of participants achieving psoriasis area severity index (PASI) 90 at week 16. Secondary end points (PASI50/75/90/100; Physician's Global Assessment) and safety were assessed to week 40. Overall, 178 participants were treated. A significantly greater proportion of participants (risk difference % [90% CI]) achieved PASI90 in the 200-mg (33.0 [18.0, 47.1], P = .0004) and 400-mg (46.5 [30.6, 60.6], P < .0001; week 16) groups versus placebo. Significant increases from placebo were observed for all secondary end points (200 and 400 mg; weeks 6-16; P < .05); increases were evident to week 40 (categorical data). PF-06826647 was well tolerated and most treatment-emergent adverse events were mild/moderate. Eighteen participants discontinued due to treatment-emergent adverse events (14 arising from laboratory abnormalities). Limitations included the large proportion of White males and non-placebo-controlled extension. PF-06826647 200 and 400 mg once daily showed significant efficacy versus placebo at week 16 and was well tolerated over 40 weeks.


Paraoxonase-2: A potential biomarker for skin cancer aggressiveness.
Cutaneous neoplasms include melanoma and non-melanoma skin cancers (NMSCs). Among NMSCs, basal cell carcinoma (BCC) represents the most common lesion. On the contrary, although accounting for less than 5% of all skin cancers, melanoma is responsible for most of cutaneous malignancy-related deaths. Paraoxonase-2 (PON2) is an intracellular enzyme exerting a protective role against production of reactive oxygen species within mitochondrial respiratory chain. Recently, a growing attention has been focused on exploring the role of PON2 in cancer. The aim of this study was to investigate the diagnostic and prognostic role of PON2 in skin neoplasms. 36 cases of BCC, distinguished between nodular and infiltrative lesions, as well as 29 melanoma samples were analysed by immunohistochemistry to evaluate PON2 protein expression. Subsequent statistical analyses were carried out to explore the existence of correlations between intratumour enzyme levels and clinicopathological features. Results obtained showed PON2 overexpression in BCCs compared with controls. In particular, distinguishing between less and more aggressive tumour forms, we found no significant differences in enzyme levels between nodular BCCs and controls. Conversely, PON2 expression was significantly higher in infiltrative BCCs compared with controls. Moreover, the enzyme was strongly upregulated in melanoma samples with respect to controls. Interestingly, PON2 levels were positively correlated with Breslow thickness, Clark level, regression, mitoses, lymph node metastases, primary tumour (pT) parameter and pathological stage. Reported findings seem to suggest that PON2 expression levels could be positively related with tumour aggressiveness of both BCC and melanoma.


[The microprobe excision as a search biopsy within the scope of cancer-trace detection on the cervix uteri].
Besides colposcopy and cytology microbiopsy as a detection method for early detection of malign cervical lesions was applied to 142 women patients of the UFK Halle. A precondition for the successfull application of this method is a carefull preliminary colposcopic examination and close co-operation with the histologist. The interim result of the microbiopsy corresponded to a high degree with the definitive result. In this way, it was possible to indicate 20% of the preclinical carcinoma for histological evidence despite of negative cytology. An individual combination of all 3 ways of research guarantee a maximum of certainty for the early finding of cervical carcinoma and their pre-stages.


Effect of bradykinin on intracellular signalling systems in a rat clonal dental pulp-cell line.
The cloned pulp-cell line RDP4-1 increases cAMP production, hydrolyses phosphoinositide (PI) and mobilizes calcium in response to prostaglandin E2 (PGE2) and PGF2-alpha. The effect of bradykinin (BK) on intracellular signalling systems and DNA synthesis was studied in these cells. BK (10 microM) transiently increased cytoplasmic free calcium ([Ca2+]i) both in the presence and absence of external calcium. After stimulation with BK (10 microM), cells did not respond significantly to PGE2 (0.5 microgram/ml). Pretreatment with indomethacin (30 microM) inhibited the [Ca2+]i increment by BK (10 microM), but not by the subsequent addition of PGE2 (0.5 micrograms/ml). Also, pretreatment with PGE2 (0.5 microgram/ml) blocked the action of BK (10 microM), BK (0.1-100 microM) stimulated PI hydrolysis and cAMP production in a dose-dependent manner. Both the PI and the cAMP responses were inhibited by indomethacin (30 microM), as was the calcium response. BK (0.01-10 microM) also stimulated release of arachidonic acid and its metabolites dose-dependently. However, prolonged exposure to BK in serum-deficient medium did not exert any effect on DNA synthesis. RDP 4-1 cells, therefore, appear to respond to BK with increased cAMP production. PI hydrolysis and calcium mobilization. The inhibition of these effects of BK by indomethacin raises the possibility that cyclo-oxygenase product(s), especially PGE2 or PGE2-like compounds, may be responsible for evoking these effects. These results indicate that BK may stimulate or modulate cell metabolism in the dental pulp.


Identification of novel lysosomal matrix proteins by proteome analysis.
The lysosomal matrix is estimated to contain about 50 different proteins. Most of the matrix proteins are acid hydrolases that depend on mannose 6-phosphate receptors (MPR) for targeting to lysosomes. Here, we describe a comprehensive proteome analysis of MPR-binding proteins from mouse. Mouse embryonic fibroblasts defective in both MPR (MPR 46-/- and MPR 300-/-) are known to secrete the lysosomal matrix proteins. Secretions of these cells were affinity purified using an affinity matrix derivatized with MPR46 and MPR300. In the protein fraction bound to the affinity matrix and eluted with mannose 6-phosphate, 34 known lysosomal matrix proteins, 4 candidate proteins of the lysosomal matrix and 4 non-lysosomal contaminants were identified by mass spectrometry after separation by two-dimensional gel electrophoresis or by multidimensional protein identification technology. For 3 of the candidate proteins, mammalian ependymin-related protein-2 (MERP-2), retinoid-inducible serine carboxypeptidase (RISC) and the hypothetical 66.3-kDa protein we could verify that C-terminally tagged forms bound in an M6P-dependent manner to an MPR-affinity matrix and were internalized via MPR-mediated endocytosis. Hence these 3 proteins are likely to represent hitherto unrecognized lysosomal matrix proteins.


Short-term storage of alginate-encapsulated protocorm-like bodies of Dendrobium nobile Lindl.: an endangered medicinal orchid from North-east India.
Synthetic seed technology is an exciting and rapidly growing area of research as deals with conservation and storage of rare, endangered and desirable genotypes along with its easy handling and transportation. As propagation of many ornamental and medicinally important plant species is labour intensive, application of different growth retardants and osmotica in simple artificial seed system would dramatically reduce labour requirement by storing the germplasm in vitro. Moreover, the primary aim of developing in vitro storage methods is to reduce the frequent demands of subculturing and preserving the unique genetic constituent of the germplasm. Dendrobium nobile is a pharmaceutically important orchid mostly used in the Chinese herbal drug industry for its medicinal property. Commercial exploitation of this species has considerably depleted their population in wild. Hence, for conserving this valuable germplasm, short term in vitro storage of Protocorm-Like Bodies (PLBs) of D. nobile was carried out using different osmotica (sucrose and mannitol). It was observed that incorporation of low sucrose and mannitol (3 and 5 %) in the encapsulating matrix showed almost similar results with that of control. In all these cases, more than half of PLBs burst out from the matrix thus making these concentrations of sucrose and mannitol along with control not suitable for storage studies. However, with the increase in concentration to 7.5 and 12.5 % in the encapsulating matrix, no outburst of encapsulated PLBs was recorded till 60 days of storage; hence it can be concluded that these concentrations play an important role in minimizing the growth of PLBs during storage condition.


Outpatient parenteral anti-infective therapy for skin and soft-tissue infections.
Skin and soft tissue infections (SSIs) are one of the many infectious diseases that can be treated by outpatient parenteral anti-infective therapy (OPAT). Determining whether a patient with SSIs is treated topically, orally, or parenterally depends on the severity of infection and host factors. The decision to hospitalize, initiate, or transition to OPAT with SSIs depends on the medical assessment and consideration of available resources for OPAT. Anti-infective selection depends on the clinical presentation, likely organisms, pharmacodynamics, pharmacokinetics, and drug stability.


Effect of lanthanide ions on the phase behavior of dipalmitoylphosphatidylcholine multilamellar liposomes.
The effect of lanthanide ions (Ln3+) and their coordination compounds of diethylenetriamine pentaacetic acid (DTPA) on the phase behavior of dipalmitoylphosphatidylcholine (DPPC) multi-lamellar liposomes has been studied by differential scanning calorimetry (DSC), Raman spectroscopy, and freeze-fracture electron microscopic techniques. The displacement of Ca2+ binding on DPPC liposomes by lanthanide ions was also studied. The results show that the binding degree of four kinds of chloride salts with DPPC liposomes is: YbCl3 > GdCl3 > LaCl3 > CaCl2. Lanthanide ions increase the phase transition temperature of DPPC liposomes and decrease the membrane fluidity. Freeze-fracture electron microscopic results show that La3+ enhances the order of DPPC membrane. The effect of coordination compounds of lanthanides with DTPA on the phase behavior of DPPC liposomes is smaller than that of their chlorides. La3+, Gd3+, and Yb3+, can displace Ca2+ binding on DPPC liposomes, but there coordination compounds of DTPA can hardly displace Ca2+. Raman spectroscopic results show that a very slight effect in lateral packing order of DPPC liposomes was observed at various concentrations of lanthanides.


The size distribution of organisms in the Celtic Sea: from bacteria to Metazoa.
The main features of the size distribution of pelagic and benthic organisms are described, with particular reference to comprehensive studies at a single station, CS2, in the Celtic Sea. These are: 1. A more or less even distribution of biomass in all size classes of pelagic autotrophs. 2. Five size groups of pelagic heterotrophs separated from each other by roughly 103 differences in individual weight, with three well-defined gaps in the size spectrum between the four smallest size modes. 3. Benthic organisms with three size modes, the microbial peak between the two smallest pelagic modes, the meiofaunal peak between the size of pelagic ciliates and herbivorous macrozooplankton, and the macrobenthic peak at about the same size as the carnivorous macrozooplankton. Differences in the positions of the microbial peaks are thought to be associated with the different nutritional environments of free-living and surface-attached bacteria. Other features of the pelagic heterotroph spectrum are explicable in terms of the known limits to size ratios between prey and predator for suspension feeders. These limits do not apply to the benthos, the size distribution of which is largely determined by physical constraints of the sedimentary environment and the optimisation of size-related life history characteristics. Thus, constraints on body size are entirely different in the two systems, and we see little evidence for coupling between the pelagos and benthos which might result in complementary patterns of size distribution, except perhaps for interactions between the pelagic larvae of macrobenthos and the permanent macrozooplankton at the upper end of the size spectrum.


Effects of dexamethasone on the hypothalamic-pituitary-adrenal axis in preterm infants.
The effects of dexamethasone therapy on the hypothalamic-pituitary-adrenal axis were tested in 10 premature infants with bronchopulmonary dysplasia by means of the corticotropin-releasing hormone stimulation test before therapy and on the seventh day of therapy. Adrenocorticotropic hormone and cortisol levels were determined by radioimmunoassay. There was significant suppression of the hypothalamic-pituitary-adrenal axis after 7 days of a currently used dexamethasone treatment regimen. A site of suppression was located at the level of the pituitary gland.


Sonodynamic antitumour effect of chloroaluminum phthalocyanine tetrasulfonate on murine solid tumour.
The sonodynamically induced antitumour effect of chloroaluminum phthalocyanine tetrasulfonate (AlPcTS) was evaluated on subcutaneously implanted colon 26 carcinoma. A time of 24 h after the administration of AlPcTS was chosen for the ultrasonic exposure, based on the analysis of the AlPcTS concentrations in the tumour, plasma, skin and muscle. The pharmacokinetic analysis showed much faster clearance of AlPcTS than photofrin II from the body, which can be an advantage in view of their potential adverse effects. At an AlPcTS dose not less than 2.5 mg kg(-1) and at a free-field ultrasonic intensity not less than 3 W cm(-2), the synergistic effect between AlPcTS administration and ultrasonic exposure on the tumour growth inhibition was significant. The ultrasonic intensity showed a relatively sharp threshold for the synergistic antitumour effect, which is typical for an ultrasonic effect mediated by acoustic cavitation. These results suggest that AlPcTS is a potential sonosensitizer for sonodynamic treatment of solid tumours.


Anaesthesia for short outpatient procedures. A comparison between thiopentone and propofol in combination with fentanyl or alfentanil.
We studied supplementation of propofol or thiopentone anaesthesia with 0.5 or 1.0 mg alfentanil or 0.05 or 0.1 mg fentanyl for minor gynaecological outpatient procedures. Four hundred patients scheduled for elective termination of pregnancy were randomly allocated to one of eight groups. Induction agent doses, peroperative complications, complaints about pain and emesis during the postoperative period, and time to discharge were studied. Propofol compared to thiopentone was associated with a shorter time to discharge, 103 +/- 28 and 115 +/- 33 minutes respectively (P < 0.05) and anxiety during recovery was more frequent in the thiopentone group (P < 0.05). The need for postoperative reserve analgesics was less in the alfentanil group (P < 0.05). We found, however, no major differences between the supplementations tested regarding the total dose of induction agent, emesis or time to discharge. Supplementation with 1.0 mg of alfentanil to propofol was found to be the best combination tested for short outpatient procedures.


Featureless retina in diabetic retinopathy: Clinical and fluorescein angiographic profile.
"Featureless retina" (FLR) has been only briefly mentioned in textbooks; this deceptively benign appearance of diabetic retinopathy (DR) merits a detailed description. Here we report the clinical profile, diagnosis, and management of FLR. The case records of consecutive type 2 diabetic patients clinically diagnosed as FLR were reviewed. The case selection was based on suggestive signs (white thread-like arterioles and atrophic retina), asymmetric presentation of DR, and fluorescein angiographic (FA) demonstration of retinal capillary nonperfusion (CNP) with/without proliferative disease (PDR). Panretinal photocoagulation (PRP) was performed as needed. The extent of CNP was correlated with diabetic macular ischemia (DMI) and neovascularization on FA, and DMI was correlated with best-corrected visual acuity using Pearson Chi-square test (P < 0.05). IBM SPSS Statistics 26 was used for analysis. Out of 46 patients, 21 (46%) patients had bilateral and 25 (54%) had unilateral involvement (67 eyes with FLR). PDR was clinically discernible in two (3%) eyes; 65 (97%) eyes had clinical features of mild-moderate NPDR. However, FA revealed extensive CNP areas in 49 (73%) and PDR in 59 (88%) eyes. DMI was found in 83% of the eyes which had best-corrected visual acuity <6/12; this association was statistically significant (P = 0.024). Fifty-seven (85%) eyes underwent panretinal photocoagulation (PRP) for extensive CNP or PDR. Behind the mild-moderate clinical profile of FLR lay extensive CNP and PDR, which were unmasked by FA, with a complete overhaul of the treatment and follow-up.


Perception of medical students about courses based on peer-assisted learning in five Peruvian universities.
Peer-assisted learning (PAL) is a supportive strategy in medical education. In Peru, this method has been implemented by few universities. However, there are no consistent studies evaluating their acceptability by medical students. The objective of this study was to evaluate the perception of medical students about PAL in five Peruvian universities. A total of 79 medical students were included in the study. The mean age was 20.1 ± 1.9 years, 54% were female, and 87% were in the first 4 years of study. Most of the students were satisfied with classes and peer teachers. Similarly, most of the students agreed with the interest in developing teaching skills. It was also observed that 97% of students approved to implement PAL in medical education programs.


MicroRNA-1205, encoded on chromosome 8q24, targets EGLN3 to induce cell growth and contributes to risk of castration-resistant prostate cancer.
The chromosome 8q24.21 locus, which contains the proto-oncogene c-MYC, long non-coding RNA PVT1, and microRNAs (miRs), is the most commonly amplified region in human prostate cancer. A long-range interaction of genetic variants with c-MYC or long non-coding PVT1 at this locus contributes to the genetic risk of prostate cancer. At this locus is a cluster of genes for six miRs (miR-1204, -1205, -1206, -1207-3p, -1207-5p, and -1208), but their functional role remains elusive. Here the copy numbers and expression levels of miRs-1204-1208 were investigated using quantitative PCR for prostate cancer cell lines and primary tumors. The data revealed that copy numbers and expression of miR-1205 were increased in both castration-resistant prostate cancer cell lines and in primary tumors. In castration-resistant prostate cancer specimens, the copy number at the miR-1205 locus correlated with the expression of miR-1205. Furthermore, functional analysis with an miR-1205 mimic, an miR-1205 inhibitor, and CRISPR/Cas9 knockout revealed that, in human prostate cancer cells, miR-1205 promoted cell proliferation and cell cycle progression and inhibited hydrogen peroxide-induced apoptosis. In these cells, miR-1205 downregulated the expression of the Egl-9 family hypoxia inducible factor 3(EGLN3) gene and targeted a site in its 3'-untranslated region to downregulate its transcriptional activity. Thus, by targeting EGLN3, miR-1205 has an oncogenic role and may contribute to the genetic risk of castration-resistant prostate cancer.


The function of Scox in glial cells is essential for locomotive ability in Drosophila.
Synthesis of cytochrome c oxidase (Scox) is a Drosophila homolog of human SCO2 encoding a metallochaperone that transports copper to cytochrome c, and is an essential protein for the assembly of cytochrome c oxidase in the mitochondrial respiratory chain complex. SCO2 is highly conserved in a wide variety of species across prokaryotes and eukaryotes, and mutations in SCO2 are known to cause mitochondrial diseases such as fatal infantile cardioencephalomyopathy, Leigh syndrome, and Charcot-Marie-Tooth disease, a neurodegenerative disorder. These diseases have a common symptom of locomotive dysfunction. However, the mechanisms of their pathogenesis remain unknown, and no fundamental medications or therapies have been established for these diseases. In this study, we demonstrated that the glial cell-specific knockdown of Scox perturbs the mitochondrial morphology and function, and locomotive behavior in Drosophila. In addition, the morphology and function of synapses were impaired in the glial cell-specific Scox knockdown. Furthermore, Scox knockdown in ensheathing glia, one type of glial cell in Drosophila, resulted in larval and adult locomotive dysfunction. This study suggests that the impairment of Scox in glial cells in the Drosophila CNS mimics the pathological phenotypes observed by mutations in the SCO2 gene in humans.


Integrative approaches in genome structure analysis.
New technological advances in integrated imaging, sequencing-based assays, and computational analysis have revolutionized our view of genomes in terms of their structure and dynamics in space and time. These advances promise a deeper understanding of genome functions and mechanistic insights into how the nucleus is spatially organized and functions. These wide arrays of complementary data provide an opportunity to produce quantitative integrative models of nuclear organization. In this article, we highlight recent key developments and discuss the outlook for these fields.


Temporal scope influences ecosystem driver-response relationships: A case study of Lake Erie with implications for ecosystem-based management.
Understanding environmental driver-response relationships is critical to the implementation of effective ecosystem-based management. Ecosystems are often influenced by multiple drivers that operate on different timescales and may be nonstationary. In turn, contrasting views of ecosystem state and structure could arise depending on the temporal perspective of analysis. Further, assessment of multiple ecosystem components (e.g., biological indicators) may serve to identify different key drivers and connections. To explore how the timescale of analysis and data richness can influence the identification of driver-response relationships within a large, dynamic ecosystem, this study analyzed long-term (1969-2018) data from Lake Erie (USA-Canada). Data were compiled on multiple biological, physical, chemical, and socioeconomic components of the ecosystem to quantify trends and identify potential key drivers during multiple time intervals (20 to 50 years duration), using zooplankton, bird, and fish community metrics as indicators of ecosystem change. Concurrent temporal shifts of many variables occurred during the 1980s, but asynchronous dynamics were evident among indicator taxa. The strengths and rank orders of predictive drivers shifted among intervals and were sometimes taxon-specific. Drivers related to nutrient loading and lake trophic status were consistently strong predictors of temporal patterns for all indicators; however, within the longer intervals, measures of agricultural land use were the strongest predictors, whereas within shorter intervals, the stronger predictors were measures of tributary or in-lake nutrient concentrations. Physical drivers also tended to increase in predictive ability within shorter intervals. The results highlight how the time interval examined can filter influences of lower-frequency, slower drivers and higher-frequency, faster drivers. Understanding ecosystem change in support of ecosystem-based management requires consideration of both the temporal perspective of analysis and the chosen indicators, as both can influence which drivers are identified as most predictive of ecosystem trends at that timescale.


Ten-year prospective follow-up study on the relationship between Helicobacter pylori infection and progression of atrophic gastritis, particularly assessed by endoscopic findings.
To ascertain the progression of atrophic gastritis due to Helicobacter pylori infection, we conducted a 10-year prospective follow-up study with annual endoscopy of the stomach. Prospective endoscopic observation was started in 53 subjects in 1989 and 1990 after informed consent was obtained. The progression of atrophic gastritis was evaluated mainly by the endoscopic pattern of atrophy. Histological assessment was performed on biopsy specimens taken from the lesser curvature of the lower corpus. By 2000, 43 patients (20 males, 23 females, mean age 56.7 years at entry) had completed at least 10 years of endoscopic follow-up. Eight H. pylori-negative patients with normal fundic mucosa showed no change endoscopically or histologically. In 35 H. pylori-positive patients, the progression of histological atrophy was observed in 46% and intestinal metaplasia was observed in 49%. Fifteen of 35 H. pylori-positive cases exhibited a cephaloid shift of the endoscopic atrophic border. The cephaloid shift of the atrophic area occured suddenly. The cumulative progression rate of atrophic patterns was 6% after 2 years, 22% after 4 years, 34% after 6 years and 43% after 10 years. These atrophic changes were related to neutrophil infiltration. The progression of atrophic gastritis is a result of chronic active gastritis caused by H. pylori infection.


Developmental patterns of plasma TSH, T4 and T3 in rats deprived of light from birth.
Plasma levels of TSH, T4 and T3 in the rat show characteristic developmental patterns within the first postnatal month, with TSH reaching a peak on day 13, T4 on day 16 and T3 on day 20. In dark-reared rats, a significant reduction in plasma T3 associated with low plasma T4 as well as high plasma TSH suggest that light-deprivation from birth impairs and/or delays maturation of pituitary-thyroid axis.


Meta-analysis of hearing outcomes of chronic otitis media surgery in the only hearing ear.
To assess the hearing outcomes of surgery for patients with chronic otitis media (COM) with or without cholesteatoma in case of the only hearing ear (OHE). This meta-analysis included COM patients with hearing in only one ear. The PubMed, Scopus, and Cochrane databases were reviewed. Thirteen studies were included, 252 excluded. The total number of operated ears was 229. The patients' ages ranged from 6 to 78 years. A change greater than 10 dB in hearing thresholds in the OHE was considered as a significant result. When both the COM with (cCOM) and without cholesteatoma (ncCOM) cases were considered, the air bone gap (ABG), air conduction (AC) and bone conduction (BC) thresholds were stable or improved in 91.06% (95% CI:81.94-97.19%), 87.91% (82.14-92.34%), and 94.99% (95% CI:90.20-97.97%) of patients, respectively. Stable or improved ABG, AC and BC thresholds were observed in 92.36% (95% CI:81.67-97.86%), 87.36% (95% CI:71.46-96.23%), and 94.85% (95% CI:81.36-99.49%) of those with ncCOM, respectively. For patients with cCOM, the results were 85.96% (95% CI:81.36-99.49%), 85.20% (95% CI:76.04-91.87%), and 97.01% (95% CI:89.62-99.63%), respectively. There were no significant differences in these thresholds between either category. Hearing deterioration in AC and BC thresholds can be expected in about 13-15% and 5-3%, respectively, of patients, with ncCOM or cCOM. Our results should not be construed as a guide for determining surgery eligibility in patients with COM in the OHE.


Review of -omics studies on mosquito-borne viruses of the Flavivirus genus.
Arboviruses are transmitted by arthropods (arthropod-borne virus) which can be mosquitoes or other hematophagous arthropods, in which their life cycle occurs before transmission to other hosts. Arboviruses such as Dengue, Zika, Saint Louis Encephalitis, West Nile, Yellow Fever, Japanese Encephalitis, Rocio and Murray Valley Encephalitis viruses are some of the arboviruses transmitted biologically among vertebrate hosts by blood-taking vectors, mainly Aedes and Culex sp., and are associated with neurological, viscerotropic, and hemorrhagic reemerging diseases, posing as significant health and socioeconomic concern, as they become more and more adaptive to new environments, to arthropods vectors and human hosts. One of the main families that include mosquito-borne viruses is Flaviviridae, and here, we review the case of the Flavivirus genus, which comprises the viruses cited above, using a variety of research approaches published in literature, including genomics, transcriptomics, proteomics, metabolomics, etc., to better understand their structures as well as virus-host interactions, which are essential for development of future antiviral therapies.


The predictive performance of the bipolarity index in a Dutch epidemiological sample manuscript.
No instrumnt exists that can predict the incidence of bipolar disorders (BD). The Bipolarity index (BI), originally developed to improve diagnostic confidence for a lifetime diagnosis of BD, may predict incident BD. To assess the predictive performance of the BI for incident BD in persons with a lifetime depression. The BI score was composed from different questionnaires and interviews in n = 1857 subjects without BD and with a lifetime unipolar depressive disorder from the Netherlands Study of Depression and Anxiety, a longitudinal cohortstudy. The incidence of DSM-IV defined BD I or II as a criterion diagnosis was established with the Composite International Diagnostic Interview after 2, 4, 6 and 9 years of follow-up. Cox regression analyses calculated whether the BI predicts incident BD during 9-years of follow-up. The area Under the Curve (AUC) was determined. At the optimal cut-off score, sensitivity, specificity, positive, and negative predictive values (PPV and NPV) were calculated. Over the course of 9 years, bipolar conversion occurred in n = 46 subjects (2.5%). Each point increase in BI score significantly predicted incident BD (HR[95%CI]= 1.047[1.018-1.076], p = 0.001). The AUC was 0.61 (95%CI: 0.54-0.68). At the optimal cut-off of 30, sensitivity was 67%, specificity 52%, PPV 3% and NPV 98%. Not all items of the BI were fully covered; mean age of the sample of 42. The BI score predicts bipolar conversion over 9 years in those with a lifetime depression. However, given the modest performance metrics, the BI cannot guide clinical decision making yet.


Spontaneous resolution of pulmonary stenosis.
Pulmonary stenosis diagnosed in infancy usually increases in severity with age or, if it is mild, may remain so for many years. We report the case of a child in whom moderately severe pulmonary stenosis in infancy appeared to completely resolve by the age of 8 years.


Melanoma-prone families: new evidence of distinctive clinical and histological features of melanomas in CDKN2A mutation carriers.
Germline mutations on the CDKN2A gene, the most important known genetic factors associated with cutaneous melanomas (CMs), predispose carriers to multiple primary CMs (MPMs) with higher frequency and younger onset compared to non-carriers. Most of the largest published studies concerning clinical and histological characteristics of CMs with CDKN2A mutation carriers did not specify if the described CMs are first or subsequent to the first, and they used sporadic CMs from non-genotyped patients as controls. We conducted a single-centre observational study to compare clinical and histological CM features of 32 unrelated carriers (MUT) of 5 germline CDKN2A mutations (one of which was never previously described) compared to 100 genotyped wild-type (WT) patients. We stratified the data based on time of diagnosis, anatomical site and histological subtype of CMs, demonstrating several significant unreported differences between the two groups. MUT developed a higher number of dysplastic nevi and MPMs. We proved for the first time that anatomical distribution of CMs in MUT was independent of gender, unlike WTs. MUTs developed in situ and superficial spreading melanomas (SSMs) more frequently, with significantly higher number of SSMs on the head/neck. In MUTs, Breslow thickness was significantly lower for all invasive CMs. When CMs were stratified on the basis of the time of occurrence, statistical significance was maintained only for SSMs subsequent to the first. In WTs, Clark level was significantly higher, and ulceration was more prevalent than in MUTs. Significant differences in ulceration were observed only in SSMs. In nodular CMs, we did not find differences in terms of Breslow thickness or ulceration between WTs and MUTs. In situ CMs developed 10 years earlier in MUTs with respect to WTs, whereas no significant differences were observed in invasive CMs. In contrast to those reported previously by other authors, we did not find a difference in skin phototype.


Convergence of somatic and visual afferent impulses in the Wulst of pigeon.
In 79 pigeons, unit discharges of Wulst neurons responding to bilateral stimulation of N. radialis and N. sciaticus and to bilateral light flashes were recorded. Of 178 such neurons, 55 showed multisensory convergence of various types: 40 of these were somatic convergent neurons, characterized as 3 types; three were binocular convergent cells; and twelve were bimodal (visual-somatosensory) convergent neurons. Of these neurons, the convergent action was either inhibitory or excitatory. These results suggest that the Wulst may function as an important centre for integrating visual and somatic sensory information.


N-(phosphonacetyl)-L-aspartate and calcium leucovorin modulation of fluorouracil administered by constant rate and circadian pattern of infusion over 72 hours in metastatic gastrointestinal adenocarcinoma.
We have reported that N-(phosphonacetyl)-L-aspartic acid (PALA) 1266 mg/m2 can safely be given 24 hours prior to the start of a 72-hour infusion of fluorouracil (FUra) and leucovorin (LV) at doses of 2000 and 500 mg/m2/day. Since inhibition of aspartate carbamoyltransferase (ACTase) activity was evident 4 hours post PALA, we wished to evaluate PALA given 1 hour prior to FUra. Further, we studied the toxicity and pharmacokinetics with FUra given by either fixed- or variable-rate infusion. Twenty-seven patients with gastrointestinal tract adenocarcinomas were treated with PALA 1266 mg/m2/15 min followed by a 72-hour infusion of FUra and LV (1750 & 500 mg/m2/day) given by fixed- or variable-rate (peak at 4:00 A.M.). Clinical toxicity was similar in two consecutive cycles in 17 patients receiving fixed- and variable-rate infusion at the same FUra dose. Overall, grade 3 stomatitis and hand-foot syndrome occurred in 12% and 4% patients receiving fixed- and in 16% and 10.5% of patients receiving variable-rate infusions. Six of 24 evaluable patients (25%) had a partial response. The profile of FUra plasma levels (Cp) over a 24-hour period during fixed- and variable-rate infusions were strikingly different, but the average Cp and area under the concentration-time curves were comparable. ACTase activity was significantly decreased at 4 and 24 hours after PALA (12% and 18% of baseline; P < 0.001), but enzyme activity had recovered to 40% by 72 hours. This regimen was active and well tolerated with similar toxicities with FUra given by either fixed- or variable rate infusion. PALA 1266 mg/m2 significantly inhibited ACTase activity for at least 24 hours.


Obstetric decision-making and counseling at the limits of viability.
The purpose of this study was to examine factors that influence obstetric decision-making and counseling for periviable deliveries and to describe counseling challenges. Twenty-one semistructured interviews were conducted with obstetricians who were recruited from 5 academic medical centers in Philadelphia. Two trained reviewers independently coded transcripts using grounded theory methods. Research software facilitated qualitative analysis. Circumscribed by institutional norms and clinical acuity, obstetric decision-making and counseling were influenced primarily by patient preferences. Perspectives on patient autonomy guided approaches to counseling. Thresholds for intervention varied from "attending to attending" and "institution to institution." Sociodemographic factors were not believed to influence clinical decision-making. However, obstetricians admittedly managed in vitro fertilization pregnancies more aggressively. Communicating uncertainty, managing expectations, assessing understanding, and relaying consistent messages across specialties were frequently described counseling challenges for obstetricians. The impact of institutional variation and in vitro fertilization on periviable decision-making warrants further consideration. Interventions to train and support obstetricians in communicating uncertainty, managing expectations, and assessing values and understanding are needed.


Subnanogram GC/NPD method for the determination of sparteine in biological fluids.
A gas chromatographic method is presented for identification and quantification of sparteine in biological fluids using cyclizine as an internal standard. No derivation is necessary and after a single alkaline extraction, GC analysis of sparteine is achieved in less than 8 min. A subnanogram limit of detection is allowed by the use of a nitrogen phosphorous detector (NPD). This method is simple, reproducible, selective, and applicable in both clinical and pharmacokinetic studies.


Myeloproliferative neoplasms in adolescents and young adults.
Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders commonly diagnosed in the seventh decade of life. With increasing access to blood surveillance, the number of adolescent and young adults (AYAs) diagnosed with MPNs is increasing. AYAs represent a unique cohort of MPN patients with differing challenges and psychosocial needs. The majority of AYA patients are females diagnosed with essential thrombocythaemia and most are asymptomatic at diagnosis. There is a striking predisposition to venous thrombotic events with a significant number experiencing splanchnic venous thrombosis (up to 70% of venous events). When compared to older patients, AYAs appear to have an indolent disease course. Interferon is the preferred cytoreductive agent in this population; indications for commencing treatment mirror those of older adults and are determined by the presence of high-risk features for thromboembolic events.


[Stimulated repopulation as a basis of antimutagenesis and the adaptive response in plants].
Wheat seeds were used to study (1) modification of the radiation adaptive response (AR) with antioxidant anphen and (2) modification of the clustogenic effect of N-methyl-N-nitrosourea (MNU) with various agents. Pretreatment with anphen enhanced AR. Each pretreatment (irradiation with 0.25 Gy, treatment with anphen, treatment with anphen followed by irradiation with 0.25 Gy) decreased aberration frequency. This parameter proved to be in a linear dependence with mitotic index (MI) with correlation coefficient -0.978; the regression line passed through the point corresponding to spontaneous MI and spontaneous aberration frequency. Upon treatment with MNU, the antimutagenic effect was observed for various pretreatments (a low concentration of MNU, antioxidant phenoxan, irradiation with 0.25 Gy). Again, MI and aberration frequency were in inverse proportion with correlation coefficient -0.99, and the regression line passed through the point with spontaneous MI and spontaneous aberration frequency. The same dependence was observed for previously published data on modification of radiation AR with phenoxan. The results were hard to explain in terms of the repair-associated mechanism of AR and the antimutagenic effect. Hence, a nonspecific inducible process of stimulated repopulation was assumed to be a common mechanism of AR and the antimutagenic effect in plants.


Major determinant factors of the extent of interaction between grapefruit juice and calcium channel antagonists.
To evaluate quantitatively the influence of bioavailability and plasma unbound fraction (f(u)) on the extent of interaction between grapefruit juice (GFJ) and calcium antagonists. The extent of drug-GFJ interaction was evaluated from reported clinical interaction studies of 11 calcium antagonists. The relationship between extent of interaction and bioavailability or f(u) was analysed. The following significant hyperbolic relationships were observed: [Extent] = 12.2/[bioavailability] + 1 and [Extent] = 0.718/[f(u)] + 1. Bioavailability and f(u) are major determinant factors of calcium antagonist-GFJ interaction: a drug with smaller bioavailability or lower f(u) is likely to exhibit a more potent interaction, and vice versa.


Pathologist's puzzle: Membranoproliferative glomerulonephritis-like features in cryoglobulinemic glomerulonephritis.
Mixed cryoglobulinemia is commonly related to chronic HCV infection, and renal complications occur frequently. Typical renal involvement presents with diffuse proliferative glomerular pathology, similar to membranoproliferative glomerulonephritis, with necrotizing arteritis of medium-sized vessels, referred to as cryoglobulinemic glomerulonephritis. However, the histological appearance may vary according to the clinical presentation and treatment applied. Not only membranoproliferative glomerulonephritis but also certain types of systemic vasculitis (Systemic Lupus Erythematosus, Polyarteritis Nodosa), thrombotic microangiopathy, and Waldenstrom's Macroglobulinemia may exhibit similar histopathological findings in the biopsy with cryoglobulinemic glomerulonephritis. For an optimal differential diagnosis, clinicopathological correlation and serological findings should accompany the pathological findings. We present a case of cryoglobulinemic glomerulonephritis, and discuss the differential diagnosis in detail.


Did the Long-Term Care Physician Workforce Change During the Pandemic? Describing MRP Trends in Ontario, Canada.
To examine the practice patterns and trends of long-term care (LTC) physicians between 2019 and 2021 in Ontario, Canada. Population-level descriptive time trend study. Most responsible physicians (MRPs) of LTC residents of publicly funded LTC homes in Ontario, Canada, from September 2019 to December 2021. We examined the number of MRPs in publicly regulated Ontario LTC homes before and during the COVID-19 pandemic using population-level administrative databases. Characteristics of MRPs and practice patterns were generated at baseline and across distinct time periods of the pandemic in descriptive tables. We created a Sankey diagram to visualize MRP practice changes over time. More than one-quarter of pre-pandemic MRPs were no longer MRPs by the end of 2021, although most continued to practice in non-LTC settings. There was a decrease from 1444 to 1266 MRPs over time. Other characteristics of MRPs remained stable over the pandemic time periods. At baseline, LTC physicians were MRP for an average of 57.3 residents. By the end of 2021, this caseload decreased to 53.3 residents per MRP. MRPs increasingly billed monthly management compensation fees over the fee-for-service model across the pandemic time periods. The number of MRPs working in an LTC home shifted to fewer MRPs per home. MRP demographic characteristics did not change over the course of the pandemic. The observed shifts in practice patterns showed a reduction in the overall LTC MRP workforce, who delivered care to fewer residents on average in LTC homes with fewer colleagues to rely on. Future work can study how changes to LTC MRPs' practice patterns impact physician coverage, access and continuity of care, and health services and quality outcomes among residents.


Transcriptomic and metabolomic analyses reveal several critical metabolic pathways and candidate genes involved in resin biosynthesis in Pinus massoniana.
Pine resin, which typically consists of terpenoids, is a natural product used in various industrial applications. Oleoresin can be obtained from the xylem tissue by wounding the stem bark. Pinus massoniana (masson pine) is an important resin-tapping tree species that originated in southern China. Masson pines with different genetic backgrounds typically have different resin-yielding capacities (RYCs). However, the mechanisms underlying high resin yield in masson pines are unclear. The aim of this study was to identify the possible genetic regulation pathways and functional genes that influence the resin yield. In this study, we conducted transcriptomic and metabolomic studies of masson pine secondary xylem with high, medium, and low RYCs. A total of 230,068 unigenes and 3894 metabolites were identified from the tissue of the secondary xylem. Several differentially expressed regulation factors, including WRKY, bHLH, and ERF, and functional genes such as PKc and LRR-RLKs, were identified among these masson pines. The Kyoto Encyclopedia of Genes and Genomes pathways were mainly focused on diterpenoid biosynthesis, plant hormone signal transduction, and ABC transporters. Furthermore, integration of the transcriptomic and metabolomic data indicated that the PKc- and LRR-RLK-related regulatory and metabolic pathways may play critical roles in the biosynthesis of terpenoids. These above results improve our understanding of the biosynthesis mechanism of oleoresin in P. massoniana and facilitate further research work into the functional analysis of these candidate genes.


Hippocampal theta rhythm persists in the permanently isolated forebrain of the cat.
In cats with high mesencephalic transections surviving for up to 90 days, the hippocampal EEG shows exaggerated percentages of 3-5 Hz theta activity. The theta rhythm has similar waveform and frequency characteristics to that seen in the intact cat and can be selectively enhanced or abolished by systemic physostigmine or atropine respectively. These data demonstrate (1) that the caudal brainstem is not essential for the spontaneous appearance of the hippocampal theta rhythm, and (2) the integrity of a major cholinergic system in the chronically isolated forebrain.


Climate change has indirect effects on resource use and overlap among coexisting bird species with negative consequences for their reproductive success.
Climate change can modify ecological interactions, but whether it can have cascading effects throughout ecological networks of multiple interacting species remains poorly studied. Climate-driven alterations in the intensity of plant-herbivore interactions may have particularly profound effects on the larger community because plants provide habitat for a wide diversity of organisms. Here we show that changes in vegetation over the last 21 years, due to climate effects on plant-herbivore interactions, have consequences for songbird nest site overlap and breeding success. Browsing-induced reductions in the availability of preferred nesting sites for two of three ground nesting songbirds led to increasing overlap in nest site characteristics among all three bird species with increasingly negative consequences for reproductive success over the long term. These results demonstrate that changes in the vegetation community from effects of climate change on plant-herbivore interactions can cause subtle shifts in ecological interactions that have critical demographic ramifications for other species in the larger community.


Morphological Asymmetry of Pelvic Rings: A Study Based on Three-Dimensional Deviation Analysis.
To evaluate the morphological asymmetry of pelvic rings existing in healthy individuals in terms of three-dimensional (3D) geometric shapes. This study was a retrospective self-control study. CT images of healthy pelvises, scanned from Jan 2014 to Jan 2019, were taken from 159 subjects (88 males and 71 females) aged 20 to 59 years (39.1 ± 8.7 years). Digital pelvic ring models were reconstructed from CT images and then flipped over the corresponding sagittal planes to obtain their mirrored models. A 3D deviation analysis of a pelvic ring was conducted between the original model and its mirrored model via model registration and quantification of the geometric differences. Next, the pelvic rings were split to the left and right hipbones. The same flipping procedures as done by pelvic rings were performed for left hipbones to obtain their mirrored models. A 3D deviation analysis was also performed between the left and right hip bones. Quantitative variables representing deviation mainly included the average deviation (AD) and the maximum deviation (MD). MDs over 4 mm and 10 mm were deemed as critical levels for evaluating the severity of asymmetry as per Matta's scoring system. The quantitative assessments of the asymmetry covered pelvic rings, bilateral hip bones and the specific anatomic regions of a hip bone. 157 out of 159 pelvic rings (98.74%) had more than 4 mm of the MD and 27 (16.98%) of them exceeded 10 mm of the MD. The MD of pelvic rings was 1.23 times as high as that for the bilateral hip bones (7.46 mm vs. 6.08 mm, P < 0.05). The ADs of pelvic rings and bilateral hip bones were 1.28 mm and 0.94 mm, respectively (P < 0.05); 2.27% of the surface points of a pelvic ring had more than 4 mm geometric deviations compared with its mirrored model, while 0.59% (P < 0.05) of bilateral hip bones were on the same level of deviation. 119 out of 159 pelvic iliac crests (74.8%) had MDs more than 4 mm, and 15 (9.4%) reached 10 mm or more. Only 15 (9.4%) pelvises presented asymmetric features in the area of obturator foramen where the MDs exceeded 4 mm. Pelvic asymmetry exists in the general population, but 3D geometric symmetry is present in specific anatomic regions. It implies that restoring the 3D symmetry of specific anatomic regions is more reliable than "restoring the symmetry of pelvic ring" in pelvic ring reduction or pelvic fixation design.


Determinants of maternal length of stay following childbirth in a rural health facility in Eritrea.
The days following childbirth are a critical phase in the lives of mothers and newborns. Postpartum length of stay is a critical indicator of the efficiency of health care delivery. This study aims to explore maternal length of hospital stay (LOS) following childbirth and associated factors in a rural health facility in Eritrea. A retrospective study of all mothers who delivered at Nakfa Hospital between 2020 and 2022 was conducted. Sociodemographic, past obstetric, and neonatal factors associated with postpartum LOS were evaluated for both vaginal delivery (VD) and cesarean delivery (CD). The determinants of LOS following VD were explored using negative binomial regression. A total of 2025 mothers [1975 (97.5%) VD and 50 (2.5%) CD] were included in the study. The median LOS following childbirth was 1 (IQR: 0-1) day for VD and 6 (IQR: 4-8) days for CD. A substantial proportion of mothers were found to have inadequate stays following VD [29% (95% CI: 27-31)], whereas 68% (95% CI: 54-81%) stayed for > 4 days following CD. In this study, VD that were attended by physicians had no inadequate stay, whereas 27.4% of deliveries attended by midwives and 31.3% by associate nurses resulted in inadequate stay (P-value < 0.001). Determinants of LOS following VD were: the presence of maternal complications (IRR = 2.8, 95% CI: 1.6-5, p-value < 0.001), delivery years 2020 and 2021 (IRR = 1.5, 95% CI: 1.2-1.8, p-value < 0.001 and IRR = 1.4, 95% CI: 1.2-1.7, p-value < 0.001, respectively), and delivery hour interval 23:00-7:00 (IRR = 0.8, 95% CI: 0.7-0.9, p-value = 0.03). A substantial proportion of mothers stay too short post-VD to allow adequate postnatal care, which can have untoward consequences for maternal and child health. Going forward, improved coverage of antenatal care for early diagnosis of maternal complications in pregnancy as well as assessing the level of knowledge and provisions of training and refresher courses for birth attendants should be worked upon. In addition, efforts to conduct studies that explore maternal and health care provider perspectives on LOS should be emphasized.


Whole-cell pertussis vaccine (DTwP) has no influence on allergic diseases and atopic sensitization in children.
Vaccine opponents indicate that the infant's immune system is inadequately developed to handle multiple vaccines which may overwhelm the immune system, leading to allergic diseases. To verify the association between the vaccine antigen overload derived from DTwP and the development of atopic sensitization and allergic diseases. Data from an earlier established birth cohort in Krakow, followed up to the 6th year of life were used. Allergic diseases such as eczema, hay fever and asthma were diagnosed by a physician and reported every half a year from the 1st to 6th year of life by the child's parent. Skin prick tests (SPT) were performed in children at 5 years of age. The data on infants' vaccination were extracted from the physician's records. The status of vaccine antigen exposure was based on different types of vaccines against pertussis (DTwP or DTaP) in a primary course. Results were determined by multiple logistic regression, adjusted to potential confounders. The analyzed population consisted of 234 children: 53.4% - boys and 46.6% - girls. Infants up to the age of 8 months were vaccinated with the primary course against pertussis, with DTwP - 60.7%, DTaP - 32.9% and further 6.4% with a mixed course (DTwP + DTaP). There were no significant relationships between any of vaccination groups and allergic disease and allergen sensitivity in the multiple logistic regression model with adjustment to potential confounders. The exposure to a large number of vaccine antigens derived from DTwP has no influence on the development of allergic diseases and atopic sensitization in children.


Phenotyping and genotyping studies of thiopurine S-methyltransferase in Kazaks.
This study was conducted to investigate the thiopurine S-methyltransferase (TPMT) activity distribution and gene mutations in Kazaks, and compared the results with those of other ethnic groups. Erythrocyte TPMT activity was measured in Kazaks (n = 327) via a validated high-performance liquid chromatography assay. Polymerase chain reaction-based methods were used to analyze three commonly reporter-inactivating mutations: G238C, G460A, and A719G. Unimodal distribution of TPMT activity was found in Kazaks. Six TPMT*3C heterozygotes and two TPMT*3A heterozygotes were found in 327 Kazaks, with allele frequencies of 0.9 and 0.3%, respectively. The subjects with TPMT*3A and TPMT*3C heterogygotes had substantial TPMT activity over the range of 6.40-11.75 U/ml RBC. Unlike in most Caucasians, TPMT*3C is a common mutant allele in Kazaks, whereas TPMT*3A is a rare mutant allele. Further studies are needed to explore the clinical impact of these TPMT mutants to thiopurine therapy in Kazak patients.


Liver metastasectomy-cytoreductive surgery- hyperthermic intraperitoneal chemotherapy and ileal pouch-anal anastomosis: A case report.
Cytoreductive surgery (CRS) with hyperthermal intraperitoneal chemotherapy (HIPEC) are established treatments for peritoneal carcinomatosis that prolong survival in carefully selected patients. At the time of diagnosis, 4-7% of patients with colorectal cancer (CRC) have metastasis to the peritoneum. There is a lack of evidence in the literature if J-pouch can be applied simultaneously with HIPEC to improve quality of life in patients with familial adenomatous polyposis syndrome (FAP) and peritoneal carcinomatosis. We describe a case of a 41-year-old Caucasian male with Familial Adenomatous Polyposis which was diagnosed as metastatic colorectal cancer in the liver and peritoneum. He was treated with systemic chemotherapy followed by total proctocolectomy with a J-shaped IPAA, liver metastasectomy, right hemidiaphragm resection, CRS and HIPEC. CRS and HIPEC have been implicated with high morbidity and mortality rates. A major independent risk factor correlated with high morbidity is anastomotic failure. J-Pouch formation although considered a technique with high complication rates, improves the quality of life of patients after total proctocolectomy and is related to high patient satisfaction. There are inconclusive data on whether anastomotic failure rates are higher when performing J-Pouch and HIPEC together. J-Pouch after CRS and HIPEC can be offered as a treatment as long as the patient is carefully selected, in high volume centers with experienced surgeons.


Characterizing the general chelating affinity of serum protein fetuin for lanthanides.
Fetuin is an abundant blood protein that participates in multiple biological processes, including the transport and regulation of calcium. Fetuin is also known to have a high affinity for uranium (as the uranyl dioxo cation) and plutonium, thus it has been suggested as one of the main endogenous chelating biomolecules involved in the transport of actinides following an internal uptake event. Nevertheless, no direct measurements of its affinity for f-elements beside these two actinides have been reported. Here, we investigate the interaction between fetuin and trivalent lanthanides, such as samarium, europium, terbium, and dysprosium, by mass spectrometry and fluorescence spectroscopy. Mass spectrometry results indicated that fetuin has four metal binding sites for the metal ions studied. Upon formation, the metal-protein complexes showed luminescence emission as a result of antenna sensitization of the metal ions, whose photophysics were characterized and exploited to perform direct spectrofluorimetric titrations. Furthermore, the thermodynamic constants were calculated for all complexes, confirming the formation of stable complexes with log [Formula: see text] values between 26 and 27. In characterizing the affinity of the serum protein fetuin for several f-elements, this study expands upon the initial findings focused on uranyl and plutonium, and contributes to a better understanding of the internal distribution and deposition of lanthanides, potentially representative of trivalent actinides.


Learned spatiotemporal correlation priors for CEST image denoising using incorporated global-spectral convolution neural network.
To develop a deep learning-based method, dubbed Denoising CEST Network (DECENT), to fully exploit the spatiotemporal correlation prior to CEST image denoising. DECENT is composed of two parallel pathways with different convolution kernel sizes aiming to extract the global and spectral features embedded in CEST images. Each pathway consists of a modified U-Net with residual Encoder-Decoder network and 3D convolution. Fusion pathway with 1 × 1 × 1 convolution kernel is utilized to concatenate two parallel pathways, and the output of DECENT is noise-reduced CEST images. The performance of DECENT was validated in numerical simulations, egg white phantom experiments, and ischemic mouse brain and human skeletal muscle experiments in comparison with existing state-of-the-art denoising methods. Rician noise was added to CEST images to mimic a low SNR situation for numerical simulation, egg white phantom experiment, and mouse brain experiments, while human skeletal muscle experiments were of inherently low SNR. From the denoising results evaluated by peak SNR (PSNR) and structural similarity index (SSIM), the proposed deep learning-based denoising method (DECENT) can achieve better performance compared to existing CEST denoising methods such as NLmCED, MLSVD, and BM4D, avoiding complicated parameter tuning or time-consuming iterative processes. DECENT can well exploit the prior spatiotemporal correlation knowledge of CEST images and restore the noise-free images from their noisy observations, outperforming state-of-the-art denoising methods.


Immunocytochemical evidence suggesting heterogeneity in the population of sea urchin egg cortical granules.
Unfertilized eggs of many species of animals contain cortical granules, which are specialized secretory granules that upon fertilization release their contents from the egg. The unfertilized eggs of the sea urchin, Strongylocentrotus purpuratus, contain cortical granules that all display an identical and elaborate internal morphology. It has been assumed that they all contain identical components. In this report we present immunocytochemical data which indicate that the cortical granule population of S. purpuratus eggs is heterogeneous. Two monoclonal antibodies are shown to react to the spiral lamellae region of approximately 20% of the cortical granules, implying that the contents of the reactive granules differ from the contents of the majority of the population. An egg protein of greater than 320 kDa is recognized by the antibody. These antibodies also stain a 130-kDa protein expressed on the surface of primary mesenchyme cells in later development. Both antibodies recognize a post-translational modification of this protein. This suggests that an antigenically similar epitope is present both on the 130-kDa primary mesenchyme cell-specific protein and in the cortical granules. To determine if the primary mesenchyme and cortical granule proteins are related, a fusion protein antibody specific for a region of the 130-kDa protein was used to stain unfertilized eggs. This antibody did not stain cortical granules. Thus, 20% of the cortical granules contain a molecule that has an epitope antigenically similar to the post-translational modification recognized in primary mesenchyme cells by the monoclonal antibodies.


Restoration of polluted waters by phytoremediation using Myriophyllum aquaticum (Vell.) Verdc., Haloragaceae.
The present study assessed the reduction of nutrients and organic matter in polluted waters using Myriophyllum aquaticum. Twelve experimental groups were established and distributed in six control groups (CG) and six plant treated groups (PTG). The following analyses were performed in three sampling sets and measured every three days: chemical oxygen demand (COD), biochemical oxygen demand (BOD), ammoniacal nitrogen (AN), organic nitrogen (ON), total Kjeldahl nitrogen (TKN), and total phosphorus (TP). Dissolved oxygen (DO), pH, electrical conductivity (EC), and temperature (TEMP). The parameters that showed variation between the experimental groups were dissolved oxygen (0.1-5.0 mg L(-1)), pH (7.5-8.5), electrical conductivity (550-750 μS cm(-1)), and temperature (15-19 °C). The highest level of removal was observed on day 30 as 75.4% for BOD; 67.4% for COD; 88.3% for TKN; and 93.6% for TP. The use of M. aquaticum demonstrated its potential application in phytoremediation, showing reductions in COD, BOD, and TP at day 15, and in AN and TKN at day 30.


Relation between Perceived Barrier Profiles, Physical Literacy, Motivation and Physical Activity Behaviors among Parents with a Young Child.
Objectives: to reveal distinct subgroups of parents by their perception of 6 types of physical activity barriers and challenges (i.e., lack of time, poor health, lack of company, lack of facilities, childcare responsibility, lack of motivation), and examine its relation with related constructs. Design: cross-sectional survey data. Method: the sample consisted of 424 parents who had at least 1 child of primary school age. Latent profile analysis was conducted to identify latent subgroups within participants. Group differences on physical literacy, autonomous motivation, and self-report physical activity (PA) levels were explored. Results: a four-profile solution was obtained from latent profile analysis, labelled as: "Struggling" (29.0%), "Family burden" (41.3%), "Lazy" (13.0%), and "Barriers free" (16.7%). The "Barriers free" profile experienced the least difficulties with physical activity, but the "Struggling" profile suffered the most severe barriers and challenges. "Family burden" and "Lazy" profiles demonstrated qualitative differences on one or two given challenges. Significant group differences on physical literacy, autonomous motivation, and PA levels were found, showing the "Barriers free" profile as the most robust and adaptive group of parents. Conclusions: the findings suggest that it is common for a substantial portion of parents to experience multiple barriers and challenges to a relatively high degree. Intervention on raising parent's physical literacy to reduce barriers and sustain their motivation may be a target for intervention.


Effect of combinations of topical anaesthesia, fentanyl, halothane or N2O on circulatory intubation response in normo- and hypertensive patients.
Attenuation of the circulatory intubation response was studied using the following combinations: oropharyngeal topical anaesthesia (OTA) + fentanyl 2 micrograms/kg (F2), OTA + 2% halothane with 70% nitrous oxide (H2N2O) or F2 + H2N2O. Firstly, it was observed in 48 normotensive patients that the combinations of OTA + F2 or F2 + H2N2O totally prevented the intubation response; OTA + H2N2O, on the other hand, was less effective. Secondly, the effect of OTA + F2 was studied in 26 hypertensive patients and their 26 normotensive controls of the same age group. The combination prevented the circulatory intubation response also in the hypertensive patients, whose circulatory reactions did not differ from those of the normotensive patients. Nitrous oxide had no beneficial effect on the intubation response.


Rapidly separating microneedles for transdermal drug delivery.
The applications of polymer microneedles (MNs) into human skin emerged as an alternative of the conventional hypodermic needles. However, dissolving MNs require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin, which may lead to the low drug delivery efficiency. To address these issues, we introduce rapidly separating MNs that can rapidly deliver drugs into the skin in a minimally invasive way. For the rapidly separating MNs, drug loaded dissolving MNs are mounted on the top of solid MNs, which are made of biodegradable polylactic acid which eliminate the biohazardous waste. These MNs have sufficient mechanical strength to be inserted into the skin with the drug loaded tips fully embedded for subsequent dissolution. Compared with the traditional MNs, rapidly separating MNs achieve over 90% of drug delivery efficiency in 30s while the traditional MNs needs 2min to achieve the same efficiency. With the in vivo test in mice, the micro-holes caused by rapidly separating MNs can heal in 1h, indicating that the rapidly separating MNs are safe for future applications. These results indicate that the design of rapidly separating dissolvable MNs can offer a quick, high efficient, convenient, safe and potentially self-administered method of drug delivery. Polymer microneedles offer an attractive, painless and minimally invasive approach for transdermal drug delivery. However, dissolving microneedles require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin due to the skin deformation, which may lead to the low drug delivery efficiency. In this work we proposed rapidly separating microneedles which can deliver over 90% of drug into the skin in 30s. The in vitro and in vivo results indicate that the new design of these microneedles can offer a quick, high efficient, convenient and safe method for transdermal drug delivery.


In vivo nuclear magnetic resonance metabolite profiling in plant seeds.
Nuclear magnetic resonance (NMR) spectroscopy has been successfully applied to profile a variety of primary and secondary metabolites in whole intact plant seeds in vivo. The nondestructive nature of NMR spectroscopy allows direct metabolic studies to be performed on the same seed throughout a given physio-logical process or key lifecycle transition, such as dormancy breakage, germination, and early postgerminative growth. Multinuclear NMR is capable of evaluating seed quality by assessing nondestructively nutrient reserves and seed protectants at seed maturity and to further monitor reserve mobilization following germination, which is critical for seedling emergence. In this chapter, we illustrate the use of several in vivo NMR techniques for metabolite profiling in seeds. Importantly, some of these methods have potential for the screening of single seeds or seed populations to identify seedlots with compromised viability either due to developmental problems or as a result of deterioration during prolonged storage.


The effect of orciprenaline sulphate on the in vitro production of postaglandins E and F by the guinea pig uterus.
The effect of orciprenaline sulphate on the in vitro production of PGs E and F by guinea pig uterine tissue homogenates has been investigated. Estmations of PGs were carried out using sensitive radioimmunoassay techniques. The results indicated that orciprenaline can effectively reduce the in vitro yield of PGs E and F from guinea pig uterine tissue. This could in turn be due to an inhibitory effect of orciprenalline on PG formation or due to stimulation of PG breadkdown by the drug. The implications of these results in relation to premature labour are discussed.


Production of toxic antigens in dialyzed cultures of microorganisms.
Data on the production of clostridial toxins in dialyzed cultures are summarized. Principal modifications of this cultivation technique suitable for both research and production are shown. If toxins are released from the cells by autolysis (neurotoxins of Clostridium tetani, C. botulinum; lethal factors of C. novyi and C. sordellii), a 10-fold increase of the antigen concentration in filtrates of dialyzed cultures is found in comparison with normal cultures. If toxins are excreted already during growth (lethal factors of C. perfringens type A, C. septicum), the positive effect of the technique is less significant. A dialyzed culture ensures a well-balanced production of toxic filtrates that contain highly concentrated, relatively pure and strongly immunogenic antigens.


Pituitary adenoma associated with intraventricular meningioma: case report.
Although rare, the association of intracranial meningiomas and pituitary adenomas has been reported. Intraventricular meningiomas are unusual, and meningiomas located in the fourth ventricle are even more so. We report a patient who harbored a prolactin-secreting pituitary adenoma and a fourth ventricle meningioma who was treated with surgical resection of the latter and medical treatment for the former. To our knowledge, this is the first report of such an unusual association.


Long-term performance of biological ion exchange for the removal of natural organic matter and ammonia from surface waters.
Anionic exchange is an effective treatment option for the removal of natural organic matter from surface waters. However, the management of the spent brine regenerant often limits the adoption of this process. The current study reports one year of operation of ion exchange resins under biological mode (BIEX, i.e. without regeneration to promote biofilm growth on the media) compared to the performance of (i) ion exchange with weekly regeneration (IEX), (ii) granular activated carbon under biological mode (BAC) and (ii) granular activated carbon under adsorption mode (GAC). Four parallel pilot filters (GAC, BAC, IEX and BIEX) were fed with a colored and turbid river water without pretreatment. Although IEX provided the best performance (80% DOC removal) throughout the study, BIEX achieved a similar performance to IEX prior to DOC breakthrough (92 days) and subsequently achieved a mean DOC removal of 62% in warm water conditions. The GAC filter was rapidly exhausted (2 weeks) while the BAC filter only provided a 5% DOC reduction. Full nitrification was observed on both the BIEX and BAC filters under warm water conditions (>15 °C). After one year of operation, BIEX was successfully regenerated with brine. According to a mass balance, 69% of DOC removal in BIEX was due to ion exchange while we assume the remainder was biodegraded. Operation of ion exchange in biological mode is a promising option to reduce spent brine production while still achieving high DOC removal.


A lectin histochemical study to detect variation in glycosylation at the feto-maternal interface in three interbreeding equine species.
In this study, we compare glycosylation at the fetomaternal interface in 3 equine species: horse, donkey and zebra, all of which can interbreed to produce hybrids, to assess their glycan similarities and differences. Sections cut from 3 specimens of horse (Equus caballus) placenta (50, 200 and 280 days gestation), one donkey (Equus asinus) placenta (65 cm crown-rump length) and 5 specimens of zebra (Equus quagga) placentae (81-239 days gestation) were stained with a panel of 24 biotinylated lectins using an avidin-peroxidase revealing system. There were only slight quantitative differences in the lectin histochemistry at the feto-maternal interface between all three specimens; zebra placentae expressed more α2,6-linked sialic acid, with α1,2fucosyl residues at the microvillous interface. However, zebra trophoblast showed histological differences from the other two species, with polarised cells, prominent supranuclear Golgi bodies, and fewer intracellular granules. Our findings appear to confirm the hypothesis that closely related, interbreeding species with epitheliochorial placentae express similar glycans at the feto-maternal interface, thereby supporting the existence of a placental glycocode. We also observed intraspecies evolutionary diversion to be associated with a different histological architecture and the absence of significant intracellular granules.


Treatment and outcome of prenatally detected newborn hydronephrosis.
For neonates with antenatally diagnosed primary ureteropelvic junction (UPJ)-type hydronephrosis, to attempt to clarify and refine criteria for establishing optimal follow-up and treatment guidelines. A total of 162 newborns (228 hydronephrotic kidneys) with this condition were prospectively followed and treated by the same surgeon in 2001-2005 for a mean of 53 (13-72) months. Ultrasonography and diuretic renogram were used for diagnosis and follow up, and Onen's grading system to determine degree of hydronephrosis. On first postnatal ultrasound, the severity of hydronephrosis was grade 1 in 152 kidneys (surgery, 0%), 2 in 41 (surgery, 19.5%), 3 in 19 (surgery, 42.1%), and 4 in 16 kidneys (surgery, 93.8%). All the grade 1 cases resolved spontaneously without renal deterioration (renal function >40%). Renal function ranged between 7% and 34% in grade 4 patients. Overall, 201 hydronephrotic kidneys (88.2%) resolved spontaneously, while 27 (11.8%) required pyeloplasty because of evidence of obstructive injury, including increased hydronephrosis in 14/27 (6/27 had less than 10% decrease in renal function), greater than 10% decrease of renal function in 9/27, and greater than 10% decrease of renal function as well as increased hydronephrosis in 4/27 patients (15%). In most cases, neonatal hydronephrosis is a relatively benign condition that can be followed safely by an initial non-operative approach unless there is evidence of obstructive injury. A follow-up protocol that permits early identification of a limited number of kidneys that may develop signs of obstruction and require pyeloplasty is crucial for a favorable outcome in patients with primary UPJ-type hydronephrosis. Onen's hydronephrosis grading system promises an easier and more appropriate follow up and timely treatment for children with this condition. A sufficient follow-up interval, especially during the first 3 years of life, is essential to help prevent permanent loss of renal function in kidneys that do develop signs of obstruction.


Evaluation of solubility and partition properties of ampicillin-based ionic liquids.
In order to overcome the problems associated with low water solubility, and consequently low bioavailability of active pharmaceutical ingredients (APIs), herein we explore a modular ionic liquid synthetic strategy for improved APIs. Ionic liquids containing L-ampicillin as active pharmaceutical ingredient anion were prepared using the methodology developed in our previous work, using organic cations selected from substituted ammonium, phosphonium, pyridinium and methylimidazolium salts, with the intent of enhancing the solubility and bioavailability of L-ampicillin forms. In order to evaluate important properties of the synthesized API-ILs, the water solubility at 25 °C and 37 °C (body temperature) as well as octanol-water partition coefficients (Kow's) and HDPC micelles partition at 25 °C were measured. Critical micelle concentrations (CMC's) in water at 25 °C and 37 °C of the pharmaceutical ionic liquids bearing cations with surfactant properties were also determined from ionic conductivity measurements.