A longitudinal, mixed methods study of sexual position identity, behavior, and fantasies among young sexual minority men.
Recent evidence suggests that young sexual minority men's sexual position identities (e.g., "top," "bottom," "versatile") may be governed by dynamic influences. Yet, no study has prospectively examined whether, how, and why this aspect of sexual minority men's sexuality changes over time. Consequently, the present study investigated the extent to which young sexual minority men use sexual position identities consistently over time, typical patterns of position identity change, explanations given for this change, and the correspondence of changing sexual position identities with changing sexual behavior and fantasies. A total of 93 young sexual minority men indicated their sexual position identity, behavior, and fantasies at two assessment points separated by 2 years. Following the second assessment, a subset (n = 28) of participants who represented the various sexual position identity change patterns provided explanations for their change. More than half (n = 48) of participants changed their sexual position identity. Participants showed a significant move away from not using sexual position identities toward using them and a significant move toward using "mostly top." Changes in position identity were reflected, although imperfectly, in changes in sexual behavior and largely not reflected in fantasy changes. Participants offered 11 classes of explanations for their identity changes referencing personal development, practical reasons, changing relationships, and sociocultural influences. Previous investigations of sexual minority men's sexual position identities have not adequately attended to the possibility of the changing use of the sexual position categories "top," "bottom," and "versatile" across young adulthood. Results of the present study suggest the possibility of a more fluid, context-dependent use of these terms than previously documented.


Bioaccumulation and biomagnification of ultraviolet absorbents in marine wildlife of the Pearl River Estuarine, South China Sea.
Bioaccumulation and trophic transfer in ecosystems is an important criterion for assessing environmental risks of contaminants. This study investigated bioaccumulation and biomagnification of 13 organic ultraviolet absorbents (UVAs) in marine wildlife organisms in the Pearl River Estuary, South China Sea. The UVAs could accumulate in the organisms with biota - sediment accumulation factors (BSAF) of 0.003-2.152. UV531 was the most abundant and showed the highest tendency to accumulate in the organisms with a median BSAF of 1.105. The UVAs demonstrated species - and compound-specific accumulation in the marine organism. Fishes showed significantly higher capability than the cephalopods and crustaceans in accumulation of the UVAs. Habitat did not demonstrate obvious impact on accumulation of the UVA. On the other hand, benzophenone-3, UV328, and UV234 showed significantly higher concentration in the detritus feeding fishes than carnivorous and planktivorous fishes, suggesting governing effect of dietary habits of the organisms on bioaccumulation of these UVAs. Direct uptake from growth media was a significant exposure pathway of the organisms to the UVAs. The estimated trophic magnification factors and biomagnification factors revealed that UV329, UV531, and octocrylene could potentially biomagnify in the marine food web.


Monosynaptic excitation of preganglionic vasomotor neurons by subretrofacial neurons of the rostral ventrolateral medulla.
Extracellular single unit recordings were made from barosensitive neurons in the subretrofacial nucleus (SRF) of the rostral ventrolateral medulla in chloralose-anaesthetised cats. At the same time, single preganglionic neuron activity was recorded from filaments of the cervical sympathetic trunk (CST); barosensitive units were selected for study. Evidence for monosynaptic connections between the two neuron groups was sought by cross-correlation analysis of their ongoing activity. Cross-correlograms of 16/16 SRF/CST neuron pairs showed a broad peak (100-200ms wide), reflecting the synchronizing action of arterial baroreceptors on both neurons' activity. Two of the 16 cross-correlograms additionally showed a robust, statistically significant, narrow peak of a single 2 ms bin width, providing the first physiological demonstration that ventrolateral medullary neurons monosynaptically excite preganglionic sympathetic neurons. Deductions are made about the strength, convergence and divergence of the connection.


Human-to-human transmission of severe fever with thrombocytopenia syndrome virus through potential ocular exposure to infectious blood.
Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease with high mortality, was first reported in 2009 in China and subsequently endemic to South Korea, Japan, Vietnam, and Myanmar. This disease is transmitted predominantly by tick bites and potentially human-to-human. Personal protective equipments (PPEs) have been recommended to prevent SFTS human-to-human transmission, whereas the specific use of PPEs and the effect on viral transmission have rarely been reported. This report identified a family cluster of six patients with SFTS virus (SFTSV) infection. All five secondary patients had been wearing gloves and masks when exposed to the blood of the index patient, but none of them wore goggles or face shields for eye protection. Ocular route was suggested as a highly possible mode for SFTSV transmission through epidemiological, serological, and phylogenetic analysis. Eye protection should be stressed for clinicians when exposed to blood or bloody secretions.


Bis(isonicotinamide-κN)silver(I) tri-fluoro-methane-sulfonate aceto-nitrile disolvate.
The central AgI atom of the title salt, [Ag(INAM)2](CF3SO3)·2CH3CN, where INAM is isonicotinamide (C6H6N2O), is twofold coordinated by the pyridine N atoms of two isonicotinamide ligands creating a slightly distorted linear mol-ecular geometry. The formation of polymeric chains {[Ag(INAM)2]+} n , held together by discrete hydrogen bonds through the amide group of the INAM ligand leaves voids for non-coordinating aceto-nitrile mol-ecules that inter-act the silver metal center via regium bonds.


Xenobiotic microsomal epoxide hydrolase: 5' sequence of the human gene.
A cDNA for human microsomal epoxide hydrolase (mEH) was used to isolate genomic clones representing the 5' portion of the corresponding human gene. A total of 1034 bases of mEH gene sequence were obtained that included exon 1 and 5' flanking information. In contrast to the structure reported for the rat mEH gene (Falany et al. (1987) J. Biol. Chem. 262, 5924-5930), the human mEH gene lacked a CAAT box, but did contain a high-affinity CTF binding site at position -278 and an SV40 core enhancer element at position -525. TATA boxes were identified at positions -32 and -29 for the human and rat genes, respectively. Sequence comparisons between 5' flanking regions of the human and rat mEH genes demonstrated 47% homology, considerably less than the 83% conservation observed in the cDNA coding areas. Primer extension experiments localized the transcription initiation site of the human gene to a position 116 bases 5' from the analogous site in the rat mEH gene.


Prostate cancer recognition based on mass spectrometry sensing data and data fingerprint recovery.
The high dimensionality and noisy spectra of Mass Spectrometry (MS) data are two of the main challenges to achieving high accuracy recognition. The objective of this work is to produce an accurate prediction of class content by employing compressive sensing (CS). Not only can CS significantly reduce MS data dimensionality, but it will also allow for full reconstruction of original data. We are proposing a weighted mixing of L1- and L2-norms via a regularization term as a classifier within compressive sensing framework. Using performance measures such as OSR, PPV, NPV, Sen and Spec, we show that the L2-algorithm with regularization terms outperforms the L1-algorithm and Q5 under all applicable assumptions. We also aimed to use Block Sparse Bayesian Learning (BSBL) to reconstruct the MS data fingerprint which has also shown better performance results that those of L1-norm. These techniques were successfully applied to MS data to determine patient risk of prostate cancer by tracking Prostate-specific antigen (PSA) protein, and this analysis resulted in better performance when compared to currently used algorithms such as L1 minimization. This proposed work will be particularly useful in MS data reduction for assessing disease risk in patients and in future personalized medicine applications.


Visual evoked potentials of Niemann-Pick type C1 mice reveal an impairment of the visual pathway that is rescued by 2-hydroxypropyl-ß-cyclodextrin.
The lysosomal storage disorder, Niemann Pick type C1 (NPC1), presents a variable phenotype including neurovisceral and neurological symptoms. 2-Hydroxypropyl-ß-cyclodextrin (HPßCD)-based therapies are presently the most promising route of intervention. While severe cerebellar dysfunction remains the main disabling feature of NPC1, sensory functions including auditory and olfactory ones are also affected. Morphological and functional anomalies of Npc1 (-/-) mouse retina have also been observed, although the functional integrity of the visual pathway from retina to visual cortex is still unsettled. We have addressed this issue by characterizing the visual evoked potential (VEP) response of Npc1 (-/-) mice and determining if/how HPßCD administration influences the VEPs of both Npc1 (-/-) and Npc1 (+/+) mice. VEP elicited by a brief visual stimulus were recorded from the scalp overlying the visual cortex of adult (PN, postnatal days 60, 75, 85 and 100) Npc1 (+/+) and Npc1 (-/-) mice that had received repeated injections of either HPßCD or plain vehicle. The first injection was given at PN4 and was followed by a second one at PN7 and thereafter by weekly injections up to PN49. Cholesterol accumulation and myelin loss were finally assessed by filipin staining and myelin basic protein immunohistochemistry, respectively. We have found that the transmission of visual signals from retina to visual cortex is negatively influenced by the loss of Npc1 function. In fact, the VEP response of Npc1 (-/-) mice displayed a highly significant increase in the latency compared to that of Npc1 (+/+) mice. HPßCD administration fully rescued this defect and counteracted the cholesterol accumulation in retinal ganglion cells and dorsal lateral geniculate nucleus neurons, as well as the myelin loss in optic nerve fibers and axons projecting to the visual cortex observed in of Npc1 (-/-) mice. By contrast, HPßCD administration had no effect on the VEP response of Npc1 (+/+) mice, further strengthening the treatment efficacy. This study pinpoints the analysis of VEP response as a potentially accurate and non-invasive approach to assess neural activity and visual information processing in NPC1 patients, as well as for monitoring the progression of the disease and assessing the efficacy of potential therapies.


Studies on the mutagenicity and tumor-initiating activity of methylated fluorenes.
Several methylated analogs of fluorene were evaluated as mutagens in Salmonella typhimurium TA98 and TA100 in the presence and absence of microsomal activation. Among the methylated derivatives of fluorene assayed were 9-methylfluorene, 2-fluoro- and 2,7-difluoro-9-methylfluorene, 1,9-, 2,9-, 3,9- and 4,9-dimethylfluorene, 2,3,9-trimethylfluorene and 2,7,9-trimethylfluorene. Mutagenic activity was observed for several of these fluorene derivatives in the presence of rat liver homogenate. The data support a previous observation that a single methyl substituent in the 9-position of fluorene is associated with mutagenic activity within this series of compounds. Substitution with fluorine at both the 2- and 7-positions of 9-methylfluorene was not associated with a loss of mutagenic activity as evidenced by the similar mutagenic activity of 2,7-difluoro-9-methylfluorene and 9-methylfluorene. However, 2,7,9-trimethylfluorene was not mutagenic under these assay conditions. 9-Methylfluorene, 1,9-, 2,9-, 3,9- and 4,9-dimethylfluorene and 2,3,9-trimethylfluorene were active as mutagens in the presence of rat liver homogenate, but were inactive as tumor initiators when assayed on mouse skin.


Induced Smoothing for the Semiparametric Accelerated Hazards Model.
Compared to the proportional hazards model and accelerated failure time model, the accelerated hazards model has a unique property in its application, in that it can allow gradual effects of the treatment. However, its application is still very limited, partly due to the complexity of existing semiparametric estimation methods. We propose a new semiparametric estimation method based on the induced smoothing and rank type estimates. The parameter estimates and their variances can be easily obtained from the smoothed estimating equation; thus it is easy to use in practice. Our numerical study shows that the new method is more efficient than the existing methods with respect to its variance estimation and coverage probability. The proposed method is employed to reanalyze a data set from a brain tumor treatment study.


Predicting performance of the HAS-BLED and ORBIT bleeding risk scores in patients with atrial fibrillation treated with Rivaroxaban: Observations from the prospective EMIR Registry.
Assessing bleeding risk during the decision-making process of starting oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients is essential. Several bleeding risk scores have been proposed for vitamin K antagonist users but, few studies have focused on validation of these bleeding risk scores in patients taking direct oral anticoagulants (DOACs). The aim was to compare the predictive ability of HAS-BLED and ORBIT bleeding risk scores in AF patients taking rivaroxaban in the EMIR ('Estudio observacional para la identificación de los factores de riesgo asociados a eventos cardiovasculares mayores en pacientes con fibrilación auricular no valvular tratados con un anticoagulante oral directo [Rivaroxaban]) Study. EMIR Study was an observational, multicenter, post-authorization, and prospective study that involved AF patients under OAC with rivaroxaban at least 6 months before enrolment. We analysed baseline clinical characteristics and adverse events after 2.5 years of follow-up and validated the predictive ability of HAS-BLED and ORBIT scores for major bleeding (MB) events.We analysed 1433 patients with mean age of 74.2 ± 9.7 (44.5% female). Mean HAS-BLED score was 1.6 ± 1.0 and ORBIT score was 1.1 ± 1.2. The ORBIT score categorised a higher proportion of patients as 'low-risk' (87.1%) compared with 53.5% using the HAS-BLED score. There were 33 MB events (1.04%/year) and 87 patients died (2.73%/year). Both HAS-BLED and ORBIT had a good predictive ability for MB{Area under the curve (AUC) 0.770, [95% confidence interval (CI) 0.693-0.847; P <0.001] and AUC 0.765 (95% CI 0.672-0.858; P <0.001), respectively}. There was a non-significant difference for discriminative ability of the two tested scores (P = 0.930) and risk reclassification in terms of net reclassification improvement (NRI) -5.7 (95% CI -42.4-31.1; P = 0.762). HAS-BLED score showed the best calibration and ORBIT score showed the largest mismatch in calibration, particularly in higher predicted risk patients. In a prospective real-world AF population under rivaroxaban from EMIR registry, the HAS-BLED score had good predictive performance and calibration compared with ORBIT score for MB events. ORBIT score presented worse calibration than HAS-BLED in this DOAC treated population.


Integrating a Secure and Generic Mobile App for Patient Reported Outcome Acquisition into an EHR Infrastructure Based on FHIR Resources.
Both patients and physicians of the University Hospital of Erlangen would welcome means of digital data exchange between patients and the hospital. This work presents a system's architecture, FHIR based data model, security measures, and application flow based on patient's smartphones and a public cloud infrastructure to obtain patient reported outcome measures and merge that information with clinical routine data.


Crystal structure of 5-O-benzoyl-2,3-O-iso-propyl-idene-d-ribono-1,4-lactone.
In the title compound, C15H16O6, obtained from the acyl-ation reaction between 2,3-O-iso-propyl-idene-d-ribono-1,4-lactone and benzoyl chloride, the known absolute configuration for the lactone moiety of the ester substituent has been confirmed. The five-membered rings of the bicyclic lactone-dioxolane moiety both show envelope conformations and form a dihedral angle of 19.82 (7)° between the lactone ring and the benzene ring. In the crystal, mol-ecules of the acyl-ated sugar are linked by very weak inter-molecular C-H⋯O inter-actions, forming a three-dimensional network.


Single center experience with the novel rotating dilator sheath TightRailTM Sub-C in transvenous lead extraction.
Transvenous lead extraction has become a frequent procedure in the context of device lead management and various tools are available. The aim of this study was to investigate the efficacy and safety of the novel short rotating dilator sheath TightRailTM Sub-C (Sub-C) in transvenous lead extraction. For this retrospective single-center analysis, we included consecutive patients undergoing transvenous lead extraction using the Sub-C from January 2018 until February 2020 at the University Heart Center Zurich. A total of 87 leads were extracted within 45 patients using the Sub-C extraction sheath. The mean dwell time of the leads was 112 ± 9.1 months. Complete procedural success was achieved in 95.6% (43/45) and clinical procedural success in 97.8% (44/45). Two major complications (4.4%, 2/45) occurred, but neither was directly related to the Sub-C. This retrospective single-center analysis suggests that transvenous lead extraction with a routine use of the TightRailTM Sub-C extraction sheath is a safe strategy resulting in high success rates that may offer useful theoretical benefits. Future studies are needed to evaluate the incremental benefit of a routine use of short extraction sheaths including the Sub-C during TLE procedures.


[GnRH agonist triggering in IVF and luteal phase support in women at risk of ovarian hyperstimulation syndrome].
To evaluate the efficacy and safety of ovulation triggering by agonists in antagonists IVF cycles with fresh embryo transfer in modulating low HCG dose for luteal phase support in patients at risk of ovarian hyperstimulation syndrome (OHSS). In an observational study from September 2011 to March 2013, we triggered with agonist 107 cycles with OHSS risk, we initially triggered 39 cycles with 2 doses of Triptorelin 0.1 mg. Injection of 1500 IU HCG was performed one hour after the pick up and a second injection of 1500 IU was made 5 days later (group 1) combined with 400 mg of natural progesterone vaginally. In the following 68 cycles we removed the second HCG injection and increased to 600 mg vaginal progesterone associated with E2 4 mg orally (group 2). Group 1: the ongoing pregnancy rate and birth rate in fresh cycle is respectively 37.1% and 34.3% and the cumulative ongoing pregnancy rate and birth rate per patient is 43.6% and 41%. We recorded three late onset OHSS in pregnant women. Group 2: ongoing pregnancy rate in fresh cycle is 39.6%, the current cumulative ongoing pregnancy rate per patient was 45.6%. We observed a case of early onset OHSS. Triggering with agonist and administering an injection of 1500 IU of HCG the day of the pick up appears to be effective in women at risk of OHSS. The exclusion of all OHSS is still not reached. The search for the best protocol and its indications should continue.


Brassica oleracea var. acephala (kale) improvement by biological activity of root endophytic fungi.
Brassica oleracea var. acephala (kale) is a cruciferous vegetable widely cultivated for its leaves and flower buds in Atlantic Europe and the Mediterranean area, being a food of great interest as a "superfood" today. Little has been studied about the diversity of endophytic fungi in the Brassica genus, and there are no studies regarding kale. In this study, we made a survey of the diversity of endophytic fungi present in the roots of six different Galician kale local populations. In addition, we investigated whether the presence of endophytes in the roots was beneficial to the plants in terms of growth, cold tolerance, or resistance to bacteria and insects. The fungal isolates obtained belonged to 33 different taxa. Among those, a Fusarium sp. and Pleosporales sp. A between Setophoma and Edenia (called as Setophoma/Edenia) were present in many plants of all five local populations, being possible components of a core kale microbiome. For the first time, several interactions between endophytic fungus and Brassica plants are described and is proved how different interactions are beneficial for the plant. Fusarium sp. and Pleosporales sp. B close to Pyrenophora (called as Pyrenophora) promoted plant growth and increased cold tolerance. On the other hand, isolates of Trichoderma sp., Pleosporales sp. C close to Phialocephala (called as Phialocephala), Fusarium sp., Curvularia sp., Setophoma/Edenia and Acrocalymma sp. were able to activate plant systemic resistance against the bacterial pathogen Xanthomonas campestris. We also observed that Fusarium sp., Curvularia sp. and Setophoma/Edenia confered resistance against Mamestra brassicae larvae.


A thyrotropin-secreting pituitary adenoma as a cause of thyrotoxic periodic paralysis.
We describe a patient with thyrotoxic periodic paralysis (TPP) caused by a thyrotropin-secreting pituitary adenoma. The diagnosis TPP was based on the combination of episodes of reversible hypokalaemic paralysis, hyperthyroidism and electrophysiological findings. A thyrotropin-secreting pituitary adenoma was diagnosed on the basis of endocrinological function tests and MRI of the pituitary gland. Before transsphenoidal resection of the adenoma, treatment with octreotide restored euthyroidism both clinically and biochemically. Immunocytochemistry of the pituitary adenoma was positive for TSH exclusively. Incubation with octreotide or quinagolide induced decreased TSH and alpha-subunit production by the cultured adenoma cells, in agreement with the pre-operative in vivo data. This paper is the first to describe in vivo and in vitro characteristics of a thyrotropin-secreting pituitary adenoma in a patient presenting with periodic paralysis.


MicroRNA-155-5p regulates the Th1/Th2 cytokines expression and the apoptosis of group 2 innate lymphoid cells via targeting TP53INP1 in allergic rhinitis.
As a key component of innate immunity, group 2 innate lymphoid cells (ILC2s) play a key role in Allergic rhinitis (AR). We previously demonstrated that both miR-155-5p and ILC2s are overexpressed in the nasal mucosa of AR patients, but the underlying mechanism remains unclear. At present study, we revealed that miR-155-5p was highly expressed in ILC2s of AR patients. Moreover, miR-155-5p promoted the secretion of Th2 cytokines of ILC2s, while inhibited the secretion of Th1 cytokines and the apoptosis of ILC2s. Meanwhile, the TP53INP1 expression was poorly expressed in ILC2s of AR patients. A dual luciferase reporter assay demonstrated that TP53INP1 was a direct target of miR-155-5p, and its expression was inversely associated with miR-155-5p in ILC2s. Furthermore, TP53INP1 inhibited the secretion of Th2 cytokines of ILC2s, while promoted the secretion of Th1 cytokines and the apoptosis of ILC2s. Notably, rescue experiments demonstrated that overexpression of TP53INP1 could partially reverse the effect of miR-155-5p on ILC2s. Taken together, these findings suggested that miR-155-5p aggravated the inflammatory response of AR dominated by ILC2s via targeting TP53INP1, which may aid in the development of novel therapeutic agents for AR.


Facile access to zinc and cadmium selones: highly active catalysts for Barbier reactions in aqueous media.
The syntheses and structures of five mononuclear zinc and cadmium selone complexes along with a polynuclear cadmium selone 1D chain were described. The mononuclear homoleptic zinc selone complexes were the first examples of structurally characterized zinc(ii) selone complexes. The spectral properties of the zinc and cadmium selone derivatives were investigated. Interesting structural diversity, coordination geometry, and variable chemical and thermal stability were observed for these zinc and cadmium selone compounds. Besides this, the first metal selone mediated Barbier coupling was reported. These catalysts were highly active for Barbier coupling reactions in aqueous alcohol media. In addition, the scope of the catalytic reactions was further explored with eleven different aldehydes.


Processing of irrelevant location information under dual-task conditions.
This study deals with the problem of whether the processing of irrelevant location information in Simon-like tasks is triggered exogenously or endogenously. In Experiment 1, the primary task required one to press, as fast as possible, a left-hand-side key or a right-hand-side key (R1) to the pitch of a tone that was presented binaurally (S1). The secondary task required identifying, without time constraints, a visual stimulus (S2) that appeared randomly to the left or right of screen center. Results showed that there was a correspondence (i.e., a cross-task Simon effect) between the location of R1 and the location of S2 when S2 was presented alone. The cross-task Simon effect became much smaller (and insignificant) when a noise stimulus was presented contralateral to S2. Experiment 2 was similar to Experiment 1, except that S2 appeared unpredictably in only one-third of the trials. Results of Experiment 2 closely replicated those of Experiment 1: the cross-task Simon effect was much greater when S2 was presented alone. Experiment 3 differed from Experiment 1 because S2 had to be processed in only one-third of the trials, in which its identity was to be reported. In the remaining two-thirds of the trials, participants could ignore S2. Results confirmed that the cross-task Simon effect was much greater when S2 was presented alone. In contrast, it did not matter whether S2 had to be processed or not. In conclusion, the present study supports the hypothesis that the task-irrelevant spatial code of the stimulus is formed automatically, likely through an exogenously triggered selection. The role of endogenously initiated selection, if any, is much less important.


Inadequate pharmacotherapeutic data for drugs used in children: what can be done?
Although infants and children are affected by many acute and chronic diseases, nearly 80% of the drugs approved in the US for use in adults have not been labelled for paediatric use. This leads to the 'off-label' use of drugs which may produce suboptimal efficacy or harmful effects. Recent regulations proposed by the US Food and Drug Administration (FDA) require the industry to conduct paediatric studies in certain situations. However, some incentives will be provided to the industry to seek paediatric labelling. Paediatric practitioners and researchers will play an active role in conducting research and disseminating data about medication use in infants and children. However, increased funding is required for paediatric research. Industry, government, associations, academia and the public should work together to develop an agenda for action, with the goal of improving clinical outcomes and quality of life in infants and children.


Analysis of IncF plasmids evolution: nucleotide sequence of an IncFIII replication region.
We determined the nucleotide sequence of RepFIII, the IncFIII replication region of the plasmid pSU316. Our data confirmed that RepFIII belongs to the RepFIIA family. The comparison of the nucleotide sequences from several RepFIIA-family plasmids revealed that pSU316 and R1 replicons are almost identical (96% similarity). Most of the differences between them are clustered in the incompatibility determinant. Analysis of the rest of the sequence suggested that the divergence between R1 and pSU316 replicons is very recent.


TCB-2 [(7R)-3-bromo-2, 5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methanamine]: A hallucinogenic drug, a selective 5-HT2A receptor pharmacological tool, or none of the above?
The development of 5-HT2A receptor agonists has been considerably marginalized since the demonstration that the tryptaminergic drugs, LSD and psilocybin, or the phenylakylamine drugs, mescaline and DOI, exert their hallucinogenic properties via the stimulation of 5-HT2A receptors. Nonetheless, the ability of drugs to stimulate 5-HT2A receptors is not necessarily associated with psychedelic experience and the hallucinogenic properties are still not understood. Several studies have increased interest in stimulating 5-HT2A receptors in various CNS diseases. (7R)-3-bromo-2, 5-dimethoxy-bicyclo[4.2.0]octa-1,3,5-trien-7-yl]methanamine (TCB-2) which was synthetized in 2006 presents a high affinity with human and rat 5-HT2A receptors. Its main feature of interest is that it preferentially stimulates the phospholipase C and not phospholipase A2 pathway, which is at variance with several hallucinogenic drugs. Preference for TCB-2 has increased in preclinical studies and it exhibits subtle differences compared to DOI or LSD in some molecular, cellular and behavioral studies. The purpose of this review is to take a position on the use of TCB-2 as a pharmacological tool. A careful reading of the literature has revealed that the suspected hallucinogenic properties of TCB-2 cannot firmly be ascertained while its pharmacological profile is unknown and likely not selective at 5-HT2A receptors. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.


A new three-step hybrid approach is a safe procedure for incisional hernia: early experiences with a single centre retrospective cohort.
In this study, a three-step novel surgical technique was developed for incisional hernia, in which a laparoscopic procedure with a mini-laparotomy is combined: so-called 'three-step incisional hybrid repair'. The aim of this study was to reduce the risk of intestinal lacerations during adhesiolysis and recurrence rate by better symmetrical overlap placement of the mesh. To evaluate first perioperative outcomes with this technique. From 2016 to 2020, 70 patients (65.7% females) with an incisional hernia of > 2 and ≤ 10 cm underwent a elective three-step incisional hybrid repair in two non-academic hospitals performed by two surgeons specialised in abdominal wall surgery. Intra- and postoperative complications, operation time, hospitalisation time and hernia recurrence were assessed. Mean operation time was 100 min. Mean hernia size was 4.8 cm; 45 patients (64.3%) had a hernia of 1-5 cm, 25 patients (35.7%) of 6-10 cm. Eight patients had a grade 1 complication (11.4%), five patients a grade 2 (7.1%), two patients (2.8%) a grade 4 complication and one patient (1.4%) a grade 5 complication. Five patients had an intraoperative complication (7.0%), two enterotomies, one serosa injury, one omentum bleeding and one laceration of an epigastric vessel. Mean length of stay was 3.3 days. Four patients (5.6%) developed a hernia recurrence during a mean follow-up of 19.5 weeks. A three-step hybrid incisional hernia repair is a safe alternative for incisional hernia repair. Intraoperative complications rate was low.


Application of new in situ hybridization probes for Ku70 and Ku80 in tissue microarrays of paraffin-embedded malignant melanomas: correlation with immunohistochemical analysis.
Ku70 and Ku80 proteins are responsible for the repair of DNA double-strand breaks and function as a regulatory subunit of the DNA-dependent protein kinase. In this study we analyzed expression of both genes in malignant melanoma tissue arrays applying in situ hybridization probes produced by our research group and using immunohistochemical analysis. Expression of both genes was down-regulated as melanoma progressed. In situ hybridization demonstrated more Ku70- and Ku80-positive cells than immunohistochemical methods, but the correlation between the two methods was highly significant (P <0.01). We conclude that the in situ hybridization assay for the detection of Ku70 and Ku80 expression used in this study is also suitable for tissue microarray analysis of paraffin-embedded melanoma samples. The laboratory procedure is much more complicated than the immunohistochemical method, however.


A comparison of T2*-weighted magnitude and phase imaging for measuring the arterial input function in the rat aorta following intravenous injection of gadolinium contrast agent.
The arterial input function (AIF) is important for quantitative MR imaging perfusion experiments employing Gd contrast agents. This study compared the accuracy of T(2)*-weighted magnitude and phase imaging for noninvasive measurement of the AIF in the rat aorta. Twenty-eight in vivo experiments were performed involving simultaneous arterial blood sampling and MR imaging following Gd injection. In vitro experiments were also performed to confirm the in vivo results. At 1.89 T and TE=3 ms, the relationship between changes in 1/T(2)* in blood (estimated from MR signal magnitude) and Gd concentration ([Gd]) was measured to be approximately 19 s(-1) mM(-1), while that between phase and [Gd] was approximately 0.19 rad mM(-1). Both of these values are consistent with previously published results. The in vivo phase data had approximately half as much scatter with respect to [Gd] than the in vivo magnitude data (r(2)=.34 vs. r(2)=.17, respectively). This is likely due to the fact that the estimated change in 1/T(2)* is more sensitive than the phase to a variety of factors such as partial volume effects and T(1) weighting. Therefore, this study indicates that phase imaging may be a preferred method for measuring the AIF in the rat aorta compared to T(2)*-weighted magnitude imaging.


CO2 LASER - A NEW TOOL IN THE SURGEONS ARMAMENTARIUM.
One hundred and sixty five patients, treated with carbondioxide (CO2) laser for benign and malignant lesions of the head and neck were studied. Alveolo-buccal complex (68/165) had the majority of benign and malignant tumors followed by larynx (23/165) and tongue (21/165). All lesions were widely excised, none were reconstructed and all defects healed well with minimal scarring. The post-operative morbidity was minimal and the hospitalization period was 1 to 5 days. Complications were not serious and could be managed easily. This study confirms the usefulness of CO2 laser surgery for both benign and malignant conditions in head and neck.


Bladder Preservation Therapy: A Review of the Literature and Future Directions.
Trimodal bladder preservation therapy (ie, transurethral resection followed by chemoradiotherapy) may be an acceptable treatment alternative to radical cystectomy with urinary diversion in the carefully selected patient with muscle invasive bladder cancer. Although no head-to-head randomized controlled trials have been performed, large retrospective cohort reviews and observational data analyses suggest comparable oncologic outcomes in select patients with the additional benefit of maximizing quality of life and maintaining the patient's native bladder. In this review, we discuss the evolution and clinical outcomes of bladder preservation therapy, highlighting its role in the contemporary management of muscle invasive bladder cancer.


Evidence for the integration of total and free testosterone levels in the management of prostate cancer.
To comprehensively assess total and calculated free testosterone levels in a consecutive group of patients with prostate cancer (PCa) and any potential impact on disease aggressiveness and recurrence outcomes. The study included a single-centre prospective cohort of 882 patients presenting for radical prostatectomy from 2009 to 2018. Data on total testosterone (TT), sex hormone-binding globulin (SHBG), and calculated free testosterone (cFT) were prospectively collected. Stepwise logistic regression models were used to assess correlations of TT and cFT with pathological Gleason Grade Group (GGG), extraprostatic extension (EPE), seminal vesicle invasion (SVI) and biochemical recurrence (BCR). Total testosterone remained nearly constant across decades (40s-80s): 0.09 decrease/year (R = 0.02), while SHBG increased 0.87/year (R = 0.32) and cFT decreased 0.08/year (R = -0.02). Low cFT of <5.5 independently predicted: very-high-risk GGG (odds ratio [OR] 0.435, 95% confidence interval [CI] 0.846-0.994; P = 0.036), EPE (OR 0.557, 95% CI 0.810-0.987; P = 0.011), SVI (OR 0.396, 95% CI 0.798-1.038; P = 0.059), and BCR within 1 year after robot-assisted radical prostatectomy (OR 0.638, 95% CI 0.971-3.512, P = 0.046). TT was not a predictor. In contrast to popular belief, testosterone remained stable in men aged 40-80 years, whereas free testosterone decreased by 2-3%/year. Low cFT was an independent predictor of very-high-risk PCa and BCR.


Pharmacokinetic analysis of a combined chemoendocrine treatment with paclitaxel and toremifene for metastatic breast cancer.
Multidrug resistance protein could be a target for improving the efficacy of paclitaxel (PXL). Toremifene (TOR) may moderate P-gp-related drug resistance in vitro. Some P-gp moderators may change the pharmacokinetic parameters of PXL in vivo. A pharmacokinetic (PK) study in metastatic breast cancer patients (MBC) was conducted to determine the safety and efficacy of PXL and TOR. Fifteen patients received 80 mg/m(2) PXL (i.v.) weekly and 120 mg/body TOR (p.o.) daily. For the pharmacokinetic study, PXL was administered on days 1, 8, 15, 32, and 39; TOR was given from day 18 to the end of study. On days 1, 8, 15, 18, 32, and 39, blood samples were collected from the patients who received either PXL alone or PXL + TOR, and these were analyzed by high-performance liquid chromatography. Among the 15 patients enrolled in the study, one showed a partial response, and eight had a stable disease. TOR caused no specific adverse events that were greater than grade 3, and its toxicity profile in combination with PXL was similar to that of PXL monotherapy. The PK profile of PXL was similar with or without TOR. The PK parameters of PXL indicated no inter- or intra-patient variability in previously treated patients with MBC. No increased PXL toxicity was observed. The PK profile of combined PXL and TOR was similar to that of PXL monotherapy. The addition of TOR to PXL in previously treated patients with MBC appears safe.


Evaluating the benefits of treating dyslipidemia: the importance of diabetes as a risk factor.
Diabetes mellitus is associated with an increased risk of cardiovascular disease. We compared the clinical effects of treating dyslipidemia in patients who had diabetes mellitus but no diagnosed cardiovascular disease with the effects of similar treatment in patients who had cardiovascular disease but no diabetes mellitus. We estimated the number of adults (ages 30 to 74 years) requiring lipid therapy using data from the third National Health and Nutrition Examination Survey and current lipid treatment guidelines. Using the Cardiovascular Life Expectancy Model, we estimated the mean increase in life expectancy that would result from lowering low-density lipoprotein cholesterol levels by 35% and increasing high-density lipoprotein cholesterol levels by 8% based on results from the Scandinavian Simvastatin Survival Study. The mean number of years of life saved ranged from 3 to 3.4 years for men with diabetes versus 2.4 to 2.7 years for men with cardiovascular disease. In women, the estimated benefits were 1.6 to 2.4 years for those with diabetes versus 1.6 to 2.1 years for those with cardiovascular disease. Total population benefits were also substantial for patients with diabetes (25.4 million person-years of life saved) and those with cardiovascular disease (16.0 million person-years of life saved). The clinical benefits of treating dyslipidemia in patients with diabetes should be at least equivalent to, if not more substantial than, the benefits observed among those with cardiovascular disease.


Apparent plateau in beta-lactamase production among clinical isolates of Haemophilus influenzae and Moraxella catarrhalis in the United States: results from the LIBRA Surveillance initiative.
Haemophilus influenzae (n=2791) and Moraxella catarrhalis (n=1249) isolated from patient specimens during 1999 were collected from 290 laboratories participating in a moxifloxacin surveillance study as part of the LIBRA Surveillance initiative. Isolates were tested for in vitro susceptibility to a panel of agents suitable for the treatment of respiratory tract infections. beta-Lactamase production was identified in 32.2% of H. influenzae and 94.2% of M. catarrhalis. These percentages differed by less than 1.5% from results of a study conducted in 1997-1998 and were similar to results from other recent US surveillance studies. Resistance among H. influenzae to trimethoprim-sulphamethoxazole increased considerably, from 2% in the 1997-1998 study (n=6588 H. influenzae) to 15.5% in the current study. One isolate of H. influenzae had an MIC of 8 mg/l to both levofloxacin and moxifloxacin; all other isolates had MICs of < or =0.5 mg/l and < or =0.25 mg/l, respectively. beta-Lactamase production was found to confer ampicillin resistance in nearly all isolates. For M. catarrhalis, beta-lactamase-negative isolates had MICs < or =0.12-0.25 mg/l for ampicillin and < or =0.03-0.12 mg/l for ceftriaxone. In contrast, beta-lactamase production resulted in MICs of < or = 0.12->16 mg/l for ampicillin and < or = 0.03-4 mg/l for ceftriaxone. All M. catarrhalis had MICs < or =0.12 mg/l for moxifloxacin and < or =1 mg/l for levofloxacin. In summary, antimicrobial susceptibilities and the prevalence of beta-lactamase production in H. influenzae and M. catarrhalis in the United States has remained essentially unchanged from 1997-1998 to 1999.


Hypertrophic hepatic osteoarthropathy. Clinical, roentgenologic, biochemical, hormonal and cardiorespiratory studies, and review of the literature.
Twenty patients with biopsy proved liver disease, and roentgenologic features of hypertrophic osteoarthropathy have been studied, and the literature has been reviewed. The syndrome is a rare association of many chronic liver diseases, including primary biliary cirrhosis, bile duct carcinoma, benign bile duct stricture, chronic active hepatitis, posthepatitic cirrhosis and alcoholic cirrhosis. Patients may be asymptomatic, although bone pain, arthralgia or arthritis may be presenting symptoms. Ninety per cent of the patients are clinical jaundiced at the time of diagnosis, and 95 per cent have digital clubbing. The distal tibia and fibula are the first bones to become involved, although wrist, foot bones, femurs, hand bones and humeri may be affected in order of frequency. There is no correlation between the presence of esophageal varices or surgical portacaval shunts and the extent of the syndrome, neither is there a correlation with the degree of liver function impairment. Serum calcium and phosphate levels are normal, as is urinary hydroxyproline and estrogen excretion. There was no evidence to implicate elevated levels of growth hormone or overdosage of vitamin A. Although the majority of patients tested had mild arterial hypoxemia, increased cardiac output and evidence of right to left shunting, these were also present in disease-matched control subjects without osteoarthropathy. For screening purposes, patients with chronic liver disease and clubbing should have roentgenologic studies of the lower tibias and fibulas, to select those patients suitable for a more extensive skeletal survey.


Nutritional status and survival of 8247 cancer patients with or without diabetes mellitus-results from a prospective cohort study.
The number of cancer patients with diabetes mellitus (DM) is steadily rising. Little is known about the nutritional status of this population. This study characterized the nutritional status and survival of cancer patients with diabetes compared with those without diabetes. A total of 8247 cancer patients were prospectively enrolled from 72 hospitals in China and followed until August 2019. A global estimation of the nutritional status was performed for each participant using standardized tools. The outcomes were cancer-specific survival (CSS) and overall survival (OS). The incidence of diabetes was 7.6% in the whole population. In comparison with the non-DM group, the DM group had greater body weight, but a similar fat-free mass, a lower handgrip strength and a decreased Karnofsky performance score. A higher proportion of patients with diabetes were overweight/obese as indicated by BMI. The percentage of patients who were at risk of malnutrition (evaluated by PG-SGA) was higher in the DM group (score ≥ 4, 56.7% vs 52.9%). Patients with DM showed a worse CSS (4-year CSS, 62% vs 73%) and OS (4-year OS 39% vs 52%). Diabetes was associated with an increased risk of both cancer-specific (hazard ratio (HR) = 1.282, 95% confidence interval (CI) 1.070-1.536) and overall (HR = 1.206, 95% CI 1.040-1.399) mortality. Cancer patients with diabetes had a larger body mass but lower muscle strength, poorer performance status and higher incidence of malnourishment. Diabetes was associated with compromised survival. Tailored nutritional intervention is necessary for this subpopulation of patients.


Comparative study of secretin and Lundh tests.
Exocrine pancreatic function in 19 patients with pancreatic disease and in 14 of 16 controls was measured by secretin stimulation and by the Lundh test on two different occasions. Peak bicarbonate concentration in the Lundh test emerged as the most reliable parameters. No additional diagnostic value was obtained by measuring enzymes after secretin injection. In 6 patients with chronic and in 8 of 13 patients with acute pancreatitis, both tests gave results that agreed with each other. The remaining 5 patients showed either an abnormal secretin value or an abnormal Lundh test. This is consistent with the wide variation seen in acute pancreatitis. It is concluded that the Lundh test as well as the secretin test were of value in the assessment of chronic pancreatic disease. The secretin test may be slightly more sensitive to mild and acute pancreatic damage than is the Lundh test. However stimulation of the pancreas by a test meal is easier to perform and more economic.


Induction of beta-glucuronidase activity during dimethylhydrazine carcinogenesis and additive effects of cholic acid and indole.
The kinetic change of beta-glucuronidase (beta-G) activity was measured in mouse large intestinal mucosa during dimethylhydrazine (DMH) carcinogenesis with addition of cholic acid and/or indole. The experiment lasted 21 weeks. The enzyme activity began to increase significantly at 5th week after treatment of DMH with cholic acid and/or indole, and at 7th week with DMH alone. Then, increased activity remained the rest of the time. Mouse intestinal cancer induced by DMH injection are also shown to have an increased beta-G activity. The induction of beta-G activity in the early stage of DMH colon carcinogenesis and additive effects of cholic acid and/or indole may imply one mechanism of action of DMH as a carcinogen and cholic acid as a promoter in large intestinal cancer.


Persistent Asymptomatic Isolated Microscopic Hematuria in Adolescents is not Associated With an Increased Risk for Early Onset Urinary Tract Cancer.
To elucidate the association between adolescent microscopic hematuria and early onset urothelial carcinoma and renal cell carcinoma. Nationwide, population-based, retrospective cohort study using medical data of 970,366 adolescents aged 16 through 19 years (58.6% male) examined for fitness for military service between 1980 and 1997. Diagnoses of persistent isolated microscopic hematuria were given after thorough work up process excluding any other renal abnormalities. Incident cases of urothelial carcinoma and renal cell carcinoma diagnosed during the years of 1982-2012 were retrieved from the Israeli National Cancer Registry. Cox proportional hazards models were used to estimate the hazard ratio (HR) separately for urothelial carcinoma and renal cell carcinoma. During a cumulative follow-up of 22,115,629 person-years (median follow-up, 22.8), persistent isolated microscopic hematuria was diagnosed among 5509 (0.6%) adolescents. Urothelial carcinoma and renal cell carcinoma developed in 332 (3 among those with persistent isolated microscopic hematuria) and 292 (2) individuals, respectively. The adjusted HR for incident urothelial carcinoma among adolescents with isolated microscopic hematuria was 1.17 (95% CI, 0.38-3.66) and the adjusted HR for renal cell carcinoma was 1.02 (95% CI, 0.25-4.12). Persistent asymptomatic isolated microscopic hematuria at adolescence was not associated with increased risk for urothelial carcinoma nor renal cell carcinoma.


Adoption is not associated with immunological and virological outcomes in children with perinatally acquired HIV infection in the Netherlands.
To provide an overview of the demographics, treatment characteristics and long-term outcomes of children with perinatal HIV-1 infection (PHIV) living in the Netherlands (NL) and to specifically investigate whether outcomes differ by children's adoption status. A prospective population-based open cohort including children with PHIV in NL. We included children with PHIV who had entered HIV care in NL since 2007, in view of a sharp increase in the number of adopted children with PHIV since that year. We compared the proportion with virologic suppression and CD4+T-cell count over time between the following groups of children with PHIV: adopted and born outside NL, non-adopted born in NL, and non-adopted born outside NL, using generalized estimating equations and linear mixed effects models, respectively. To account for the variation in cohort inclusion, we analyzed data of children exposed to at least one year of antiretroviral therapy (ART). We included 148 children (827.5 person-years of follow-up, 72% adopted, age at start care in NL 2.4 (0.5-5.3)). Under-18 mortality was zero. Over the years, a boosted PI-based regimen was most often prescribed. The use of integrase inhibitors increased since 2015. Non-adopted children born in NL were less likely to achieve virological suppression compared to adopted children (OR 0.66, 95%CI 0.51-0.86, p = 0.001), which disappeared after excluding one child with suspected treatment nonadherence (OR 0.85, 95%CI 0.57-1.25, p = 0.400). CD4+T-cell Z-score trajectories were not significantly different between groups. Despite considerable and increasing diversity of the population of children with PHIV in NL, geographical origin and adoption status do not seem to pose important challenges in achieving good immunological and virological outcomes.


microRNAs in liver and kidney ischemia reperfusion injury: insight to improve transplantation outcome.
Ischemia reperfusion injury (IRI) is a condition that occurs wherever blood flow and oxygen is reduced or absent, such as trauma, vascular disease, stroke, and solid organ transplantation. This condition can lead to tissue damage, especially during organ transplantation. Under such circumstances, some signaling pathways are activated, leading to up- or down- regulation of several genes such as microRNAs (miRNAs) that might attenuate or ameliorate this status. Therefore, by manipulating miRNAs level, they can be used as a biomarker for early diagnosis of IRI or suggestive to be therapeutic agents in clinical situation in future.


Meat tenderization using acetaminophen (paracetamol/APAP): A review on deductive biochemical mechanisms, toxicological implications and strategies for mitigation.
Meats consist of edible portions originating from domestic and wild animals. Meat's palatability and sensory accessibility largely depend on its tenderness to consumers. Although many factors influence meat tenderness, the cooking method cannot be neglected. Different chemical, mechanical, and natural means of meat tenderization have been considered healthy and safe for consumers. However, many households, food vendors, and bars in developing countries engage in the unhealthy use of acetaminophen (paracetamol/APAP) in meat tenderization due to the cost reduction it offers in the overall cooking process. Acetaminophen (paracetamol/APAP) is one of the most popular, relatively cheap, and ubiquitous over-the-counter drugs that induce serious toxicity challenges when misused. It is important to note that acetaminophen during cooking is hydrolyses into a toxic compound known as 4-aminophenol, which damages the liver and kidney and results in organ failure. Despite the reports on the increase in the use of acetaminophen for meat tenderizing in many web reports, there have not been any serious scientific publications on this subject. This study adopted classical/traditional methodology to review relevant literature retrieved from Scopus, PubMed, and ScienceDirect using relevant key terms (Acetaminophen, Toxicity, Meat tenderization, APAP, paracetamol, mechanisms) and Boolean operators (AND and OR). This paper provides in-depth information on the hazard and health implications of consuming acetaminophen tenderized meat via genetic and metabolic pathways deductions. Understanding these unsafe practices will promote awareness and mitigation strategies.


Cancer in mice: effects of prednisolone or mepacrine alone and with cytotoxic drugs.
WHT/Ht mice were transplanted s.c. with NC carcinoma, and the tumours were excised after 2 weeks. The mice were treated orally throughout the experiments with prednisolone 500 micrograms kg-1 or mepacrine 3.6 mg kg-1, starting the day after tumour transplantation or, with prednisolone, the day after tumour excision. In some experiments the mice were also treated with the cytotoxic drugs methotrexate 2 mg kg-1 and melphalan 1.4 mg kg-1. The excised tumours were weighed; some of them, and samples of serum, were extracted for prostanoids which were measured by radioimmunoassay. The chemotherapy lengthened the survival of the mice, but prednisolone or mepacrine had little or no effect on survival, metastasis, the response to chemotherapy, tumour size or the formation of tumour prostanoids.


The role of laparoscopy and laparoscopic ultrasound in the preoperative staging of patients with resectable colorectal liver metastases: a meta-analysis.
The role of staging laparoscopy (SL) with laparoscopic ultrasound (LUS) in patients with resectable colorectal liver metastases (CRLM) remains controversial. A meta-analysis of all studies (from 1998 to the present) on the effect of SL/LUS in patients with potentially resectable CRLM with respect to alteration in surgical management was performed. Twelve studies satisfied the inclusion criteria. A total of 1,047 patients underwent SL/LUS. The true yield of SL/LUS for CRLM was 19% (95% confidence interval [CI], 16%-22%), with a diagnostic odds ratio of 132 (95% CI, 56-310) and an overall sensitivity of 59% (95% CI, 53%-65%). Subgroup analysis for detection of other liver and peritoneal lesions showed a sensitivity of 59% (95% CI, 49%-67%) and 75% (95% CI, 63%-85%) respectively. There was major between-study heterogeneity for all analyses, with no obvious cause revealed by meta-regression. The true benefit of using SL/LUS universally seems limited. It appears more useful as an adjunct in patients when peritoneal disease is suspected.


Post-infectious Non-paraneoplastic Autoimmune Retinopathy in Paediatric age group: A high index of suspicion, Multimodal Imaging and Early treatment can restore vision.
To report a case of non-paraneoplastic Auto-immune retinopathy (npAIR) in a paediatric patient who showed excellent visual recovery with early diagnosis and prompt treatment. Retrospective Case report. A five year old girl presented to us with bilateral profound vision loss of sub-acute onset following an episode of high fever, without any previous visual abnormality. A diagnosis of npAIR was made based on history, clinical findings and multimodal imaging. Intravenous methylprednisolone was started urgently followed by oral steroid. Visual acuity showed good improvement along with gradual restoration of anatomy of retinal layers in Optical Coherence Tomography (OCT) over a period of three months. Our case highlights the importance of suspecting npAIR in paediatric patients presenting with sudden bilateral painless progressive loss of vision without prior visual difficulties and the role of multimodal imaging to aid in diagnosis. The recovery of vision with restoration of photoreceptor layer also shows the nature of the disease to recover with early intervention despite a negative anti-retinal antibody test but with features highly suggestive of npAIR.


With or without human interference for precise age estimation based on machine learning?
Age estimation can aid in forensic medicine applications, diagnosis, and treatment planning for orthodontics and pediatrics. Existing dental age estimation methods rely heavily on specialized knowledge and are highly subjective, wasting time, and energy, which can be perfectly solved by machine learning techniques. As the key factor affecting the performance of machine learning models, there are usually two methods for feature extraction: human interference and autonomous extraction without human interference. However, previous studies have rarely applied these two methods for feature extraction in the same image analysis task. Herein, we present two types of convolutional neural networks (CNNs) for dental age estimation. One is an automated dental stage evaluation model (ADSE model) based on specified manually defined features, and the other is an automated end-to-end dental age estimation model (ADAE model), which autonomously extracts potential features for dental age estimation. Although the mean absolute error (MAE) of the ADSE model for stage classification is 0.17 stages, its accuracy in dental age estimation is unsatisfactory, with the MAE (1.63 years) being only 0.04 years lower than the manual dental age estimation method (MDAE model). However, the MAE of the ADAE model is 0.83 years, being reduced by half that of the MDAE model. The results show that fully automated feature extraction in a deep learning model without human interference performs better in dental age estimation, prominently increasing the accuracy and objectivity. This indicates that without human interference, machine learning may perform better in the application of medical imaging.


Familial aggregation of bone mineral density and bone mineral content in a Chinese population.
Familial aggregation of bone mineral density (BMD) and bone mineral content (BMC) has been shown in twin and familial studies, but most sample sizes were small. We here report a large familial aggregation study in a Chinese population. A total of 13,973 siblings aged 25-64 years from 3,882 families were enrolled from Anhui, China. We assessed the whole-body, hip and lumbar spine BMD and BMC by dual-energy X-ray absorptiometry (DXA). Intra-class correlation coefficients of BMD and BMC between siblings varied among different skeletal sites and between different age groups of male sib-pairs and premenopausal and postmenopausal female sib-pairs, with a range of 0.228 to 0.397. The sibling recurrence risk ratio (lambdas) of osteoporosis was 2.6 in our population. We also evaluated the joint association of the BMD values of the first siblings and the second siblings with the risk of low BMD (defined as less than the 10th percentile of the same group population) of their younger siblings. If both the first and second siblings' BMDs were in the lowest tertile, the odd ratios (ORs) of low BMD in their subsequent siblings were 8.32 [95% confidence interval (CI) 5.59-12.39)], 8.71 (95% CI 5.74-13.22) and 5.90 (95% CI 3.57-9.76) for total body, total hip and lumbar spine, respectively. This study demonstrates a significant familial aggregation of BMD and BMC in a large sample of rural Chinese adults.


Sarcoidosis imitating metastatic cervical cancer.
Sarcoidosis rarely coincides with gynecologic malignancy and thus, may be misdiagnosed as metastatic cancer. We present a 50-year-old patient who was initially treated for cervical carcinoma. She later presented with persistent coughing and mediastinal lymphadenopathy, suspicious for metastatic disease. Following final pathology, a diagnosis of sarcoidosis was made. Sarcoidosis is rarely associated with cervical carcinoma. However, the disease should be considered when metastatic pulmonary disease is suspected in order to avoid excessive or inappropriate treatment.


Return of phacoemulsification after emergency status related to COVID-19: experience of a tertiary referral center.
To present a protocol of priority criteria for phacoemulsification after the backlog due to severe acute respiratory syndrome coronavirus (SARS-CoV)-2 pandemic status. Ophthalmology department of Centro Hospitalar e Universitário do Porto (CHUP), Oporto, Portugal. Cross-sectional, nonrandomized, retrospective study. Data of all patients waiting for cataract surgery were analyzed at the beginning of May 2020, after 2 months without performing elective surgery. The waiting time since surgical inscription was considered an independent and overriding factor. In addition, higher priority was given to patients with white or brunescent cataracts and patients with low visual acuity: corrected distance visual acuity (CDVA) of 20/200 or less in binocular patients or CDVA of 20/63 or less in monocular patients. Criteria of medium priority included patients who remained with anisometropia and patients with glaucoma or low to moderate risk for chronic angle closure. Data of scheduled surgeries in the following months were then analyzed. A total of 717 patients were waiting for phacoemulsification. One hundred ninety-one patients (26.64%) were on the waiting list more than 4.5 months; the medium waiting time was 3.51 ± 1.57 months. According to both priority criteria and waiting time, 348 (48.6%) were categorized as priority cases. A total of 158 patients (22.0%) met the highest priority; 61 patients (8.5%) met the medium priority criteria. In 129 patients (18.0%), priority was considered based solely on higher waiting time. This algorithm allowed surgeons to operate on all priority cases within the first 3 months. The presented protocol showed to be effective, providing a timely surgical opportunity for priority cases.


Binding of two zinc finger nuclease monomers to two specific sites is required for effective double-strand DNA cleavage.
Custom-designed zinc finger nucleases (ZFNs) are becoming powerful tools in gene targeting-the process of replacing a gene within a genome by homologous recombination. Here, we have studied the DNA cleavage by one such ZFN, DeltaQNK-FN, in order to gain insight into how ZFNs cleave DNA and how two inverted sites promote double-strand cleavage. DNA cleavage by DeltaQNK-FN is greatly facilitated when two DeltaQNK-binding sites are close together in an inverted orientation. Substrate cleavage was not first order with respect to the concentration of DeltaQNK-FN, indicating that double-strand cleavage requires dimerization of the FokI cleavage domain. Rates of DNA cleavage decrease as the substrate concentrations increase, suggesting that the DeltaQNK-FN molecules are effectively "trapped" in a 1:1 complex on DNA when the DNA is in excess. The physical association of two ZFN monomers on DNA was monitored by using the biotin-pull-down assay, which showed that the formation of DeltaQNK-FN active complex required both binding of the two DeltaQNK-FN molecules to specific DNA sites and divalent metal ions.


Dietary Information to Support a Healthy Pregnancy in Vietnamese Americans.
Because optimal nutrition is vital during pregnancy, there are specific U.S. dietary guidelines and recommendations for pregnant individuals. However, Vietnamese Americans often have insufficient access to dietary recommendations for pregnancy that pertain specifically to their culture and cuisine. Healthful components of the traditional Vietnamese diet include vegetables, herbs, fruits, fish, and some unsaturated fats. Adjustments to the traditional and acculturated Vietnamese diet, such as reduced sodium intake from fermented foods and sauces, less sugar, more diverse carbohydrate consumption, more fiber, and less fat intake, would improve overall health and potentially reduce the common pregnancy complications pregnant Vietnamese women face, including gestational diabetes and certain micronutrient deficiencies. Understanding the traditional Vietnamese diet can help nurses provide culturally competent care to Vietnamese Americans.


Effects of Deep Reductions in Energy Storage Costs on Highly Reliable Wind and Solar Electricity Systems.
We use 36 years (1980-2015) of hourly weather data over the contiguous United States (CONUS) to assess the impact of low-cost energy storage on highly reliable electricity systems that use only variable renewable energy (VRE; wind and solar photovoltaics). Even assuming perfect transmission of wind and solar generation aggregated over CONUS, energy storage costs would need to decrease several hundred-fold from current costs (to ∼$1/kWh) in fully VRE electricity systems to yield highly reliable electricity without extensive curtailment of VRE generation. The role of energy storage changes from high-cost storage competing with curtailment to fill short-term gaps between VRE generation and hourly demand to near-free storage serving as seasonal storage for VRE resources. Energy storage faces "double penalties" in VRE/storage systems: with increasing capacity, (1) the additional storage is used less frequently and (2) hourly electricity costs would become less volatile, thus reducing price arbitrage opportunities for the additional storage.


Neuropathic Gaucher's disease with normal 4-methylumbelliferyl-beta-glucosidase activity in the liver.
beta-Glucosidase activity was measured in control subjects and in five patients with neuropathic Gaucher's disease. In three patients with Gaucher's disease, methylumbelliferyl- and p-nitrophenyl-beta-d-glucopyranoside (4MU- and PNP-beta-glucosidase) activity was almost normal in the liver but markedly reduced in the spleen and fibroblasts. In the other patients with Gaucher's disease 4MU- and PNP-beta-glucosidase activity was also very much reduced in the liver, spleen, and fibroblasts. DEAE-cellulose column chromatography with a chloride gradient elution of the liver extract from a control subject and from two patients with Gaucher's disease, exhibiting normal 4MU- and PNP-beta-glucosidase activity, revealed the presence of two peaks of 4MU- and PNP-beta-glucosidase activity (fractions 1 and 2). pH activity curves of beta-glucosidases and Km measured with 4MU-beta-glucoside in fractions 1 and 2 from patients with Gaucher's liver were identical to those from the control liver. However, fractions 1 and 2 from infantile Gaucher's liver exhibited no activity measured with glucocerebroside whereas those from juvenile Gaucher's liver showed a considerable activity. Glucocerebroside was greatly accumulated in the liver, even though an almost normal activity of 4MU-beta-glucosidase was detected in three of the five patients studied.


Profiling Specific Inner Ear Cell Types Using Cell Sorting Techniques.
Studies of specific tissue cell types are becoming increasingly important in advancing our understanding of cell biology and gene and protein expression. Prospective isolation of specific cell types is a powerful technique as it facilitates such investigations, allowing for analysis and characterization of individual cell populations. Such an approach to studying inner ear tissues presents a unique challenge because of the paucity of cells of interest and limited cell markers. In this chapter, we describe methods for selectively labeling and isolating different inner ear cell types from the neonatal mouse cochlea using fluorescence-activated cell sorting.


Analysis of isoquinoline alkaloids in medicinal plants by capillary electrophoresis-mass spectrometry.
The technique of capillary electrophoresis - mass spectrometry (CE-MS) was applied for determination of isoquinoline alkaloids in crude methanolic extracts of medicinal plants. For the CE separations ammonium formate buffer solutions (70 or 100 mM, pH 3.0 or 4.0) containing 10% methanol or 20-60% acetonitrile as additives were used. The applied voltage was 25 kV, the thermostating temperature was kept constant at 25 degrees C. Coupling with the mass spectrometer was performed via an atmospherical pressure ionization (API) interface and the electrospray ionization technique (ESI). As sheath liquid 5 mM formic acid in acetonitrile at a flow rate of 3 microL/min was used. The spray voltage was 4.5 kV and the temperature of the heated capillary was chosen to be 200 degrees C. Detection in the positive ionization mode resulted in mass spectra showing either the molecular ions [M]+ or the protonated molecular ions [M+H]+. The presented method allows detection and identification of isoquinoline alkaloids in crude methanolic extracts of medicinal plants as Eschscholzia californica CHAM. (Papaveraceae), Hydrastis canadensis L. (Ranunculaceae), Berberis vulgaris L. (Berberidaceae), Jateorhiza palmata (LAM.) MIERS (Menispermaceae) and Chelidonium majus L. (Papaveraceae).


Severe exacerbation of liver disease during pregnancy in a thalassemic GBV-C/HGV-positive patient and neonatal hepatitis in offspring.
The case of a young woman with GB virus C/hepatitis G virus (GBV-C/HGV) infection and with a severe exacerbation of chronic hepatitis of unknown etiology during pregnancy is described. In the offspring, severe neonatal hepatitis with subsequent mild chronic liver disease of at least 16-month duration was followed by the development of antibodies to the envelope protein (E2) of GBV-C/HGV, suggesting that the child was recovering from GBV-C/HGV infection. There was an improvement in clinical and biochemical parameters in the mother following delivery and alpha-interferon therapy was associated with a transient biochemical response.


Osteoblast elastic modulus measured by atomic force microscopy is substrate dependent.
The actin and microtubule cytoskeleton have been found to contribute to the elastic modulus of cells, which may be modulated by adhesion to extracellular matrix (ECM) proteins and subsequent alterations in the cytoskeleton. In this study, the apparent elastic modulus (Eapp) of osteoblast-like MC3T3-E1 cells adhered to fibronectin (FN), vitronectin (VN), type I collagen (COLI), fetal bovine serum (FBS), or poly-l-lysine (PLL), and bare glass were determined using an atomic force microscope (AFM). The E(app) of osteoblasts adhered to ECM proteins (FN, VN, COLI, and FBS) that bind cells via integrins were higher compared to cells on glass and PLL, which adhere cells through nonspecific binding. Also, osteoblasts adhered to FN, VN, COLI, and FBS had F-actin stress fiber formation, while osteoblasts on glass and PLL showed few F-actin fibers. Disruption of the actin cytoskeleton decreased E(app) of osteoblasts plated on FN to the level of osteoblasts plated on glass, while microtubule disruption had no significant effect. This suggests that the elevated modulus of osteoblasts adhered to FN was due to remodeling of the actin cytoskeleton upon adhesion to ECM proteins. Modulation of cell stiffness upon adhesion to various substrates may influence mechanosignal transduction in osteoblasts.


[Genomic "dactyloscopy" with the use of bacteriophage M13 as a DNA probe (the expertise of material evidence and personal identification)].
In this article the authors give a scientific evaluation of genetic dactyloscopy method in which the sites of human chromosomal DNA, possessing structural polymorphism, act as genetic markers. Technology of genome "dactyloscopy" including both the series of standard conventional methods and new methods is presented. The method is highly sensitive and requires small amounts of material for investigation. A practical case is described when genome "dactyloscopy" gave positive results which led to a conclusion on suspect's involvement in the crime.


Effect of prescribed fire on soil properties and N transformation in two vegetation types in South China.
Prescribed fire is a common site preparation practice in forest management in southern China. However, the effect of fire on soil properties and N transformations is still poorly understood in this region. In this study, soil properties and N transformations in burned and unburned site of two vegetation types (Eucalyptus plantation and shrubland) were compared in rainy and dry seasons after 2 years' prescribed fire. Soil pH and soil NH4-N were all higher in the burned site compared to the unburned control. Furthermore, burned sites had 30-40 % lower of soil total phosphorus than conspecific unburned sites. There was no difference in soil organic matter, total N, soil exchangeable cations, available P or NO3-N. Nitrogen mineralization rate of 0-5 cm soil in the unburned site ranged from 8.24 to 11.6 mg N kg(-1) soil month(-1) in the rainy season, compared to a lower level of 4.82-5.25 mg N kg(-1) soil month(-1) in the burned sites. In contrast, 0-5 cm layer nitrification rate was overall 2.47 mg N kg(-1) soil month(-1) in the rainy season, and was not significantly affected by burning. The reduced understory vegetation coverage after burning may be responsible for the higher soil NH4-N in the burned site. This study highlights that a better understanding the effect of prescribed burning on soil nutrients cycling would provide a critical foundation for management decision and be beneficial to afforestation in southern China.


Effect of walnut protein hydrolysate on scopolamine-induced learning and memory deficits in mice.
A walnut protein hydrolysate (WPH) was prepared by using a mixture of pancreatin and viscozyme L from industrially available defatted walnut meal. The antioxidant effects of WPH were confirmed and quantified by reducing power, oxygen radical absorbance capacity, hydroxyl radical radical-scavenging activity and ABTS+· radical-scavenging activity assays. The protective effects of WPH on scopolamine-induced learning and memory deficits in mice were also evaluated based on in vivo behavioral tests. Results showed that WPH administration would lead to significantly decreased latencies while increased crossing times and target times in the spatial probe test, and increased escape latency and decreased error times in the step-down avoidance test for the scopolamine-induced dementia mice. Biochemical results indicated that the ameliorative effects of WPH on scopolamine-induced dementia mice could be attributed to the significantly increased amount of acetylcholine receptors. Therefore, WPH may be a potential therapeutic agent against Alzheimer's disease.


Stress, coping, and quality of life in the United States during the COVID-19 pandemic.
While research has widely explored stress, coping, and quality of life (QOL) individually and the potential links between them, a critical dearth exists in the literature regarding these constructs in the context of the COVID-19 pandemic. Our study aims to identify the salient stressors experienced, describe the coping strategies used, and examine the relationships between stressors, coping, and QOL among individuals during the pandemic. Data are from a sample of 1,004 respondents who completed an online survey. Key measures included stressful life events (SLEs), coping strategies, and the physical and psychological health domains of QOL. Staged multivariate linear regression analyses examined the relationships between SLEs and the two QOL domains, controlling for sociodemographic and pre-existing health conditions and testing for the effects of coping strategies on these relationships. The most common SLEs experienced during the pandemic were a decrease in financial status, personal injury or illness, and change in living conditions. Problem-focused coping (β = 0.42, σ = 0.13, p < 0.001 for physical QOL; β = 0.57, σ = 0.12, p < 0.001 for psychological QOL) and emotion-focused coping (β = 0.86, σ = 0.13, p < 0.001 for psychological QOL) were significantly related to higher levels of QOL, whereas avoidant coping (β = -0.93, σ = 0.13, p < 0.001 for physical QOL; β = -1.33, σ = 0.12, p < 0.001 for psychological QOL) was associated with lower QOL. Avoidant coping partially mediated the relationships between experiencing SLEs and lower physical and psychological QOL. Our study informs clinical interventions to help individuals adopt healthy behaviors to effectively manage stressors, especially large-scale, stressful events like the pandemic. Our findings also call for public health and clinical interventions to address the long-term impacts of the most prevalent stressors experienced during the pandemic among vulnerable groups.


Intracranial Intraosseous Catheter Placement to Temporize an Epidural Hematoma.
Acute epidural hematomas can lead to rapid neurologic decompensation and death. Epidural hematomas may require emergency surgical clot removal, but many patients live far away from a trauma center. This case report describes a pediatric patient with an acute epidural hematoma with significant neurologic compromise who initially presented to a nontrauma center. The emergency department (ED) had no neurosurgeon or equipment to perform burr hole craniostomy. The emergency physician at the nontrauma ED inserted an intraosseous catheter intracranially to temporarily decompress the hematoma due to long transport times. The patient survived with complete neurologic recovery. This is the youngest known patient in whom an intraosseous catheter was used to drain an intracranial hematoma.


Changing mouth care practice in intensive care: implications of the clinical setting context.
The purpose of the study was to identify the prerequisites for achieving research-based mouth care practice in a district general hospital intensive care unit. An action research approach was adopted and a convenience sample of 10 qualified nurses was studied. Initial identification of current mouth care practice was achieved by observation and interview of these nurses. Following this an in-service teaching and support programme was introduced, after which the identification of any change in practice was made by re-interviewing the same nurses and observing for any change in the availability and use of suitable toothbrushes. Data analysis consisted of comparing information from the before teaching and after teaching observation schedules, and performing content analysis on the before and after teaching interview data. The results indicated that the use of toothbrushes had increased as had the knowledge of oral hygiene after the teaching programme. Factors which were identified as facilitating a change in practice included eliciting the perceptions of those experiencing change so that information and support could be tailored to meet the nurses' needs as they perceived them, the importance of context relevant information and practical instruction, the influence of role models and the availability of suitable brushes. Inhibiting factors included misconceptions about the risk to patient safety associated with toothbrushing.


Understanding the low uptake of long-acting reversible contraception by young women in Australia: a qualitative study.
Australia has high rates of teenage pregnancy compared with many Western countries. Long-acting reversible contraception (LARC) offers an effective method to help decrease unintended pregnancies; however, current uptake remains low. The aim of this study was to investigate barriers to LARC use by young women in Australia. Healthcare professionals were recruited through publicly available sources and snowball sampling to complete an interview about young women's access to and use of LARC. The sample consisted of general practitioners, nurses, medical directors of reproductive and sexual health organisations, a sexual health educator, and health advocates. In addition, four focus groups about LARC were conducted with young women (aged 17-25 years) recruited via health organisations and a university. The data were analysed thematically. Fifteen healthcare professionals were interviewed and four focus groups were conducted with 27 young women. Shared barriers identified included norms, misconceptions, bodily consequences, and LARC access issues. An additional barrier identified by young women was a perceived lack of control over hormones entering the body from LARC devices. Healthcare professionals also raised as a barrier limited confidence and support in LARC insertions. Strategies identified to increase contraceptive knowledge and access included increasing nurses' role in contraceptive provision and education, improving sex education in schools, and educating parents. Challenges remain for young women to be able to make informed choices about contraception and easily access services. More research is needed around innovative approaches to increase LARC knowledge and access, including examining the role of nurses in enhancing young women's reproductive health.


Convulsions induced by hyperbaric oxygen: inhibition by phenobarbital, diazepam and baclofen.
1. The anticonvulsive potencies of diazepam, phenobarbital and baclofen against convulsions induced by oxygen under high pressure (OHP), by isoniazid and by strychnine were investigated in mice and rats. 2. The anticonvulsive potency of diazepam was much higher than that of phenobarbital and baclofen against all three types of convulsions. 3. The selective activity of diazepam against isoniazid induced convulsions in rats (dose ratio ED50 phenobarbital/ED50 diazepam: 400) could not be confirmed in mice (dose ratio ED50 phenobarbital/ED50 diazepam: 20-40), where diazepam was equipotent against all three types of convulsions. 4. Baclofen which does not inhibit strychnine induced convulsions was equipotent in inhibiting convulsions evoked by isoniazid and OHP in mice. 5. The results are in agreement with the postulated GABA-inhibitory mechanism of OHP induced convulsions, whereas they make a glycine inhibitory mechanism very unlikely. Although the results do not allow further conclusions about the mode of action of diazepam, a clinical trial of diazepam in OHP-induced convulsions should be considered.


Treatment of Obesity: Pharmacotherapy Trends of Office-Based Visits in the United States From 2011 to 2016.
To examine pharmacotherapy for obesity in the United States from 2011 to 2016 using a large, nationally representative sample. Data were obtained during 6 years, 2011 to 2016, from the National Ambulatory Medical Care Survey. There were 3 types of visits identified: patients with obesity and an antiobesity drug mention; patients with obesity and no antiobesity drug mention; and patients without obesity and with antiobesity drug mention. The χ2 test was used to compare characteristics across each type of visit. To predict the odds of an antiobesity medication mention for patients with obesity, a logistic regression analysis was conducted. Of the overall weighted 196,872,870 office-based physician visits made by patients with obesity from 2011 to 2016, 1% mentioned an antiobesity drug. In addition, there were 760,470 office-based physician visits by patients without obesity but with an antiobesity medication mention. An antiobesity drug mention was more likely for those aged 51 years or older and those residing in the South (adjusted odds ratio, 5.31 95% CI, 1.19 to 23.59). There was a slight increase in antiobesity medication mentions, from 0.26% in 2011 to 0.28% in 2016, but only 1% of office-based visits for patients with obesity received a prescription for an antiobesity medication. Physicians tended to prescribe antiobesity medications to those with obesity aged 51 years or older and residing in the South. Antiobesity medication for treatment of obesity is significantly underused.


A three-dimensional simulation model of cardiomyocyte integrating excitation-contraction coupling and metabolism.
Recent studies have revealed that Ca(2+) not only regulates the contraction of cardiomyocytes, but can also function as a signaling agent to stimulate ATP production by the mitochondria. However, the spatiotemporal resolution of current experimental techniques limits our investigative capacity to understand this phenomenon. Here, we created a detailed three-dimensional (3D) cardiomyocyte model to study the subcellular regulatory mechanisms of myocardial energetics. The 3D cardiomyocyte model was based on the finite-element method, with detailed subcellular structures reproduced, and it included all elementary processes involved in cardiomyocyte electrophysiology, contraction, and ATP metabolism localized to specific loci. The simulation results were found to be reproducible and consistent with experimental data regarding the spatiotemporal pattern of cytosolic, intrasarcoplasmic-reticulum, and mitochondrial changes in Ca(2+); as well as changes in metabolite levels. Detailed analysis suggested that although the observed large cytosolic Ca(2+) gradient facilitated uptake by the mitochondrial Ca(2+) uniporter to produce cyclic changes in mitochondrial Ca(2+) near the Z-line region, the average mitochondrial Ca(2+) changes slowly. We also confirmed the importance of the creatine phosphate shuttle in cardiac energy regulation. In summary, our 3D model provides a powerful tool for the study of cardiac function by overcoming some of the spatiotemporal limitations of current experimental approaches.


Use of radionuclide imaging to identify malignant mammary tumor bone metastases in dogs.
Radionuclide imaging techniques were used to indicate the location and incidence of bone metastases in 30 dogs with malignant mammary tumors. The method was successful in distinguishing mammary tumor metastases in the sternum of one dog.


[Radiotherapy of prostatic cancer: staging and radiotherapy planning with transrectal ultrasound].
Transrectal ultrasound of the prostate is a cheap and well-reproducible examination for the prostate and seminal vesicles. The local tumor extension of a prostatic carcinoma can be visualized. By documentation of the ultrasound image on a polaroid paper picture, the topometric section of the prostate can be obtained. This picture can be used for dosimetry in individual radiation therapy-planning. Computed tomography is performed for detection of enlarged regional lymph nodes and demonstration of the topographic anatomy of the prostate in the lower pelvis.


The effect of long-term left ventricular assist device support on myocardial sympathetic activity in patients with non-ischaemic dilated cardiomyopathy.
Dilated cardiomyopathy (DCM) patients have abundant levels of norepinephrine secondary to failure of the norepinephrine transporter uptake mechanism. Little is known about the effects of an LV assist device (LVAD) on cardiac sympathetic innervations and norepinephrine transporter dysfunction. This study examines the effects of continuous-flow HeartMate II LVAD on cardiac sympathetic innervations using [(123)I]metaiodobenzylguanidine ([(123)I]MIBG) nuclear imaging. After injecting 431 ± 21 MBq of [(123)I]MIBG, planar scintigraphy was performed at 15 min and 4 h in 14 consecutive non-diabetic non-ischaemic DCM patients. Scans were executed early post-LVAD implantation (T1) and prior to either device explantation for myocardial recovery or transplant listing (T2). [(123)I]MIBG measured parameters included early and delayed heart-mediastinum (H/M) ratios and washout rate (W/O). Catecholamine levels were measured using liquid chromatography-mass spectrometry. Following 208.4 ± 85.5 days of LVAD support, both early and delayed H/M ratios increased by 42.1% (P < 0.001) and 54.7% (P < 0.001), respectively. The W/O rate decreased by 46% (P = 0.003). Plasma norepinephrine, epinephrine, and dopamine decreased significantly in correlation with [(123)I]MIBG parameters. Ten patients had recovered and had their device explanted as they had demonstrated a higher percentage change in delayed H/M ratio, W/O rate, and norepinephrine levels. Linear regression analysis revealed a strong correlation between percentage changes in both norepinephrine and epinephrine and myocardial recovery. Combination therapy with LVAD and drug resulted in enhancement of [(123)I]MIBG uptake in DCM patients.


FOXO1 regulates osteogenic differentiation of periodontal ligament stem cells through the METTL3 signaling pathway.
Periodontitis is a chronic inflammation that occurs in periodontal tissue and has a high incidence rate. Periodontal ligament stem cells (PDLSCs) are ideal candidates for periodontal tissue and bone regeneration in patients with periodontitis. The purpose of this work was to analyze the molecular mechanisms that affect the osteogenic differentiation of PDLSCs. In this work, qRT‒PCR was used to detect the mRNA expression level of FOXO1 in clinical tissues and PDLSCs. Alkaline phosphatase (ALP) staining and Alizarin red S (ARS) staining were used to detect the degree of osteogenic differentiation of PDLSCs. qRT‒PCR and western blotting were used to measure the levels of the early osteogenic markers COL1A1 and RUNX2. The JASPAR online database was used to predict FOXO1-regulated genes. FOXO1 was generally expressed at low levels in clinical samples from patients with periodontitis. We provided evidence that overexpression of FOXO1 promoted osteogenic differentiation in PDLSCs. In addition, both in vitro and rescue experiments showed that FOXO1 regulated METTL3. FOXO1 affected osteogenic differentiation mainly by regulating METTL3 modification of the PI3K/AKT pathway. FOXO1 activated the PI3K/AKT signaling pathway by transcriptionally activating METTL3. This effect promoted the osteogenic differentiation of PDLSCs.


Hydrogen peroxide, an inhibitor of platelet function: effect on adenine nucleotide metabolism, and the release reaction.
The in vitro effects of H2O2 on platelet adenine nucleotide metabolism and on the ADP-induced platelet release reaction were examined. All studies were performed on human platelet-rich plasma (PRP) preincubated with (3H)-adenine. Within 3 min of incubation with PRP, H2O2 (100-500 micronM) caused an irreversible reduction in the (3H)-ATP level with a concomitant increase in (3H)-IMP and (3H)-inosine and hypoxanthine levels. The adenylate energy charge (AEC) initially decreased while the ATP level fell. The AEC, however, returned to levels slightly lower than the control during further incubation. No leakage of ATP and ADP to plasma was observed. The fall in the steady-state levels of (3H)-ATP increased with increase of the H2O2 concentration (decrease of 8.7-40% at H2O2 concentrations from 5 to 600 micronM). H2O2 pretreatment of PRP caused absence of ADP-induced biphasic aggregation, partial inhibition of the primary wave, and complete inhibition of release of platelet nonmetabolic ATP and ADP. Our in vitro findings support the view that part of the inhibitory effect of H2O2 may be related to the lowering of metabolic ATP levels in platelets.


Absorption of odourous substances using selective gas-liquid separation processes.
Absorption is one of the most widely used techniques for treating odourous waste gases. An improvement of the effectiveness of gas scrubbers can be achieved by using adapted washing liquids. A screening test is proposed as a low cost tool for testing washing liquids on industrial waste gases. The odour index is used to identify the main cause of the specific smell and to simplify the analysis of absorptive performances of washing liquids. The method is verified by experiments at a chocolate factory and a fat and oil refinery.


Gene-rich X chromosomes implicate intragenomic conflict in the evolution of bizarre genetic systems.
Haplodiploidy and paternal genome elimination (HD/PGE) are common in invertebrates, having evolved at least two dozen times, all from male heterogamety (i.e., systems with X chromosomes). However, why X chromosomes are important for the evolution of HD/PGE remains debated. The Haploid Viability Hypothesis posits that X-linked genes promote the evolution of male haploidy by facilitating purging recessive deleterious mutations. The Intragenomic Conflict Hypothesis holds that conflict between genes drives genetic system turnover; under this model, X-linked genes could promote the evolution of male haploidy due to conflicts with autosomes over sex ratios and genetic transmission. We studied lineages where we can distinguish these hypotheses: species with germline PGE that retain an XX/X0 sex determination system (gPGE+X). Because evolving PGE in these cases involves changes in transmission without increases in male hemizygosity, a high degree of X linkage in these systems is predicted by the Intragenomic Conflict Hypothesis but not the Haploid Viability Hypothesis. To quantify the degree of X linkage, we sequenced and compared 7 gPGE+X species' genomes with 11 related species with typical XX/XY or XX/X0 genetic systems, representing three transitions to gPGE. We find highly increased X linkage in both modern and ancestral genomes of gPGE+X species compared to non-gPGE relatives and recover a significant positive correlation between percent X linkage and the evolution of gPGE. These empirical results substantiate longstanding proposals for a role for intragenomic conflict in the evolution of genetic systems such as HD/PGE.


Effect of carbon dioxide injection on production of wood cement composites from waste medium density fiberboard (MDF).
The possibility of recycling waste medium density fiberboard (MDF) into wood-cement composites was evaluated. Both new fibers and recycled steam exploded MDF fibers had poor compatibility with cement if no treatment was applied, due to interference of the hydration process by the water soluble components of the fiber. However, this issue was resolved when a rapid hardening process with carbon dioxide injection was adopted. It appears that the rapid carbonation allowed the board to develop considerable strength before the adverse effects of the wood extractives could take effect. After 3-5 min of carbon dioxide injection, the composites reached 22-27% of total carbonation and developed 50-70% of their final (28-day) strength. Composites containing recycled MDF fibers had slightly lower splitting tensile strength and lower tensile toughness properties than those containing new fibers especially at a high fiber/cement ratio. Composites containing recycled MDF fibers also showed lower values of water absorption. Unlike composites cured conventionally, composites cured under CO(2) injection developed higher strength and toughness with increased fiber content. Incorporation of recycled MDF fibers into wood cement composites with CO(2) injection during the production stage presents a viable option for recycling of this difficult to manage waste material.


Organic cation/carnitine transporter OCTN2 (SLC22A5) -207C>G (rs2631367) polymorphism is not associated with male infertility.
Carnitine is an important factor in the initiation of progressive sperm motility and end stage of sperm maturation. The compound is transported by an organic cation/carnitine transporter (OCTN2), which is expressed in the male reproductive system. OCTN2 is encoded by SLC22A5 gene with proven -207C>G functional polymorphism. The aim of the case-control study was to investigate a potential association between the -207C>G SLC22A5 polymorphism and male infertility. The -207C>G SLC22A5 polymorphism was determined by means of TaqMan assay in 206 infertile Caucasian males and 256 ethnically matched controls. Besides genotyping study, sperm mitochondrial function was assessed using NADH-dependent NBT assay. The distribution of SLC22A5 genotypes in infertile men was as follows: CC - 29.6%, CG - 53.9%, GG - 16.5% and in fertile men: CC - 32.0%, CG - 50.0%, GG - 18.0%, and was comparable in both evaluated groups. Likewise, the studied polymorphism did not affect sperm mitochondrial function. The results of the current study demonstrated that -207C>G polymorphism of the SLC22A5 gene is not associated with male infertility.


Practical Method for Freezing Buck Semen.
Although several protocols for cryopreserving buck semen are described in the literature, they differ widely in factors such as season and method of semen collection, extender and sperm concentration. Therefore, choosing a protocol that is suitable for a particular on-farm situation can be problematic. In the present study, semen was collected by artificial vagina from seven bucks on a farm located approximately 90 minutes' drive away from the laboratory, about 6 weeks before the start of the goat breeding season. The semen was immediately extended in warm semen extender containing soy lecithin and was placed in an insulated box with a cold pack for up to 4 h, during semen collection from the remaining bucks and subsequent transport to the laboratory. Following centrifugation at 4 °C and resuspension in the soy lecithin extender to a sperm concentration of 800 × 106 spermatozoa/mL, 0.25 mL plastic straws were filled and frozen in racks 4 cm above the surface of liquid nitrogen. This simple protocol resulted in an acceptable post-thaw quality for all seven bucks, with a mean post-thaw motility of 55 ± 21% and mean fragmented chromatin of 3.27 ± 1.39%. Normal sperm morphology was >90% in all ejaculates. The semen was sent to a gamete bank for long-term storage.


Validation of the Besta Neurological Institute rating scale for myasthenia gravis.
We validated the scale for myasthenia gravis (MG) developed at the Neurological Institute Foundation of Milan (INCB-MG scale). A total of 174 patients were evaluated with the INCB-MG and compared with the MG Composite (MGC) as the gold standard. Dimensionality, reliability, and validity of the INCB-MG scale were studied by principal component factor analysis, Cronbach alpha, and Pearson correlation coefficients; interobserver reliability was calculated by the weighted Cohen K coefficient. Generalized and bulbar INCB-MG subscales were unidimensional with excellent consistency; the INCB-MG and MGC scales were strongly correlated. Fatigability assessment was correlated with the INCB-MG generalized, bulbar, and respiratory subscales. The INCB-MG scale is a reliable tool to assess MG and is strongly correlated with the MGC. The INCB-MG scale is a valid tool for every day practice and should be further investigated for its application in clinical trials.