Association between driving a car and retention of brain volume in Japanese older adults.
Driving cessation is a major negative life event that has been associated with a decline in health conditions including dementia. The increase in activity owing to the expansion of life space is a possible explanation for the positive relationship between driving and brain health. The present study examined the association between driving, life space, and structural brain volume in older individuals. High-resolution magnetic resonance imaging was employed to examine the brain volume in 1063 older adults. Participants were classified as non-drivers, those who drove <7 days a week, and everyday drivers. They were further classified into a non-driving group, an active group (drove 10 km at least once a week), and a less-active group (drove 10 km less than once a week). The hippocampal volume was greater in drivers than in non-drivers. Occipital cortex volume was greater in low-frequency drivers than in non-drivers and high-frequency drivers. Active drivers exhibited larger temporal cortex volumes than less-active drivers, larger cingulate cortex volumes than non-drivers and less-active drivers, and larger hippocampal volumes than non-drivers. Driving was associated with hippocampal brain atrophy attenuation, with active drivers exhibiting decreased brain atrophy in the temporal and cingulate cortices.


A practical, clinical approach to the assessment and management of suspected insulin allergy.
Although allergic reactions to insulin are uncommon, they can be difficult to diagnose and management may be very difficult in subjects with Type 1 diabetes with severe allergy. Access to allergists and specialist diagnostic tests is limited and few diabetes specialists are familiar with desensitization as a means of treating allergy. People with diabetes may develop symptoms which mimic insulin allergy but are attributable to other conditions. Here we describe three cases of insulin allergy. One patient presented with severe, albeit localized, urticarial reactions at injection sites. The most severe case was a woman with recent-onset Type 1 diabetes who presented with grade 2 anaphylaxis. The third patient presented with generalized urticaria and angioedema. Insulin allergy was confirmed in all three cases. Assessment involved measurement of immunoglobulin and anti-insulin antibody levels. Skin testing was performed in two cases. Treatments included desensitization in one case, alternative insulin preparations, antihistamines and continuous subcutaneous insulin infusion. In all three cases of insulin allergy there has been successful resolution of symptoms. The clinical assessment and investigation in cases of suspected insulin allergy is described, along with detailed algorithms for skin testing and desensitization. This case series demonstrates an approach to challenging cases of suspected insulin allergy which will be helpful for diabetes specialists.


[Quantitative characteristics of the cortex area 4y associative projections to subfields of the sensomotor and parietal cerebral cortex in cat].
The ipsilateral association connections of the motor cortex area 4y after its local electrolytic lesion in the cat were studied using Nauta-Gigax method. Relative quantitative distribution of the efferent association fibers projecting from area 4y to the somatosensory regions I and II, motor and parietal cortex, was determined. It was shown that the major projections from area 4y are directed to area 2pri (secondary somatosensory zone) and to area 5ab. Sparse degenerating fibers were found in the areas 1, 2, 3a and 3b of the primary somatosensory cortical zone. No efferent fibers were traced projecting from area 4y to the areas 4fu, 4sfu, 6aa, 6ab and 6ifu. It is suggested that the morphological basis of the motor reactions implemented by area 4y is formed not by fundal (4fu, 4sfu, 6ifu) or premotor (6aa, 6ab) subfields, but by the areas 2pri and 5ab which are involved to a maximum degree.


Does bladder wall thickness decrease when obstruction is resolved?
The aim of the current study was to determine if sonographic bladder wall thickness diminishes after symptomatic obstruction is resolved in female patients after stress incontinence surgery. Between December 2008 and December 2010, 62 female patients with symptomatic bladder outlet obstruction, as defined by Blaivas, who had undergone prior surgery for urinary stress incontinence were included in the study. The patients' history was taken and symptoms were noted. Patients underwent gynaecological examination, and multichannel urodynamic assessment was performed. Vaginal sonographic assessment of the bladder wall thickness (BWT) was performed before and after urethrolysis. 62 patients were included in this study, 55 of whom had undergone suburethral sling insertion and seven had Burch colposuspension. Postoperatively, BWT decreased significantly from 9.1 mm ± 2.1 to 7.6 mm ± 2.2 (p < 0.0001). In seven patients, obstruction was still unresolved postoperatively; of these, two had undergone a retropubic sling insertion and two had a Burch colposuspension. An ROC curve analysis showed a significant positive association between residual urine and persistent obstruction before surgery (AUC 0.76, 95%CI 0.58-0.94; p < 0.05). If obstruction is resolved, bladder wall thickness decreases. Preoperatively elevated residual urine may increase the risk of persistent obstruction after urethrolysis.


[Comparative study of the antidepressant and anxiolytic activity of fluoxetine and tianeptine].
The activity of fluoxetine (prozac) and tianeptine (coaxil) was studied in outbred male rats under Porsolt and S. Nomura modified forced swim tests. The antidepressant effect of tianeptine was much more pronounced that that of fluoxetine. In the conflict situation test, fluoxetine produced anxiogenic action. In contrast, tianeptine decreased (albeit not reliably) the anxiety. In combination with bicuculline (GABAA receptor blocker), the anxiolytic action was more pronounced for both antidepressants, which was manifested by a significant increase in the number of punished water takes. A neural network explaining the observed behavior is proposed, which includes GABA-ergic intemeurons inhibiting serotonin release from serotoninergic terminals.


[Solitary bone cysts of the pelvis. A frequently misinterpreted entity].
Solitary bone cyst of the pelvis is a rare lesion. The diagnosis is relatively simple providing sufficient material is accumulated during biopsy or surgery. Calcifying forms often cause difficulties in terms of differential diagnosis. Radiographic imaging can be complex when examining large lesions of the pelvis. Biopsy is the method of choice for definitive diagnosis, which should be verified against material gathered surgically or during curettage. Bone tumors of the pelvis have to be considered in the differential diagnosis of the lesion. Large cystic lesions of the pelvis in particular are to be reviewed pathohistologically to avoid false diagnosis. The consequences for the patient in terms of quality of life and life expectancy can be serious. The need for interdisciplinary cooperation is greater than ever to ensure correct diagnosis and therapy of bone lesions.


Uncooled Microwave Ablation as a Treatment Option to Preserve Thyroid Function in Patients with Benign Thyroid Nodules.
The objective is to evaluate the long-term efficacy and safety of uncooled MWA for the treatment of benign thyroid nodules and its long-term effect on thyroid functions. The study was conducted on 40 patients with 40 nodules. They were treated between September 2019 and December 2020. Nodules' volumes, thyroid functions (triiodothyronine, free thyroxine, thyrotropin) and anti-thyroid peroxidase and anti-thyroglobulin antibodies were measured before treatment and at 3rd, 6th and 12th month following the treatment. Volume reduction rates and changes in clinical findings were evaluated. The mean volume reduction rate was 49.88, 65.3, and 79.06% at 3rd, 6th, and 12th month, respectively. Antibody levels and thyroid function tests have remained within normal limits and were not exhibited significant change during follow-ups (p > 0.05), except for a significant increase in free thyroxin level at 12th-month (p = 0.007). Subjective symptoms and cosmetic scores were significantly improved all follow-up (p < 0.0001). The only complication was a first-degree skin burn in a patient. In conclusion, uncooled microwave ablation is an effective and safe method for the treatment of benign thyroid nodules and preserves thyroid function.


Seasonal and spatial variation in Toxoplasma gondii contamination in soil in urban public spaces in California, United States.
Toxoplasma gondii is a zoonotic parasite that can have severe implications for human health. Acutely infected cats shed environmentally resistant T. gondii oocysts in their faeces that contaminate soil, and soil can serve as a reservoir of infection for humans. Free-roaming domestic cats are thought to play an important role in environmental contamination with T. gondii, but few studies have directly measured the direct contribution of free-roaming cats to T. gondii in soil. Our goals were to determine whether T. gondii soil contamination occurs in public areas with free-roaming cat colonies in central California and examine spatial and temporal variation in soil contamination. We initially performed spiking experiments to compare the limit of T. gondii detection in soil using three conventional nested PCR assays and one real-time quantitative PCR. The nested PCR targeting the internal transcribed spacer (ITS-1) of the small subunit ribosomal RNA was the most sensitive assay, with a limit of detection between 20 and 200 oocysts per gram of soil. We applied the ITS1 PCR assay on soil from sites in city and state parks, public playgrounds and community gardens in central California, USA. Samples were collected during spring, summer and fall and in sites located along the coast and inland. We detected and sequence-confirmed T. gondii in 5.6% of all of our soil sub-samples, but with large seasonal and spatial variation in soil contamination: we only detected T. gondii during fall and only in coastal sites (44.3% soil prevalence), despite similar sampling intensity across space and time. Our results suggest that free-roaming cat colonies are an important source of T. gondii in spaces where people recreate and grow food and that soil contamination is highly seasonal and spatially variable. Management of free-roaming cats could prevent T. gondii infections by reducing environmental contamination with this zoonotic pathogen.


Salivary IgA antibodies to antigens from Streptococcus mutans in human dental caries.
1) Subjects of low caries experience (DMF 7) had significantly lower IgA antibody titers to antigens from S. mutans serotype c than subjects of high caries experience (DMF 13). 2) Subjects with carious lesions and a high DMF had significantly lower salivary antibody titers than subjects without carious lesions. 3) Sequential studies revealed that in the absence of caries salivary antibody titers decreased over a 9 month period. 4) Treatment of caries was associated with a rise in salivary IgA antibodies. No significant changes were associated with the development of caries. 5) No relationship with caries experience was found with antibodies to S. mutans BHT (serotype b), S. sanguis OMZ-9 or S. mitis CHT. 6) The results do not support the hypothesis that salivary antibodies in man play a role in protection against caries.


Relationships Between Cross-Cultural Adaption, Perceived Stress and Psychological Health Among International Undergraduate Students From a Medical University During the COVID-19 Pandemic: A Moderated Mediation Model.
International university students may be at greater risk for developing psychological problems due to the unique stressors in them, particularly during the COVID-19 pandemic. The purpose of present study is to propose and test a moderated mediation model that would illuminate the underlying relationships of cross-cultural adaption, perceived stress and psychological health as well as the moderating effect of optimism and resilience among international medical undergraduates in China during the COVID-19 pandemic. The study was conducted via a web-based survey in November 2020. Electronic informed consents were obtained from all participants. A total of 453 students including 233 males and 220 females aged 18 to 28 years with an average age of 22.09 (SD = 2.73) completed the questionnaires. Symptom Checklist 90, the measurement of cross-cultural adaption, the Perceived Stress Scale, the Life Orientation Test-Revised and the Resilience Scale were used for the survey. Results for the moderated mediation model testing revealed that cross-cultural adaption significantly and negatively associated with the Global Severity Index (GSI) of the Symptom Checklist 90 (β = -0.24, P < 0.01), and perceived stress partially mediated the relationship. Optimism (β = -0.29, P < 0.01) and confidence in COVID-19 control (β = -0.19, P < 0.01) had direct negative effects on perceived stress. Furthermore, optimism and resilience negatively moderated the indirect effect of cross-cultural adaption on psychological health through perceived stress. Findings of this study suggest that university educators ought to promote or make use of programs that cope with stress and boost optimism and resilience in order to support students not only adapt well to a new culture, but also keep good psychological health during the period of COVID-19 pandemic.


Psychosocial contributors to patients' and partners' postprostate cancer sexual recovery: 10 evidence-based and practical considerations.
Sexual recovery after prostate cancer (PCa) treatment is challenging. When expectations are that erectile response will quickly return to baseline, patients can often struggle when this does not happen. Further difficulty is experienced when patients encounter physical, psychological, and relational barriers to sexual adjustment. Drawing on the psychosocial research literature and on 15 years of clinical experience counseling PCa patients about sexual recovery, this paper outlines considerations for clinical practice. Suggestions include broadening the target for successful outcomes after Pca treatment beyond erectile function to include sexual distress and other sources of sexual concern. Clinicians are urged to consider individual differences such as the larger context of the patient, including their values and preferences, their treatment goals, and their relationship situation and status, in order to promote successful sexual adaptation. When introducing treatment approaches, the role of grief and loss should be assessed, and patients should be supported to foster realistic expectations about the recovery process. Suggestions for how to introduce various sexual strategies to patients are also offered, including ways to support patients in making and sustaining behavioral changes associated with sexual intervention. Clinicians are offered suggestions to promote patients' sexual flexibility, prevent long periods of sexual inactivity, and help patients to identify various sexual motivators. Consideration of these psychological, relational, and social factors are all likely to help facilitate better sexual outcomes for PCa patients.


Cell biology and pathophysiology of the diacylglycerol kinase family: morphological aspects in tissues and organs.
Diacylglycerol kinase phosphorylates diacylglycerol to produce phosphatidic acid. These lipids serve not only as intermediate products in the synthesis of several lipids but also as bioactive molecules. Therefore diacylglycerol kinase is thought to play one of the central roles in lipid signal transduction via the metabolism of two messenger molecules. Molecular and cellular studies have revealed that diacylglycerol kinase consists of a family of isozymes and each has a unique character in terms of regulatory mechanism, binding partner, and subcellular localization. This review focuses on pathophysiological findings of the enzyme family, principally from a morphological point of view in tissues and organs in animal studies, which helps us to develop a picture of how diacylglycerol kinase works in our body.


Enhanced osseointegration of double network hydrogels via calcium polyphosphate incorporation for bone regeneration.
To overcome the low mechanical strength and difficult bonding of hydrogels to bones which are the major limitations of hydrogels used in bone-regeneration, a new type of calcium polyphosphate incorporated into bioinspired alginate/polyacrylic acid (CPP/PAA-Alg) hybrid double network (DN) hydrogel with both high strength and enhanced osseointergration was prepared by a two-step polymerization with alginate and polyacrylic acid for bone regeneration. The morphology, mechanical properties, swelling, biocompatibility, osseointegration and osteogenic ability of this CPP/PAA-Alg DN hydrogel were investigated. The results show that CPP/PAA-Alg DN hydrogel with highly porous microstructure possesses high water absorption capacity and highly strength properties which meet the requirements of bone repairing. The results of in vitro studies revealed that the CPP/PAA-Alg DN hydrogels can support the spread of cells and promote the cell proliferation. Animal studies demonstrated that the CPP incorporated would enhance the osseointegration of DN hydrogel with host bone at an early stage after implantation to accelerate the regeneration of bone. This research may provide a new way to develop biocompatible biomaterials with high mechanical strength and good osseointegration to meet the needs of bone regeneration.


Determination of the new monoamine oxidase inhibitor moclobemide and three of its metabolites in biological fluids by high-performance liquid chromatography.
A sensitive high-performance liquid chromatographic method has been developed for the determination of moclobemide and three of its metabolites in plasma and urine. The four substances and the internal standard were extracted from basified plasma (pH 11) with dichloromethane, with recoveries of generally more than 70%. A column packed with 5-microns Spherisorb hexyl phase and an eluent consisting of acetonitrile and aqueous phosphate buffer 30:320 (v/v) with a pH of 3.9 were found most suitable for the chromatographic separation of the four compounds of interest. Non-ideal interactions of the basic compounds and the N-oxide metabolite occurred with many other reversed-phase materials, as indicated by broad and tailing peaks. Limits of quantitation for moclobemide and its three metabolites in the range 20-30 ng/ml and a good intra-assay reproducibility ranging between 2 and 5% for concentrations over 100 ng/ml could be achieved for plasma, which increased to ca. 8-10% at a concentration of 50 ng/ml.


Interleukin-1 Mediates Ischemic Brain Injury via Induction of IL-17A in γδ T Cells and CXCL1 in Astrocytes.
As a prototypical proinflammatory cytokine, interleukin-1 (IL-1) exacerbates the early post-stroke inflammation, whereas its neutralization is protective. To further investigate the underlying cell-type-specific IL-1 effects, we subjected IL-1 (α/β) knockout (Il1-/-) and wildtype (WT) littermate mice to permanent middle cerebral artery occlusion (pMCAO) and assessed immune cell infiltration and cytokine production in the ischemic hemisphere by flow cytometry 24 h and 72 h after stroke. Il1-/- mice showed smaller infarcts and reduced neutrophil infiltration into the ischemic brain. We identified γδ T cells and astrocytes as target cells of IL-1 signaling-mediated neutrophil recruitment. First, IL-1-induced IL-17A production in γδ T cells in vivo, and IL-17A enhanced the expression of the main neutrophil attracting chemokine CXCL1 by astrocytes in the presence of tumor necrosis factor (TNF) in vitro. Second, IL-1 itself was a potent activator of astrocytic CXCL1 production in vitro. By employing a novel FACS sorting strategy for the acute isolation of astrocytes from ischemic brains, we confirmed that IL-1 is pivotal for Cxcl1 upregulation in astrocytes in vivo. Our results underscore the pleiotropic effects of IL-1 on immune and non-immune cells within the CNS to mount and amplify the post-stroke inflammatory response.


Extremely Widespread Parthenogenesis and a Trade-Off Between Alternative Forms of Reproduction in Mayflies (Ephemeroptera).
Studying alternative forms of reproduction in natural populations is of fundamental importance for understanding the costs and benefits of sex. Mayflies are one of the few animal groups where sexual reproduction co-occurs with different types of parthenogenesis, providing ideal conditions for identifying benefits of sex in natural populations. Here, we establish a catalog of all known mayfly species capable of reproducing by parthenogenesis, as well as species unable to do so. Overall, 1.8% of the described species reproduce parthenogenetically, which is an order of magnitude higher than reported in other animal groups. This frequency even reaches 47.8% if estimates are based on the number of studied rather than described mayfly species, as reproductive modes have thus far been studied in only 17 out of 42 families. We find that sex is a more successful strategy than parthenogenesis (associated with a higher hatching success of eggs), with a trade-off between the hatching success of parthenogenetic and sexual eggs. This means that improving the capacity for parthenogenesis may come at a cost for sexual reproduction. Such a trade-off can help explain why facultative parthenogenesis is extremely rare among animals despite its potential to combine the benefits of sexual and parthenogenetic reproduction. We argue that parthenogenesis is frequently selected in mayflies in spite of this probable trade-off because their typically low dispersal ability and short and fragile adult life may frequently generate situations of mate limitation in females. Mayflies are currently clearly underappreciated for understanding the benefits of sex under natural conditions.


Gamma knife radiosurgery for neuroepithelial tumors: radiological and histological changes.
Gamma knife radiosurgery (RS) has been introduced as a modern therapy for brain tumors. However, the effects of RS for neuroepithelial tumors are still obscure. The present study investigates the radiological and histological changes after RS to elucidate the biological effect. There were seven cases (two males and five females), ranging from 4 to 71 years with a mean age of 33 years. Two cases were located in the brainstem, another two in the cerebellum, and one each in the thalamus, the hypothalamus, and the frontal lobe. Histologically, two cases had gangliogliomas, four astrocytomas (1 pilocytic, 1 fibrillary, 2 anaplastic), and one glioblastoma. RS was performed after surgery with a central dose of 30-36 Gy. All cases were evaluated radiologically on MRI before and after RS. Four cases (3 astrocytomas and 1 glioblastoma) which neurologically deteriorated after RS were reoperated. These cases were examined using HE and immunohistochemical studies with antibodies of CD34, alpha-smooth muscle actin (SMA), p53, p21 and MIB-1 on the sections before and after RS. MRI demonstrated perifocal edema and intratumoral hypointensity on T2 weighted imaging (T2WI), suggesting radionecrosis in most of the cases within 6 months after RS. In the central part of the RS, destructive changes were observed in the tumor cells and endothelial cells: decrease in the tumor cell population, coagulation necrosis, and fibrinoid degeneration of vascular walls were revealed. In the peripheral part, however, some tumors contained viable tumor cells intermingled with blood vessels showing endothelial and pericytic proliferations. The increase of MIB-1 staining index was found in only one case. The p21 immunoreactivity was increased in endothelial cells, although the p53 immunoreactivity was unchanged. These results suggested that radionecrosis occurred earlier and more frequently in neuroepithelial tumors after RS than after conventional radiation.


Contextual Influences on Distress Intolerance: Priming Effects on Behavioral Persistence.
Distress intolerance (DI), the inability to tolerate stressful experiences, has been linked to multiple psychiatric conditions and maladaptive coping patterns. Although DI is often considered a trait-like variable, evidence indicates that self-report and behavioral indices of DI can be manipulated by contextual factors. Understanding such contextual influences is important given evidence of unexpected variability in these presumed trait-like measures over brief intervals. The current study examined the influence of context (manipulated by priming concepts of "Interminability" and "Brevity") in predicting behavioral persistence, in relation to self-reported DI. Results indicated that priming Brevity was associated with terminating a cold-pressor task more quickly. Self-reported DI was linked to earlier termination, but there was no interaction between self-reported DI and priming condition. Results indicate that contextual cues modulate performance on behavioral measures of DI. Hence, models of DI should consider both trait-like and contextual factors in understanding variability in DI measures.


Incomplete collisions in strongly dispersion-managed return-to-zero communication systems.
Incomplete collisions in wavelength-division-multiplexed return-to-zero transmission systems are analyzed by asymptotic methods. Formulas for frequency and timing shifts are obtained. The results agree with direct numerical calculations.


Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo-controlled trials in adults with severe constipation.
Patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) often experience severe symptoms. The current aim was to evaluate plecanatide in adults with CIC or IBS-C with severe constipation. Data were analyzed post hoc from randomized, placebo-controlled trials (CIC [n = 2], IBS-C [n = 2]) of plecanatide 3 mg, 6 mg, or placebo administered for 12 weeks. Severe constipation was defined as no complete spontaneous bowel movements (CSBMs) and an average straining score ≥3.0 (CIC; 5-point scale) or ≥8.0 (IBS-C; 11-point scale) during a 2-week screening. Primary efficacy endpoints were durable overall CSBM responders (CIC: ≥3 CSBMs/week, plus increase from baseline of ≥1 CSBM/week, for ≥9 of 12 weeks, including ≥3 of the last 4 weeks) and overall responders (IBS-C: ≥30% reduction from baseline in abdominal pain and ≥1 CSBM/week increase for ≥6 of 12 weeks). Severe constipation was observed in 24.5% (646/2639) and 24.2% (527/2176) of CIC and IBS-C populations, respectively. The CIC durable overall CSBM response rate (plecanatide 3 mg, 20.9%; plecanatide 6 mg, 20.2%; placebo, 11.3%) and IBS-C overall response rate (plecanatide 3 mg, 33.0%; plecanatide 6 mg, 31.0%; placebo, 19.0%) were significantly greater with plecanatide versus placebo (p ≤ 0.01 for all). Median time to first CSBM in CIC and IBS-C populations were significantly shorter with plecanatide 3 mg versus placebo (p = 0.01 for both). Plecanatide was effective in the treatment of severe constipation in adults with CIC or IBS-C.


[Legislation on logopedics. Documentation on the draft for a federal law on the profession of speech therapist].
A law for studying logopedics was established by the authorities of the Federal Republic of Germany. On account of a political concept of education the conditions for admittance studying logopedics are based on an extremely low level. Reasons for rejecting these admitting conditions are displayed from a phoniatrical view.


Locating the sources for cross-modal interactions and decision making during judging the visual-affected auditory intensity change.
Audiovisual interaction has been one of the most important topics in cognitive neurosciences. Visual stimuli could significantly impact the auditory perception, and vice versa. Nevertheless, how much the change in visual stimuli would influence the perception of auditory change remains to be investigated. In this paper, we designed an audiovisual experiment in which subjects were required to judge whether there is a change in the intensities of two sounds with 150 ms interval, while there are two simultaneously presented size-changed visual stimuli. Behavioral results demonstrated that incongruent audiovisual change could result in the illusory perception of the change in sound intensity. For the correctly judged trials, source analysis showed two characteristic windows post the first auditory stimulus, i.e., (i) the 160-200 ms window including the auditory P200 and visual N100 wave, which was related to audiovisual interaction and working memory of the first stimulus with localized sources in insula and agranular retrolimbic area; and (ii) the 300-400 ms window for P300 with sources in premotor cortex and caudate nucleus, which were related to later audiovisual interaction, change discrimination and working memory. These preliminary results implied two stages in the audiovisual change perception task, with the involvement of insula, agranular retrolimbic, premotor cortex and caudate nucleus.


[A method for testing the phagocytic capacity and activation of neutrophilic granulocytes. Enhancement after preincubation in the subjects own serum and intravenous immunoglobulin preparations (preliminary communication)].
Heat inactivated S. cerevisiae as phagocytic particle and subsequent staining with trypan blue-eosin solution is suitable to give evidence of phagocytic capacity and the number of human polymorphonuclear leucocytes which are engaged in phagocytosis. After preincubation of the yeasts with i.v. IgG-preparations--and on a higher rate--with volunteers' own serum increase of phagocytic capacity and of the number of granulocytes which take part in phagocytosis occurs. The test is suitable to compare this granulocyte function of patients under different clinical conditions depending on the underlying disease and seems to be of use to decide where clinical application of polyvalent immunoglobulin therapy is indicated.


Unexpected identification and characterization of a cathinone precursor in the new psychoactive substance market: 3',4'-methylenedioxy-2,2-dibromobutyrophenone.
3',4'-methylenedioxy-2,2-dibromobutyrophenone has been identified and fully characterized in a sample obtained from an anonymous consumer acquired as ketamine through the Internet market. The substance has been deeply characterized by using standard and high performance analytical techniques such as: attenuated total reflectance-infrared spectroscopy, gas chromatography-mass spectrometry, high-resolution mass spectrometry, elemental analysis, and nuclear magnetic resonance, including 1H, 13C, distortionless enhancement by polarization transfer, two dimensional homonuclear 1H-1H correlation spectroscopy, and 1H-13C heteronuclear single-quantum correlation spectra. 3',4'-methylenedioxy-2,2-dibromobutyrophenone is a precursor or intermediate in the synthesis of several synthetic cathinone derivatives, such as pentylone and methylenedioxy pyrovalerone. It is expected that 3',4'-methylenedioxy-2,2-dibromobutyrophenone does not act as psychoactive substance through disruption nor dysregulation of central and peripheral nervous systems, due to the absence of the characteristic amine group of cathinone derivatives. Although it cannot be considered a trend in new psychoactive substances consumption, the presence in the market and the unknown toxicity of this substance makes it a relevant fact.


Acetylcholine and adenosine activate the G protein-gated muscarinic K+ channel in ferret ventricular myocytes.
The properties of the K+ channel activated by acetylcholine (ACh) and adenosine (Ado) were examined in single ferret ventricular myocytes using patch-clamp techniques. In the whole-cell configuration, ACh and Ado induced an inwardly rectifying K+ current and shortened the action potential duration. The effect of ACh was blocked by atropine, while the Ado effect was interrupted by 8-cyclopentyl,1,2-dipropyl xanthine, a specific Ado A1 receptor antagonist. In cell-attached recordings, ACh and Ado added to the pipette solution activated a single population of inwardly rectifying K+ channels, distinct from the iK1 channel. The channel had a slope conductance of approximately 40 pS in symmetrical 150 mM K+ solutions and a mean open time of 0.8 ms. Excision of the patch into the inside-out patch configuration in guanosine triphosphate (GTP)-free solution abolished the channel activity. The channel was reversibly reactivated by adding GTP to the intracellular side of the patch. GTP gamma S activated the channel irreversibly. When the inside-out patch was treated with the A protomer of pertussis toxin (PTX), intracellular GTP no longer activated the K+ channel. The results show that ferret ventricular myocytes possess a K+ channel activated by both muscarinic and Ado A1 receptors. Its electrophysiological properties and the gating by a PTX-sensitive G protein in a membrane-delimited fashion are identical with those of the muscarinic K+ channels in nodal and atrial tissues of other species. In conclusion, the G protein-gated muscarinic K+ channel is expressed in ferret ventricular myocardium and may underlie the direct negative inotropism of ACh and Ado in this tissue.


Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration.
Poly(D,L-lactide-co-glycolide) nanoparticles (PLGA-NP) have been extensively used as a drug delivery system for proteins and peptides. However, their negative surface charge decreases bioavailability under oral administration. Recently, cationically modified PLGA-NP has been introduced as novel carriers for oral delivery. The characteristics of the nanoparticles, such as particle size, surface charge, and bioadhesion are considered the most significant determinants of the effect of these nanoparticles both in vitro and in vivo. Our aim was to introduce and evaluate the physiochemical characteristics, bioadhesion, and biological activity of positively charged chitosan-coated PLGA-NP (CS-PLGA-NP), using insulin as a model drug. Results were compared to those of common negatively charged PLGA-NP and the in vitro cytotoxicity of the two types of nanoparticles was examined. These results indicate that both CS-PLGA-NP and PLGA-NP had a narrow size distribution, averaging less than 150 nm. CS-PLGA-NP was positively charged (+43.1 ± 0.3 mV), exhibiting the cationic nature of chitosan, whereas PLGA-NP showed a negative surface charge (-1.72 ± 0.2 mV). CS-PLGA-NP exhibited stronger bioadhesive potency than PLGA-NP and much greater relative pharmacological availability with regard to orally delivered insulin. In addition, an evaluation of cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed no increase in toxicity in either kind of nanoparticle during the formulation process. The study proves that CS-PLGA-NP can be used as a vector in oral drug delivery systems for proteins and peptides due to its positive surface charge and bioadhesive properties.


The effects of aging and driving experience on reaction times of professional drivers.
Professional drivers are part of the active working population, so there is a need for continuous improvement of operating efficiency and safety in driving. Reaction time is a very important driver's trait. The aim of this study was to examine the effects of age and driving experience on reaction times of professional drivers. This study assesses part of driving efficiency of professional drivers by measuring simple reaction time and complex reaction time which are important to driving safety. Reaction times of 278 male professional drivers were tested using a hardware-software system for determining the speed of response to psychomotor simple and complex audio-visual stimuli. Our results showed a positive correlation between ageing and slowing of reaction times. This suggests that the natural ageing process clearly slows down reaction times. The response times of professional drivers are more dependent on age than on driving experience.


Enhanced Learning and Retention of Medical Knowledge Using the Mobile Flash card Application Anki.
As medical schools condense the basic science phase of undergraduate medical education, it has become increasingly important to identify methods and tools that facilitate learning, mastery, and application of medical knowledge. One increasingly popular tool that promotes engagement with content is Anki, a web-based flash card system. Using Anki, medical students can access pre-made flash cards specifically tailored to prepare students for the United States Medical Licensing Exam (USMLE) Step 1 exam. The objective of this study was to identify Anki use and its association to USMLE Step 1 performance. In March 2020, medical students in years 2, 3, and 4 who had completed USMLE Step 1 were administered a survey to measure Anki usage. The survey was locally developed and was reviewed by survey experts on campus. Survey responses were paired with USMLE Step 1 results for analyses. Descriptive and inferential statistics were used for analysis. Anki usage was associated with higher USMLE Step 1 scores. Additionally, amongst those who used Anki, those with more consistent use had higher USMLE Step 1 scores and higher perceived levels of knowledge retention. This research suggests that Anki is an effective educational tool that should be recommended to medical students alongside other evidenced-based study tools, such as the popular question bank USMLE World. Future research should attempt to identify a relationship between Anki usage and future clinical performance to demonstrate the implications that Anki has on clinical skills. The online version contains supplementary material available at 10.1007/s40670-021-01386-9.


Changes in lysosomes during ageing of parenchymal and nonparenchymal liver cells.
Intact and viable parenchymal and non-parenchymal liver cell preparations were isolated by enzyme perfusion techniques from young and old rats. The distribution of the lysosomal enzymes acid phosphatase, beta-galactosidase, cathepsin D, acid DNAse, and arylsulphatase B over parenchymal and non-parenchymal cells was determined. In addition, morphological and morphometric changes which occur in parenchymal cells with age were investigated. All lysosomal enzymes studied are present in both cell classes, but non-parenchymal cells possess much ligher activities per mg protein than do parenchymal cells. This phenomenon is most pronounced for cathepsin D with a 13-times higher specific activity in non-parenchymal cells. Electron microscopic observations demonstrated that the lysosomal activities in non-parenchymal cells can be attributed mainly to the large and numerous lysosomal structures in Kupffer cells. Parenchymal cells from old rats have higher lysosomal enzyme activities per mg protein than do hepatocytes from young rats. This observation is in agreement with the general increase with age in the cytoplasmic volume fraction occupied by lysosomal structures in parenchymal cells. In general, non-parenchymal cells show no increase in specific enzyme activities with age. The results obtained suggest an increase in the heterogeneity--in both appearance and enzyme content--of the lysosomal structures in parenchymal cells with age.


Effect of malignant catarrhal fever virus infection on the immune response of rabbits to sheep red blood cells.
Rabbits infected with African Malignant catarrhal fever virus mounted a depressed antibody response to sheep red blood cells compared to the antibody response of uninfected rabbits. Immunodepression was observed in rabbits immunised 0, 3, 5, 7 and 10 days after infection. Antibody response was not depressed in the rabbits immunised 1 day after infection. Despite the depressed antibody response to SRBC, the rabbits died with rising virus neutralising antibody to the virus. The possible causes of the immunodepression are discussed.


Accuracy of conventional versus cone-beam CT-synthesised lateral cephalograms for cephalometric analysis: A systematic review.
To assess the accuracy of cone-beam computed tomography (CBCT)-synthesised lateral cephalograms (CSLCs) compared with conventional lateral cephalograms for cephalometric analysis in human participants and skull models. The authors performed a search of PubMed, Scopus, Google Scholar and Embase databases on 4 October 2021. Included studies met the following criteria: published in English; compared conventional lateral cephalograms and CSLCs; assessed hard- and soft-tissue landmarks; and were performed on human or skull models. Data extraction from eligible studies was performed by two independent reviewers. The quality of evidence was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist tool - diagnostic accuracy studies. A total of 20 eligible articles were included in this systematic review. Of these 20 studies, 17 presented with a low risk of bias, while three were found to have a moderate risk of bias. Hard- and soft-tissue analyses were evaluated for each imaging modality. The findings reveal that CSLCs are accurate and comparable to conventional lateral cephalograms for cephalometric analysis and demonstrate good inter-observer reliability. Four studies reported a higher accuracy with CSLCs. Overall, the diagnostic accuracy and reproducibility of CSLCs were comparable to conventional lateral cephalograms in cephalometric analysis. It is justified that patients who have an existing CBCT scan do not need an additional lateral cephalogram, minimising unnecessary radiation exposure, expenses and time for the patient. Larger voxel sizes and low-dose CBCT protocols can be considered to minimise radiation exposure. This study was registered with PROSPERO (CRD42021282019).


Depression-related phenotypes at early stages of Aβ and tau accumulation in inducible Alzheimer's disease mouse model: Task-oriented and concept-driven interpretations.
Depression is highly prevalent in Alzheimer Disease (AD); however, there is paucity of studies that focus specifically on the assessment of depression-relevant phenotypes in AD mouse models. Conditional doxycycline-dependent transgenic mouse models reproducing amyloidosis (TetOffAPPsi) and/or tau (TetOffTauP301L) pathology starting at middle age (6 months) were used in this study. As AD patients can experience depressive symptoms relatively early in disease, testing was conducted at early, pre-pathology stages of Aβ and/or tau accumulation (starting from 45 days of transgenes expression). Tau-related differences were detected in the Novelty Suppressed Feeding task (NSF), whereas APP-related differences were observed predominantly in measures of the Open Field (OF) and Forced Swim tasks (FST). Effects of combined production of Aβ and tau were detected in immobility during the 1st half of the Tail Suspension task (TST). These data demonstrate that results from different tasks are difficult to reconcile using task/variable-centered interpretations in which a single task/variable is assigned an ad-hoc meaning relevant to depression. An alternative, concept-oriented, approach is based on multiple variables/tests, with an understanding of their possible inter-dependence and utilization of statistical approaches that handle correlated data sets. The existence of strong correlations within and between some of the tasks supported utilization of factor analyses (FA). FA explained a similar amount of variability across the genotypes (∼80%) and identified two factors stable across genotypes and representing motor activity and anxiety measures in OF. In contrast, variables related to FST, TST, and NSFT did not demonstrate a structure of factor loadings that would support the existence of a single integral factor of "depressive state" measured by these tasks. In addition, factor loadings varied between genotypes, indicating that genotype-specific between-task correlations need to be considered for interpretations of findings in any single task. In general, this study demonstrates that utilization of multiple tasks to characterize behavioral phenotypes, an approach that is finally gaining more widespread adoption, requires a step of data integration across different behavioral tests for appropriate interpretations.


Metabolism and pharmacokinetics of dibromodulcitol (DBD, NSC-104800) in man--II. pharmacokinetics of DBD.
Dibromodulcitol (DBD), labelled with [3H] at position C-1, was administered orally to 6 patients in a single dose of 15 mg/kg. Kinetic parameters were calculated for the effective drug (DBD + BrEpG + DAG), protein-bound hexitol moieties and free metabolites. Approximate values were estimated for the oral bioavailability of DBD. Disposal of the drug by metabolism and excretion was described by a simplified catenary model. The results indicated that 8-20% of the drug became firmly bound to macromolecules, probably by alkylation. The slow rate of alkylation in vivo (half-life 14 hr) may imply conversion of DBD into epoxides and their alkylating interaction with the target nucleophiles. The long retention of the firmly bound hexitol moieties in the body may be an indicator of the cumulative potency of DBD and must be taken into consideration by developing dosage schedules.


Identification of T- and B-cell epitopes associated with a restricted component of the Epstein-Barr virus-induced early antigen complex.
Experiments were designed in an attempt to identify T- and B-cell epitopes expressed on the 17-kDa early-antigen-restricted (EA-R) polypeptide of the EBV-induced early antigen complex. Using Berzofsky's algorithm, 3 hypothetical T-cell epitopes on p17 were synthesized and employed in EBV-specific lymphoproliferative assays. Lymphocytes from all EBV-infected donors responded against one of these epitopes (p17.1) irrespective of their serological status relative to antibodies to EA-R. Both CD4+ and CD8+ T-cell subpopulations from seropositive donors proliferated in the presence of p17.1 in short-term cultures. These experiments therefore identified one T-cell epitope on the 17-kDa polypeptide. In contrast, sera from anti-Ea antibody-positive individuals reacted with all 3 synthetic peptides to varying degrees, with p17.1 being the most frequently reactive epitope. When the sera were grouped according to diagnosis, it was noted that 82% of the sera from patients with aggressive lymphomas, whether Africans with Burkitt's lymphoma or North Americans with intermediate-grade large-cell or high-grade B-cell lymphoma, contained antibody reactive with p17.1, while 64% were reactive with p17.2 and 29% with p17.3. In contrast, high anti-EA antibody-positive sera from nasopharyngeal carcinoma patients were relatively less reactive with these synthetic peptides (23% positive with p17.1; 19% with p17.2; and 13% with p17.3). These results therefore identified 3 B-cell EA-R epitopes which might be potentially useful for clinical or epidemiological studies of EBV-associated lymphoproliferative diseases.


Cytokines as emerging regulators of central nervous system synapses.
Cytokines are key messengers by which immune cells communicate, and they drive many physiological processes, including immune and inflammatory responses. Early discoveries demonstrated that cytokines, such as the interleukin family members and TNF-α, regulate synaptic scaling and plasticity. Still, we continue to learn more about how these traditional immune system cytokines affect neuronal structure and function. Different cytokines shape synaptic function on multiple levels ranging from fine-tuning neurotransmission, to regulating synapse number, to impacting global neuronal networks and complex behavior. These recent findings have cultivated an exciting and growing field centered on the importance of immune system cytokines for regulating synapse and neural network structure and function. Here, we highlight the latest findings related to cytokines in the central nervous system and their regulation of synapse structure and function. Moreover, we explore how these mechanisms are becoming increasingly important to consider in diseases-especially those with a large neuroinflammatory component.


Single excitation three color folded DNA probe for SNP typing.
A single fluorophore based multi-color emission probing system has been developed in the current work. dA(py) was used as the fluorophore, which was incorporated at the end of folded oligonucleotide with increasing number. Depending on the number of dA(py) three different color emissions were observed, viz. blue, green and red. These interesting color patterns were further used for the SNP typing of DNA. Every folded oligonucleotide with different number of dA(py)s could discriminate the full matched target sequence from one base mismatched and two base mismatched sequences. Furthermore, this probing system has a simple structure and also exhibited large Stokes shifted signal for discriminating the target DNA.


Crystal structure of human synbindin reveals two conformations of longin domain.
Transport protein particle (TRAPP) is a large multiprotein complex that involves in ER-to-Golgi and intra-Golgi traffic. Synbindin, the human ortholog of yeast Trs23, is one component of the TRAPP complexes. In the hippocampal neurons the synbindin/syndecan complex is involved in synaptic membrane trafficking and thereby regulates the formation of dendritic spines. Here we present the three-dimensional structure of human synbindin, which contains a longin domain (LD) and an atypical PDZ domain (APD). In the crystal, synbindin forms a hexamer, in which the LD forms two different conformations and the APD is quite disordered. These conformational changes of synbindin suggest a possible interaction mode of the LD.


Does the physiology of chondrichthyan fishes constrain their distribution in the deep sea?
The deep sea is the largest ecosystem on Earth but organisms living there must contend with high pressure, low temperature, darkness and scarce food. Chondrichthyan fishes (sharks and their relatives) are important consumers in most marine ecosystems but are uncommon deeper than 3000 m and exceedingly rare, or quite possibly absent, from the vast abyss (depths >4000 m). By contrast, teleost (bony) fishes are commonly found to depths of ∼ 8400 m. Why chondrichthyans are scarce at abyssal depths is a major biogeographical puzzle. Here, after outlining the depth-related physiological trends among chondrichthyans, we discuss several existing and new hypotheses that implicate unique physiological and biochemical characteristics of chondrichthyans as potential constraints on their depth distribution. We highlight three major, and not mutually exclusive, working hypotheses: (1) the urea-based osmoregulatory strategy of chondrichthyans might conflict with the interactive effects of low temperature and high pressure on protein and membrane function at great depth; (2) the reliance on lipid accumulation for buoyancy in chondrichthyans has a unique energetic cost, which might increasingly limit growth and reproductive output as food availability decreases with depth; (3) their osmoregulatory strategy may make chondrichthyans unusually nitrogen limited, a potential liability in the food-poor abyss. These hypotheses acting in concert could help to explain the scarcity of chondrichthyans at great depths: the mechanisms of the first hypothesis may place an absolute, pressure-related depth limit on physiological function, while the mechanisms of the second and third hypotheses may limit depth distribution by constraining performance in the oligotrophic abyss, in ways that preclude the establishment of viable populations or lead to competitive exclusion by teleosts.


Effects of desglycinamide9, (Arg8) vasopressin and vasopressin antiserum on the acquisition of intravenous cocaine self-administration in the rat.
The effect of the vasopressin neuropeptide desglycinamide9, (Arg8) vasopressin (DGAVP) on the acquisition of intravenous cocaine self-administration was studied. Rats were tested under conditions of reduced body weight in a continuous reinforcement operant procedure, during five daily 3 h sessions. Under these conditions, the rate of self-administration obtained with 0.125 and 0.25, but not 0.063 mg.ml-1 cocaine, exceeded the rate obtained with saline. Daily pretreatment with DGAVP (5 micrograms/rat, s.c.) decreased self-administration of 0.125 and 0.25 mg.ml-1 cocaine to the level obtained with saline, but had no effect on self-administration of 0.063 mg.ml-1 cocaine and saline. Using a similar procedure, it was shown that daily intracerebroventricular pretreatment with vasopressin antiserum significantly increased self-administration of 0.125 mg.ml-1 cocaine, without affecting self-administration of 0.063 and 0.25 mg.ml-1 cocaine and saline. The results support previous findings obtained with vasopressin neuropeptides in drug self-administration studies and suggest that DGAVP decreases the acquisition of cocaine self-administration by attenuating the reinforcing effects of cocaine and that endogenous vasopressin may be involved in the acquisition of cocaine self-administration.


In vivo therapeutic genome editing via CRISPR/Cas9 magnetoplexes for myocardial infarction.
CRISPR/Cas9-mediated gene-editing technology has gained attention as a new therapeutic method for intractable diseases. However, the use of CRISPR/Cas9 for cardiac conditions such as myocardial infarction remains challenging due to technical and biological barriers, particularly difficulties in delivering the system and targeting genes in the heart. In the present study, we demonstrated the in vivo efficacy of the CRISPR/Cas9 magnetoplexes system for therapeutic genome editing in myocardial infarction. First, we developed CRISPR/Cas9 magnetoplexes that magnetically guided CRISPR/Cas9 system to the heart for efficient in vivo therapeutic gene targeting during heart failures. We then demonstrated that the in vivo gene targeting of miR34a via these CRISPR/Cas9 magnetoplexes in a mouse model of myocardial infarction significantly improved cardiac repair and regeneration to facilitate improvements in cardiac function. These results indicated that CRISPR/Cas9 magnetoplexes represent an effective in vivo therapeutic gene-targeting platform in the myocardial infarction of heart, and that this strategy may be applicable for the treatment of a broad range of cardiac failures.


Nanoencapsulation of hydroxytyrosol in chitosan crosslinked with sodium bisulfate tandem ultrasonication: Techno-characterization, release and antiproliferative properties.
This research includes production of chitosan nanocapsules through ionic gelation with sodium bisulfate for nanoencapsulation of hydroxytyrosol (HT) using ultrasonication in tandem. The resulting nanocapsules encapsulating HT were analyzed for particle size, ζ-potential, packaging characteristics, FESEM, ATR-FTIR, XRD, DSC, in vitro release, antioxidant potential and antiproliferative properties. The nanocapsules (size 119.50-365.21 nm) were spherical to irregular shaped with positive ζ-potential (17.50-18.09 mV). The encapsulation efficiency of 5 mg/g HT (HTS1) and 20 mg/g HT (HTS2) was 77.13% and 56.30%, respectively. The nanocapsules were amorphous in nature with 12.34% to 15.48% crystallinity and crystallite size between 20 nm and 27 nm. Formation of nanocapsules resulted in increasing the glass transition temperature. HTS2 delivered 67.12% HT (HTS1 58.89%) at the end of the simulated gastrointestinal digestion. The nanoencapsulated HT showed higher antioxidant and antiproliferative (against A549 and MDA-MB-231 cancer cell lines) properties than the free HT.


Isolated Infarction of the Medullary Pyramid - A Rare Pure Motor Stroke.
Acute pure motor hemiparesis can occur due to a vascular insult along the cortico spinal pathway. Rarely such a stroke can occur as a result of involvement of the pyramids located on the ventral aspect of the medulla. Neurological localization can be difficult in such strokes and moreover they can also pose imaging challenges since they are missed on the CT scans. So far only 4 such cases have been reported in literature. Here we present two cases of pure motor strokes caused by infarction of the medullary pyramids. We have described the anatomical correlates of the symptoms and signs and also highlight the importance of MRI in picking up these rare strokes.


A large-scale replication study for the association of rs17039192 in HIF-2α with knee osteoarthritis.
Osteoarthritis (OA) is a common disease with a genetic component for its etiology. Recently, a genetic association of a single nucleotide polymorphism (SNP), rs17039192 in HIF-2α with knee OA has been reported in a Japanese population; however, controversy exits for its replication and a role of HIF-2α in OA. This study aimed to evaluate the association of the SNP by a large-scale replication study. A total of 8,457 subjects (3,129 OA cases and 5,328 controls) from seven independent cohorts from six countries (Japan, China, Taiwan, Korea, Greece, and Australia) were recruited and genotyped. The association of rs17039192 with knee OA was evaluated by meta-analyses. The association of the HIF-2α SNP was not replicated in any of the populations. Contrary to the previous report, the odds ratios (ORs) of the risk allele frequency were all less than 1. A combined analysis for the seven populations also showed no replication of the association (OR = 0.91, 95% confidence interval = 0.81-1.03). Our large-scale meta-analysis showed that the association of rs17039192 in HIF-2α with knee OA is negative. The significance of HIF-2α in human OA (idiopathic OA as a common disease) should be further evaluated carefully.


Practicability of magnetoencephalography-guided neuronavigation.
Magnetoencephalography (MEG) is a noninvasive option for localizing electroneurophysiological activity on the human cortex. The purpose of this study was to evaluate the practicability and reliability of MEG imaging integrated into a neuronavigation system to identify the sensorimotor cortex intraoperatively in patients with brain tumors in or near the central motor strip. It was performed prior to surgery in 30 patients with space-occupying lesions in or around the central region to localize the primary somatosensory cortex. These functional brain maps were superimposed on MR images obtained prior to surgery and transferred in the operating room for intraoperative functional neuronavigation. During surgery, the phase reversal technique identified a generator which coincided with the somatosensory cortex as displayed by the MEG-based functional neuronavigation system. Following surgery, the motor deficit improved in seven patients, was unchanged in five, and showed a slight transient deterioration in five. One patient suffered a deterioration of motor function with incomplete recovery. The MEG-based functional neuronavigation was found to be practicable and useful in finding a safe approach to tumors in or adjacent to the central region. The accuracy of MEG was concluded to be reliable as verified by the phase reversal technique.


Application of two versions of the WHO/international society of hypertension absolute cardiovascular risk assessment tools in a rural Bangladeshi population.
To estimate the absolute cardiovascular disease (CVD) risk burden in a remote rural Bangladeshi population using the 'With' and 'Without' Cholesterol versions of the WHO/International Society of Hypertension (WHO/ISH) CVD risk assessment chart (particularly suitable for low and middle-income countries due to less reliance on laboratory testing) and to evaluate the agreement between the two approaches. Cross-sectional study using data from a large prospective cohort of the North Bengal Non-Communicable Disease Programme (NB-NCDP) of Bangladesh. General rural population from Thakurgaon district of Bangladesh. 563 individuals who were categorised as having 'no CVDs' on screening by a questionnaire-based survey using the 'WHO CVD-Risk Management Package' developed in 2002. Absolute CVD risk burden assessed using two versions of the WHO/ISH risk assessment charts for the South-East Asian Region-D. 10-year risk (moderate, high and very high) positivity was present among 21.5% and 20.2% of participants, respectively, using with and without cholesterol versions of the tool. The overall concordance rate for the two versions was 89.5% and they did not differ significantly in estimating the proportion of overall participants having higher levels of CVD. The projected drug requirement, however, showed a significant overestimation in the proportion of participants at both the threshold levels (p<0.002) on using 'without' as compared to 'with' cholesterol versions. About one-fifth of the adult population in Bangladesh, even in a remote rural area, seem to be at risk of developing CVDs (25% of them at high risk and 25% at very high risk) within 10 years with males and females being almost equally vulnerable.


The proliferation of epidermal cells in mouse ear organ culture.
Mouse ear fragments were cultured for up to 1 day in a chemically defined fluid medium and for 2-3 days in a solid Agar medium. Within 24 h of incubation, the epidermal cells were found to migrate towards the cut edges, a process which led to an epithelialization of the denuded surface. Concomitantly, the epidermal cell proliferation was enhanced: an entry of increasing numbers of interfollicular cells into S phase occurred after 7-10 h of incubation and was maximal around the 20th h. Correspondingly, the mitotic rate rose after 20 h. During an incubation period of 48-72 h in solid medium, the mitotic activity of the proliferating tissues in mouse ear skin continued, and the interfollicular epidermis in the proximity of the cut edges became hyperplastic. Thus, mouse ear epidermis kept in this organ culture seems to resemble a wounded epidermis in vivo. Epidermal cell proliferation was studied by determining (a) the mitotic rate and (b) the incorporation of tritiated thymidine by means of liquid scintillation spectrometry and autoradiography. Various factors affecting the incorporation of tritiated thymidine were investigated, and it was concluded that liquid scintillation spectrometry proves to be a rapid and suitable method for determining the effects of both growth-promoting and growth-inhibiting agents on epidermal cell proliferation.


Otoacoustic emissions in young adults: Effects of blood group.
Previous research findings have suggested that individuals with different blood groups demonstrate varied haematological risk factors for a wide range of disorders, including noise-induced hearing loss. The present study investigated the effects of blood group on several features of otoacoustic emissions (OAEs) including magnitude, as OAE status is indicative of cochlear function. A total of 60 normal hearing females aged between 18 and 26 years were included in the study. Measurements of spontaneous otoacoustic emissions (SOAEs), transient-evoked emissions (TEOAEs) and distortion-product otoacoustic emissions (DPOAEs) were obtained from both ears for all participants, who included equal numbers of A, B, O and AB positive blood groups. Participants with blood group O had significantly fewer occurrences of SOAEs and lower DPOAE amplitudes at some frequencies compared to participants with blood group B. There was a general trend for blood group O individuals to show reduced OAE amplitudes compared to participants from A, B, and AB groups. These findings are consistent with the hypothesis that individuals with different blood groups may have different OAE amplitude values. The results support the need for further investigation on the effects of blood group on OAE status.


Seasonal variations of the airborne microbial assemblages of the Seoul subway, South Korea from 16S and ITS gene profiles with chemical analysis.
In this study, we determined the seasonal airborne microbial diversity profiles at SMRT stations by sequencing the 16S rRNA and ITS. Particulate matter samples were collected from air purifiers installed in the platform area of the SMRT subway stations. Three stations that included the most crowded one were selected for the sampling. The sampling was done at each season during 2019. After extracting the total DNA from all seasonal samples, PCR was performed with Illumina overhang adapter primers for the V3-V4 region of the 16S rRNA gene and ITS2 region of the ITS gene. The amplified products were further purified, and sequencing libraries were made. Sequencing was carried with the Illumina Miseq Sequencing system (Illumina, USA) followed by in-depth diversity analyses. The elemental composition of the particulate matter samples collected from the different subway stations were obtained using a WD-XRF spectrometer. The SMRT microbiome showed extensive taxonomic diversity with the most common bacterial genera at the subway stations associated with the skin. Overall, the stations included in this study harbored different phylogenetic communities based on α- and β-diversity comparisons. Microbial assemblages also varied depending upon the season in which the samples were taken and the station. Major elements present at the subway stations were from aerosols generated between wheels and brake cushions and between the catenaries and the pantographs. This study shows that the microbial composition of the SMRT subway stations comes from a diverse combination of environmental and human sources, the season and the lifestyle of commuters.


Complete Draft Genome Sequence of Escherichia coli KRX, a Strain for Efficient Cloning and High-Yield Expression of Proteins under Control of the T7 RNA Polymerase.
Escherichia coli KRX is a strain offering both a high transformation efficiency and the possibility to produce the target protein to high yields in one host, avoiding additional cloning steps. Here, the draft genome sequence of E. coli KRX is presented and provides the genetic basis for additional biotechnological applications.


Copper-Mediated Dichotomic Borylation of Alkyne Carbonates: Stereoselective Access to (E)-1,2-Diborylated 1,3-Dienes versus Traceless Monoborylation Affording α-Hydroxyallenes.
A mild copper-mediated protocol has been developed for borylation of alkynyl cyclic carbonates. Depending on the nature of the borylating reaction partner, either stereoselective diborylation of the propargylic surrogate takes place, providing convenient access to (E)-1,2-borylated 1,3-dienes, or traceless monoborylation occurs, which leads to α-hydroxyallenes as the principal product. The dichotomy in this borylation protocol has been scrutinized by several control experiments, illustrating that a relatively small change in the diboron(4) reagent allows for competitive alcohol-assisted protodemetalation to forge an α-hydroxyallene product under ambient conditions.


Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases.
The magnitude of association between homocysteine metabolism and inflammatory bowel diseases (IBD) remains unknown, whereas the association between hyperhomocysteinaemia and thrombosis remains controversial in IBD. To conduct a systematic review and meta-analysis to examine these issues. The literature search was conducted using MEDLINE database and international conference abstracts from January 1966 to April 2011 and included all studies that evaluated plasma homocysteine level in IBD. Twenty-eight studies evaluated the plasma homocysteine level and/or hyperhomocysteinaemia risk in IBD patients. Five studies assessed the association of hyperhomocysteinaemia with thrombosis. The mean plasma homocysteine level was significantly higher in IBD patients when compared with controls (weighted mean difference (WMD)=3.75 μmol/L; 95% CI, 2.23-5.26 μmol/L; P<0.0001; reference ranges for plasma homocysteine level: 5-12 μmol/L). The mean plasma homocysteine level did not differ between ulcerative colitis (UC) and Crohn's disease (CD) (WMD=0.41 μmol/L; 95% CI, -2.45 to 3.06 μmol/L; P=0.76). The risk of hyperhomocysteinaemia was significantly higher in IBD patients when compared with controls [odds ratio (OR)=4.65; 95% CI, 3.04-7.09; P<0.0001]. The risk of hyperhomocysteinaemia was not higher among IBD patients who experienced thromboembolic complications (OR=1.97; 95% CI, 0.83-4.67; P=0.12). Plasma folate level was inversely correlated with IBD risk associated with MTHFR C677T polymorphism (P=0.006). The risk of hyperhomocysteinaemia is significantly higher in IBD patients when compared with controls. The risk assessment of hyperhomocysteinaemia-related thrombosis in IBD requires further investigation. Deficient folate status is associated with a higher impact of MTHFR C677T polymorphism on IBD risk.


Coronary arteritis in nonspecific aortoarteritis.
Nonostial distal coronary artery involvement in nonspecific aortoarteritis is rare. We report a 35-year-old patient with features of nonspecific aortoarteritis who had an inferolateral myocardial infarction and on coronary angiography was shown to have severe disease of the left circumflex artery in its middle third.


Percutaneous drainage of traumatic pancreatic pseudocysts in children.
To determine the effectiveness of percutaneous drainage of traumatic pancreatic pseudocysts, we reviewed the courses of 13 children. Six pseudocysts resolved on complete bowel rest and total parenteral nutrition. Seven required further therapy. Two pseudocysts were treated operatively; five were drained percutaneously with fluoroscopic guidance. These five ranged from 5 to 15 cm in diameter and were present for 10 to 42 days (mean, 26 days). In all cases, the cyst fluid was clear, had an amylase level of greater than 40,000 IU/L, and grew no organisms. The pigtail catheters left in place in four of the five children were removed when drainage stopped. Patients were followed by ultrasound while still in the hospital and 1 month after discharge. There were no complications nor any pseudocyst recurrence. Percutaneous drainage of traumatic pancreatic pseudocysts in children is an effective alternative to the standard operative therapy of pseudocystenteric anastomosis.


Passing the baton: Mentoring for adoption of active-learning pedagogies by research-active junior faculty.
There are barriers to adoption of research-based teaching methods. Professional development workshops may inform faculty of these methods, but effective adoption often does not follow. In addition, newly-minted research-active faculty are often overwhelmed by the many new responsibilities (grant writing, group management, laboratory setup, teaching) that accompany the position and normally do not have the time to consider novel teaching approaches. This case study documents how over a three-year period, the responsibility for teaching a nontraditional "Introduction to Biochemistry" course in a problem-based learning format was successfully transferred from a senior faculty member nearing retirement (HBW) to a newly-hired research-active assistant professor (CLG). We describe our apprenticeship project involving modeling, scaffolding, fading, and coaching. We suggest that involving faculty in active-learning pedagogy early in their career with mentoring by senior faculty overcomes barriers to adopting these methods. This case describes a specific example from which potentially useful elements can be adopted and adapted wherever biochemistry is taught.


The four steps in the prevention of human papillomavirus-associated neoplasia: considerations for preventive measures, screening, disease impact, and potential overtreatments in HPV-related pathology.
There is no cure currently available for HPV infections, although ablative and excisional treatments of some dysplasias often result in a clinical and virological cure. Effective control measures of HPV-associated cancers rely on the prevention at four different levels. Apart from sexual abstinence, primary prevention is realized through vaccines targeting the most frequent HPV types: negative attitudes towards HPV vaccination and high costs are the main obstacles. The aim of secondary prevention is to detect precancerous changes before they develop into invasive cancer, while tertiary prevention involves actual treatment of high-grade lesions: in many countries routine screening with cytology is being challenged with HPV DNA testing. Quaternary prevention comprehends those actions adopted to mitigate or avoid unnecessary or excessive medical interventions, and may well be addressed in avoiding treatments for low-grade intraepithelial neoplasia. Though some gynecologists commonly recommend treatment for low-grade disease and women tend to prefer active management if not properly informed, harms arising from unnecessary treatments, increased costs, work overload for second-level health services, and induced psychosocial distress are causing on-going problems. Prevention efforts of genital HPV-associated cancers should concentrate in: (1) enhancing primary prevention through vaccination of all eligible subjects, (2) achieving high levels of adherence to routine screening programs, (3) treating precancerous lesions, and (4) monitoring current guidelines recommendations to avoid overtreatments. Novel research projects should be designed to study the delicate mechanisms of immune response to HPV.


c-Met upregulates aquaporin 3 expression in human gastric carcinoma cells via the ERK signalling pathway.
Aquaporin 3 (AQP3) and c-Met are both overexpressed in human gastric carcinoma and highly associated with its metastasis and invasion. However, it still remains unknown whether c-Met and AQP3 correlate with each other. Herein, we demonstrated that c-Met expression in gastric cancer tissues significantly correlated with differentiation, lymph node metastasis and lymphovascular invasion, and c-Met exhibited marked association with AQP3 expression. Immunoblotting assays showed that hHGF phosphorylated c-Met in SGC7901 and AGS cells and upregulated AQP3 expression in a dose- or time-dependent way. RNAi against c-Met reduced total c-Met levels by about two thirds in both AGS and SGC7901 cells and attenuated hHGF-induced AQP3 expression significantly. In vitro migration and proliferation assays showed that siRNA against AQP3 noticeably restrained HGF-promoted migration and proliferation of these cells. Furthermore, Immunoblotting studies revealed that HGF induced phosphorylation of ERK, and pre-treatment with U0126, a MAPK/ERK inhibitor, partially inhibited hHGF-induced increase in AQP3 expression. Together, these data provide initial evidence that c-Met regulates the expression of AQP3 via the ERK signalling pathway in gastric carcinoma. These findings assist in understanding the mechanism of growth and invasion of gastric carcinoma, and provide a possible strategy for the inhibition of gastric tumor metastasis.


K469E polymorphism of the intracellular adhesion molecule 1 gene is associated with proliferative diabetic retinopathy in Caucasians with type 2 diabetes.
In proliferative diabetic retinopathy (PDR) increased levels of cytokines, inflammatory cells and angiogenic factors are present.These factors increase the expression of cellular adhesion molecules (CAMs)The objective of this study was to investigate the association between the polymorphisms of the ICAM-1 gene (K469E, G241A) and the development of PDR among patients with type 2 diabetes in the Slovenian population (Caucasians). For the purpose, 195 subjects with type 2 diabetes with PDR were compared with 143 subjects with type 2 diabetes of duration of more than 10 years who had no clinical signs of diabetic retinopathy. We analysed serum ICAM levels in 54 subjects with type 2 diabetes and 25 subjects without diabetes. A significantly higher frequency of the EE genotype of the K469E polymorphism of the ICAM-1 was found in the patients with PDR compared with those without diabetic retinopathy (OR = 2.0, 95% confidence interval [CI] = 1.1-3.5; P = 0.013), whereas the G241A polymorphism of the ICAM-1 gene failed to yield an association with PDR. Moreover, significantly higher sICAM-1 serum levels were demonstrated in diabetics with the EE genotype compared with those with the other (EK + KK) genotypes (918 +/-104 vs. 664 +/-209 microg/L; P = 0.001). The G241A polymorphism of the ICAM-1 gene, on the hand, failed to affect sICAM-1 serum levels in diabetics. We may conclude that the EE genotype of the K469E polymorphism of the ICAM-1 might be a risk factor for PDR in the Slovenian population (Caucasians) with type 2 diabetes.


Synthesis and full characterisation of 6-chloro-2-iodopurine, a template for the functionalisation of purines.
A simple and efficient synthesis of 6-chloro-2-iodopurine from hypoxanthine has been achieved. This strategy relied on a regiospecific lithiation/quenching sequence of 6-chloro-9-(tetrahydropyran-2-yl)purine using Harpoon's base and tributyltin chloride. HMBC NMR studies on the product and intermediates confirmed the regioselectivity of this methodology. The molecular structures of the final dihalogenopurine and its 9-protected precursor were determined by single crystal X-ray diffraction.


Servant leadership in nursing: a framework for developing sustainable research capacity in nursing.
In the current professional climate, research activities are highly valued with nurses in all sectors actively encouraged to participate. However, working environments for many nurses are such that it can be difficult to privilege research activities in any sustained way. A number of organisational challenges coalesce to impede participation in research activities, including limited resources, lack of skills, knowledge and opportunities, and a culture of individualism. Strong, effective research leadership is essential to help mediate some of these negative aspects of organisational life, and promote creative environments to facilitate the development of research capacity. Servant leadership is a service-oriented approach that focuses on valuing and developing people, and offers a participatory and collaborative framework within which to build creative and productive research communities. Such communities can encourage connectedness between people, deepen the capacity for supportive collegiality, and foster a holistic social learning milieu to support researchers of all levels, including early career researchers and research higher degree candidates.


Plasmodial slime molds and the evolution of microbial husbandry.
Detailed analyses into the life cycle of the soil-dwelling microbe Dictyostelium discoideum led to the conclusion that this "social amoeba" practices some form of "non-monoculture farming" via the transfer of bacteria to novel environments. Herein, we show that in myxomycetes (plasmodial slime molds or myxogastrids) a similar "farming symbiosis" has evolved. Based on laboratory studies of two representative species in the genera Fuligo and Didymium, the sexual life cycle of these enigmatic microbes that feed on bacteria was reconstructed, with reference to plasmo- and karyogamy. We document that the spores carry and transfer bacteria and hence may inoculate new habitats. The significance of this finding with respect to Ernst Haeckel's work on myxomycetes and his concept of ecology are addressed.


Cerebral perfusion and the risk of cognitive decline and dementia in community dwelling older people.
The arterial spin labeling-spatial coefficient of variation (sCoV) is a new vascular magnetic resonance imaging (MRI) parameter that could be a more sensitive marker for dementia-associated cerebral microvascular disease than the commonly used MRI markers cerebral blood flow (CBF) and white matter hyperintensity volume (WMHV). 195 community-dwelling older people with hypertension were invited to undergo MRI twice, with a three-year interval. Cognition was evaluated every two years for 6-8 years using the mini-mental state examination (MMSE). We assessed relations of sCoV, CBF and WMHV with cognitive decline during follow-up. We also registered dementia diagnoses, up to 9 years after the first scan. In an additional analysis, we compared these MRI parameters between participants that did and did not develop dementia. 136/195 completed the second scan. sCoV and CBF were not associated with MMSE changes during 6-8 years of follow-up. Higher WMHV was associated with declining MMSE scores (-0.02 points/year/ml, 95%CI=-0.03 to -0.00). ScOv and CBF did not differ between participants who did (n=15) and did not (n=180) develop dementia, whereas higher WMHV was reported in participants who developed dementia after the first MRI (13.3 vs 6.1mL, p<0.001). There were no associations between longitudinal change in any of the MRI parameters and cognitive decline or subsequent dementia. Global sCoV and CBF were less sensitive longitudinal markers of cognitive decline and dementia compared to WMHV in community-dwelling older people with hypertension. Larger longitudinal MRI perfusion studies are needed to identify possible (regional) patterns of cerebral perfusion preceding cognitive decline and dementia diagnosis.


Ovsynch synchronization and fixed-time insemination in goats.
This study assessed the efficacy of an Ovsynch protocol (vs. the classical cronolone containing vaginal sponge+eCG treatment) to generate fixed-time insemination in goats during the breeding season. Each regimen was applied to 24 Boer goat does. Onset and duration of estrus were determined with an aproned male and follicular development was monitored by ultrasonography. Ovulation and quality of the corpora lutea were established from progesterone concentrations. In 10-11 goats per group, LH concentrations were determined throughout the preovulatory period. Does were inseminated at pre-determined times (16 h after the second GnRH injection and 43 h after sponge removal). Estrus was identified in 96% of the Ovsynch-treated goats (at 49 h after prostaglandin injection) and in 100% of the goats synchronized with sponges (at 37 h after sponge removal). Low progesterone concentrations at the time of AI were observed in 21/24 and 24/24 goats synchronized by Ovsynch and sponges, respectively. Synchronization of the LH surge was tighter following Ovsynch compared to sponge treatment. Kidding rates (at 58 and 46% in the Ovsynch and sponge groups, respectively) and prolificacy (at 1.86 and 1.83 in the Ovsynch- and sponge-treated goats) were similar for both groups, as were the number of ovulations (2.9 and 3.3) and the proportion of does with premature corpus luteum regression (29 and 17%). When excluding does with premature luteal regression and those with low progesterone levels when receiving prostaglandins, kidding rate reached 87.5% (14/16) after Ovsynch. During the breeding season, the Ovsynch protocol may thus be an useful alternative to the sponge-eCG treatment.


Self-expandable valved stent of large size: off-bypass implantation in pulmonary position.
To evaluate the feasibility of the off-bypass implantation of a self-expandable valved stent of large size in pulmonary position. A glutaraldehyde preserved valved bovine jugular xenograft with internal diameter = 22 mm, mounted in two rings of nitinol 'Z' stent, expandable from 7 to 24 mm of internal diameter, was acutely evaluated in 6 adult pigs, mean body weight 55.6 kg (range 47-67 kg). Through a stent-graft delivery system (24 French) the self expandable valved stent was implanted off-bypass in pulmonary valve position by trans-ventricular approach through median sternotomy. The mean diameter of the main pulmonary artery measured was 21.7 +/- 1.6 mm. The mean length of the self expandable valved stent was 23.1 +/- 0.7 mm, the mean internal diameter 21.6 +/- 0.7 mm and the mean external diameter 26.3 +/- 0.7 mm. The mean peak pressure gradient recorded across the valve was 6.33 +/- 2.8 mmHg (range 4.5-9.6 mmHg) at Doppler echocardiography, and 4.5 +/- 3.1 mmHg (range 0-7 mmHg) at invasive measurement, with a pulmonary blood flow of 3.03 +/- 0.05 l/min. Intra-vascular ultrasound showed complete opening and closure of the valve (mean area reduction from 315.08 +/- 54.13 to 0 mm2). (a) Off-bypass implantation of self-expandable valved stent is feasible in pulmonary position; (b) off-bypass surgical approach allows for valved stent implantation of adult size with adequate hemodynamic functioning; and (c) intra-vascular ultrasound makes implantation and evaluation easy and reproducible.


[Closed distraction epiphysiolysis for leg lengthening and axis correction of the leg in children].
The distraction-epiphyseolysis is a method of leg-lengthening and allows to correct leg-deformities. A daily lengthening of 1 mm enhances ossification and enables a maximum lengthening of 8-10 cm. The indications, contra-indications and the method are described.


Impact of the COVID-19 pandemic on hospital admissions due to viral hepatitis in Spain.
Before the advent of COVID-19 vaccines, hospitalizations due to SARS-CoV-2 infection during 2020 collapsed most medical centers worldwide. Disruptions in health care for clinical conditions other than COVID-19 were not uniform. Herein, we report the impact of COVID-19 on hospitalizations due to viral hepatitis in Spain. Retrospective study of all hospitalizations in Spain during 10 months before (pre-pandemic period) and after (pandemic period) March 1st 2020. Admissions with a diagnosis of hepatitis B, C and/or delta were retrieved and compared using the Spanish National Registry of Hospital Discharges. Nationwide hospitalizations declined 14.6% during the pandemic period, from 3,144,164 to 2,684,845. This reduction was significantly more pronounced for admissions due to viral hepatitis (18.1% drop), falling from 46,521 to 38,115. During the pandemic period, patients admitted with viral hepatitis died significantly more frequently than during the pre-pandemic period (7.2% vs 6.1%; p < 0.001). Liver transplants significantly declined during the pandemic period. COVID-19 was diagnosed in 10.3% of patients hospitalized with viral hepatitis during the pandemic period. This subset of patients was older and died 2.4-fold more frequently than the rest, despite having advanced liver disease less frequently. Hospitalizations due to viral hepatitis significantly declined in Spain during the COVID-19 pandemic. Patients admitted with viral hepatitis experienced a greater mortality during the pandemic period. Deaths were more pronounced when coinfected with SARS-CoV-2 despite having advanced liver disease less frequently.


[Simultaneous determination of free cholesterol and total cholesteron on an AA I Technicon autoanalyzer (authors transl)].
A procedure for the simultaneous enzymatic determination of free cholesterol and total cholesterol on a 2 channel AA I Technicon autoanalyzer system is described. The quantitation of free cholesterol is compared with the determination by gas chromatography. The investigation reveals a high correlation between both methods. In contrast to classical procedures the proposed quantitation of free cholesterol can be performed easily and quickly for routine analyses.


Defibrillation efficacy with endocardial electrodes is influenced by reductions in cardiac preload.
Little is known about the effects of cardiac preload and cardiac geometry on defibrillation efficacy with endocardial electrodes. We studied nine pigs implanted with an endocardial lead system in the normal and reduced preload state. In the reduced preload state, a balloon catheter was inflated in the inferior vena cava (IVC) for 20 seconds prior to the induction of ventricular fibrillation (VF). Complete occlusion of the IVC and reductions in preload were confirmed by observing deformation of the contrast-filled balloon, a reduction in cardiac size by fluoroscopy, and reductions in ventricular pressures. Biphasic shocks were delivered after 10 seconds of VF using a recursive up-down protocol. VF was induced 20 times for each preload state, and the 50% effective doses (ED50) for energy, current, and voltage were estimated by averaging all shocks for that state. At reduced preloads, energy decreased from 12.1 +/- 3.0 J (+/- SD) to 10.5 +/- 2.9 J (p < 0.01), voltage decreased from 415 +/- 51 V to 390 +/- 51 V (p < 0.05), and current decreased from 8.6 +/- 1.5 A to 7.6 +/- 1.5 A (p < 0.01), while impedance rose from 49.2 +/- 3.8 omega to 52.8 +/- 4.4 omega (p < 0.001). We conclude that reducing cardiac preload and cardiac size significantly lowers ED50 defibrillation energy, current, and voltage. This outcome may be caused directly by the decrease in blood volume as evidenced by increased impedance and/or may be due to changes in heart geometry and stretch.


Hydroxyurea in stage D carcinoma of prostate.
Thirty patients with histologically proved metastatic prostatic adenocarcinoma Stage D were treated with a single oral dose of 80 mg. per Kg. hydroxyurea every third day (based on ideal or actual weight, whichever is less) and 12 mg. chlorotrianisene per day. Toxicity was mild. The most common manifestations were nausea, occasional vomiting, and leukopenia. A definite attempt was made to depress the white blood count to approximately 2,000 cells per cu. mm. Hydroxyurea was not discontinued unless the white blood count decreased to less than 2,000 cells per cu. mm., after which a single dose was usually omitted. Omission of a single dose would allow the white blood count to return promptly to more than 2,000 cells per cu. mm. Objective tumor regression was demonstrated in 15 of the 30 patients, and most patients had a definite improvement in the quality of life.


The dynamic experience of pain in burn patients: A phenomenological study.
Although pain is one of the main sources of suffering during the acute phase and rehabilitation in burn patients, it remains as a major challenge for burn care, and clinical management not always correlates with the experience felt by patients. The aim of this study was to understand the experience of pain from people who has suffered severe burns, to identify personal strategies used to cope with this challenging event. A qualitative phenomenological study with purposive sampling was carried out with severe burn patients admitted to a Burn Unit. Through individual in-depth interviews, verbatim transcription and content analysis, two main categories were isolated: a dynamic and changing experience of pain, from the onset to the hospital discharge, and diverse strategies developed by patients to cope with pain, being distraction the most frequently used. Pain experienced acquires its maximum intensity during wound care, and divergent patients' opinions about sedation are present. This study highlights how understanding subjective experiences is an invaluable aid to improve care in pain assessment and management. Furthermore, it points out the need to guarantee patient involvement in the organization and improvement of burn care, inasmuch as traditional professional centered approach is not ensuring an optimal management.


Sea urchin spine arthritis in the foot.
We present a case of sea urchin spine arthritis (SUSA) in a 33-year-old woman who sustained penetrating trauma to the interphalangeal (IP) joint of the hallux while snorkeling in Japan. Serial radiographs and MRI were obtained over a period from 7 weeks to 10 months following injury. At 7 weeks radiographs revealed periarticular osteopenia and subtle marginal erosion, similar to the appearance of tuberculous arthritis. Over the ensuing months, radiographs and MRI documented progressive marginal and periarticular erosions with synovitis, despite preservation of cartilage space and restoration of bone mineral density. Delayed radiographs and imaging features mimic gouty arthropathy. Only the history points to the proper diagnosis, which was confirmed by histopathology, demonstrating necrobiotic granuloma with central fibrinoid necrosis following synovectomy and arthrodesis. The majority of previous case reports affected the hand, with few cases in the feet. In all, radiographic illustrations were limited and demonstrated only minimal osteolysis and periosteal reaction. No other report included MRI or serial radiographs over a long period to illustrate the natural progression of the disease.


Myo-inositol, glucose and zinc concentrations determined in the preconceptional period, during and after pregnancy.
To determine the blood concentrations of myo-inositol, glucose and zinc before, during and after normal pregnancy. Preconceptionally, at 6, 10, 20, 30 and 37 weeks amenorrhea, and 6 weeks after delivery, blood samples of 18 nulliparae and 19 multiparae were obtained and concentrations of serum inositol and glucose, and red blood cell zinc were determined. The data were analyzed using a linear mixed model. The preconceptional mean (S.E.M.) inositol concentration of 21.7 (1.03) micromol/L was comparable to the concentrations at 6 and 37 weeks amenorrhea, 22.2 (1.03) micromol/L, and 19.9 (1.10) micromol/L, respectively. However, the inositol concentrations at 10 and 20 weeks amenorrhea and post partum were significantly lower than the preconceptional inositol concentration, p<0.05. The preconceptional mean (S.E.M.) glucose concentration of 3.9 (1.03) mmol/L was comparable to the concentration at 6 and 10 weeks amenorrhea, 3.9 (1.04) mmol/L and 3.8 (1.04) mmol/L respectively. Also at 20, 30 and 37 weeks amenorrhea and after delivery the glucose concentration was significantly lower than the preconceptional glucose concentration, p<0.05. Preconceptional red blood cell zinc concentrations were comparable to concentrations at 6, 10 and 20 weeks amenorrhea. At 30 and 37 weeks amenorrhea and post partum the zinc concentrations were significantly higher than in the preconceptional period (p<0.01). The concentrations of inositol, glucose and zinc significantly change during pregnancy. However, the preconceptional blood concentrations reflect the concentrations determined in the first pregnancy trimester rather well, which is important information to be used in future studies into the role of inositol, glucose and zinc in reproductive disorders.


Subtle sensory and labeling modifications have minimal impact on expected appetitive sensations in chewy bars.
Given the contribution of frequent hunger and overeating to the rising incidence of obesity, strategies to increase the satiating and satiety-inducing properties of snacks and meals are needed. In this study, we conducted three experiments to explore the contribution of sensory and labeling modifications to expected satiation and satiety in a popular and versatile snack: a chewy bar. For each experiment, we chose subtle interventions that could be incorporated into a variety of products without requiring significant reformulation. In experiment one, participants evaluated ten chewy bar samples (five flavors, two peanut form conditions) and rated five expected appetitive sensations. In experiment two, participants viewed one of six packaging images with various labeling interventions (control, protein bar label, "good for you" logo, meal bar label, calorie content logo, and "satisfies hunger longer" logo). The strongest sensory and labeling interventions from the first two experiments were combined and simultaneously evaluated in experiment three. Although we did not detect any significant effects of sensory or labeling modifications in any of the experiments, exploratory post-hoc analysis suggested that whole peanuts suppressed expected hunger and increased expected fullness, and that protein labeling increased expected satiety. Additionally, through a penalty-benefit analysis of check-all-that-apply (CATA) product characteristics, we identified several attributes that consumers may positively (wholesome, indulgent, sweet, heavy, rich) and negatively (processed) associate with expected appetitive sensations. Incorporation of sensory and packaging cues that elicit (or avoid, in the case of "processed") these attributes may aid in the creation of functional products to help manage appetite. Combining several intrinsic and extrinsic product modifications is likely necessary to meaningfully alter expected appetitive sensations.


Immune-evasive human islet-like organoids ameliorate diabetes.
Islets derived from stem cells hold promise as a therapy for insulin-dependent diabetes, but there remain challenges towards achieving this goal1-6. Here we generate human islet-like organoids (HILOs) from induced pluripotent stem cells and show that non-canonical WNT4 signalling drives the metabolic maturation necessary for robust ex vivo glucose-stimulated insulin secretion. These functionally mature HILOs contain endocrine-like cell types that, upon transplantation, rapidly re-establish glucose homeostasis in diabetic NOD/SCID mice. Overexpression of the immune checkpoint protein programmed death-ligand 1 (PD-L1) protected HILO xenografts such that they were able to restore glucose homeostasis in immune-competent diabetic mice for 50 days. Furthermore, ex vivo stimulation with interferon-γ induced endogenous PD-L1 expression and restricted T cell activation and graft rejection. The generation of glucose-responsive islet-like organoids that are able to avoid immune detection provides a promising alternative to cadaveric and device-dependent therapies in the treatment of diabetes.