Interaction of fish myoglobin and myofibrillar proteins.
Interactions between fish myoglobin (Mb) and myofibrillar proteins were investigated in a Mb-natural actomyosin (NAM) model at 4 degrees C. Increases in metmyoglobin (MetMb) formation and the relative content of bound Mb were observed, as were decreases in whiteness and Ca(2+)-ATPase activity (P < 0.05). During the first 6 h of incubation, Mb bound preferably to myosin at domains other than the head portion, as evidenced by measurable ATPase activity. The potential binding of Mb to myosin heads occurred after 24-h incubation as evidenced by the marked decrease in Ca(2+)-ATPase activity of the NAM-Mb mixture when compared to that of NAM alone (P < 0.05). The interaction between fish Mb and myofibrillar proteins was more pronounced with increased storage time; formation of high-molecular-weight aggregates (> 206 kDa) also increased with time. Electrophoretic study revealed that disulfide bonds were not involved in Mb-NAM interactions.


Effect of temperature on the size of Escherichia coli cells.
The distributions of cell volumes of steady-state Escherichia coli ML30G cultures at various temperatures were measured. For cultures in a minimal medium, the distributions were indistinguishable at several temperatures between 15 and 30 C; at higher temperatures the cells were slightly smaller, and at lower temperatures they were slightly larger. For cultures in a complex medium, the cells were slightly larger at both high and low temperatures of growth. An abrupt change of temperature within the middle range led to a transient change in the distribution of cell volume, suggesting that the size of dividing cells is well regulated. No synchrony of division was induced by a change in temperature.


Dammarane-type triterpene ginsenoside-Rg18 inhibits human non-small cell lung cancer A549 cell proliferation via G1 phase arrest.
A previous study reported that a novel dammarane-type triterpene saponin, ginsenoside-Rg18, derived from the root of Panax ginseng, displayed hydroxyl radical scavenging, anti-bacterial and cytotoxic activities. However, the underlying molecular mechanisms of its anti-proliferative effect on non-small cell lung cancer (NSCLC) A549 cells remains unclear. In the present study, it was determined that Rg18 inhibited the proliferation of A549 cells with a half-maximal inhibitory concentration of 150 µM. Flow cytometry analysis indicated that cell cycle progression was blocked by Rg18 at G1 phase in A549 cells, which was accompanied by downregulation of cyclin-dependent kinase 2 (CDK2), CDK4, CDK6, cyclin D1, cyclin D2, cyclin E and phosphorylated retinoblastoma protein expression at the protein level. In addition, the CDK inhibitors (CDKNs), CDKN1A and CDKN1B, were upregulated following Rg18 treatment. Furthermore, Rg18 treatment resulted in the intracellular accumulation of reactive oxygen species (ROS), and a dose-dependent inhibition of p38 mitogen activated protein kinase (p38), c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB)/p65 phosphorylation. Taken together, Rg18-mediated G1 phase arrest was closely associated with the generation of intracellular ROS, and p38, JNK and NF-κB/p65 inhibition in A549 human NSCLC cells.


Tracing apoptosis and stimulation in individual cells by fluorescence intensity and anisotropy decay.
Presented is the use of fluorescence lifetime (FLT), anisotropy decay, and associated parameters as differential indicators of cellular activity. A specially designed combination of a frequency mode based time resolved microscope and a picoliter well-per-cell array have been used to perform temporal measurements in individual cells under various biological conditions. Two biological models have been examined: mitogenic activation of peripheral blood mononuclear cells (PBMC) and induction of programmed cell death (apoptosis) in Jurkat T cells (JTC). The FLT of fluorescein stained PBMC was found to increase from 4+/-0.02 to 4.5+/-0.025 ns due to mitogenic activation, whereas during apoptosis in fluorescein stained JTC, the FLT remained constant. Notably, the rotational correlation times changed in both models: decreased in PBMC from 2.5+/-0.08 to 2+/-0.1 ns, and increased in JTC from 2.1+/-0.07 to 3.3+/-0.09 ns. FLT and rotational correlation time were used to calculate the steady state fluorescence anisotropy (FA) which was compared to directly measured FA values. The present study suggests that in addition to bioindication, the said parameters can provide valuable information about cellular mechanisms that may involve complex molecular diffusion dynamics, as well as information about structural changes that a cellular fluorophore undergoes in the course of cell activation.


The evaluation and management of obscure and occult gastrointestinal bleeding.
Gastrointestinal (GI) bleeding is a common clinical presentation increasing in an aging population, frequently requiring hospitalization and emergent intervention, with significant morbidity, mortality, and costs. It may manifest overtly as hematemesis, melena, or hematochezia, or as an asymptomatic occult bleed. Management typically involves an esophagogastroduodenoscopy or a colonoscopy; these in combination sometimes do not identify a source of bleeding, with the source remaining obscure. Further work up to identify an obscure source frequently requires radiologically detecting the leakage of an intravascular tracer (using tagged red blood cells or angiography) with brisk bleeding or in other cases CT enterography (CTE) to detect bowel wall changes consistent with a bleeding source. Recent advances including capsule endoscopy, CTE, and double-balloon endoscopy have helped to identify bleeding sources beyond the reach of conventional endoscopy. Clinical decision-making about their use is complex and evolving. Knowing their relative merits and weaknesses including yield, contraindications, complications, and cost is essential in coming up with an appropriate management plan. This review covers the rationale for clinical management of obscure sources of GI bleeding, mentioning the approach to and the yield of conventional methods, with an emphasis on the recent advances mentioned above.


[Psoriasis capitis and seborrhoic eczema of scalp diseases].
The scalp may be affected by various diseases with equally varying manifestations. Erythema and scaling is often accompanied by agonizing itch. Scalp psoriasis and seborrheic eczema represent the most frequent diseases, which can be differentiated into classical cases; however, overlap and similarities are seen. Sharply demarcated erythematosquamous plaques across the natural hairline in psoriasis are opposed to blurred dark-red erythema and yellowish, greasy scales in seborrheic eczema. Whereas with the latter diffuse alopecia may frequently be found, hair loss is rarely seen in psoriasis and may also be related to therapeutic agents. Treatment is based on acuity as well as extent of disease and individual life quality aspects of the patients. It is mainly based on topical corticosteroids, combined with vitamin D derivatives in psoriasis and antimycotic agents in seborrheic eczema. In severe cases and widespread psoriatic disease, systemic treatment may be necessary, including the classic agents methotrexate, fumarates and ciclosporin as well as biologicals. Systemic treatment of seborrheic eczema is rarely necessary and resides on corticosteroids, antimycotic agents and vitamin A derivatives. In addition, intensive counseling of patients on the necessity of consequent and long-term treatment as well as use of mild skin care products is mandatory.


Antimonocyte serum. Preparation and characterization.
Cell suspensions enriched with monocytes were obtained from the blood of Vietnam normal pig and rabbits injected with avirulent Welshimer strain of L. monocytogenes by velocity sedimentation on BSA gradient and separation on Ficoll-Triosil gradient. They were used for immunization of rabbits and a sheep, respectively. The antisera specific for monocytes (RAMS and SAMS) were obtained by scrupulous absorption with lymphocytes and granulocytes.


LIN-12/Notch trafficking and regulation of DSL ligand activity during vulval induction in Caenorhabditis elegans.
A novel mode of crosstalk between the EGFR-Ras-MAPK and LIN-12/Notch pathways occurs during the patterning of a row of vulval precursor cells (VPCs) in Caenorhabditis elegans: activation of the EGFR-Ras-MAPK pathway in the central VPC promotes endocytosis and degradation of LIN-12 protein. LIN-12 downregulation in the central VPC is a prerequisite for the activity of the lateral signal, which activates LIN-12 in neighboring VPCs. Here we characterize cis-acting targeting sequences in the LIN-12 intracellular domain and find that in addition to a di-leucine motif, serine/threonine residues are important for internalization and lysine residues are important for post-internalization trafficking and degradation. We also identify two trans-acting factors that are required for post-internalization trafficking and degradation: ALX-1, a homolog of yeast Bro1p and mammalian Alix and the WWP-1/Su(dx)/Itch ubiquitin ligase. By examining the effects of mutated forms of LIN-12 and reduced wwp-1 or alx-1 activity on subcellular localization and activity of LIN-12, we provide evidence that the lateral signal-inhibiting activity of LIN-12 resides in the extracellular domain and occurs at the apical surface of the VPCs.


Nocturnal selective pressures on the evolution of human musicality as a missing piece of the adaptationist puzzle.
Human musicality exhibits the necessary hallmarks for biological adaptations. Evolutionary explanations focus on recurrent adaptive problems that human musicality possibly solved in ancestral environments, such as mate selection and competition, social bonding/cohesion and social grooming, perceptual and motor skill development, conflict reduction, safe time-passing, transgenerational communication, mood regulation and synchronization, and credible signaling of coalition and territorial/predator defense. Although not mutually exclusive, these different hypotheses are still not conceptually integrated nor clearly derived from independent principles. I propose The Nocturnal Evolution of Human Musicality and Performativity Theory in which the night-time is the missing piece of the adaptationist puzzle of human musicality and performing arts. The expansion of nocturnal activities throughout human evolution, which is tied to tree-to-ground sleep transition and habitual use of fire, might help (i) explain the evolution of musicality from independent principles, (ii) explain various seemingly unrelated music features and functions, and (iii) integrate many ancestral adaptive values proposed. The expansion into the nocturnal niche posed recurrent ancestral adaptive challenges/opportunities: lack of luminosity, regrouping to cook before sleep, imminent dangerousness, low temperatures, peak tiredness, and concealment of identity. These crucial night-time features might have selected evening-oriented individuals who were prone to acoustic communication, more alert and imaginative, gregarious, risk-taking and novelty-seeking, prone to anxiety modulation, hedonistic, promiscuous, and disinhibited. Those night-time selected dispositions may have converged and enhanced protomusicality into human musicality by facilitating it to assume many survival- and reproduction-enhancing roles (social cohesion and coordination, signaling of coalitions, territorial defense, antipredatorial defense, knowledge transference, safe passage of time, children lullabies, and sexual selection) that are correspondent to the co-occurring night-time adaptive challenges/opportunities. The nocturnal dynamic may help explain musical features (sound, loudness, repetitiveness, call and response, song, elaboration/virtuosity, and duetting/chorusing). Across vertebrates, acoustic communication mostly occurs in nocturnal species. The eveningness chronotype is common among musicians and composers. Adolescents, who are the most evening-oriented humans, enjoy more music. Contemporary tribal nocturnal activities around the campfire involve eating, singing/dancing, storytelling, and rituals. I discuss the nocturnal integration of musicality's many roles and conclude that musicality is probably a multifunctional mental adaptation that evolved along with the night-time adaptive landscape.


Targeting integrin beta4 for cancer and anti-angiogenic therapy.
The integrins play key roles in the signaling networks that drive pathological angiogenesis and tumor progression. Integrin beta4 is a laminin receptor upregulated in tumor cells and angiogenic endothelial cells. Biochemical studies have indicated that beta4 combines with and enhances the signaling function of multiple receptor tyrosine kinases, including ErbB2, EGF-R and Met. Genetic studies have revealed that beta4 signaling promotes both angiogenesis and tumorigenesis. Here, I discuss the hypothesis that beta4 promotes both processes by amplifying receptor-tyrosine-kinase signaling. Therefore, I propose that a simultaneous blockade of beta4 and receptor-tyrosine-kinase signaling represents a rational approach to cancer and anti-angiogenic therapy.


Penile ulcerative pyoderma gangrenosum: A rare entity.
Pyoderma gangrenosum (PG) is a rare, chronic, ulcerative, neutrophilic, and inflammatory skin disease. It most commonly affects the lower limb, may affect peristomal skin, and rarely involves mucosal and internal sites. Genital involvement has been rarely reported. Hereby, we report a case of penile PG in a 70-year-old male treated with oral steroids.


[Radionuclide and ultrasound studies in nodular (colloid) goiter].
The informative value of scintigraphy and ultrasonic investigation (USI) was analyzed in 110 patients with nodular colloid goiter. The patients were operated upon, and diagnosis was made on the basis of histological findings. Scintigraphy was more preferable for the assessment of atypical position of the thyroid and function of its different parts but USI was better for the detection of its nodular, diffuse and other structural changes. Both methods contained no specific information pertaining to histology.


Variation in genome organization of the plant pathogenic fungus Colletotrichum lindemuthianum.
The genome structure of Colletotrichum lindemuthianum in a set of diverse isolates was investigated using a combination of physical and molecular approaches. Flow cytometric measurement of genome size revealed significant variation between strains, with the smallest genome representing 59% of the largest. Southern-blot profiles of a cloned fungal telomere revealed a total chromosome number varying from 9 to 12. Chromosome separations using pulsed-field gel electrophoresis (PFGE) showed that these chromosomes belong to two distinct size classes: a variable number of small (< 2.5 Mb) polymorphic chromosomes and a set of unresolved chromosomes larger than 7 Mb. Two dispersed repeat elements were shown to cluster on distinct polymorphic minichromosomes. Single-copy flanking sequences from these repeat-containing clones specifically marked distinct small chromosomes. These markers were absent in some strains, indicating that part of the observed variability in genome organization may be explained by the presence or absence, in a given strain, of dispensable genomic regions and/or chromosomes.


Seasonal variations in acute toxoplasmosis in pregnant women in Slovenia.
Between December 1999 and December 2004, 40 081 pregnant women were examined for toxoplasmosis with Toxo-IgG, Toxo-IgM enzyme immunoassay. Women with positive results were then retested with the Toxo-IgG avidity assay for recent toxoplasmosis. Recent acute toxoplasmosis in pregnant women was found to be significantly more frequent (p < 0.01) during winter than summer. The incidence of acute toxoplasmosis during winter-spring was also significantly more frequent (p < 0.025) than summer-autumn. This phenomenon should be taken into account when formulating preventive measures for toxoplasmosis, especially for pregnant women.


Effects of weightlifting exercise, traditional resistance and plyometric training on countermovement jump performance: a meta-analysis.
Jump performance is considered an important factor in many sports. Thus, strategies such as weightlifting (WL) exercises, traditional resistance training (TRT) and plyometric training (PT) are effective at improving jump performance. However, it is not entirely clear which of these strategies can enable greater improvements on jump height. Thus, the purpose of the meta-analysis was to compare the improvements on countermovement jump (CMJ) performance between training methods which focus on WL exercises, TRT, and PT. Seven studies were included, of which one study performed both comparison. Therefore, four studies comparing WL exercises vs. TRT (total n = 78) and four studies comparing WL exercises vs. PT (total n = 76). The results showed greater improvements on CMJ performance for WL exercises compared to TRT (ESdiff: 0.72 ± 0.23; 95%CI: 0.26, 1.19; P = 0.002; Δ % = 7.5 and 2.1, respectively). The comparison between WL exercises vs. PT revealed no significant difference between protocols (ESdiff: 0.15 ± 0.23; 95%CI: -0.30, 0.60; P = 0.518; Δ % = 8.8 and 8.1, respectively). In conclusion, WL exercises are superior to promote positive changes on CMJ performance compared to TRT; however, WL exercises and PT are equally effective at improving CMJ performance.


Vertical leadership in highly complex and unpredictable health systems.
This article explores how the concept of vertical leadership development might help health organizations cope with and thrive within highly complex and unpredictable health systems, looking at concepts of VUCA (volatility, uncertainty, complexity and ambiguity) and RUPT (rapid, unpredictable, paradoxical and tangled).


Efficacy of clear aligners in controlling orthodontic tooth movement: a systematic review.
To assess the scientific evidence related to the efficacy of clear aligner treatment (CAT) in controlling orthodontic tooth movement. PubMed, PMC, NLM, Embase, Cochrane Central Register of Controlled Clinical Trials, Web of Knowledge, Scopus, Google Scholar, and LILACs were searched from January 2000 to June 2014 to identify all peer-reviewed articles potentially relevant to the review. Methodological shortcomings were highlighted and the quality of the studies was ranked using the Cochrane Tool for Risk of Bias Assessment. Eleven relevant articles were selected (two Randomized Clinical Trials (RCT), five prospective non-randomized, four retrospective non-randomized), and the risk of bias was moderate for six studies and unclear for the others. The amount of mean intrusion reported was 0.72 mm. Extrusion was the most difficult movement to control (30% of accuracy), followed by rotation. Upper molar distalization revealed the highest predictability (88%) when a bodily movement of at least 1.5 mm was prescribed. A decrease of the Little's Index (mandibular arch: 5 mm; maxillary arch: 4 mm) was observed in aligning arches. CAT aligns and levels the arches; it is effective in controlling anterior intrusion but not anterior extrusion; it is effective in controlling posterior buccolingual inclination but not anterior buccolingual inclination; it is effective in controlling upper molar bodily movements of about 1.5 mm; and it is not effective in controlling rotation of rounded teeth in particular. However, the results of this review should be interpreted with caution because of the number, quality, and heterogeneity of the studies.


Laparoscopic cryptorchidectomy with a vessel-sealing device in dorsal recumbent horses: 43 cases.
To document laparoscopic cryptorchidectomy with a vessel-sealing device in dorsal recumbent horses. Retrospective study. Forty-three male horses. Food was withheld for 36 hours before horses were placed under general anesthesia and positioned in dorsal recumbency. One laparoscopic portal and 2 instrument portals were placed for the laparoscopic procedure. A third instrument portal was created in bilateral cryptorchid horses. A vessel-sealing device was used for hemostasis and transection of retained testes. Descended testes were removed via closed castration with primary closure of the scrotal incision. Time required for removal of the retained testis and perioperative complications were recorded. Short-term (14, 30, 60 days) and long-term follow-up (>1.5 years) consisted of telephone interview with owners and referring veterinarians. Forty-three male horses underwent laparoscopic cryptorchidectomy. Thirteen horses were bilateral cryptorchids, 19 were unilateral cryptorchids with a descended testis, and 11 were unilateral cryptorchids with 1 testis previously removed. Inguinal testes, identified in 5 horses, were pulled into the abdomen prior to excision. The vaginal ring was apposed with endoscopic staples in 3 of 5 horses. Mean surgery time was 31.34 ± 7.41 minutes. No intraoperative or immediate postoperative complications were encountered. No short-term or long-term complications were reported. Laparoscopic cryptorchidectomy can be safely performed with a vessel sealing-device in dorsal recumbent horses. This method was effective and did not result in any complication in our case series.


The protective effect of pericytes on vascular permeability after hemorrhagic shock and their relationship with Cx43.
Vascular hyperpermeability is a complication of hemorrhagic shock. Pericytes (PCs) are a group of mural cells surrounded by microvessels that are located on the basolateral side of the endothelium. Previous studies have shown that damage to PCs contributes to the occurrence of many diseases such as diabetic retinopathy and myocardial infarction. Whether PCs can protect the vascular barrier function following hemorrhagic shock and the underlying mechanisms are unknown. A hemorrhagic shock rat model, Cx43 vascular endothelial cell (VEC)-specific knockdown mice, and VECs were used to investigate the role of PCs in vascular barrier function and their relationship with Cx43. The results showed that following hemorrhagic shock, the number of PCs in the microvessels was significantly decreased and was negatively associated with an increase in pulmonary and mesenteric vascular permeability. Exogenous infusion of PCs (106 cells per rat) colonized the microvessels and improved pulmonary and mesenteric vascular barrier function. Upregulation of Cx43 in PCs significantly increased the number of PCs colonizing the pulmonary vessels. In contrast, downregulation of Cx43 expression in PCs or knockout of Cx43 in VECs (Cx43 KO mice) significantly reduced PC colonization in pulmonary vessels in vivo and reduced direct contact formation between PCs and VECs in vitro. It has been suggested that PCs have an important protective effect on vascular barrier function in pulmonary and peripheral vessels following hemorrhagic shock. Cx43 plays an important role in the colonization of exogenous PCs in the microvessels. This finding provides a potential new shock treatment measure.


Comparison of Interfacial Electron Transfer Efficiency in [Fe(ctpy)2]2+-TiO2 and [Fe(cCNC)2]2+-TiO2 Assemblies: Importance of Conformational Sampling.
Fe(II)-polypyridines have limited applications as chromophores in dye-sensitized solar cells due to the short lifetimes (∼100 fs) of their photoactive metal-to-ligand charge transfer (MLCT) states formed upon photoexcitation. Recently, a 100-fold increase in the MLCT lifetime was observed in a [Fe(CNC)2]2+ complex (CNC = 2,6-bis(3-methylimidazole-1-ylidine)pyridine) which has strong σ-donating N-heterocyclic carbene ligand in comparison to the weaker field parent [Fe(tpy)2]2+ complex (tpy = 2,2':6',2″-terpyridine). This study utilizes density functional theory (DFT), time-dependent DFT, and quantum dynamics simulations to investigate the interfacial electron transfer (IET) in [Fe(cCNC)2]2+ (cCNC = 4'-carboxy-2,6-bis(3-methylimidazole-1-ylidine)pyridine) and [Fe(ctpy)2]2+ (ctpy = 4'-carboxy-2,2':6',2″-terpyridine) sensitized TiO2. Our results suggest that the replacement of tpy by CNC ligand does not significantly speed up the IET kinetics in the [Fe(cCNC)2]2+-TiO2 assembly in comparison to the [Fe(ctpy)2]2+-TiO2 analogue. The high IET efficiency in the [Fe(cCNC)2]2+-TiO2 assemblies is therefore due to longer lifetime of [Fe(cCNC)2]2+ photoactive 3MLCT states rather than faster electron injection kinetics. It was also found that the inclusion of conformational sampling in the computational model is important for proper description of the IET processes in these systems, as the models relying on the use of only fully optimized structures may yield misleading results. The simulations presented in this work also illustrate various pitfalls of utilizing properties such as electronic coupling, number of available acceptor states, and driving force, as well as calculations based on Fermi's golden rule framework, to reach conclusions on the IET efficiency in dye-semiconductor systems.


Comparing ligand interactions with multiple receptors via serial docking.
Standard uses of ligand-receptor docking typically focus on the association of candidate ligands with a single targeted receptor, but actual applications increasingly require comparisons across multiple receptors. This study demonstrates that comparative docking to multiple receptors can help to select homology models for virtual compound screening and to discover ligands that bind to one set of receptors but not to another, potentially similar, set. A serial docking algorithm is furthermore described that reduces the computational costs of such calculations by testing compounds against a series of receptor structures and discarding a compound as soon as it fails to satisfy specified bind/no bind criteria for each receptor. The algorithm also realizes substantial efficiencies by taking advantage of the fact that a ligand typically binds in similar conformations to similar receptors. Thus, once detailed docking has been used to fit a ligand into the first of a series of similar receptors, much less extensive calculations can be used for the remaining structures.


Hangzhou criteria as downstaging criteria in hepatocellular carcinoma before liver transplantation: A multicenter study from China.
The downstaging of hepatocellular carcinoma (HCC) has been confirmed to benefit liver transplantation (LT) patients whose tumors are beyond the transplantation criteria. Milan criteria (MC), a tumor size and number-based assessment, is currently used as the endpoint in these patients. However, many studies believe that tumor biological behavior should be added to the evaluation criteria for downstaging efficacy. Hence, this study aimed to explore the feasibility of Hangzhou criteria (HC), which introduced tumor grading and alpha-fetoprotein in addition to tumor size and number, as an endpoint of downstaging. We performed a multicenter and retrospective study of 206 patients accepted locoregional therapy (LRT) as downstaging/bridge treatment prior to LT in three centers of China. Recipients were divided into four groups: failed downstaging to the HC (group A, n = 46), successful downstaging to the HC (group B, n = 30), remained within the HC all the time (group C, n = 113), and tumor progressed (group D, n = 17). The 3-year HCC recurrence probabilities of groups B and C were not significantly different (10.3% vs. 11.6%, P = 0.87). The HCC recurrent rate was significantly higher in group A (52.3%) compared with that in group B/C (P < 0.05). Seven patients (7/76, 9.2%) whose tumor exceeded the the HC were successfully downstaged to the MC, and 39.5% (30/76) to the the HC. In group B, 23 patients remained beyond the MC and their survivals were as well as those of patients within the MC. Compared to the MC, HC downstaging criteria can give more HCC patients access to LT and furthermore, the outcome of these patients is the same as those matching MC downstaging criteria. Hangzhou downstaging criteria therefore is applicable in clinical practice.


Renal tuberculosis in a multi-racial community.
There were 44 new cases of renal tuberculosis at the Waikato Hospital, 1961-1975. Thirty-three patients were Maoris or Polynesians and 10 Europeans. Most patients were adults. Culture of the urine and intravenous urography were the most useful diagnostic tests. The patients were treated with antituberculous chemotherapy. Seventeen had surgical procedures including 10 nephrectomies. In all there was one death. Factors concerned with prevention in high risk groups are discussed.


Anti-glomerular basement membrane disease: Case series from a tertiary center in North India.
Anti-glomerular basement (anti-GBM) disease is an uncommon disorder with a bimodal age of presentation. Patients presenting with dialysis-dependent renal failure have poor renal outcomes. There is limited data regarding the clinical presentation and outcomes of anti-GBM disease from India. We conducted this prospective study to analyze the clinical presentation and outcomes of anti-GBM disease at a large tertiary care hospital in North India over 1½ years. Subjects with a biopsy proven anti-GBM disease (light microscopic examination showing crescents and immunofluorescence examination showing linear deposition of IgG) with or without positive anti-GBM antibodies in serum were included in the study and followed-up for at least 12 months. All the patients were treated with steroids, cyclophosphamide, and plasma exchange. A total of 17 patients (nine males) were included. The mean age at presentation was 39.11 ± 16.58 (range 11-72) years. Twelve patients (70%) presented with rapidly progressive glomerulonephritis (RPGN), 4 (23.5%) presented with Goodpasture syndrome, while 1 (5.8%) had nephritic syndrome, 7 (41%) were hypertensive, and 14 (82.3%) required dialysis at the time of presentation. Four patients (23.5%) had associated anti-neutrophil cytoplasmic antibody positivity (anti-myeloperoxidase antibodies in all). Fourteen (87.5%) patients had crescentic glomerulonephritis, while 5 (31.25%) showed necrotizing (n = 4) or granulomatous (n = 1) in the vasculitis. Of 16 patients who received treatment, four (23.25%) achieved complete remission. In this single-center study, the majority of anti-GBM disease patients presented with RPGN and had crescentic glomerulonephritis on biopsy with poor treatment outcome.


Analysis of electroencephalogram characteristics of anti-NMDA receptor encephalitis patients in China.
To explore the characteristics of electroencephalogram (EEG) in patients with anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis. Anti-NMDAR encephalitis patients admitted to the Department of Neurology between January 2012 and June 2016 were enrolled. All patients underwent electroencephalogram (EEG) at least once in the disease peak stage, and received tumor screening, symptomatic therapy, and immunotherapy. Patients received outcome evaluation every 6months after the immunotherapy, and modified Rankin scale (mRS) 0-2 was defined as favorable outcome. This study enrolled 62 cases of anti-NMDAR encephalitis patients, including 29 males (46.8%) and 33 females (53.2%). The patient ages were between 10 and 59 (mean 26.3±11.3) years. A total of 93 instances of EEG monitoring were performed on 62 patients. At the peak stage, EEG presentations showed 61 cases (98.4%) were abnormal, cranial MRI showed 29 cases (46.8%) were abnormal among all 62 patients. The main presentations of abnormal EEG were diffuse slowing (25 cases, 40.3%), epileptiform discharges (11 cases, 17.7%), extreme delta brush (EDB) (10 cases, 16.1%), polymorphic delta rhythm (6 cases, 9.7%), focal slowing (5 cases, 8.1%), and diffuse beta activities (4 cases, 6.5%). Patients with normal background, epileptiform discharges, polymorphic delta rhythm, and diffuse beta activity in EEG all had favorable long-term outcome. The majority of anti-NMDAR encephalitis patients had abnormal EEG. EEG could sensitively reflect the abnormal brain functions of patients and could assist with early clinical diagnosis and prognosis prediction. Diffuse slowing was the most common presentation on the EEG in patients with anti-NMDAR encephalitis. The EEG pattern of normal background, epileptiform discharges, polymorphic delta rhythm, and diffuse beta activities at the peak stage might suggest favorable long-term prognosis.


Molecular Neurobiology of Depression: PET Findings on the Elusive Correlation with Symptom Severity.
Molecular mechanisms in the brain are assumed to cause the symptoms and severity of neuropsychiatric disorders. This review concerns the elusive nature of relationships between the severity of depressive disorders and neuromolecular processes studied by positron emission tomography (PET). Recent PET studies of human depression have focused on serotonergic, dopaminergic, muscarinic, nicotinic, and GABAergic receptors, as well as central processes dependent on monoamine oxidase, phosphodiesterase type 4, amyloid plaques, neurofibrillar tangles, and P-glycoprotein. We find that reliable causal links between neuromolecular mechanisms and relief from depressive disorders have yet to be convincingly demonstrated. This situation may contribute to the currently limited use of PET for exploring the neuropathways that are currently viewed as being responsible for beneficial effects of antidepressant treatment regimes.


Detection of zeta-globin chains in the cord blood by ELISA (enzyme-linked immunosorbent assay): rapid screening for alpha-thalassemia 1 (Southeast Asian type).
Fetuses with homozygous alpha-thalassemia 1, in which the deletion of all four alpha-globin genes results in the absence of any alpha-globin chains, are severely anemic with clinical features of hydrops fetalis. Definitive diagnosis of alpha-thalassemia 1 carriers is difficult since there are few red cell abnormalities. Recently Chui et al. found that minute amounts of embryonic zeta-globin chains are present in adult hemoglobin of the Southeast Asian type of alpha-thalassemia 1 carriers. In this study, we screened 521 cord bloods for alpha-thalassemia 1. Hemoglobin analysis, including quantitation of Hb Bart's, was performed using the automated HPLC, alpha-thalassemia short program (VARIANT, Bio-Rad, Hercules, CA). Of these, 200 cord blood samples in which Hb Bart's was demonstrated were tested for the presence of zeta-globin chains by ELISA using labeled anti-zeta monoclonal antibody. Zeta-globin ranged between 0.21 and 0.83% in 19 specimens carrying alpha-thalassemia 1 gene. In the remaining 90 out of 109 specimens in which Hb Bart's was greater than 1.2%, zeta-globin was less than 0.17%. DNA analysis revealed the presence of normal alpha-genotype and other types of alpha-thalassemia including alpha-thalassemia 2 and Hb Constant Spring. One false positive was found in which the zeta-globin was 0.25% by ELISA but in which PCR indicated an alpha-thalassemia 2 heterozygote. Ninety-one samples with Hb Bart's of less than 1.2% by HPLC are most likely normal with a zeta-globin range between 0 and 0.14%. This study also showed that the frequency of alpha-thalassemia 1 in Bangkok is 3.65%.


Myeloproliferative disease in two young siblings.
Two siblings developed a myeloproliferative disease. One of them was a 9-year-old girl with a short history of bleeding, whose initial clinical and hematologic features were concordant with idiopathic myelofibrosis. Shortly afterwards this disorder evolved to a leukemic phase which subsequently resulted in the death of the patient. Four years later, at the age of 16, her brother was diagnosed as having acute myelofibrosis, and some months afterwards he died from fulminant pneumonia coincidently with pancytopenia and presence of scarce blast cells in peripheral blood. From the pathogenetic point of view, neither exposure to bone marrow toxins nor bone marrow chromosome abnormalities could be detected. HLA-typing disclosed the same haplotype (A2, A9, B5, B21, C5) in both patients.


Analysis of RPGR gene mutations in 41 Chinese families affected by X-linked inherited retinal dystrophy.
Background: This study analyzed the phenotypes and genotypes of 41 Chinese families with inherited retinal dystrophy (IRD) and RPGR gene mutations. Methods: This retrospective analysis evaluated a cohort of 41 patients who were subjected to a specific Hereditary Eye Disease Enrichment Panel (HEDEP) analysis. All (likely) pathogenic variants were determined by Sanger sequencing, and co-segregation analyses were performed on the available family members. All cases were subjected to Sanger sequencing for RPGR open reading frame 15 (ORF15) mutations. Results: A total of 41 probands from different families with a clinical diagnosis of retinitis pigmentosa (RP; 34 cases) and cone-rod dystrophy (CORD; 7 cases) were included in this cohort. According to clinical information, 2, 18, and 21 cases were first assigned as autosomal dominant (AD), sporadic, and X-linked (XL) inheritance, respectively. Several cases of affected females who presented with a male phenotype have been described, posing challenges at diagnosis related to the apparent family history of AD. Mutations were located in RPGR exons or introns 1-14 and in ORF15 of 12 of 41 (29.3%) and 29 of 41 (70.7%) subjects, respectively. Thirty-four (likely) pathogenic mutations were identified. Frameshifts were the most frequently observed variants, followed by nonsense, splice, and missense mutations. Herein, a detailed description of four RP patients carrying RPGR intronic mutations is reported, and in vitro splice assays were performed to confirm the pathogenicity of these intronic mutations. Conclusion: Our findings provide useful insights for the genetic and clinical counseling of patients with XL IRD, which will be useful for ongoing and future gene therapy trials.


Cholesterol 7alpha-hydroxylase deficiency in mice on an APOE*3-Leiden background increases hepatic ABCA1 mRNA expression and HDL-cholesterol.
High-density lipoprotein (HDL) plays a key role in protection against development of atherosclerosis by reducing inflammation, protecting against LDL oxidation, and promoting reverse cholesterol transport from peripheral tissues to the liver for secretion into bile. Cholesterol 7alpha-hydroxylase (Cyp7a1) catalyzes the rate-limiting step in the intrahepatic conversion of cholesterol to bile acids that may have a role in HDL metabolism. We investigated the effect of Cyp7a1 deficiency on HDL metabolism in APOE*3-Leiden transgenic mice. Reduced bile acid biosynthesis in Cyp7a1-/-.APOE*3-Leiden mice versus APOE*3-Leiden mice did not affect total plasma cholesterol levels, but the distribution of cholesterol over various lipoproteins was different. Cholesterol was decreased in apoB-containing lipoproteins (ie, VLDL and IDL/LDL), whereas cholesterol was increased in HDL. The activity of PLTP and LCAT, which play a role in HDL catabolism, were not changed, and neither was HDL clearance. However, the hepatic cholesterol content was 2-fold increased, which was accompanied by a 2-fold elevated expression of hepatic ABCA1 and increased rate of cholesterol efflux from the liver to HDL. Strongly reduced bile acid synthesis in Cyp7a1-/-.APOE*3-Leiden mice leads to increased plasma HDL-cholesterol levels, as related to an increased hepatic expression of ABCA1.


Alarm Photosynthesis: Calcium Oxalate Crystals as an Internal CO2 Source in Plants.
Calcium oxalate crystals are widespread among animals and plants. In land plants, crystals often reach high amounts, up to 80% of dry biomass. They are formed within specific cells, and their accumulation constitutes a normal activity rather than a pathological symptom, as occurs in animals. Despite their ubiquity, our knowledge on the formation and the possible role(s) of these crystals remains limited. We show that the mesophyll crystals of pigweed (Amaranthus hybridus) exhibit diurnal volume changes with a gradual decrease during daytime and a total recovery during the night. Moreover, stable carbon isotope composition indicated that crystals are of nonatmospheric origin. Stomatal closure (under drought conditions or exogenous application of abscisic acid) was accompanied by crystal decomposition and by increased activity of oxalate oxidase that converts oxalate into CO2 Similar results were also observed under drought stress in Dianthus chinensis, Pelargonium peltatum, and Portulacaria afra Moreover, in A. hybridus, despite closed stomata, the leaf metabolic profiles combined with chlorophyll fluorescence measurements indicated active photosynthetic metabolism. In combination, calcium oxalate crystals in leaves can act as a biochemical reservoir that collects nonatmospheric carbon, mainly during the night. During the day, crystal degradation provides subsidiary carbon for photosynthetic assimilation, especially under drought conditions. This new photosynthetic path, with the suggested name "alarm photosynthesis," seems to provide a number of adaptive advantages, such as water economy, limitation of carbon losses to the atmosphere, and a lower risk of photoinhibition, roles that justify its vast presence in plants.


Optimizing e-commerce warehousing through open dimension management in a three-dimensional bin packing system.
In the field of e-commerce warehousing, maximizing the utilization of packing bins is a fundamental goal for all major logistics enterprises. However, determining the appropriate size of packing bins poses a practical challenge for many logistics companies. Given the limited research on the open-size 3D bin packing problem as well as the high complexity and lengthy computation time of existing models, this study focuses on optimizing multiple-bin sizes within the e-commerce context. Building upon existing research, we propose a hybrid integer programming model, denoted as the three dimensional multiple option dimensional rectangular packing problem (3D-MODRPP), to address the multiple-bin size 3D bin packing problem. Additionally, we leverage well-established hardware and software technologies to propose a 3D bin packing system capable of accommodating multiple bin types with open dimensions. To reduce the complexity of the model and the number of constraints, we introduce a novel assumption method for 0-1 integer variables in the overlap and rotation constraints. By applying this approach, we significantly streamline the computational complexity associated with the model calculations. Furthermore, we refine the dataset by developing a customized version based on the classical Three-Dimensional One-Size Dependent Rectangular Packing Problem (3D-ODRPP) dataset, leading to improved outcomes. Through comprehensive analysis of the research results, our model exhibits remarkable advancements in addressing the strong heterogeneous bin packing problem, the weak heterogeneous bin packing problem, the actual bin packing problem, and the bin packing problem with multiple bin types and open sizes. Specifically, it significantly reduces model complexity and computation time and increases space utilization. The system designed in this study paves the way for practical applications based on the proposed model, providing researchers with broader research prospects and directions to expand the scope of investigation in the field of 3D bin packing. Consequently, this system contributes to solving complex 3D packing problems, reducing space waste, and enhancing transportation efficiency.


Gold nanoparticles functionalized with peptides for specific affinity aggregation assays of estrogen receptors and their agonists.
Nuclear receptors regulate the transcription of genes and various functions such as development, differentiation, homeostasis, and behavior by formation of complexes with ligand and co-activator. Recent findings have shown that agonists of a ligand may have a toxic effect on cellular/tissular function through improper activation of nuclear receptors. In this study, a simple assay system of hetero-complexes of three different molecules (estrogen receptor, ligand, and co-activator peptide) has been developed. This assay system employs functionalized gold nanoparticles (GNPs: 15 nm in diameter). The surfaces of the GNPs were modified by a 12- or 20-amino-acid peptide that contains the sequence of co-activator for activating nuclear receptor by an agonist ligand. Owing to the affinity of the peptide, the functionalized GNPs aggregate faster when the nuclear receptor and the agonist ligand are also present. The aggregation of GNPs can be identified by shifts in adsorption spectrum, which give information about the specificity of agonist ligands. Similarly, this spectrum shift can measure concentration of known agonist ligand. This simple agonist screening will be employed as high through-put analysis (HTA) in the discovery of drugs that act through nuclear receptors.


B7-H3 role in the immune landscape of cancer.
The field of immunotherapy is a continually expanding niche in cancer biology research. In the last two decades, there has been significant progress in identifying better targets and creating more specific agents for therapy in the field. B7-H3 (CD276) is an immune checkpoint from the B7 family of molecules, many of whom interact with known checkpoint markers including CTLA4, PD-1, and CD28. This is an exciting molecule that is overexpressed in many cancers, although the receptor of B7-H3 has not been characterized. Initially, B7-H3 was thought to co-stimulate the immune response, but recent studies have shown that it has a co-inhibitory role on T-cells, contributing to tumor cell immune evasion. Therefore, its overexpression has been linked to poor prognosis in human patients and to invasive and metastatic potential of tumors in in vitro models. Moreover, recent evidence has shown that B7-H3 influences cancer progression beyond the immune regulatory roles. In this review, we aim to characterize the roles of B7-H3 in different cancers, its relationship with other immune checkpoints, and its non-immunological function in cancer progression. Targeting B7-H3 in cancer treatment can reduce cell proliferation, progression, and metastasis, which may ultimately lead to improved therapeutic options and better clinical outcomes.


Formation of Superlattices of Gold Nanoparticles Using Ostwald Ripening in Emulsions: Transition from fcc to bcc Structure.
An efficient method to form 3D superlattices of gold nanoparticles inside oil emulsion droplets is presented. We demonstrate that this method relies on Ostwald ripening, a well-known phenomenon occurring during the aging of emulsions. The key point is that the nanoparticle concentration inside the smaller droplets is increasing very slowly with time, thus inducing the crystallization of the nanoparticles into superlattices. Using oil-in-water emulsions doped with hydrophobic gold nanoparticles, we demonstrate that this method is efficient for different types of oils (toluene, cyclohexane, dodecane, and hexadecane). 3D superlattices of the nanoparticles are obtained, with dimensions reaching a hundred nanometers. The kinetics of the crystallization depends on the solubility of the oil in water but also on the initial concentration of the gold nanoparticles in oil. This method also provides an innovative way to obtain the complete phase diagram of nanoparticle suspensions with concentration. Indeed, during this slow crystallization process, a transition from a disordered suspension to a fcc structure is observed, followed by a transition toward a bcc structure. This evolution with time provides key results to understand the role played by the ligands located at the surface of the nanoparticles in order to control the type of superlattices which are formed.


Affective spectrum disorders: how to recognize and treat depression.
Depression often goes undiagnosed. Even when pharmacotherapy is initiated, many patients discontinue therapy and thus risk relapse. Depression may occur at any age; however, the average age of onset is the late twenties. Acronyms have been developed to help the clinician recognize depression in the clinical setting. Common medications, abused substances, and medical disorders may cause and/or mimic depression. If pharmacotherapy is deemed appropriate, the choice of antidepressant is based on personal/family history of response to a particular agent and the side effect profile of the agent, as well as suicide risk. The tricyclic antidepressants and monoamine oxidase inhibitors are associated with anticholinergic effects, orthostasis, and risk of death in overdose. The selective serotonin reuptake inhibitors may have more tolerable adverse effects. Newer agents have also been marketed; however, the selective serotonin reuptake inhibitors are generally the drugs of first choice.


Efficacy and tolerance of cicletanine, a new antihypertensive agent: overview of 1226 treated patients.
The data gathered from 1226 patients for 20 controlled therapeutic studies performed during the phase-III development of cicletanine, a new antihypertensive agent, were pooled in a computerized database. An extensive statistical analysis of these data collected over 1-2 years was performed to give a clear interpretation of long-term efficacy and tolerance of this drug. In mild to moderate hypertension, the dose-response relationship observed after one month of treatment on diastolic (DBP) and systolic (SBP) blood pressure disappeared during the third month. After a 3-month treatment in monotherapy with the recommended dosage (50-100 mg/day) we observed a mean decrease of 29.7 +/- 17.8 mmHg for SBP and 23.3 +/- 13.2 mmHg for DBP. At this stage 70.9% of patients were stabilized (SBP less than 160 mmHg and DBP less than 95 mmHg) with cicletanine. After this initial regular decrease of blood pressure values, an additional decrease of several mmHg was observed during the 24 months of treatment, thus significantly augmenting the number of stabilized patients. No significant difference in efficacy was observed in adult and elderly (65 to 95 years) patients. The clinical tolerance was very good, only a few slight and transitory side-effects have been reported. Biological tolerance was also very good. Depending on the dosage used, only a slight and transitory variation in sodium and potassium levels was observed. Glucose, creatinine and lipids either remained stable or were improved during treatment. This analysis demonstrates the beneficial effect and the good tolerance of cicletanine (50-100 mg/day) in the treatment of hypertension, which can be explained by its special mode of action.


Palatal rugae patterns in Australian aborigines and Caucasians.
The purpose of this study was to determine whether rugae patterns change with age and to compare the number and pattern of rugae in Australian Aborigines with those of Caucasians. For the longitudinal part of the study, serial dental casts of ten Aborigines, from 6 to 20 years of age, were examined and rugae patterns were recorded. To enable comparisons to be made between different ethnic groups an additional 100 dental casts of Australian Aborigines and 200 casts of caucasians, ranging in age from 13 to 17 years, were examined. Characteristics observed were number, length, shape, direction and unification of rugae. The length of rugae increased significantly with age but the total number of rugae remained constant. Thirty-two per cent of rugae showed changes in shape, while 28 per cent displayed a change in orientation. In contrast to studies suggesting that rugae move forward with age, the majority of Aboriginal rugae that changed direction moved posteriorly. Changes in rugae patterns have been assumed to result from palatal growth but alterations in pattern were observed in the Aboriginal sample even after palatal growth had ceased. The mean number of primary rugae in Aborigines was higher than in Caucasians, although more primary rugae in Caucasians exceeded 10 mm in length than in Aborigines. The most common shapes in both ethnic groups were wavy and curved forms, whereas straight and circular types were least common. There was a statistically significant association between rugae forms and ethnicity, straight forms being more common in Caucasians whereas wavy forms were more common Aborigines.


Adenovirus-mediated expression of Tob1 sensitizes breast cancer cells to ionizing radiation.
To investigate the effect of the Tob1 gene, a member of the Transducing Molecule of ErbB2/B-cell Translocation Ggene (TOB/BTG) family, by using the adenovirus-mediated expression of Tob1 on radiosensitivity in a human breast cancer cell line MDA-MB-231. Cell survival was determined by clonogenic assay. Apoptosis was evaluated by DNA fragmentation gel electrophoresis and terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Protein expression was analyzed by Western blot assay and DNA repair was measured by a host cell reactivation assay. We demonstrated that pre-irradiation treatment with Ad5-Tob1 significantly increased radiosensitivity, accompanying the increased induction of apoptosis and the repression of DNA damage repair. Furthermore, Ad5-Tob1-mediated radiosensitivity correlates with the upregulation of the pro-apoptotic protein Bax and the downregulation of several DNA double strand break repair proteins, including DNA-dependent protein kinases, Ku70 and Ku80, and X-ray-sensitive complementation group 4. Tob1, as a new radiosensitizer, is a new target in the radiotherapy of breast cancer via increasing apoptosis and suppressing DNA repair.


Benzimidazole resistance of equine strongyles: critical tests of several classes of compounds against population B strongyles from 1977 to 1981.
From 1977 to 1981, critical tests were conducted on 10 horses naturally infected with population B strongyles. Drugs tested were: oxibendazole (OBZ), 10 mg/kg of body weight (n = 1); albendazole, 10 mg/kg (n = 1); a mixture of thiabendazole (TBZ), 44 mg/kg and trichlorfon, 40 mg/kg (n = 1); a mixture of TBZ at 44 mg/kg with piperazine (PPZ) at 55 mg of base/kg (n = 1); febantel (FBT), 6 mg/kg (n = 3), 12 mg/kg (n = 1), or 24 mg/kg (n = 1); and pyrantel (PRT) pamoate, 6.6 mg of base/kg (n = 1). Large strongyles, Strongylus vulgaris (9 horses) and S edentatus (5 horses), were effectively removed (100%) by each compound and mixture. Five species of small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus), previously singled out in this population as resistant to 5 benzimidazoles (TBZ, mebendazole, cambendazole, fenbendazole, and oxfendazole), but not OBZ, were efficaciously removed by OBZ, albendazole, the mixture of TBZ plus PPZ, FBT (24 mg/kg), or PRT. These 5 small strongyle species were resistant to FBT (6 mg/kg) in 3 foals and Cylicostephanus minutus was also resistant in 2 of 3 foals to FBT (6 mg/kg). Doubling the dose of FBT to 12 mg/kg increased the average removal of the 5 basic species plus Cylicostephanus minutus to 88%. The mixture of TBZ and trichlorfon was relatively ineffective against 3 species (C catinatum, C coronatum, and Cylicostephanus longibursatus), but unexpectedly efficacious (86% to 99%) for 2 species (Cylicocyclus nassatus and Cylicostephanus goldi).(ABSTRACT TRUNCATED AT 250 WORDS)


The power of visual training.
Recent evidence suggests that the capacity to alter human function, including visual function, is substantially greater than previously thought possible. Implications of this research for the modifiability of visual function through vision therapy are discussed.


[Influence of a xylanase feed additive on Lactobacillus species in the jejunum of piglets].
rRNA extracts from the jejunum of rearing piglets fed a wheat/rye based diet with or without a xylanase feed additive were hybridized against eight Lactobacillus spp. specific digoxigenin labelled oligonucleotide probes. Known concentrations of sample- or culture RNA extracts were used to calibrate and quantify hybridization signals from different sample extracts and hybridizations. The xylanase feed additive tended to increase total eubacterial rRNA in the terminal jejunum, probably a result of increased Lactobacillus spp. rRNA in the central and terminal jejunum. However, individual animal variations were high. L. reuteri was the major Lactobacillus species followed by L. acidophilus and L. mucosae. L. amylophilus and L. crispatus were not detected in all RNA extracts. The results of this study show that the xylanase feed additive modifies Lactobacillus spp. populations on the species level in piglets in addition to their well known effects on digesta viscosity and nutrient digestibility. The implications of these effects for the intestinal microbiota require further analysis.


Evaluation of an interprofessional education intervention in partnership with patient educators.
Patient involvement in interprofessional education is a novel approach to building collaborative and empathic skills in students. However, this area of teaching is lacking in rigorous studies. The project aimed to evaluate whether an interprofessional education intervention in partnership with patient educators (IPE-PE) would increase readiness for interprofessional learning and empathy in health sciences students. This is the report of a didactic innovation project. Participants included 310 undergraduate health sciences students who took part in an IPE-PE intervention. Data were collected before and after the training, using the Readiness for Interprofessional Learning Scale (RIPLS) and the Jefferson Scale of Empathy-Health Professions Student version (JSE-HPS). Only at the end of the intervention, a data collection form was administered to explore the value of the patient educator in the training and to investigate the socio-demographic variables. The mean age of participants was 21±3.2 SD years and 76% were female. A paired t-test showed significant changes from before to after the IPE-PE in the mean total RIPLS score (42.7±5.8 SD vs 44.62±5.9 SD, P<0.001) and the mean total JSE-HPS score (112.7±12.5 SD vs 116.03±12.8 SD, P<0.001). Conclusions: Our students reported that IPE-PE had helped them to become more effective healthcare team members, to think positively about other professionals, and to gain empathic understanding of the perspective of the person being cared for. The results of the project confirm that the intervention promoted the development of empathy, fostering a better understanding of the patient-centred perspective.


Antibiotic-Induced Pathobiont Dissemination Accelerates Mortality in Severe Experimental Pancreatitis.
Although antibiotic-induced dysbiosis has been demonstrated to exacerbate intestinal inflammation, it has been suggested that antibiotic prophylaxis may be beneficial in certain clinical conditions such as acute pancreatitis (AP). However, whether broad-spectrum antibiotics, such as meropenem, influence the dissemination of multidrug-resistant (MDR) bacteria during severe AP has not been addressed. In the currently study, a mouse model of obstructive severe AP was employed to investigate the effects of pretreatment with meropenem on bacteria spreading and disease outcome. As expected, animals subjected to biliopancreatic duct obstruction developed severe AP. Surprisingly, pretreatment with meropenem accelerated the mortality of AP mice (survival median of 2 days) when compared to saline-pretreated AP mice (survival median of 7 days). Early mortality was associated with the translocation of MDR strains, mainly Enterococcus gallinarum into the blood stream. Induction of AP in mice with guts that were enriched with E. gallinarum recapitulated the increased mortality rate observed in the meropenem-pretreated AP mice. Furthermore, naïve mice challenged with a mouse or a clinical strain of E. gallinarum succumbed to infection through a mechanism involving toll-like receptor-2. These results confirm that broad-spectrum antibiotics may lead to indirect detrimental effects during inflammatory disease and reveal an intestinal pathobiont that is associated with the meropenem pretreatment during obstructive AP in mice.


Recurrent hypoxia in rats during development increases subsequent respiratory sensitivity to fentanyl.
In children with a history of significant obstructive sleep apnea who undergo adenotonsillectomy, postsurgical administration of opiates has been alleged to be associated with an increased risk for respiratory complications, including respiratory depression. The authors hypothesize that this association is due to an effect of recurrent hypoxemia that accompanies more severe obstructive sleep apnea on altered responsiveness to subsequent exogenous opiates. The current study was designed to test the effect of recurrent hypoxia in the developing rat on respiratory responses to subsequent administration of the mu-opioid agonist fentanyl. Rats were exposed to 12% oxygen balance nitrogen for 7 h daily for 17 days, from postnatal day 17 to 33, a period equivalent to human childhood. After 17 additional days in room air, rats were given a fentanyl dose and tested for their respiratory response to fentanyl using a whole body plethysmograph. Rats undergoing similar protocols without recurrent hypoxia served as controls. As compared with controls, rats preexposed to recurrent hypoxia displayed a more profound depression with fentanyl in minute ventilation, respiratory frequency, tidal volume, and tidal volume divided by inspiratory time that represents respiratory drive. These results indicated an increased respiratory sensitivity to fentanyl after recurrent hypoxia. Previous recurrent hypoxia increases respiratory sensitivity to subsequent opiate agonists. If these findings are applicable to humans, opiate dosing in children must be adjusted depending on history of recurrent hypoxemia to avoid respiratory depression.


[The role of clinical suicidology in the system of measures directed towards lowering early mortality and increasing population life span].
The level of early mortality has increased substantially in Russia within the last fifteen years, having exceeded the same parameter in developed countries and in the entire post-Soviet area. The second frequent reason for early mortality is a group of factors that includes accidents, suicides, murders, and other external causes. The proportion of suicides in this group is 45 to 50%. As a result, in the recent years the suicide rate in Russia has filled the second place in the world. The authors of this article analyze the suicide rate in different Russian regions, distinguishing between regions with the highest and lowest rate, and characterizing population risk factors of suicidal danger, a special place among which is filled by socioeconomic condition of the regions and the ethnic composition of their population. Increase of the effectiveness of suicide prevention depends on creation of adequate scientific basis, which clinical suicidology can become. The authors substantiate the necessity to distinguish suicidology as a separate field of clinical medicine, and formulate its definition, goals and objectives. Basing on the obtained results, the authors come to a conclusion on the medico-social importance of the development of clinical suicidology in lowering early mortality and increasing the country's population life span.


Compact 1×4 wavelength demultiplexer based on directional coupling of periodic dielectric waveguides.
A compact 1×4 wavelength demultiplexer is proposed based on the directional coupling of periodic dielectric waveguides for optical communication wavelengths. With appropriate optimization, the 1×4 wavelength demultiplexer can route 1130, 1310, 1490, and 1700 nm wavelengths to corresponding out ports with a transmittance of more than 95%. This provides a simple and compact demultiplexer that is expected to be applied to highly dense photonic integrated circuits.


Need for mentorship to improve learning in low-performers.
About 15% of medical students perform poorly in examinations. This study was done to ascertain the causes for low performance and the effectiveness of counselling and advice regarding study skills in improving performance in a subsequent assessment. Of the 353 students who appeared for the first internal assessment examination in pathology, 83 (23.5%) scored less than 30% marks. These 83 low-performers were given a questionnaire listing stress-inducing factors and academic problems; 81 filled the questionnaire. Of these, 73 attended sessions on study skills and counselling where they interacted on a one-to-one basis regarding their personal problems. Their performance was evaluated in an internal assessment 6 months later. The low-performers included 52 boys and 29 girls, 19-20 years of age. Non-academic problems contributing to low performance included language problems, problems in adjustment to life outside home, lack of self-confidence, fear of failure and worrying about the future. Academic problems included difficulty in managing study time, lack of concentration while studying, inability to retain what is studied, anxiety before examinations and inability to write an examination. Paired t-test revealed a statistically significant improvement in the post-programme performance of the 73 students who participated in the counselling sessions (p<0.001), while that of the 10 who did not participate in the project, showed no statistically significant difference (p=0.54, Wilcoxon signed rank test). A majority of students felt that the sessions helped to improve their performance (average score 3.83/6.00), change their study behaviour (3.74/6.00) and change their attitude (3.46/6.00). The programme also improved their confidence and self-esteem. Low-performers can benefit from tailored remedial programmes which include counselling and training in stress-coping strategies.


Terminal ileal micro-perforation from an ingested fish bone incidentally diagnosed with 111In-leukocyte scintigraphy in an asymptomatic patient.
111In-leukocyte scintigraphy has generally been considered a sensitive diagnostic test for the evaluation of infectious or inflammatory processes in the abdomen due to a lack of normal physiologic bowel activity. Herein we present a case of a patient status post endovascular repair of an abdominal aortic aneurysm for which an 111In-leukocyte scan was ordered to assess for graft infection. Planar imaging revealed an abnormal focus of radiotracer activity in the right lower quadrant of the abdomen. A SPECT-CT obtained to further delineate the anatomic location of abnormal activity showed abnormal leukocyte activity localizing to the terminal ileum secondary to a micro-perforation from an ingested fishbone. This case underscores the principle that in the absence of known intra-abdominal pathology, 111In-leukocyte activity in the abdomen should always be considered abnormal, and that further evaluation with dedicated cross-sectional imaging should be performed to assist with the localization of abnormal activity.


Association between action kinematics and emotion perception across adolescence.
Research with adults suggests that we interpret the internal states of others from kinematic cues, using models calibrated to our own action experiences. Changes in action production that occur during adolescence may therefore have implications for adolescents' understanding of others. Here we examined whether, like adults, adolescents use velocity cues to determine others' emotions and whether any differences in emotion perception would be those predicted based on differences in action production. We measured preferred walking velocity in groups of early (11-12 years old), middle (13-14 years old), and late (16-18 years old) adolescents, as well as adults, and recorded their perception of happy, angry, and sad "point-light walkers." Preferred walking velocity decreased across age, and ratings of emotional stimuli with manipulated velocity demonstrated that all groups used velocity cues to determine emotion. Importantly, the relative intensity ratings of different emotions also differed across development in a manner that was predicted based on the group differences in walking velocity. Further regression analyses demonstrated that emotion perception was predicted by participants' own movement velocity, rather than age or pubertal stage per se. These results suggest that changes in action production across adolescence are indeed accompanied by corresponding changes in how emotions are perceived from velocity. These findings indicate the importance of examining differences in action production across development when interpreting differences in how individuals understand others. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Tinea corporis/cruris: new treatment options.
We undertook a prospective, multicentre, double-blind, placebo controlled, randomised, parallel-group study to evaluate the efficacy and safety of the topical 1% emulsion gel formulation of Lamisil in the treatment of tinea corporis/cruris. Eighty-three patients with clinically and mycologically confirmed tinea corporis/cruris were enrolled from 6 dermatology practices. Of the 62 patients in the intent-to-treat population, 29 were randomised to 1% Lamisil emulsion gel (23 male, 6 female; mean age 42 years, range 19-79 years) and 33 to placebo (25 male, 8 female; mean age 36 years, range 16-73 years). The gels were applied once daily for 1 week. Mycological cure (negative microscopy and culture results) and effectiveness of treatment (mycological cure plus no or minimal signs and symptoms) were measured on day 7, weeks 2, 4 and 8, and at the end of the study. At the study end, rates mycological cure were 83% for Lamisil 1% emulsion gel and 27% for placebo gel (p < 0.001), with respective rates for effective treatment of 83 and 21% (p < 0.001). Complete cure was recorded for 59% of patients receiving Lamisil 1% emulsion gel and 13% of patient receiving placebo gel (p < 0.001). We conclude that a 1-week course of Lamisil 1% emulsion gel is significantly more effective in the treatment of tinea corporis/cruris than placebo gel in respect of complete cure, mycological cure and effective treatment.


Local excision and radiotherapy for cancer of the oral tongue. A preliminary report.
A group of 18 patients with squamous cell carcinoma of the mid one-third of the tongue was treated by local resection and planned postoperative radiotherapy between 1976 and 1980. Tumors 0.5 cm or greater in thickness were included; no patients had cervical adenopathy. Six were categorized as T1, 10 as T2 and two as T3. In eight patients, histologic review showed tumor extension at or near the resection margin, despite a tumor-free margin at frozen section, while in 10 patients the margins were clear. Local tumor control was achieved in 16 patients (89%). Two failures were evident within 3 months after completion of treatment. The relatively short follow-up of such a small series limits the conclusions from this preliminary study, but the excellent results thus far merit further study.


Acquisition of Pitjantjatjara Clause Chains.
In Pitjantjatjara, a central Australian Indigenous language, speakers typically describe sequences of actions using clause chaining constructions. While similar constructions are common among the world's languages, very little is known about how children acquire them. A notable exception are the converb constructions of Turkish, which have been relatively well-studied. The present paper examines the acquisition of Pitjantjatara clause chaining constructions and compares this with the acquisition of Turkish converb constructions. Data is drawn from a naturalistic corpus recorded between 2016 and 2019. The corpus contains over 4000 utterances from 23 children aged between 10 months and 10 years, five of whom are recorded at multiple ages. The corpus also includes approximately 1600 utterances from 21 adults, aged between 16 and 70. Results show that the acquisition of Pitjantjatjara clause chains consists of three stages. Stage 1 features juxtaposition of finite verb forms. In Stage 2, children make regular use of clause chain morphology, but primarily for modification purposes. In Stage 3, clause chains are the preferred strategy for sequential actions as well as modification purposes. The initial use of verb juxtaposition followed by increasing use of dedicated morphology is consistent with findings for Turkish converb acquisition, with speakers of both languages utilizing dedicated forms from around 2;6 onwards. A notable difference between the acquisition of Pitjantjatjara clause chains and Turkish converbs is in the order of acquisition of semantic functions. In Turkish, children acquire temporal functions, such as sequential actions, before modifying functions, such as manner specification. In Pitjantjatjara, the order is reversed, with children first using clause chaining constructions for modification and simultaneous aspects of events before utilizing them to combine sequential actions. This raises questions regarding the distribution and relative timing of event combination and modification strategies.


Ultraviolet difference spectral studies in the gamma-radiolysis of DNA and model compounds. II. Oxygen and temperature dependence in adenine radiation chemistry.
Ultraviolet difference spectra between gamma-irradiated and unirradiated aqueous solutions of oxygenated adenine reveal spectral maxima at 224, 286 and 360 nm, and suggest the existence of multiple radiation products. The presence of long-wavelength absorbing products implies the extension of the conjugation of the adenine ring. The product absorbing at 360 nm appears only in the presence of oxygen, with its yield dependent on both oxygen concentration and temperature. The absorbance peak at 360 nm in the UV difference spectra appears to demonstrate simple first-order decay kinetics, with a half-life of 50 min at 3 degrees C. At temperatures below 23 degrees C relative yields of the radiation products are approximately constant, suggesting a common mechanism. Higher temperatures apparently induce a mechanistic alteration. Since the temperature during and subsequent to irradiation, as well as the oxygen concentration of the solution, affects the absolute yields and distribution of the radiation products, great care must be exercised in controlling these variables.


Determination of in vitro isoflavone degradation in rumen fluid.
The aim of this study was to determine the degradation of dietary isoflavones in rumen fluid under 2 feeding regimens. The experiments were performed in vitro using a rumen fluid buffer system. The rumen fluid was taken from cows fed either a hay diet or a concentrate-rich diet (the diet consisted of 34.6% maize silage, 17.6% haylage, 12.8% alfalfa hay, and 35.0% supplemental mixture on a dry matter basis). As a source of isoflavones, 40% soybean extract (Biomedica, Prague, Czech Republic) at levels of 5, 25, 50, and 75 mg per 40 mL of rumen fluid was used. Samples of soybean extract were incubated in triplicate at 39°C for 0, 3.0, 6.0, 12.0, and 24.0 h in incubation solution. The metabolism of daidzein and genistein was faster under concentrate-rich diet conditions. In general, production of equol started after 3 to 6 h of incubation and reached the highest rate after approximately 12 h of incubation regardless of the type of diet or concentration of extract. In most of the experiments, production of equol continued after 24 h of incubation. Generally, equol production was greater under the hay diet conditions. Furthermore, experiments with higher amounts of added soybean extract revealed possible inhibitory effects of high levels of isoflavones on the rumen microflora.


Growth restriction induced by chronic prenatal hypoxia affects breathing rhythm and its pontine catecholaminergic modulation.
Impaired transplacental supply of oxygen leads to intrauterine growth restriction, one of the most important causes of perinatal mortality and respiratory morbidity. Breathing rhythm depends on the central respiratory network modulated by catecholamines. We investigated the impact of growth restriction, using prenatal hypoxia, on respiratory frequency, on central respiratory-like rhythm, and on its catecholaminergic modulation after birth. At birth, respiratory frequency was increased and confirmed in en bloc medullary preparations, where the frequency of the fourth cervical (C4) ventral root discharge was increased, and in slice preparations containing the pre-Bötzinger complex with an increased inspiratory rhythm. The inhibition of C4 burst discharge observed in pontomedullary preparations was stronger in the growth-restricted group. These results cannot be directly linked by the tyrosine hydroxylase activity increase of A1/C1 and A2/C2 cell groups in the medulla since blockade of α1- and α2-adrenergic receptors did not abolish the difference between both groups. However, in pontomedullary preparations, the stronger inhibition of C4 burst discharge is probably supported by an increased inhibition of A5, a respiratory rhythm inhibitor pontine group of neurons displaying increased tyrosine hydroxylase activity, because blockade of α2-adrenergic receptors abolished the difference between the two groups. Taken together, these results indicate that growth restriction leads to a perturbation of the breathing frequency, which finds, at least in part, its origin in the modification of catecholaminergic modulation of the central breathing network.


The effect of cerebrospinal fluid pressure on the size of drainage pathways.
The cerebrospinal fluid drainage pathways were studied using labeled molecules of different sizes. Following determination of the limiting size, the cerebrospinal fluid pressure was raised above the normal range and changes in transfer were measured. These data show that molecules smaller than the limiting size will transfer at an increased rate in response to elevated pressures. Larger molecules did not demonstrate an increased transfer with raised cerebrospinal fluid pressures, suggesting that the pathways did not enlarge.


Medial prefrontal cortex dopamine controls the persistent storage of aversive memories.
Medial prefrontal cortex (mPFC) is essential for initial memory processing and expression but its involvement in persistent memory storage has seldom been studied. Using the hippocampus dependent inhibitory avoidance learning task and the hippocampus-independent conditioned taste aversion paradigm together with specific dopamine receptor agonists and antagonists we found that persistence but not formation of long-term aversive memories requires dopamine D1/D5 receptors activation in mPFC immediately after training and, depending on the task, between 6 and 12 h later. Our results indicate that besides its well-known participation in retrieval and early consolidation, mPFC also modulates the endurance of long-lasting aversive memories regardless of whether formation of the aversive mnemonic trace requires the participation of the hippocampus.


Laser activation of endodontic irrigants with improved conical laser fiber tips for removing smear layer in the apical third of the root canal.
With a tube etching process, conical-ended optical fibers for middle infrared lasers that have lateral emissions can be produced, a feature of benefit for delivering laser energy onto the root canal walls. This study examined the ability of these improved laser tips when Er:YAG and Er,Cr:YSGG lasers were used in root canals in which thick smear layers had been created intentionally to provide a challenge for the laser system. Smear layer was assessed from scanning electron microscopy images with an objective digital method. Lasing improved the action of ethylene diamine tetraacetic acid with cetavlon (EDTAC) in removing smear layer. Conical fibers performed better than plain fibers, but there was no difference in performance between the 2 laser systems when matched for all other parameters. These results provide a "proof of concept" for lateral emitting fibers for endodontic procedures and illustrate the novel contribution of lasing to the action of EDTAC in dissolving smear layer.


Are cytokines and cortisol important predictors for the severity of pediatric croup: A case control study.
Üzüm Ö, Çağlar A, Küme T, Sayıner A, Er A, Akgül F, Ulusoy E, Yılmaz D, Duman M. Are cytokines and cortisol important predictors for the severity of pediatric croup: A case control study. Turk J Pediatr 2017; 59: 281-287. The aim of this study is to investigate the role of cytokines (TNF-α, IL-6, IL-10, and PAF), cortisol, and IgE in the pathogenesis of croup and the factors determining its clinical severity. Patients diagnosed with croup at the Pediatric Emergency Department were included and thirty healthy children were included as a control group. Patients` demographic characteristics, clinical findings, recurrent croup history, and patient-family atopy history were recorded. Patients were grouped according to the Westley croup scoring system. Blood samples were taken from the control group and the patients for cytokines and cortisol. Respiratory pathogens were studied with PCR. Sixty-nine pediatric cases who were diagnosed as croup were included in the study (34 mild, 31 moderate, 4 severe). Group comparisons were made in terms of mild and moderate/severe groups. In the moderate/severe group, IL-10 and cortisol levels were higher than the mild group. The moderate/severe cortisol levels between 12:00 am-6:00 pm were found to be higher. PAF and TNF-alpha levels were detected to be higher in patients with a history of atopy. Viral agents were isolated in 45 patients; rhinovirus PCR tests were positive in 22 patients. In this study, rhinovirus was the most common etiology for croup. Increased levels of IL-10 and cortisol in the moderate/severe group indicate that different systemic and local mechanisms may play a role in the pathogenesis of croup.


Future Perspectives in Sleep Surgery.
Over the past few decades there has been a significant increase in research focusing on the pathophysiology, diagnosis, and treatment of sleep apnea. However, there is still a long way to go in creating standard evidence-based medical practice for the diagnosis, evaluation, and treatment of sleep apnea patients. Current and future directions of sleep surgery and other treatments are discussed here.


Some endocrine and morphological aspects of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Hormonal status was evaluated in TCDD-treated rats and in pair-fed and ad libitum-fed controls in order to separate hormonal changes resulting from the toxic insult of TCDD from those arising from progressive feed deprivation as it occurs in pair-fed controls. TCDD-treated rats received either a usually non-lethal (25 micrograms/kg) or a usually lethal (125 micrograms/kg) dose of TCDD whereas pair-fed and ad libitum-fed controls were given vehicle alone. Animals were terminated at predetermined time intervals and several hormones measured in serum or plasma. In addition, the morphology of the thyroid, pancreas, and pituitary was also examined. In both dosage groups, TCDD-treatment had the following effects: decreased TT4, FT4, insulin, and glucagon; mixed effects upon TT3, FT3, TSH, and GH. Pair-feeding to the non-lethal dose of TCDD had no effect on any of the hormones measured. Pair-feeding to the lethal dose of TCDD had the the following effects: slightly decreased TT4, FT4, TT3, TSH, and insulin; no effect on FT3 and glucagon. It is concluded that the endocrine status of TCDD-treated rats was different from that of pair-fed rats suggesting that some hormonal changes represent responses to an insult other than that due to starvation stress alone. A differential response between TCDD-treated and pair-fed rats was also observable morphologically in the corresponding endocrine glands indicating the importance of this additional control for morphologic observations in instances when reduced feed intake and body weight loss are prominent features of toxicity.


A background-free assay for cells forming antibody to glucose oxidase coupled with an enzyme-linked immunosorbent assay (ELISA) to quantitate antibody secretion.
We describe an immunocytochemical assay for cells forming antibody to glucose oxidase (GO). The method is specific in that only cells containing intracytoplasmic antibody capable of binding the immunogen (GO binding cells; GOBC) are stained. The method is sensitive because there is no GO activity in mammalian tissues. This lack of background readily permits detection of one GOBC among 10(6) nucleated lymphohemopoietic cells. The technique is reliable because purified chemicals are used. Although it is not possible to determine the Ig class of antibody formed by an individual cell, as can be done with the hemolytic plaque assay, the amount and class of secreted antibody to GO can be quantitated by an indirect enzyme-linked immunosorbent assay (ELISA), which is also described. GO is immunogenic and stimulates the formation of large numbers of GOBC in the popliteal lymph nodes after injection with adjuvant into the footpads of mice, but 1-mg doses injected IV or IP are lethal because of its enzymatic activity, which causes hypoglycemia and methemoglobinemia.


Order in the optic nerve of goldfish.
A small amount of horseradish peroxidase, injected into the goldfish optic nerve and transported into the retina, filled an annulus of ganglion cells. Since the retina grew by annular addition of cells, this result shows that axons from cells of similar age clustered together in the nerve.


Infection of Mouse Macrophages by Seasonal Influenza Viruses Can Be Restricted at the Level of Virus Entry and at a Late Stage in the Virus Life Cycle.
Airway epithelial cells are susceptible to infection with seasonal influenza A viruses (IAV), resulting in productive virus replication and release. Macrophages (MΦ) are also permissive to IAV infection; however, virus replication is abortive. Currently, it is unclear how productive infection of MΦ is impaired or the extent to which seasonal IAV replicate in MΦ. Herein, we compared mouse MΦ and epithelial cells for their ability to support genomic replication and transcription, synthesis of viral proteins, assembly of virions, and release of infectious progeny following exposure to genetically defined IAV. We confirm that seasonal IAV differ in their ability to utilize cell surface receptors for infectious entry and that this represents one level of virus restriction. Following virus entry, we demonstrate synthesis of all eight segments of genomic viral RNA (vRNA) and mRNA, as well as seven distinct IAV proteins, in IAV-infected mouse MΦ. Although newly synthesized hemagglutinin (HA) and neuraminidase (NA) glycoproteins are incorporated into the plasma membrane and expressed at the cell surface, electron microscopy confirmed that virus assembly was defective in IAV-infected MΦ, defining a second level of restriction late in the virus life cycle. Seasonal influenza A viruses (IAV) and highly pathogenic avian influenza viruses (HPAI) infect macrophages, but only HPAI replicate productively in these cells. Herein, we demonstrate that impaired virus uptake into macrophages represents one level of restriction limiting infection by seasonal IAV. Following uptake, seasonal IAV do not complete productive replication in macrophages, representing a second level of restriction. Using murine macrophages, we demonstrate that productive infection is blocked late in the virus life cycle, such that virus assembly is defective and newly synthesized virions are not released. These studies represent an important step toward identifying host-encoded factors that block replication of seasonal IAV, but not HPAI, in macrophages.


[Hematemesis in an 11-month-old child: an unusual symptom revealing a foreign body in the stomach].
Ingestion of foreign body has often no consequence. We report on a case in an 11-month-old girl who was referred for mild hematemesis and anorexia. Upper digestive tract endoscopy found a small metallic foreign body in the gastric antrum. After its removal, all symptoms disappeared. It is usually recommended to remove foreign bodies by endoscopy when they are in esophageal position, or are more than 3 to 5 cm long, or have a shape that may hurt the gut mucosa. Although rare, a gastric foreign body should be searched for in face of an upper gastrointestinal bleeding in an infant.


Membrane glycoconjugates expressed on sheep airway epithelium.
In mammalian lung, selective airway inflammatory reactions have been associated with viral infections, transplant rejection, and autoimmune diseases. Although the molecular basis for this selective reactivity is unknown, the importance of carbohydrates in immunologic processes suggests a potential role for membrane glycoconjugates in tissue-specific inflammatory reactions. In the present work we examined a panel of 39 lectins for their pattern of reactivity in the peripheral airways of the sheep lung. The size of the panel facilitated a comprehensive description of the glycoconjugate localization on the airway epithelium. Four lectins (agglutinins for Helix aspersa, Psophocarpus tetragonolobus, Trichosanthes kirilowii, and Griffonia simplifolia II) revealed selective reactivity with the small airway epithelium. On lectin Western blotting, these four lectins demonstrated a common low molecular weight banding profile that was distinct from control lectins. The histochemical staining patterns and Western blotting profiles provided evidence for the selective expression of membrane glycoconjugates in the peripheral airways of the sheep lung.


Activation of the trigeminal system as a likely target of SARS-CoV-2 may contribute to anosmia in COVID-19.
Clinical publications show consistently that headache is a common symptom in the coronavirus disease of 2019 (COVID-19). Several studies specifically investigated headache symptomatology and associated features in patients with COVID-19. The headache is frequently debilitating with manifold characters including migraine-like characteristics. Studies suggested that COVID-19 patients with headache vs. those without headache are more likely to have anosmia. We present a pathophysiological hypothesis which may explain this phenomenon, discuss current hypotheses about how the coronavirus SARS-CoV-2 enters the central nervous system and suggest that activation of the trigeminal nerve may contribute to both headache and anosmia in COVID-19.


[Genetic polymorphism of 6 short tandem repeat loci in Chinese Han population in Shanxi].
To obtain the polymorphism data of six short tandem repeat (STR) loci, i.e. D9S925, D11S2368, D14S608, D15S659, D17S1290 and D20S470, in Chinese Han population in Shanxi province, and to evaluate the usefulness of the polymorphism data in forensic science. The D9S925, D11S2368, D14S608, D17S1290 and D20S470 primers were synthesized according to GenBank, while the D15S659 primers were self-designed. These primers were used to amplify DNA from 194 unrelated individuals collected from Shanxi Han population. Then the amplified fragments were separated by electrophoresis in 3130 Genetic Analyzer. GeneMapper3.2 software was used to analyze the results. The distributions of genotypes for the six STR loci were in accordance with Hardy-Weinberg equilibrium. The polymorphism information content (PIC) of the six STR loci were from 0.750 to 0.860, and the heterozygosity ranged from 0.756 to 0.894, and the discrimination power were from 0.920 to 0.965, and the probability of exclusion were from 0.519 to 0.784. The combined probability of exclusion and the combined discrimination power were 0.9988 and 0.99999998, respectively. The data indicated that D9S925, D11S2368, D14S608, D15S659, D17S1290 and D20S470 loci have high probability of exclusion and discrimination power. They can be used as genetic markers in forensic test and personal identification.


Characterization of plasmid-mediated aphA-3 kanamycin resistance in Campylobacter jejuni.
A total of 254 isolates of Campylobacter jejuni and three isolates of Campylobacter coli, isolated from Sweden, Canada, and Egypt, were screened for kanamycin resistance. Eight strains of C. jejuni contained large plasmids that carried the aphA-3 kanamycin-resistance marker. In six plasmids, the aphA-3 gene was located downstream of an apparent insertion sequence, designated IS607*, which showed a considerable similarity to IS607, characterized on the chromosome of some Helicobacter pylori strains. In contrast, the other plasmids carried the aphA-3 gene as a part of a resistance cluster. This included three resistance markers encoding 6'-adenylyltransferase (aadE), streptothricin acetyltransferase (sat), and 3'-aminoglycoside phosphotransferase type III (aphA-3). The genetic organization of this resistance cluster suggests that it has been acquired by C. jejuni from a Gram-positive organism. The IS607* element was also observed in kanamycin-susceptible strains of C. jejuni on plasmids mediating tetracycline resistance. The kanamycin-resistance phenotype transferred along with tetracycline resistance by conjugation from four representative C. jejuni strains to a recipient strain of C. jejuni. The kanamycin-resistance determinant (aphA-3) was stably transferred from one of the four C. jejuni strains to a recipient strain of Escherichia coli. However, the C. jejuni plasmid, which also carries the tetO gene, was not maintained in E. coli. Pulsed-field gel electrophoresis revealed the integration of approximately 50 kb of the plasmid into the chromosome of the E. coli recipient.


Intelligent Identification Method of Geographic Origin for Chinese Wolfberries Based on Color Space Transformation and Texture Morphological Features.
Geographic origins play a vital role in traditional Chinese medicinal materials. Using the geo-authentic crude drug can improve the curative effect. The main producing areas of Chinese wolfberry are Ningxia, Gansu, Qinghai, and so on. The geographic origin of Chinese wolfberry can affect its texture, shape, color, smell, nutrients, etc. However, the traditional method for identifying the geographic origin of Chinese wolfberries is still based on human eyes. To efficiently identify Chinese wolfberries from different origins, this paper presents an intelligent identification method for Chinese wolfberries based on color space transformation and texture morphological features. The first step is to prepare the Chinese wolfberry samples and collect the image data. Then the images are preprocessed, and the texture and morphology features of single wolfberry images are extracted. Finally, the random forest algorithm is employed to establish a model of the geographic origin of Chinese wolfberries. The proposed method can accurately predict the origin information of a single wolfberry image and has the advantages of low cost, fast recognition speed, high recognition accuracy, and no damage to the sample.


Rabbit blastocysts accumulate [3H]prostaglandins in vitro.
Rabbit blastocysts obtained on days 5, 6, and 6.8 of pregnancy were incubated in vitro in Tyrode's buffer with 3H-labeled prostaglandins (PGs). Accumulation of PGs was studied, using Whatman GF/F filters to separate bound and free ligands. The uptake and efflux of [3H]PGs were studied as a function of PG type, incubation time, temperature, and effect of metabolic inhibitors as well as age and number of blastocysts. Blastocysts of the same age accumulated approximately the same amount of [3H]PGE2 and [3H]PGF2 alpha from their environment; however, there was no apparent saturation over a PG concentration range of 1-1000 nM. Both the uptake and efflux of PG were age dependent, with older blastocysts accumulating more PGs. Approximately 90% of the [3H]PGs appear to be transported into the blastocoelic fluid, with little PG remaining in the blastomeres. PG accumulation was relatively insensitive to azide, ouabain, cyanide, or bromcresol green, but was affected by incubation at 0 C or the addition of indomethacin (10 micrograms/ml). No catabolism of the accumulated PGs was observed. The release of PGE2 in general did not differ from that of PGF2 alpha, except on day 6.8 of pregnancy when PGE2 was released more rapidly than on day 6. We conclude that rabbit blastocysts can accumulate PGs from their environment, which may imply a storage potential in the blastocyst and release before implantation.


A Novel Actinic Keratosis Field Assessment Scale for Grading Actinic Keratosis Disease Severity.
Actinic keratosis (AK) lesions are surrounded by field cancerization (areas of subclinical, non-visible sun damage). Existing AK grading tools rely on AK counts, which are not reproducible. An Actinic Keratosis Field Assessment Scale (AK-FAS) for grading the severity of AK/field was developed. Standardized photographs of patients representing the full range of AK severity were collected. Six investigators independently rated each photograph according to 3 criteria: AK area (total skin area affected by AK lesions), hyperkeratosis and sun damage. Inter-rater reproducibility was good for all 3 criteria. Validation of the AK-FAS showed good reproducibility for AK area and hyperkeratosis, even for dermatologists untrained on use of the scale. In conclusion, the AK-FAS is objective, easy to use and implement, and reproducible. It incorporates assessment of the entire field affected by AK instead of relying on lesion counts. Use of the AK-FAS may standardize AK diagnosis, making it relevant to routine clinical practice.


Diuretic dosing in acute decompensated heart failure: lessons from DOSE.
The mainstay of treatment for acute decompensated heart failure (ADHF) is intravenous (IV) diuretic therapy either as a bolus or via continuous infusion. Despite being available for decades, few randomized trials exist to guide dosing and administration of these drugs. In 2011, the Diuretic Optimization Strategies Evaluation (DOSE) trial used a prospective, randomized design to compare bolus versus continuous infusion of IV furosemide, as well as high-dose versus low-dose therapy. The study found no difference in the primary end point for continuous versus bolus infusion. High-dose diuretics were more effective than low dose without clinically important negative effects on renal function. Although limited by patient selection criteria and protocol design, the study challenges long-held beliefs that continuous infusion is more effective than bolus dosing. The study also challenges the notion that high-dose diuretics carry clinically important renal toxicity risks for patients.