The physician-patient-parent communication: a qualitative perspective on the child's contribution.
The aim of the present study was to explore (1) how and with which specificity the young patient contributes to the visit; (2) the communicative-relational manner with which adults handle the child's interventions. Ten videoed visits with patients aged 2-6 years were selected. A content and discourse analysis was realized. Results showed three macro-categories that seem to fully describe the young patient interventions: (1) The subjective experience regarding the illness; (2) The child's own learning process; (3) The child's medical knowledge. These contributions seem to be handled by the adults in processes that may or may not integrate the patient contributions. Results confirmed the quantitatively limited child's contribution, but they also showed an active child, who communicates with the adults about the subjective experience of the visit or the illness, and who autonomously handle the learning process about the roles in the visit. Physicians should improve their communication skills to integrate the child's interventions.


Ascorbic acid mitigates cadmium-induced stress, and contributes to ionome stabilization in fission yeast.
Cadmium is a highly toxic environmental pollutant which through enhancement of reactive oxygen species (ROS) production triggers oxidative stress to the cell. Cell growth, a fundamental feature of all living organisms is closely connected to the cell shape and homeostasis. As these processes largely depend on cell fitness status and environmental conditions we have analyzed, the impact of different cadmium concentrations and the effect of ascorbic acid (ascorbate, AsA) supplementation on cell growth parameters, cell morphology, and ionome balance maintenance in Schizosaccharomyces pombe. We show that cadmium causes membrane lipid peroxidation resulting in cell shape alterations leading to growth impairment and through mineral elements disequilibrium affects ionome homeostasis in a dose- and time-dependent manner. AsA recognized as one of the most prominent antioxidants, when overdosed, displays considerable pro-oxidant activity, though precise dosing of its supplementation is desired. We present here that AsA under efficacious concentration largely improves cell condition affected by cadmium. Although, we clearly demonstrate the beneficial feature of AsA, further studies are required to fully understand its protective nature on cell homeostasis maintenance under conditions of the broken environment.


The conformation of histone H5 bound to DNA. Maintenance of the globular structure after binding.
Trypsin digestion is used to investigate the conformation of histone H5 when bound to DNA. A central region of H5 comprising residues (22--100) is found to be resistant to digestion and it is concluded that this region is compacted whilst the remaining N- and C-terminal regions are more extended. Since this is the same result found previously for the free solution conformation of histone H5 it follows that a 3-domain structure is preserved on DNA binding. The binding of H5 and the central region (22--100) to DNA is also studied using proton magnetic resonance (270 MHz) and a precipitation approach. It is concluded that all 3 domains of H5 bind to DNA at low ionic strengths. The central domain (residues 22--100) is released at 0.3--0.4 M NaCl, but 0.7 M NaCl is required to release the N- and C-terminal regions. Comparison is made of H5 binding to DNA with that of the related histone H1.


Use of hydrochlorothiazide and risk of nonmelanoma skin cancer in Koreans: a retrospective cohort study using administrative healthcare data.
The incidence of skin cancer is increasing because of the ageing population and ultraviolet exposure, and previous studies have revealed that long-term use of hydrochlorothiazide (HCTZ), an antihypertensive agent, has been associated with an increased risk of nonmelanoma skin cancer (NMSC). However, the association of NMSC and HCTZ within East Asian populations is unclear. To investigate the risk of NMSC in Korean subjects using HCTZ. A retrospective cohort study was conducted using the administrative healthcare data. The study enrolled 62 243 patients exposed to HCTZ with a cumulative dose of ≥ 2500 mg and 62 243 unexposed subjects matched 1 : 1 with the patients for age, sex and income level. There was a significant difference in the cumulative incidence of NMSC between the two groups (log-rank P < 0.01). Cox regression analysis was conducted after adjusting for potential confounders, and showed the risk for NMSC in the group exposed to HCTZ was significantly higher than that of the unexposed group (hazard ratio = 1.48; 95% CI 1.03-2.13). In the subgroup analysis, the oldest age group (≥ 70 years) showed increased cumulative incidence of NMSC with statistical significance compared with the unexposed control group (log-rank P < 0.01). In this study, we revealed that the cumulative use of HCTZ (≥ 2500 mg) could increase the risk of NMSC in Koreans, especially the older age group. Thus, HCTZ could be a risk factor for NMSC in East Asian as well as white populations.


Scintigraphy of the parathyroid glands with 201TI: experience with 250 operated patients.
Parathyroid scintigraphy confirmed its validity in the preoperative localization of enlarged parathyroids, showing a sensitivity of 82% in a series of 250 patients suffering from primary hyperparathyroidism and successfully operated on. The glands better visualized were in an ectopic site or they were completely or partially outside the thyroid so that they were easily visible without employing digital image subtraction. This is nevertheless necessary to visualize parathyroids in a retrothyroid site but some problems arise, related not only to movements of the patient but also to the instrumentation to perform a correct image subtraction.


New dyes based on anthraquinone derivatives for color filter colorants.
Two new compounds which substituted quinoline group in 1,4-position and 1,8-position of anthraquinone were synthesized for color filter. The change in physical properties according to the substituted position of the synthesized compound was systematically identified from the perspectives of optical property and thermal property. The extinction coefficient (ε) of the synthesized substance has a very high value more than 4.26 in log scale. Td value is more than 300 °C, which shows high thermal stability. This showed quite excellent results in optical property and thermal stability.


Histone deacetylase inhibitor Trichostatin A induces neural tube defects and promotes neural crest specification in the chicken neural tube.
Epigenetic mechanisms serve as key regulatory elements during vertebrate embryogenesis. Histone acetylation levels, controlled by the opposing action of histone acetyl transferases (HATs) and histone deacetylases (HDACs), influence the accessibility of DNA to transcription factors and thereby dynamically regulate transcriptional programs. HDACs execute important functions in the control of proliferation, differentiation, and the establishment of cell identities during embryonic development. To investigate the global role of the HDAC family during neural tube development, we employed Trichostatin A (TSA) to locally block enzymatic HDAC activity in chick embryos in ovo. We found that TSA treatment induces neural tube defects at the level of the posterior neuropore, ranging from slight undulations to a complete failure of neural tube closure. This phenotype is accompanied by morphological changes in neuroepithelial cells and induction of apoptosis. As a molecular consequence of HDAC inhibition, we observed a timely deregulated cadherin switching in the dorsal neural tube, illustrated by induction of Cadherin 6B as well as reciprocal downregulation of N-Cadherin expression. Concomitantly, several neural crest specific markers, including Bmp4, Pax3, Sox9 and Sox10 are induced, causing a premature loss of epithelial characteristics. Our findings provide evidence that HDAC function is crucial to control the regulatory circuits operating during trunk neural crest development and neural tube closure.


Amyloid cascade in Alzheimer's disease: Recent advances in medicinal chemistry.
Alzheimer's disease is of major concern all over the world due to a number of factors including (i) an aging population (ii) increasing life span and (iii) lack of effective pharmacotherapy options. The past decade has seen intense research in discovering disease-modifying multitargeting small molecules as therapeutic options. The pathophysiology of Alzheimer's disease is attributed to a number of factors such as the cholinergic dysfunction, amyloid/tau toxicity and oxidative stress/mitochondrial dysfunction. In recent years, targeting the amyloid cascade has emerged as an attractive strategy to discover novel neurotherapeutics. Formation of beta-amyloid species, with different degrees of solubility and neurotoxicity is associated with the gradual decline in cognition leading to dementia. The two commonly used approaches to prevent beta-amyloid accumulation in the brain include (i) development of beta-secretase inhibitors and (ii) designing direct inhibitors of beta-amyloid (self-induced) aggregation. This review highlights the amyloid cascade hypothesis and the key chemical features required to design small molecules that inhibit lower and higher order beta-amyloid aggregates. Several recent examples of small synthetic molecules with disease-modifying properties were considered and their molecular docking studies were conducted using either a dimer or steric-zipper assembly of beta-amyloid. These investigations provide a mechanistic understanding on the structural requirements needed to design novel small molecules with anti-amyloid aggregation properties. Significantly, this work also demonstrates that the structural requirements to prevent aggregation of various amyloid species differs considerably, which explains the fact that many small molecules do not exhibit similar inhibition profile toward diverse amyloid species such as dimers, trimers, tetramers, oligomers, protofibrils and fibrils.


Thromboprophylaxis Timing After Blunt Solid Organ Injury: A Systematic Review and Meta-analysis.
Trauma patients with blunt abdominal solid organ injuries are at high risk for venous thromboembolism (VTE), but the optimal time to safely administer chemical thromboprophylaxis is controversial, especially for patients who are managed nonoperatively due to increased risk of hemorrhage. We sought to compare failure of nonoperative management (NOM) and VTE events based on timing of chemical thromboprophylaxis initiation. A systematic review was conducted in PubMed and Embase databases. Studies were included if they evaluated timing of initiation of chemical thromboprophylaxis in trauma patients who underwent NOM of blunt solid organ injuries. Outcomes included failure of NOM and incidence of VTE. A random-effects meta-analysis was performed comparing patients who received late (>48 h) versus early thromboprophylaxis initiation. Twelve retrospective cohort studies, comprising 21,909 patients, were included. Three studies, including 6375 patients, provided data on adjusted outcomes. Pooled adjusted analysis demonstrated no difference in failure of NOM in patients receiving late versus early thromboprophylaxis (odds ratio [OR] 0.92, 95% confidence interval [CI]:0.4-2.14). When including all unadjusted studies, even those at high risk of bias, there remained no difference in failure of NOM (OR 1.16, 95% CI:0.72-1.86). In the adjusted analysis for VTE events, which had 6259 patients between two studies, patients receiving late chemical thromboprophylaxis had a higher risk of VTE compared with those who received early thromboprophylaxis (OR 1.89, 95% CI:1.15-3.12). Based on current observational evidence, initiation of prophylaxis before 48 h is associated with lower VTE rates without higher risk of failure of NOM.


How often does oral treatment of toenail onychomycosis produce a disease-free nail? An analysis of published data.
To analyze studies on oral treatment of toenail onychomycosis so as to aid clinicians and patients in making informed decisions. Studies dealing with treatment of toenail onychomycosis were identified by means of 2 MEDLINE search strategies. One was a title search using the word "toenail"; the other search used the combined Medical Subject Headings "onychomycosis" and "therapy". Articles were read to ascertain that they (1) described results in toenails, (2) used both culture and microscopy, and (3) included a clinical evaluation. Not included were case reports, series of fewer than 15 subjects, reports that combined fingernail onychomycosis and toenail onychomycosis in their statistics, and articles reporting only the total number of toenails cured without providing data as to how many subjects were cured. This elimination process left 26 articles, which were then analyzed by means of a checklist that included a morphologically normal nail, mycological findings, and methodological items including recurrence rate, intent-to-treat analysis, placebo group, and whether terms were defined. When there was sufficient data, the frequency with which the treatment achieved normal mycological results, a clinically normal nail, and a disease-free nail (normal-appearing nail plus normal mycological results) was calculated. Confidence intervals were calculated for disease-free nail results. Standard courses of terbinafine achieved a disease-free nail in approximately 35% to 50% of patients. For itraconazole, the relevant disease-free nail rate was about 25% to 40%. Disease reappearance is an important issue; unfortunately data are lacking as to its frequency.


[Frontal fibrosing alopecia-update].
The number of patients presenting with frontal fibrosing alopecia (FAA) is increasing not only in hair clinics. The recognition of the peculiar clinical pattern and associated symptoms is an important prerequisite to ensure adequate counseling and therapeutic management of the patients. Experimental studies and a range of case series give first insights into the pathogenesis, possible trigger factors, clinical course of disease and treatment options. The clinical spectrum of FFA extends beyond the typical recession of the frontal hair line initially observed in postmenopausal women. Younger women, men and rarely adolescents may also be affected. Band-like extension to the occiput, diffuse bitemporal hair thinning, eyebrow and body hair involvement as well as facial papules are part of the clinical spectrum. Similar to lichen planopilaris, inflammation and fibrosis with involvement of the stem cell region result in permanent loss of hair follicles. Which additional factors contribute to the characteristic pattern remains to be elucidated. Currently, therapeutic management largely relies on anti-inflammatory treatment with combined topical, intralesional and systemic administration depending on disease activity. The chronic progressive course, sometimes even in the absence of pronounced inflammation remains a challenge for both the affected individuals and the treating physicians. Controlled studies are required to develop evidence-based recommendations and to explore novel treatment strategies.


miR-218-5p in endometrial microenvironment prevents the migration of ectopic endometrial stromal cells by inhibiting LASP1.
Our previous two-dimensional electrophoresis experiment showed that the expression of LASP1 in patients with endometriosis was significantly higher than that of control endometrium. However, the molecular mechanism by which LASP1 is regulated in endometriosis/adenomyosis is unknown. Herein, qPCR was performed to analyze the expression levels of LASP1 and miR-218-5p between endometriosis (Ems) cells and control cells. Fluorescence in situ hybridization was carried out to measure the expression level of miR-218-5p in ectopic endometrium versus normal endometrium. After miR-218-5p mimic or inhibitor were transfected, the transwell experiment was carried out to see the effect of miR-218-5p on the migration of endometrial stromal cells (ESCs). EdU was used to measure cell proliferation rate. Dual-luciferase reporter assay was used to verify the binding of hsa-miR-218-5p to the 3'UTR of LASP1. Western blot and immunofluorescence analysis were carried out to identify the protein expression pattern of LASP1 and EMT markers in endometrial tissue. The miR-218-5p is mainly secreted from blood vessels and expressed in the muscle layer around the endometrium, which inhibits the expression level of LASP1 by binding the 3'UTR region of LASP1 in normal ESCs. Overexpression of miR-218-5p impedes the epithelial-to-mesenchymal transition (EMT) and prevents the migration of ESCs and the expression of Vimentin in Ems. Our findings revealed that miR-218-5p in endometrial microenvironment prevents the migration of ectopic endometrial stromal cells by inhibiting LASP1.


Successful outcome of acute graft-versus-host disease in a liver allograft recipient by withdrawal of immunosuppression.
Graft-versus-host disease (GVHD) after liver transplantation is uncommon, and the outcome is almost always fatal. Since 1987, about 30 cases have been described, and patient survival is mostly exceptional. A 29-year-old man underwent retransplantation due to chronic cholestatic syndrome, 5 years after his first liver transplantation. Indication for the first liver transplantation was acute liver failure caused by exsiccosis. After the second transplantation, the patient had an initially uneventful course, developing thrombocytopenia at day 21 followed by skin rash and septic complications. Diagnosis of acute GVHD was made by using serological techniques for HLA-A and HLA-DRB and subsequently by fluorogenic sequence-specific primed polymerase chain reaction. In addition, donor lymphocytes were marked by immunohistochemical methods via biopsies of the skin. Immunosuppressive therapy was withdrawn to allow the patient's own immune system to eliminate donor cells. By withdrawing the immunosuppressive therapy, clinical and morphological signs of GVHD vanished. The patient is doing well without recurrence 13 months after transplantation. Withdrawal of immunosuppressive therapy is a promising approach in the treatment of acute GVHD to allow the patient's immune system to reconstitute itself, reject offending lymphocytes, and avoid lethal septic complications.


Characterization of the novel HLA-DQA1*02:01:14 allele by sequencing-based typing.
HLA-DQA1*02:01:14 differs from HLA-DQA1*02:01:01:02 by one nucleotide substitution in codon 105 in exon 3.


Comparative effect of tube drain on post operative inflammatory complications of impacted mandibular third molar surgery College Hospital, Ibadan, Nigeria.
Swelling, pain and trismus are acute reversible inflammatory complications of impacted mandibular third molar (M3) surgery. They contribute to the deterioration of quality of life and loss of several useful working hours. This study aimed to investigate whether the use of a surgical drain following M3 surgery can minimise these inflammatory complications. Eighty consecutive patients who gave consent were enrolled into the study. Patients were assigned into two groups (drain and no drain) by systematic sampling method which was modified to ensure matching of patients by age, sex and spatial relationship of the impacted mandibular third molar. The patients in the drain group (n=40) had a Foley's catheter drain inserted into the wound after the surgical procedure while the patients in the no drain group (n=40) had their wound closed without the use of drain. All patients had primary wound closure with 3.0 black silk sutures after the procedure. Demographic data, cheek dimension and maximal mouth opening were recorded before the procedure. Pain, swelling and trismus were evaluated in the two groups at 24 hours, 48 hours and 7th day after surgery. Post operative swelling and visual analogue scale score for pain were comparatively lesser in the drain group patients. The maximal interincisal distance was also more in the drain group patients. The findings from this study indicated that there is a significant benefit of using a surgical drain in minimising postoperative oedema, pain and trismus following surgical removal of impacted mandibular third molar.


Reprogramming Human Fibroblasts to Induced Pluripotent Stem Cells Using the GFP-Marked Lentiviral Vectors in the Chemically Defined Medium.
Much investigation is needed to understand the underlying molecular mechanisms of iPSC reprogramming and to improve this technology. Lentivirus-mediated iPSC reprogramming remains the most effective method to study human pluripotency reprogramming. iPSC production is more efficient and consistent in the chemically defined medium. Fibroblasts are the most common starting cells for iPSC generation. Here, we provide a detailed protocol for iPSC generation from human fibroblasts using the GFP-expressing lentiviral vectors in the chemically defined medium.


In Vivo Pelvic and Hip Joint Kinematics in Patients With Cam Femoroacetabular Impingement Syndrome: A Dual Fluoroscopy Study.
Femoroacetabular impingement syndrome (FAIS) may alter the kinematic function of the hip, resulting in pain and tissue damage. Previous motion analysis studies of FAIS have employed skin markers, which are prone to soft tissue artifact and inaccurate calculation of the hip joint center. This may explain why the evidence linking FAIS with deleterious kinematics is contradictory. The purpose of this study was to employ dual fluoroscopy (DF) to quantify in vivo kinematics of patients with cam FAIS relative to asymptomatic, morphologically normal control participants during various activities. Eleven asymptomatic, morphologically normal controls and seven patients with cam FAIS were imaged with DF during standing, level walking, incline walking, and functional range of motion activities. Model-based tracking calculated the kinematic position of the hip by registering projections of three-dimensional computed tomography models with DF images. Patients with FAIS stood with their hip extended (mean [95% confidence interval], -2.2 [-7.4, 3.1]°, flexion positive), whereas controls were flexed (5.3 [2.6, 8.0]°; p = 0.013). Male patients with cam FAIS had less peak internal rotation than the male control participants during self-selected speed level-walking (-0.2 [-6.5, 6.1]° vs. -9.8 [-12.2, -7.3]°; p = 0.007) and less anterior pelvic tilt at heel-strike of incline (5°) walking (3.4 [-1.0, -7.9]° vs. 9.8 [6.4, 13.2]°; p = 0.032). Even during submaximal range of motion activities, such as incline walking, patients may alter pelvic motion to avoid positions that approximate the cam lesion and the acetabular labrum. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:823-833, 2020.


Craniofacial polyostotic fibrous dysplasia.
Three cases of gross craniofacial polyostotic fibrous dysplasia are presented, together with a brief review of the condition, and pertinent points regarding the cases are discussed. As complete excision of the lesion and immediate reconstruction is rarely feasible or possible, and partial excision may result in accelerated growth of the lesion during the patient's active growth phase, resection only to protect, maintain or restore certain important functions (e.g. vision) during this period are advocated, after which close follow-up is mandatory until the lesion becomes quiescent, when further surgical procedures may be undertaken.


Possible protective and curative effects of selenium nanoparticles on testosterone-induced benign prostatic hyperplasia rat model.
Men over the age of 40 are more likely to develop benign prostatic hyperplasia (BPH). BPH is characterised by proliferation of the prostatic epithelium and stroma. Selenium in the form of nanoparticles is an essential metalloid mineral and antioxidant. In this study, selenium nanoparticles (SeNPs) were tested for their potential protective and curative impacts on BPH in rats. Fifty male Sprague-Dawley rats were randomly divided into five groups: Group I (Control group); Group II (Orchiectomised group): bilateral orchiectomy was conducted on rats; Group III (BPH group): testosterone (TE) enanthate injection was used to induce BPH; Group IV (Protective group): rats were given SeNPs before subjecting rats to BPH; Group V (Curative group): rats were succumbed to BPH, followed by administration of SeNPs. Measurement of prostate specific antigen (PSA) and TE in serum was performed and prostates were weighed and prepared for histological, immunohistochemical and ultrastructural examination. In the BPH group, serum TE and PSA levels, as well as prostate weight, increased significantly and significant decreases were observed in the protective and curative groups. Reduced acinar lumen, expansion of stroma and epithelial hyperplasia were noticed in the BPH group, which were ameliorated significantly in both the protective and curative groups. There was an increase in proliferating cell nuclear antigen immunoreaction in the BPH group and a decrease in both the protective and curative groups. On transmission electron microscopy of BPH group, the nuclei appeared irregular with dilated endoplasmic reticulum, loss of cell boundaries and apical microvilli. The protective group showed more improvement than the curative group. The effects of SeNPs on BPH induced by TE in rats, were both protective and curative, although the protective effects were more pronounced.


3D surface defect map for characterising the buccolingual profile of peri-implant tissues.
To describe a novel, noninvasive, intraoral optical scanning-based approach for characterising the buccolingual profile of peri-implant tissues using a 3D surface defect map. Intraoral optical scans of 20 isolated dental implants with peri-implant soft tissue dehiscence in 20 subjects were captured. The digital models were then imported into image analysis software, where an examiner (LM) performed a 3D surface defect map analysis characterising the buccolingual profile of the peri-implant tissues in respect to the adjacent teeth. Ten linear divergence points that were 0.5 mm apart in a corono-apical direction were identified at the midfacial aspect of the implants. Based on these points, the implants were grouped into three different buccolingual profiles. The method for creating the 3D surface defect map of isolated implant sites was outlined. Eight implants displayed pattern 1 (coronal profile of peri-implant tissues more lingual/palatal than their apical portion), six implants exhibited pattern 2 (opposite of pattern 1) and six sites showed pattern 3 (relatively uniform and "flat"). A novel method for assessing the buccolingual profile/position of peri-implant tissues using a single intraoral digital impression was proposed. The 3D surface defect map visualises the volumetric differences in the region of interest compared to the adjacent sites, allowing for objective quantification and reporting of profile/ridge deficiencies of isolated sites.


Temperature and humidity effects on off-host survival of the Northern fowl mite (Acari: Macronyssidae) and the chicken body louse (Phthiraptera: Menoponidae).
Off-host survival of the northern fowl mite, Ornithonyssus sylviarum (Canestrini & Fanzago) (Acari: Macronyssidae), and the chicken body louse, Menacanthus stramineus (Nitzsch) (Phthiraptera: Menoponidae), was studied at 12 combinations of temperature (15, 21, 27, and 33 degrees C) and humidity (31, 65, and 85% RH). Mite protonymphs and louse third instars survived longer on average than the respective adult stages. Higher temperatures significantly reduced survival of adult and immature stages of both ectoparasites, whereas relative humidity had significant effects on O. sylviarum (especially protonymphs) but not M. stramineus. The LT50 values for adult northern fowl mites ranged from 1.9 (at 33 degrees C, 31%RH) to 8.3 d (at 15 degrees C, 85%RH), LT50 values for mite protonymphs ranged from 2.0 (at 33 degrees C, 31%RH) to 18.1 d (at 15 degrees C, 85%RH), LT50 values for adult lice ranged from 0.5 (at 33 degrees C, 31%RH) to 1.7 d (at 15 degrees C, 65%RH), and LT50 values for nymphal lice ranged from 1.2 (at 33 degrees C, 65%RH) to 3.3 d (at 21 degrees C, 31%RH). Maximum survival of the northern fowl mite was up to 35 d for adults and 29 d for protonymphs. Maximum survival for the chicken body louse was 3.3 d for adults and 5.8 d for nymphs. The data provide minimum guidelines for leaving poultry houses vacant long enough to allow ectoparasites to die before introduction of subsequent new flocks.


Case report: Spontaneous hemothorax following anticoagulation for microthrombi in severe COVID pneumonia.
Anticoagulant therapy has become a hallmark of treatment for critically ill COVID patients. Gastrointestinal and intracranial hemorrhage are known major complications of anticoagulation, but spontaneous hemothorax is a rare event, particularly in the absence of pre-existing structural lung disease, vascular malformations, or genetic bleeding diatheses. Herein is a case of spontaneous hemothorax following anticoagulation for microthrombi in a patient with acute hypoxic respiratory failure due to Covid pneumonia. A 49 year old male with hypertension, asthma, and obesity was admitted for acute hypoxic respiratory failure due to Covid pneumonia. He was treated with dexamethasone, baricitinib, and therapeutic enoxaparin as empiric therapy for severe COVID disease. He subsequently developed a massive right hemothorax with associated hemorrhagic shock, which required initiation of massive transfusion protocol, vasopressor support and mechanical ventilation. No clear etiology for the hemothorax was determined upon investigations. The patient eventually improved and was discharged to a skilled nursing facility on chronic oxygen therapy. Various mechanisms have been proposed for the development of non-traumatic hemothoraces, including tearing of adhesions and rupture of vascularized bullae. Such explanations find support in radiologic and pathologic studies of pleural changes in Covid pneumonia, and likely played a role in the hemorrhage experienced by our patient.


Hopx distinguishes hippocampal from lateral ventricle neural stem cells.
In the adult dentate gyrus (DG) and in the proliferative zone lining the lateral ventricle (LV-PZ), radial glia-like (RGL) cells are neural stem cells (NSCs) that generate granule neurons. A number of molecular markers including glial fibrillary acidic protein (GFAP), Sox2 and nestin, can identify quiescent NSCs in these two niches. However, to date, there is no marker that distinguishes NSC origin of DG versus LV-PZ. Hopx, an atypical homeodomain only protein, is expressed by adult stem cell populations including those in the intestine and hair follicle. Here, we show that Hopx is specifically expressed in RGL cells in the adult DG, and these cells give rise to granule neurons. Assessed by non-stereological quantitation, Hopx-null NSCs exhibit enhanced neurogenesis evident by an increased number of BrdU-positive cells and doublecortin (DCX)-positive neuroblasts. In contrast, Sox2-positive, quiescent NSCs are reduced in the DG of Hopx-null animals and Notch signaling is reduced, as evidenced by reduced expression of Notch targets Hes1 and Hey2, and a reduction of the number of cells expressing the cleaved, activated form of the Notch1 receptor, the Notch intracellular domain (NICD) in Hopx-null DG. Surprisingly, Hopx is not expressed in RGL cells of the adult LV-PZ, and Hopx-expressing cells do not give rise to interneurons of the olfactory bulb (OB). These findings establish that Hopx expression distinguishes NSCs of the DG from those of the LV-PZ, and suggest that Hopx potentially regulates hippocampal neurogenesis by modulating Notch signaling.


Cyclosporine's effect on canine pancreatic endocrine function.
This study was designed to investigate the mechanism, and reversibility, of glucose intolerance following the acute administration of cyclosporine (CsA) in a canine model. Three groups underwent a baseline intravenous glucose tolerance test (IVGTT; 0.5 g/kg of glucose), with simultaneous insulin determinations. In groups A and B, repeat IVGTTs were performed, at three-day intervals, after 2, 4, and 6 mg/kg of intravenous CsA + solvent (group A; n = 8), or the solvent alone (group B; n = 5). Repeat IVGTTs were performed in group A, 24 and 72 hr after the last CsA infusion. In group C (n = 5), IVGTTs were performed, 4, 24, 48, and 72 hr after oral CsA (12.5 mg/kg). In each group, the rate of glucose clearance (k value,--per cent min), and basal-to-peak insulin difference (uU/ml), for each IVGTT were compared with the baseline results. In group A, the basal-to-peak insulin difference was significantly lower than baseline (81.9 +/- 13.6) after 2 mg/kg (27.3 +/- 3.1; P less than 0.005), 4 mg/kg (22.7 +/- 3.7; P less than 0.001); and 6 mg/kg (16.8 +/- 3.2; P less than 0.001) of CsA, and returned to baseline within 24 hr (81.4 +/- 3.7). Corresponding K values were also significantly different in group A. In group B, there were no significant differences in these parameters from controls, at the equivalent doses of the solvent alone. At 4 hr after oral CsA (group C), there was a reduction in the basal-to-peak insulin difference (37.2 +/- 9.1 vs. 22.5 +/- 4.1) and K values (-3.20 +/- 0.4 vs. -1.96 +/- 0.3), with the change in K values being statistically significant (P less than 0.05). A return to baseline levels was present at 24 h. This study demonstrates that, in the canine model, therapeutic doses of intravenous and oral CsA acutely impair glucose regulation. This acute effect is secondary to decreased peripheral insulin levels, is reversible at 24 h, and is not evident with CsA solvent alone. The mechanism of decreased insulin secretion following CsA administration requires further elucidation.


Quantification of the mycotoxins patulin and ochratoxin A by stable isotope dilution assays.
For analysis of trace compounds, stable isotope dilution assays (SIDAs) have gained increasing importance in the past years. This methodology is based on the use of stable isotopically labelled analogues of the analytes as internal standards (IS). To take the mycotoxins patulin and ochratoxin A as examples, the benefits of SIDAs were demonstrated both for foods and for clinical analyses.Regarding PAT, an isotopomer labelled with(13)C was used as IS and enabled quantitation of the mycotoxin in tissues and blood. By applying this technology, a fast passive diffusion into tissue was proven with the model of the perfused rat stomach. Furthermore, rapid degradation of PAT was observed when it was reacted with blood, which was attributed to the formation of PAT-GSH adducts detected by LC-MS/MS.For OTA, a SIDA was based on the use of [(2)H5]-OTA as the IS and proved to be more accurate when compared to alternative methods such as HPLC-FD or ELISA. In contrast to PAT, OTA was detectable in human blood and urine samples. Under the assumption that the majority of OTA is circulating in blood, an urinary excretion rate of about 1% of the whole body content per day was calculated.


Cohesin loading factor Nipbl localizes to chromosome axes during mammalian meiotic prophase.
Sister chromatid cohesion mediated by the cohesin complex is essential for accurate chromosome segregation during mitosis and meiosis. Loading of cohesin onto chromosomes is dependent on another protein complex called kollerin, containing Nipbl/Scc2 and Mau2/Scc4. Nipbl is an evolutionarily conserved large protein whose haploinsufficiency in humans causes a developmental disorder called Cornelia de Lange syndrome. Although the function of Nipbl homologues for chromosome cohesion in meiotic cells of non-vertebrate models has been elucidated, Nipbl has not been characterized so far in mammalian spermatocytes or oocytes. Here we describe our analyses on the expression and localization of Nipbl in nuclei of mouse spermatocytes and oocytes at different stages of meiotic prophase. In both spermatocytes and oocytes we found that Nipbl is associated with the axial/lateral element of the synaptonemal complex (AE/LE) to which cohesin also localizes. Interestingly, Nipbl in spermatocytes, but not in oocytes, dissociates from the AE/LE at mid-pachytene stage coincident with completion of DNA double-strand break repair. Our data propose that cohesin loading activity is maintained during early stages of meiotic prophase in mammalian spermatocytes and oocytes.


Ultrahigh-temperature melt printing of multi-principal element alloys.
Multi-principal element alloys (MPEA) demonstrate superior synergetic properties compared to single-element predominated traditional alloys. However, the rapid melting and uniform mixing of multi-elements for the fabrication of MPEA structural materials by metallic 3D printing is challenging as it is difficult to achieve both a high temperature and uniform temperature distribution in a sufficient heating source simultaneously. Herein, we report an ultrahigh-temperature melt printing method that can achieve rapid multi-elemental melting and uniform mixing for MPEA fabrication. In a typical fabrication process, multi-elemental metal powders are loaded into a high-temperature column zone that can be heated up to 3000 K via Joule heating, followed by melting on the order of milliseconds and mixing into homogenous alloys, which we attribute to the sufficiently uniform high-temperature heating zone. As proof-of-concept, we successfully fabricated single-phase bulk NiFeCrCo MPEA with uniform grain size. This ultrahigh-temperature rapid melt printing process provides excellent potential toward MPEA 3D printing.


Measurement of brain glutamate using TE-averaged PRESS at 3T.
A method is introduced that provides improved in vivo spectroscopic measurements of glutamate (Glu), glutamine (Gln), choline (Cho), creatine (Cre), N-acetyl compounds (NAtot, NAA + NAAG), and the inositols (mI and sI). It was found that at 3T, TE averaging, the f1 = 0 slice of a 2D J-resolved spectrum, yielded unobstructed signals for Glu, Glu + Gln (Glx), mI, NA(tot), Cre, and Cho. The C4 protons of Glu at 2.35 ppm, and the C2 protons of Glx at 3.75 ppm were well resolved and yielded reliable measures of Glu/Gln stasis. Apparent T1/T2 values were obtained from the raw data, and metabolite tissue levels were determined relative to a readily available standard. A repeatibility error of <5%, and a coefficient of variation (CV) of <10% were observed for brain Glu levels in a study of six normal volunteers.


Do patients know their post-operative plan? A prospective cohort study of orthopaedic trauma patients at a level I trauma center.
Patient compliance with weight bearing and physical therapy recommendations is critical following an orthopedic injury. Proper compliance requires knowledge of the postinjury plan, but there is little published data regarding comprehension of postinjury recommendations among orthopedic trauma patients. We hypothesized that patient knowledge of weight bearing and physical therapy instructions following an orthopaedic injury would be poor. Prospective Observational Cohort SETTING: Level I Trauma Center PATIENTS: 194 prospectively enrolled patients completed a questionnaire testing their knowledge of their weight bearing status and physical therapy plan at their first clinic visit following an inpatient admission with an orthopedic injury RESULTS: Despite the fact that 73% of patients were participating in physical therapy following hospital discharge, only 66% (95% CI 60-73%) of patients correctly identified their postinjury weight bearing status. A multivariate analysis found no significant correlation between chance of knowing postoperative weightbearing status or physical therapy plan and any of the socioeconomic patient factors we collected. Orthopedic trauma patients had a relatively poor understanding of even basic postinjury physical therapy instructions. This did not appear to be affected by age, gender, or socioeconomic factors. Orthopedic trauma surgeons should be aware of the significant potential for knowledge deficits among their patients and should make specific efforts to identify and correct those deficits.


[Comparison of the effectiveness between long-term instillation of mitomycin C and short-term prophylaxis with MMC or bacille Calmette-Guérin. Study of patients with non-muscle-invasive urothelial cancer of the urinary bladder].
Adjuvant instillation therapy with chemo- or immunotherapeutic agents is an integral component in the treatment of non-muscle-invasive bladder cancer. There is, however, no general consensus on the choice of medication and the optimal duration of therapy. This multicenter trial compared a long-term treatment regimen with mitomycin C (MMC) with two short-term treatment approaches with MMC or bacille Calmette-Guérin (BCG) for intermediate-/high-risk bladder tumor after transurethral resection. In patients with low-risk bladder tumors, the effectiveness of six weekly MMC instillations was determined and compared with the results of patients not receiving adjuvant treatment. A total of 495 patients with intermediate-/high-risk bladder tumor (recurrent and/or multifocal pTaG1, pTaG2-3, or pT1G1-3) were randomly administered either BCG-RIVM 2x108 CFU in six weekly instillations, MMC 20 mg in six weekly instillations, or MMC 20 mg in six weekly instillations with subsequent monthly instillations for 3 years. A total of 132 low-risk patients (first diagnosis of a unifocal pTaG1 bladder tumor) were randomly allocated to two treatment arms. In the first arm, 20 mg MMC were instilled weekly six times. In the control arm, the patients received no adjuvant therapy. The 3-year recurrence-free rate in the patients of the intermediate-/high-risk group was 65.5% (95% CI: 55.9-73.5%) in the BCG arm and 68.6% (95% CI: 59.9-75.7%) in the MMC short-term arm. In the MMC long-term arm, the 3-year recurrence-free rate was significantly higher at 86.1% (95% CI: 77.9-91.4%, log-rank test: p=0.001). There was no increased toxicity observed with long-term administration of MMC. In the low-risk group, the 3-year recurrence-free rate after adjuvant therapy was 74% (95% CI: 60.0-83.8%) and in the patients receiving no adjuvant treatment 63% (95% CI: 46.6-75.5%, corresponding to a hazard ratio of 0.58 (95% CI: 0.28-1.18%). The difference between the treatment arms was not significant. Long-term prophylaxis with MMC results in a significantly reduced recurrence rate in intermediate-/high-risk bladder cancer with a comparable toxicity profile in comparison to short-term MMC or short-term BCG. Our study showed no significant decrease of the recurrence rate in low-risk tumors with six adjuvant MMC instillations. This treatment approach thus does not represent an alternative to early instillation.


Women's responses to information about overdiagnosis in the UK breast cancer screening programme: a qualitative study.
To explore the influence of overdiagnosis information on women's decisions about mammography. A qualitative focus group study with purposive sampling and thematic analysis, in which overdiagnosis information was presented. Community and university settings in London. 40 women within the breast screening age range (50-71 years) including attenders and non-attenders were recruited using a recruitment agency as well as convenience sampling methods. Women expressed surprise at the possible extent of overdiagnosis and recognised the information as important, although many struggled to interpret the numerical data. Overdiagnosis was viewed as less-personally relevant than the possibility of 'under diagnosis' (false negatives), and often considered to be an issue for follow-up care decisions rather than screening participation. Women also expressed concern that information on overdiagnosis could deter others from attending screening, although they rarely saw it as a deterrent. After discussing overdiagnosis, few women felt that they would make different decisions about breast screening in the future. Women regard it as important to be informed about overdiagnosis to get a complete picture of the risks and benefits of mammography, but the results of this study indicate that understanding overdiagnosis may not always influence women's attitudes towards participation in breast screening. The results also highlight the challenge of communicating the individual significance of information derived from population-level modelling.


Acinar cell cystadenoma of the pancreas: report of three cases and literature review.
Acinar cell cystadenoma (ACC) of the pancreas was first described as a distinct pancreatic cystic neoplasm in 2002. We have encountered three cases of ACC at our institution in addition to the 15 cases reported to date in the world literature. The gender distribution in the total cohort of patients with ACC slightly favored females (61 % female), and the median age was 49.5 years. Almost half (53 %) of the cases were identified incidentally, while the remainder presented with abdominal pain. The median tumor diameter was 5 cm in size, and no patients have had documented disease recurrence or progression, even in the setting of an incomplete resection. These findings suggest a relatively indolent biology, and that complete resections are curative. As we will show, surgical resection is warranted to treat symptoms and prevent local extension or malignant transformation.


Symptomatology and Neuropathology of patients presenting with focal cortical signs.
Here, we describe two patients who presented with focal cortical signs and underwent neuropathological examination. Case 1 was a 73-year-old woman with progressive speech disorder and abnormal behavior. She showed agraphia of the frontal lobe type, featured by the omission of kana letters when writing, other than pyramidal tract signs, pseudobulbar palsy, and frontal lobe dementia. Neuropathological examination, including TAR DNA-binding protein 43 (TDP-43) immunohistochemistry, revealed bilateral frontal and anterior temporal lobe lesions accentuated in the precentral gyrus and posterior part of the middle frontal gyrus. Both upper and lower motor neurons showed pathological changes compatible with amyotrophic lateral sclerosis. Case 2 was a 62-year-old man with progressive speech disorder and hand clumsiness. He had a motor speech disorder, compatible with apraxia of speech, and limb apraxia of the limb-kinetic and ideomotor type. Neuropathological examination revealed degeneration in the left frontal lobe, including the precentral gyrus, anterior temporal, and parietal lobe cortices. Moreover, numerous argyrophilic neuronal intracytoplasmic inclusions (Pick body) and ballooned neurons were observed in these lesions and the limbic system. The pathological diagnosis was Pick disease involving the peri-Rolandic area and parietal lobe. In these two cases, the distribution of neuropathological changes in the cerebral cortices correlated with the clinical symptoms observed.


Clip Closure Does Not Reduce Risk of Bleeding After Resection of Large Serrated Polyps: Results From a Randomized Trial.
Serrated polyps are important colorectal cancer precursors and are most commonly located in the proximal colon, where post-polypectomy bleeding rates are higher. There is limited clinical trial evidence to guide best practices for resection of large serrated polyps (LSPs). In a multicenter trial, patients with large (≥20 mm) non-pedunculated polyps undergoing endoscopic mucosal resection (EMR) were randomized to clipping of the resection base or no clipping. This analysis is stratified by histologic subtype of study polyp(s), categorized as serrated [sessile serrated lesions (SSLs) or hyperplastic polyps (HPs)] or adenomatous, comparing clip vs control groups. The primary outcome was severe post-procedure bleeding within 30 days of colonoscopy. A total of 179 participants with 199 LSPs (191 SSLs and 8 HPs) and 730 participants with 771 adenomatous polyps were included in the study. Overall, 5 patients with LSPs (2.8%) experienced post-procedure bleeding compared with 42 (5.8%) of those with adenomas. There was no difference in post-procedure bleeding rates between patients in the clip vs control group among those with LSPs (2.3% vs 3.3%, respectively, difference 1.0%; P = NS). However, among those with adenomatous polyps, clipping was associated with a lower risk of post-procedure bleeding (3.9% vs 7.6%, difference 3.7%; P = .03) and overall serious adverse events (5.5% vs 10.6%, difference 5.1%; P = .01). The post-procedure bleeding risk for LSPs removed via EMR is low, and there is no discernable benefit of prophylactic clipping of the resection base in this group. This study indicates that the benefit of endoscopic clipping following EMR may be specific for >2 cm adenomatous polyps located in the proximal colon. gov, Number: NCT01936948.


Intestinal metaplasia and adenocarcinoma induced in the stomach of rats by N-propyl-N'-nitro-N-nitrosoguanidine.
PNNG, the propyl derivative of MNNG, was administered to Wistar rats by a concentration of 59.5 micrograms/ml in the drinking water for 4, 8, and 12 months and the rats were killed in the 15th month. Intestinal metaplasia was induced in the glandular stomachs of 25%, 75%, and 83% of the rats treated with PNNG for 4, 8, and 12 months, respectively. Metaplastic glands were found in the pyloric region, especially near the pyloric ring. These glands contained goblet cells and columnar cells with striated borders. No tumors were found in the stomach of rats after 4-months treatment, but adenomas were found after 8-months treatment, and both adenomas and adenocarcinomas after 12-months treatment.


Effect of Cd toxicity on root morphology, ultrastructure, Cd uptake and accumulation of wheat under intercropping with Solanum nigrum L.
In order to evaluate the effect of intercropping of the hyperaccumulator, Solanum nigrum L. and wheat on the absorption and accumulation of cadmium (Cd) in wheat. The experiment was conducted with three replicates, which conducted on four Cd concentrations (0, 20, 40, 60 μmol L-1) in the Hoagland solution and using two planting patterns [monoculture wheat (MW), intercropping wheat and Solanum nigrum L. (IW,IS)]. The results showed that the addition of Cd in the solutions reduced the total root length by 19.08-55.98%, total root area by 12.35-44.48%, and total root volume by 16.01-46.00% of wheat plants. Intercropping with Solanum nigrum L. significantly reduced Cd contents by 28.3-47.2% and Cd accumulations by 10.08-32.43% in the roots of wheat. Transmission electron microscope (TEM) revealed that the root-tip cells of the monoculture wheat treated with Cd exhibited swollen spheres of intracellular mitochondria, disorderly arranged inner ridges of mitochondria, some damaged mitochondrial membranes, and deformed nuclear membranes. Many dense electron particles in the form of Cd were deposited in the cell gap, and the cell nucleus became smaller or even disappeared. Under the same Cd concentrations, root-tip cells of intercropped wheat showed much less density of electron particles, starch granules, and the damage to the nucleus and nuclear membrane by Cd.These results indicated that intercropping with Solanum nigrum L. reduced the Cd toxicity to wheat roots and decreased Cd uptake and accumulation in both the shoots and roots of the wheat.


Phonological memory in young children who stutter.
This study investigated phonological memory in 5- and 6-year old children who stutter. Participants were 11 children who stutter matched on general language abilities, maternal education level, and sex to 11 typically fluent children. Participants completed norm-referenced nonword repetition and digit span tasks, as well as measures of expressive and receptive vocabulary and articulation. The nonword repetition task included stimuli that ranged from 1 to 7 syllables, while the digit naming task contained number strings containing 2-10 digits. Standardized tests of vocabulary and articulation abilities were tested as well. Groups were comparable on measures expressive vocabulary, receptive vocabulary, and articulation. Despite the fact that the majority of participants scored within typical limits, young children who stutter still performed significantly less well than children who do not stutter on the nonword repetition task. No between-group differences were revealed in the digit naming task. Typically fluent children demonstrated strong correlations between phonological memory tasks and language measures, while children who stutter did not. These findings indicate that young children who stutter may have sub-clinical differences in nonword repetition.


Definitive repair in patients with pulmonary atresia and intact ventricular septum.
Between 1977 and 1988, 22 patients underwent definitive repair for pulmonary atresia with intact ventricular septum. Fifteen underwent biventricular repair (mean age 24 months). All had mild to moderate right ventricular hypoplasia at the time of definitive repair. Repair consisted of closure of the atrial septal defect with enlargement of the right ventricular cavity and outflow tract with a patch in eight, insertion of a valved homograft in three, and superior vena cava-pulmonary artery connection in four. There was one operative death (7%). Seven patients had severe right ventricular hypoplasia at the time of definitive repair and underwent a Fontan procedure (mean age 46 months). In two a valved connection was made to the right ventricle and in five a right atrial-pulmonary artery nonvalved connection. There were two operative deaths (29%). Three patients had right ventricular-coronary sinusoids: Two of them underwent a Fontan procedure and one a biventricular repair. We conclude that with adequate early palliation a biventricular repair may be successfully performed for patients with mild or moderate right ventricular hypoplasia, and the Fontan procedure may be used for those with severe right ventricular hypoplasia.


Technical tips for (dry) arthroscopic reduction and internal fixation of distal radius fractures.
Contrary to general belief, arthroscopic assisted reduction in distal radius fractures can be done in an expeditious manner and with minimal consumption of operating room resources. This article presents the steps for a pleasant arthroscopic experience in detail. The technique proposed combines the benefits of rigid fixation with volar locking plates (for the extra-articular component) and arthroscopic control of the reduction (for the articular component). It is important that the operation be carried out using the dry arthroscopic technique. However, arthroscopy is just an addition to conventional methods. Thorough knowledge of and facility with classic techniques of distal radius fracture treatment is essential for a good result.


Stratified and cryogenically stored (SACS) vaccines, a new concept in emergency foot-and-mouth disease vaccine formulation and storage.
Strategic reserves of foot-and-mouth disease (FMD) antigen have become an integral part of FMD control policy for many countries. They are based on two principles, ready formulated vaccine stored at +4 degrees C, or concentrated antigen preparations held at ultra-low temperature for later formulation. However, the latter is more economical, since ready formulated vaccine, based on oil or aluminium hydroxide/saponin adjuvants, requires regular replacement. This is primarily the result of the vaccine's limited shelf-life, nominally 18 months at +4 degrees C. Unfortunately, lowering the temperature of storage, in a bid to extend its shelf-life, has a detrimental effect on the vaccine's potency. Montanide ISA 206 and 25, two 'ready-to-formulate' oil adjuvants which can be used in all target species, are ideal for emergency vaccination. Their potential is enhanced by the ease in which they are formulated into oil emulsion vaccines. Here we describe a novel approach of layering the individual components of FMD vaccine in the same primary container and then storing the product at ultra-low temperature. This avoids the detrimental effect on potency, normally observed with frozen formulated FMD vaccine, and could substantially extend the products shelf-life. The implications of this approach for emergency vaccination strategy are discussed.


Testicular Tumors: New Developments in Germ Cell and Sex Cord Stromal Tumors.
This article reviews the recent advances and potential future changes in the classification of testicular germ cell and sex cord stromal tumors, highlighting changes in the classification system and terminology with description on newer entities. A discussion on approaching difficult areas and diagnostic pitfalls is also included along with the utility of ancillary investigations. Areas with limited knowledge are highlighted to providing direction for future studies and a bulleted summary in the form of critical care points is provided.


Hepatoma derived growth factor (HDGF) dynamics in ovarian cancer cells.
As a leading cause of cancer death among women, identification of pathophysiologically-relevant biomarkers for ovarian cancer is important. The heparin binding, hepatoma-derived growth factor (HDGF) is overexpressed in ovarian cancer cell lines and may have prognostic value, but the mechanism by which this predominantly nuclear protein is secreted or functions is unknown. In this study, we focused on the circumstances under which HDGF is released by cells and the functional relevance of extracellular HDGF in the context of ovarian cancer. Immunofluorescence imaging showed nuclear localization of HDGF in ovarian cells, but unlike what is reported for other cell types, HDGF was minimally secreted into the media. However, HDGF was passively released by necrotic and late apoptotic cells. Extracellular HDGF was functionally relevant as it stimulated phosphorylation of ERK 1/2 and P38 in both non-cancer and ovarian cancer cells, and enhanced cellular migration. Overall, our study uncovers a novel function of HDGF as a messenger of cellular condition (alarmin) which in-turn modulates cellular function-aspects that could be used as a biomarker for ovarian cancer.


Lactoferrin immunomodulation of DTH response in mice.
Improved nontoxic adjuvants, especially adjuvants capable of inducing cell-mediated immunity (CMI), are needed for research in immunology and for development of human and veterinary vaccines. Bovine Lactoferrin, an effector molecule shown to directly participate in host defense, was assessed at various concentrations as an adjuvant component for induction of DTH responses to sheep red blood cells (SRBC). Subcutaneous immunization with Lactoferrin enhanced delayed type hypersensitivity (DTH) in CBA mice in a dose-dependent fashion; DTH responses were most significantly increased when sensitization was accomplished using Lactoferrin at 50 microg/dose and 250 microg/dose. Furthermore, Lactoferrin admixed with suboptimal dose of SRBC enhanced DTH responses by over 17-fold. Peritoneal cells collected from mice intraperitoneally injected with a 100 microg/dose of Lactoferrin demonstrated modest, but significant, production of TNF-alpha, IL-12 and MIP-1alpha when cultured in vitro, compared to saline-injected controls. J774A.1 murine macrophages stimulated with Lactoferrin resulted in increased TNF-alpha protein production, and upregulated IL-12 and IL-15 mRNA. Levels of message for chemokines MIP-1alpha and MIP-2 were also increased in a dose-dependent way. Taken together, these results indicate that Lactoferrin as an adjuvant may stimulate macrophages to generate a local environment likely to push immune responses towards development and maintenance of CMI.


Evaluation of transient-evoked otoacoustic emissions in a healthy 1 to 10 year pediatric cohort in Sub-Saharan Africa.
Transient-evoked otoacoustic emissions (TEOAEs) monitor cochlear function. High pass rates have been reported for industrialized countries. Pass rates in low and middle income countries such as Sub-Saharan Africa are rare, essentially lower and available for children up to 4 years of age and frequently based on hospital recruitments. This study aims at providing additional TEOAE pass rates of a healthy Sub-Saharan cohort aged 1-10 years with data from Gabon, Ghana and Kenya. Potentially confounding factors (recruitment site, age) are taken into consideration. Healthy children were recruited in hospitals, schools and kindergartens. Inclusion criteria were age 1-10 years and normal otoscopic findings. Exclusion criteria were any sickness or physical ailment potentially impairing the hearing capacity. Five measurements per ear were performed with Capella Cochlear Emission Analyzer (MADSEN, Germany). An overall wave reproducibility of above 60% served as pass-criterion. Pass rates were compared between recruitment sites and age groups (1-5 and 6-10 years). Overall pass rate was 87.5% (n = 264; 231 passes vs. 33 fails). Of these 84.0% of hospital recruited children passed (n = 156; 131 passes vs. 25 fails), compared to 92.6% of community recruitments (n = 108; 100 passes vs. 8 fails), which was significantly different p = 0.039). If analyzed by age groups, this difference was only observed in children younger than 6 years (p = 0.007). Hospitals as recruitment sites for healthy controls seem to affect TEOAE pass rates. We advise for a cautious approach when recruiting healthy TEOAE control collectives under the age of 6 in a hospital setting. In children older than 6 years conventional pure-tone audiometry remains the standard method for hearing screening.


Phenotypic variation of floral organs in flowering crabapples and its taxonomic significance.
In angiosperms, phenotypic variation of floral organs is often considered as the traditional basis for the evolutionary relationship of different taxonomic groups above the species level. However, little is known about that at or below the species level. Here, we experimentally tested the phenotypic variation of Malus floral organs using combined methods of intraspecific uniformity test, interspecific distinctness analysis, principal component analysis, Pearson correlation analysis, and Q-type cluster analysis. The ancestor-inclined distribution characteristic analysis of Malus species and cultivars floral attributes was also carried out, so as to explore its taxonomic significance. 15/44 phenotypic traits (e.g., flower shape, flower type, flower diameter, ...) were highly consistent, distinguishable, and independent and could be used as the basis for Malus germplasm taxonomy. The studied 142 taxa were divided into two groups (A, B) and five sub-groups (A1, A2, B1, B2, B3), with significantly variable floral phenotypic attributes between groups and within sub-groups. Malus natural species were relatively clustered in the same section (series) while homologous cultivars showed evidence of ancestor-inclined distribution characteristics. However, no significant correlation between the evolutionary order of sections (Sect. Docyniopsis → Sect. Chloromeles → Sect. Sorbomalus → Sect. Eumalus) and group/sub-groups (B3 → B2 → B1 → A). Phenotypic variation of floral organs could better explore the genetic relationship between Malus taxa. The findings improved our cognition of floral phenotypic variation taxonomic significance under the species level.


Selective preservation of oral spelling without semantics in a case of multi-infarct dementia.
A 70 year old retired van driver, with a diagnosis of multi-infarct dementia, showed features associated with transcortical sensory aphasia, with excellent repetition, a severe anomia, poor semantic comprehension and fluent speech. He was able to spell orally words which he did not understand, as well as nonwords; he wrote to dictation only after first spelling the words orally. Some of his spellings provided evidence for a dissociation between semantics and the graphemic output lexicon, the application of sub-word rules and partial lexical knowledge. These findings are interpreted in terms of a cognitive neuropsychological model.


Succession of bacterial and fungal communities during natural coffee (Coffea arabica) fermentation.
Bacteria, yeasts and filamentous fungi were isolated during natural coffee processing. Bacteria were isolated in greater numbers at the beginning of the fermentation, when the moisture of the coffee beans was around 68%. Gram-positive bacteria represented 85.5% of all bacteria isolated, and Bacillus was the predominant genus (51%). Gram-negative species of the genera Serratia, Enterobacter and Acinetobacter were also found. Approximately 22% of 940 randomly chosen isolates of microorganisms were yeasts. Debaryomyces (27%), Pichia (18.9%) and Candida (8.0%) were the most commonly found genera, and these three genera tended to appear more often as the fruit was fermented and dried. Aspergillus was the most abundant genus besides Penicillium, Fusarium and Cladosporium, with 42.6% of the total fungi isolates. The genera and species identified included members known to have pectinase and cellulase activities. Of the 10 organic acids analyzed and quantified in coffee beans, acetic and lactic acids may have been generated by microbial activity. Butyric acid was not detected in any sample.


Transcatheter implantation of covered stents serving as extravascular conduits-Proof of a CT-based approach in three cases.
Covered stents perform similar to surgically implanted conduits, although the stents work inside of vessels. We present a computed tomography (CT)-based workflow for the implantation of covered stents as extravascular conduits. We selected three different use cases: 1. Connecting a left-sided partially anomalous drainage of a pulmonary vein to the left atrium. 2. Bypassing an outgrown Dacron conduit in aortic recoarctation. 3. Re-directing hepatic venous blood to the left lung in a Fontan patient with heterotaxy, connecting the innominate vein to the right pulmonary artery like a right-sided cavopulmonary connection. By postprocessing and analyzing CT scans for planning and by the use of long needles under biplane fluoroscopy for the realization of the procedure, we projected and performed the exit of a long needle out of a vessel, the re-entering of a target vessel, and the bridging of the extravascular distance by implantation of covered stents. In all three cases, the covered stents were placed successfully, connecting vessels of 15-50 mm distance from each other with very good hemodynamic results. In one case, two stents were placed consecutively, overlapping each other to accomplish an exact fitting at the connection sites to the native vessels.


Audiovisual tau effect.
This study investigated how spatial intervals between successive visual flashes are influenced by the temporal intervals between auditory pure tones presented concurrently with the flashes. Three successive visual flashes defined two spatial intervals with different extents as well as two equal temporal intervals. The onsets of the first and third tones were temporally aligned with those of the first and third flashes, while the onset of the second tone was temporally offset to that of the second visual flash, resulting in shorter or longer temporal intervals between pairs of tones. Observers judged which of the first or second spatial intervals between flashes was shorter. The results showed that the shorter temporal interval between tones caused underestimation of the spatial interval between flashes. On the other hand, stimuli without the first and third tones did not result in underestimation of spatial intervals between flashes. These results indicate an audiovisual tau effect, which is triggered by a constant velocity assumption applied to moving objects defined by more than one modality.


Dietary fibre in relation to asthma, allergic rhinitis and sensitization from childhood up to adulthood.
Dietary fibre may reduce the risk of allergy. Our aim was to investigate the association between fibre intake in childhood, asthma, allergic rhinitis and IgE sensitization up to adulthood. The individual fibre intake of 2285 participants from the Swedish population-based birth cohort BAMSE was estimated between 98- and 107-item food frequency questionnaires at ages 8 and 16 years, respectively. At 8, 16 and 24 years, asthma and allergic rhinitis symptoms were assessed by questionnaires, and sensitization to common allergens by serum IgE. Longitudinal associations were analysed by generalized estimating equations, adjusting for potential confounders. An inverse overall association was indicated between fibre intake at 8 years and allergic rhinitis symptoms up to 24 years (OR per 5 g/d 0.86; 95% CI 0.77-0.96), particularly in combination with airborne (0.74; 0.62-0.89) and food (0.69; 0.54-0.88) allergen sensitization. Higher fibre intake was also associated with specific allergen sensitization, for example, birch (0.77; 0.67-0.88) and soy (0.68; 0.53-0.87). No association was observed with asthma. Regarding sources, fruit (0.79; 0.67-0.94) and other (potatoes, chips/popcorn, legumes, and nuts, 0.71; 0.50-0.99), but not cereal or vegetable fibre were associated with allergic rhinitis. In additional analyses, including long-term fibre intake at 8 and 16 years, excluding participants with food-related allergic symptoms to examine reverse causation, as well as adjusting for antioxidant intake, associations were attenuated and became non-significant. Higher fibre intake in mid-childhood may be inversely associated with allergic rhinitis and sensitization to specific allergens up to adulthood. However, avoidance of food triggers of allergic symptoms in allergic rhinitis patients may contribute to the protective associations.


Primary mucinous sweat gland carcinoma of the eyelid simulating metastatic carcinoma.
A 78-year-old man suffered an unusual variant of sweat gland carcinoma of the eyelid. This disorder is seldom recognized, and is frequently confused with inflammation, benign neoplasms, and metastatic carcinomas. On the basis of clinicopathologic and ultrastructural features found by both light and electron microscopy, we diagnosed sweat gland carcinoma of the eyelid. We considered the possibility of metastasis from a primary carcinoma elsewhere in the patient.


Three-dimensional echocardiography in congenital heart disease: a continuum of unfulfilled promises? No. A presently clinically applicable technology with an important future? Yes.
Three-dimensional echocardiography has important clinical applications to congenital heart disease. Such applications include assessment of ventricular volumes, and unique imaging planes and projections of septae and atrio-ventricular and semi-lunar valves. Advances in ultrasound and computer technology will improve the process of three-dimensional echocardiography to continue to bring it to everyday clinical utility application.


More severe hypoxemia is associated with better subjective sleep quality in obstructive sleep apnea.
Perceived sleep quality may play an important role in diagnosis and therapy for obstructive sleep apnea (OSA). However, few studies have assessed factors that are associated with perceived sleep quality in OSA patients. Hypoxemia depresses the central nervous system and attenuates the perceived respiratory load in asthmatic patients. This study aimed to investigate the factors related to perceived sleep quality, focusing on the role of hypoxemia. Polysomnography studies of 156 OSA patients were reviewed. Traditional polysomnographic parameters, including parameters of oxy-hemoglobin saturation (SpO2), were calculated, and the sleep questionnaire and scales were used. Considering the possible pitfalls of absolute values of SpO2 and individualized responses to hypoxemia, the amplitude of desaturation was further computed as "median SpO2 minus lowest 5 % SpO2 "and "highest 5 % SpO2 minus median 5 % SpO2". Correlations between these parameters and perceived sleep quality, represented as the Pittsburgh sleep quality index (PSQI), were performed. Multiple linear regression analysis was also conducted to investigate the factors associated with the PSQI. Although the PSQI was not correlated with the apnea-hypopnea index (r = -0.113, p = 0.162) and oxygen desaturation index (r = -0.085, p = 0.291), the PSQI was negatively correlated with "median SpO2 minus lowest 5 % SpO2" (r = -0.161, p = 0.045). After adjusting for age, total sleep time, the periodic limb movements index, tendency of depression, and the lowest 5 % SpO2, the "median SpO2 minus lowest SpO2" was still a significant predictor for a lower PSQI (β = -0.357, p = 0.015). More severe hypoxemia is associated with better perceived sleep quality among OSA patients. This paradox may be associated with hypoxemia-related impairment of perception. The effect of hypoxemia did not appear to be significant in relatively mild hypoxemia but become significant in severe hypoxemia." Median SpO2 minus lowest 5 % SpO2" may also be a better predictor of perceived sleep quality than the apnea-hypopnea index because of the disproportionate effects of hypoxemia. Additionally, further studies are necessary to confirm the role of hypoxemia on perceived sleep quality and identify the possible threshold of hypoxemia in OSA patients.


CSF1R regulates schizophrenia-related stress response and vascular association of microglia/macrophages.
Microglia are known to regulate stress and anxiety in both humans and animal models. Psychosocial stress is the most common risk factor for the development of schizophrenia. However, how microglia/brain macrophages contribute to schizophrenia is not well established. We hypothesized that effector molecules expressed in microglia/macrophages were involved in schizophrenia via regulating stress susceptibility. We recruited a cohort of first episode schizophrenia (FES) patients (n = 51) and age- and sex-paired healthy controls (HCs) (n = 46) with evaluated stress perception. We performed blood RNA-sequencing (RNA-seq) and brain magnetic resonance imaging, and measured plasma level of colony stimulating factor 1 receptor (CSF1R). Furthermore, we studied a mouse model of chronic unpredictable stress (CUS) combined with a CSF1R inhibitor (CSF1Ri) (n = 9 ~ 10/group) on anxiety behaviours and microglial biology. FES patients showed higher scores of perceived stress scale (PSS, p < 0.05), lower blood CSF1R mRNA (FDR = 0.003) and protein (p < 0.05) levels, and smaller volumes of the superior frontal gyrus and parahippocampal gyrus (both FDR < 0.05) than HCs. In blood RNA-seq, CSF1R-associated differentially expressed blood genes were related to brain development. Importantly, CSF1R facilitated a negative association of the superior frontal gyrus with PSS (p < 0.01) in HCs but not FES patients. In mouse CUS+CSF1Ri model, similarly as CUS, CSF1Ri enhanced anxiety (both p < 0.001). Genes for brain angiogenesis and intensity of CD31+-blood vessels were dampened after CUS-CSF1Ri treatment. Furthermore, CSF1Ri preferentially diminished juxta-vascular microglia/macrophages and induced microglia/macrophages morphological changes (all p < 0.05). Microglial/macrophagic CSF1R regulated schizophrenia-associated stress and brain angiogenesis.


Effect of 5-hydroxytryptamine on the rate of cerebrospinal fluid production in rabbit.
Infusion of 5-hydroxytryptamine in mock cerebrospinal fluid of rabbits lowered cerebrospinal fluid production dose-dependently by nearly 30%. The effect was amplified in the presence of the monoamine oxidase inhibitor, nialamide. The 5-hydroxytryptamine-induced inhibition was partly counteracted by ketanserin, and further addition of practolol completely blocked the reduction in cerebrospinal fluid formation, suggesting that both 5-hydroxytryptamine receptors and beta 1-adrenergic receptors were involved in the response mediated by both the secretory epithelium and the vascular bed of the plexus.


Risk of extrapyramidal side effects comparing continuous vs. bolus intravenous metoclopramide administration: a systematic review and meta-analysis of randomised controlled trials.
To provide evidence about whether intravenous metoclopramide continuous infusion is associated with fewer extrapyramidal side effects than bolus infusion. Many studies have described the effects produced by the administration of metoclopramide, as a continuous intravenous infusion or intravenous bolus directly, but there is a lack of consensus about the best administration of this drug to minimise extrapyramidal side effects. A meta-analysis was conducted. The search data base was conducted in: Cochrane Library, PubMed, Web of Knowledge and Scopus, to collect randomised controlled trials examining the association between extrapyramidal side effects and intravenous metoclopramide continuous or bolus infusion. Meta-analyses were conducted for the eligible randomised controlled trials by Comprehensive Meta-Analysis. Risk difference and 95% CIs were calculated with the Cochran's Q-statistic, and heterogeneity was assessed with the I(2) test. Eleven randomised controlled trials were included. Meta-analysis showed that continuous intravenous infusion of metoclopramide produced less extrapyramidal side effects (8%; 95% CI, 5-11%; p < 0·001; I(2) = 65%). These improvements were particularly strong in studies scored ≥3 in the Jadad scale (12%; 95% CI, 3-24%; I(2) = 0%), in emergency patients (12%; 95% CI, 2-25%; I(2) = 0%), in patients who used concomitant drugs (9%; 95% CI, 5-12%; I(2) = 80%) and when observation (8%; 95% CI, 5-14%; I(2) = 69%) or analogue scale (7%; 95% CI, 1-13%; I(2) = 64%) were used to quantify the number of extrapyramidal reactions in patients. Compared with bolus administration, continuous intravenous infusion of metoclopramide reduces the appearance of extrapyramidal side effects. Continuous infusion is an effective intervention to reduce in patients discomfort caused by the extrapyramidal side effects of metoclopramide. Clinicians also reduce the time spent on alleviating these unwanted effects.


Ethanol metabolism and memory impairment in American Indian and white women social drinkers.
American Indian women metabolized a moderate dose of ethanol significantly more rapidly than did White women of similar age, education, weight and drinking history; however, the two groups demonstrated a similar memory decrement due to ethanol.


Delayed responses to electrical stimuli reflect C-fiber responsiveness in human microneurography.
The slowing of impulse conduction during the relative refractory period has often been used to assess activation of C-fibers, in particular, in human microneurography. This study aimed to evaluate the sensitivity of this method and the factors affecting it. Thirty cutaneous C-fibers were recorded from the peroneal nerves of healthy human subjects. Intracutaneous electrical stimulation in the receptive field at 4 s intervals, after some minutes of adaptation, induced spike discharges at constant latency. One or more conditioning stimulus pulses were interpolated at different intervals and the increase in latency after the subsequent regular pulse was assessed. The latency shift was found to depend on the number of interposed pulses, on the time interval between conditioning and conditioned stimulus, and on the conduction velocity of the C-unit. The increase in latency was larger with greater distance between stimulating and recording electrodes, indicating a contribution of the conductile membrane over its whole length. On the other hand, slowing was more pronounced, on average, in slower conducting C-units and conduction velocities were slower when recordings were performed more distally. These findings indicate that the slower terminal nerve branches contribute most to the latency increases. Even a single additional spike in between two regular pulses caused a reliable latency shift of 1.2 +/- 0.2 ms (mean +/- SEM) and additional pulses lead to an approximately linear latency increase (2 pulses: 2.3 +/- 0.3 ms; 4 pulses: 5.9 +/- 0.7 ms). In contrast to the number of interposed stimuli, different intervals between interposed and regular stimuli had only a minor impact on the latency shifts.(ABSTRACT TRUNCATED AT 250 WORDS)


New potential therapeutic approaches targeting synovial fibroblasts in rheumatoid arthritis.
Synovial cells play a key role in joint destruction during chronic inflammation. In particular, activated synovial fibroblasts (SFs) undergo intrinsic alterations leading to an aggressive phenotype mediating cartilage destruction and bone erosion in rheumatoid arthritis (RA). Recent research has revealed a number of targets to control arthritogenic changes in SFs. Therefore, identification of SF phenotypes, control of epigenetic changes, modulation of cellular functions, or regulation of the activity of cation channels and different signaling pathways has been investigated. Although many of these approaches have shown efficacy in vitro and in animal models of RA, further research is needed to select the most relevant targets for drug development. This review is focused on the role of SFs as a potential strategy to discover novel therapeutic targets in RA aimed at preserving joint architecture and function.


Faecal endotoxin and activity of the gut-associated lymphoid tissue in patients with malignant (B-cell) lymphoma.
On the basis of previously obtained evidence that Gram-negative bacteria may influence the activity of leukaemia, a study of the composition of the flora, the immune stimulation by the Gram-negative bacteria and the endotoxin concentration in faeces was conducted in patients with low-grade malignant B-cell lymphoma as well as in patients with acute leukaemia. In these patients it was investigated whether the number of facultative anaerobic Gram-negative bacteria in the faeces correlated with endotoxin concentration. In addition, IgA coating of Gram-negative bacteria in the faeces was determined and the titre of circulating antibodies to endogenous Enterobacteriaceae species from the faeces of the corresponding patient was studied. No clear difference was found to exist in the percentage of IgA-coated Gram-negative bacteria in the faeces and in the circulating antibody titres to endogenous Enterobacteriaceae between healthy control persons, lymphoma patients and patients with acute leukaemia. Antimicrobial treatment to establish selective decontamination (SD) of Enterobacteriaceae species from the digestive tract did cause a significant decrease in the faecal endotoxin concentration in a subset of patients treated for SD with polymyxin.


The decays of (109,111)Pd and (111)Ag following neutron capture by Pd.
Improved precisions of the energies and intensities of the γ rays emitted in the decays of (109)Pd and (111g,m)Pd have been obtained based on a high-resolution spectroscopic study of these γ emissions from radioactive samples produced by neutron capture by natural Pd. Correspondingly improved values of the energies and β feedings of the levels in the (109,)(111)Ag daughters have been deduced. More precise energies and intensities have also been determined for the γ rays emitted in the decays of the (111)Pd daughter activities (111g,m)Ag to (111)Cd.


Caspr2 antibodies in limbic encephalitis with cerebellar ataxia, dyskinesias and myoclonus.
Here we report on a case of contactin-associated protein-2 (Caspr2) antibody positive but voltage gated potassium channel (VGKC) antibody negative limbic encephalitis associated with cerebellar ataxia, myoclonus and dyskinesias with favorable response to immunotherapy. This case underlines the importance of Caspr2-specific antibody testing and demonstrates that Caspr2 antibodies are associated with a broader clinical spectrum than hitherto described.


Revisiting the relationship between regenerative ability and aging.
Contrary to the longstanding view that newts (Notophthalamus viridescens), but not axolotls (Ambystoma mexicanum), can regenerate a lens, a recent report in BMC Biology by Panagiotis Tsonis and colleagues shows axolotls indeed possess this ability during early larval stages. In contrast, they show that zebrafish never posses this ability, even as embryos. This underscores the importance of comparing regenerative ability across species and reinforces the need to consider organ regeneration in the context of evolution, development, and aging.


Goals of Care Documentation: Insights from A Pilot Implementation Study.
The Life Sustaining Treatment Decision Initiative is a national effort by the Veterans Health Administration to ensure goals of care documentation occurs among all patients at high risk of life-threatening events. Examine likelihood to receive goals of care documentation and explore associations between documentation and perceived patient care experience at the individual and site level. Retrospective, quality improvement analysis of initiative pilot data from four geographically diverse Veterans Affairs (VA) sites (Fall 2014-Winter 2016) before national roll-out. Goals of care documentation according to gender, marital status, urban/rural status, race/ethnicity, age, serious health condition, and Care Assessment Needs scores. Association between goals of care documentation and perceived patient care experience analyzed based on Bereaved Family Survey outcomes of overall care, communication, and support. Veterans were more likely to have goals of care documentation if widowed, urban residents, and of white race. Patients older than 65-years and those with a higher Care Assessment Needs score were twice as likely as a frail patient to have goals of care documented. One pilot site demonstrated a positive association between documentation and perceived support. Pilot site was a statistically significant predictor of the occurrence of goals of care documentation and Bereaved Family Survey scores. Older and seriously ill patients were most likely to have goals of care documented. Association between a documented goals of care conversation and perceived patient care experience were largely unsupported. Site-level largely contributed to understanding the likelihood of documentation and care experience.


Understanding the Arterial Anatomy and Dermal Perfusion of the Lower Extremity with Clinical Application.
Respecting vascular territories is crucial for flap design and viability. There are 6 angiosomes in the foot and ankle originating from the posterior tibial, anterior tibial, and peroneal arteries. Reliable perforators from the 3 major source vessels of the lower extremity are found in 5-cm intervals within intermuscular septa. Computed tomography angiography, Doppler, and infrared cameras can be used preoperatively to help identify the perforators of the lower extremity.


Long-term observations in gerbil brain following transient cerebral ischemia: autoradiographic and histological study.
We investigated the long-term changes that occur in the gerbil brain following transient cerebral ischemia using histology and receptor autoradiography. Transient ischemia was induced for 3 and 10 min, and animals were allowed to survive for 8 months. A histological study showed that 3-min ischemia caused neuronal damage and mild atrophy only in the hippocampal CA1 sector, and that 10-min ischemia produced severe neuronal damage and marked shrinkage in the hippocampal CA1 and CA3 sectors. Furthermore, severe neuronal damage was seen in the striatum after 10-min ischemia. Autoradiography study revealed that 3-min ischemia caused a significant reduction in [3H] naloxone binding in the frontal cortex, striatum, dentate gyrus, and thalamus, whereas [3H]SCH 23390 and [3H] forskolin binding was not significantly altered in all regions. In contrast, 10-min ischemia produced marked alteration in these binding sites in the striatum, hippocampus, thalamus, and substantia nigra. The alteration was especially notable in the hippocampal region and substantia nigra. These results indicate that hippocampal damage after transient ischemia, compared with that in other regions, is not static, but particularly progressive. Furthermore, they demonstrate a reduction in adenylate cyclase system in the striatum and substantia nigra after transient ischemia. Moreover, our results suggest that long-term survival after ischemia may induce synaptic modification of neurotransmitter and adenylate cyclase system in the hippocampus.


Investigation of pelvic symmetry using CAD software.
Severe pelvic fractures often prove difficult for surgeons as they require patient-specific surgical treatment plans and customized equipment. Developing virtual patient-specific 3D pelvis models would ease the surgical planning process and enable development of custom fixation plates. This paper aims to examine pelvic symmetry to conclude whether the contralateral side may be used as a reference model for the fractured side of the pelvis. Fourteen subjects with intact pelvises were involved in this study. CT scans of the pelvises were converted to 3D models and the right sides of the pelvises were reflected and aligned with the left sides. A deviation analysis was then performed for each set of models and results showed that the average root mean square (RMS) of values was 1.14 ± 0.26 mm and the average percentage of points below a deviation threshold of ± 2 mm was 91.9 ± 5.55%. The deviation color maps (DCMs) showed that the largest deviations were on the non-articular surfaces. The volume and surface area of each model were also examined and showed no significant differences between left and right sides. These results indicate that the pelvis displays bilateral symmetry and this concept can be used to develop fully intact patient-specific 3D pelvis models for fracture reconstruction using the unfractured contralateral side. Graphical Abstract.


Laparoscopic nephrectomy in children: systematic review of transperitoneal and retroperitoneal approaches.
To perform a systematic review of the available medical data concerning laparoscopic nephrectomy in children. For many pediatric urologists, the laparoscopic approach to nephrectomy has become the standard of care. Access can be obtained using a retroperitoneal (RP) or transperitoneal (TP) approach. Previously, debates have argued the advantage of each technique relative to the other. We performed a data search through MEDLINE and PubMed to find reports of laparoscopic nephrectomy, nephroureterectomy, and partial nephrectomy in children. We analyzed the operative time, hospital stay, and rate of complication with each approach. Specifically, we assessed the rate of vascular, solid organ, and bowel injuries. We found 51 articles that reported the outcomes of 689 pediatric nephrectomies. Of these, 401 were RP and 288 were TP laparoscopic renal surgeries in children. The mean patient age for RP and TP was 5.4 years and 4.8 years, respectively. The mean operative time was 129 minutes for RP and 154 minutes for TP. The hospital stay was 2.5 days for RP and 2.3 days for TP. The overall complication rate for RP was 4.3% and for TP was 3.5% (P = .58). The number of vascular injuries for RP was 2 and for TP was 0 (P = .12). The number of bowel injuries for RP was 2 and for TP was 1 (P = .68). According to the available published data, no significant advantage is gained by a RP or TP approach for laparoscopic nephrectomy. Although the operative time for RP was slightly shorter than for TP, the types of cases performed were not directly matched and thus were more challenging to compare. The incidence of vascular and bowel injuries was rare for both approaches. Therefore, the choice of approach should be determined by surgeon preference, patient anatomy, or the procedure to be performed.


Recording of the electrocardiogram from the sinus node and direct measurement of the sinuatrial conduction time in children.
Using a simple technique, the electrocardiogram from the sinus node, which had been previously recorded in adults, was for the first time derived successfully in 27 of 31 children (87%). The values of the sinuatrial conduction time were then precisely measured directly according to the electrocardiogram from the sinus node. The sinuatrial conduction time measured directly was significantly longer in 6 children with sick sinus syndrome (138.3 +/- 10.3 msec, mean +/- standard deviation) than in 21 normal children (66.9 +/- 14.4 msec, mean +/- standard deviation). No overlap was found between them. Furthermore, comparison was made between the children and the adults (7 cases with sick sinus syndrome, 32 cases with normal sinus nodal function). The results suggested that the electrocardiogram recorded from the sinus node may be a valuable and promising technique for the evaluation of sinus nodal function and in the accurate diagnosis of the sick sinus syndrome in children.


Identification of genomic regions of wheat associated with grain Fe and Zn content under drought and heat stress using genome-wide association study.
Wheat is the staple food crop of global importance for its grain nutrient quality. Grain iron and zinc content of the wheat grain is an important quantitatively inherited trait that is influenced by the environmental factors such as drought and heat stress. Phenotypic evaluation of 295 advanced breeding lines from the wheat stress breeding program of IARI was carried out under timely sown irrigated (IR), restricted irrigated, and late-sown conditions at New Delhi during the cropping season of 2020-21, and grain iron (GFeC) and zinc (GZnC) contents were estimated from both control and treatments. A statistically significant increase in GFeC and GZnC was observed under stress conditions compared to that of the control. Genotyping was carried out with the SNPs from the 35K Axiom Breeder's array, and marker-trait association was identified by GWAS analysis. Of the 23 MTAs identified, seven were linked with GFeC and sixteen were linked with GZnC. In silico analysis revealed a few important transcripts involved in various plant metabolism, growth, and development activities such as auxin response factor, root UVB sensitive proteins, potassium transporter, glycosyl transferase, COBRA, and F-box-like domain. The identified MTAs can be used for molecular breeding after validation and also for rapid development of micronutrient-rich varieties of wheat to mitigate hidden hunger.


Depression and affective flexibility: A valence-specific bias.
Depression might be associated with poor affective flexibility, defined as the ability to switch between emotional and non-emotional aspects of a stimulus. However, it is unclear whether affective inflexibility in depression is valence-specific, whether it predicts future depressive symptoms, and whether affective flexibility following a stressor, compared to before a stressor, better predicts depressive symptoms. Before and after a stressor, participants (N = 300) completed an affective switching task during which they categorized pictures either by the valence or by the number of humans present in the pictures. Slower shifting from emotional aspects of negative material before stress was uniquely associated with higher levels of prospective depressive symptoms. This negative bias in affective flexibility may hinder disengagement from negative information, thereby exacerbating depressive symptoms.


Analysis of radiofrequency lesions in egg whites in vitro produced by application of the Tew electrode for different temperatures and times.
Understanding the size and shape of radiofrequency lesions is important to reduce side effects when applied to patients. To investigate the radiofrequency lesions produced by the application of the Tew electrode for different temperatures and times. The white from a fresh hen's egg was placed in a rectangular glass container and warmed to 37 °C. After immersion of the Tew electrode in the egg white, radiofrequency lesions were produced at 65 °C, 70 °C, 75 °C, 80 °C, 85 °C and 90 °C. For each temperature, photographs were taken at 10 s, 20 s, 30 s, 40 s, 50 s, 60 s, 70 s, 80 s, 90 s, 100 s, 110 s and 120 s. The size of the lesion was measured at each temperature and time. A mixed model was used to analyze the data. The size of the lesion increased with increasing temperature and time. There were statistically significant differences in the size of the internal radius between the 65 °C and 70 °C groups and the 70 °C and 75 °C groups, as well as in the 70 °C and 75 °C groups in the size of the external radius and the 60 °C to 80 °C groups in the size of the distal radius. The maximum lesion size was produced at 90 °C and 120 s, and was 1.06±0.16 mm in internal radius, 0.37±0.15 mm in external radius, 0.39±0.04 mm in distal radius. The Tew electrode produces lesions following the contour of the tip, and the internal radius is larger than the external and distal radius. The best combination of temperature and time for lesioning using the Tew electrode is 80 °C, for 60 s to 90 s.


Prospective multicentre clinical trial of stapled transanal rectal resection for obstructive defaecation syndrome.
This prospective multicentre study assessed the safety and effectiveness of stapled transanal rectal resection (STARR) for treatment of obstructive defaecation syndrome (ODS). Between February 2001 and June 2006, 104 patients diagnosed with ODS were treated with STARR. Follow-up was scheduled for 1, 3 and 6 months after surgery, and annually thereafter. Variables related to the patient, surgical technique and outcome were analysed. Mean operating time was 46.7 min. Haemorrhage at the staple line occurred in 55 patients (52.9 per cent). Three patients required surgical revision in the first 48 h owing to persistent bleeding. The median postoperative pain score was 2.4 on a scale from 1 to 10. Mean hospital stay was 2.2 days. The mean constipation score improved from 13.5 before surgery to 5.1 at 1-year follow-up (P = 0.006). Twenty-three patients reported faecal incontinence at 4 weeks after surgery, but only nine still had minor residual incontinence by 1 year. At a median follow-up of 26 (range 12-72) months, ODS had recurred or persisted radiologically and/or clinically in 11 patients. STARR is associated with low morbidity and a short hospital stay, and is an effective alternative treatment for ODS.