Formation of a DNA triple helical structure at BOLF1 gene of human herpesvirus 4 (HH4) genome.
Eukaryotic genomes contain a large number of pyrimidine-purine rich regions and such regions can assume varied DNA conformations, including triple-stranded structures. These structures have fascinated scientists because of their considerable therapeutic applications. These structures have also profound implications in the field of nanotechnology as they can be used to develop DNA-based nanostructures and materials. Therefore, for any application, it is important to understand the formation of triplex structures, both in quantitative and qualitative terms. A combination of gel electrophoresis, UV-thermal denaturation and circular dichroism (CD) spectroscopy was used to investigate the formation of inter- as well as intramolecular triplex, in pyrimidine motif at BOLF1 gene of human herpesvirus 4 (HH4) genome. This gene codes for inner tegument protein, which plays crucial roles in viral replication. The said oligopurine•oligopyrimidine duplex was targeted via a designed triple helix forming oligopyrimidine nucleotide (TFO) in intermolecular as well as intramolecular fashion. Our studies revealed that intramolecular triplex formation takes place at acidic as well as at neutral pH; whereas low pH is required for its intermolecular version. This comparative study between inter- and intramolecular triplex allowed us to demonstrate that intramolecular structure is more stable to its intermolecular counterpart. Numerous models for mono-, bi- and trimolecular structures adopted by these DNA sequences have been suggested. This report adds to our existing knowledge about DNA triple helical structures.


Understanding trajectories of externalizing problems: Stability and emergence of risk factors from infancy to middle adolescence.
Despite considerable efforts to understand the processes that underlie the development of externalizing behavior problems, it is still unclear why externalizing problems remain chronically high for some children, emerge early and cease by late childhood for others, and arise in adolescence in some cases. The purpose of this study was to examine how a wide range of child and family risk factors are linked to trajectories of externalizing behavior and how these relationships vary from infancy to middle adolescence. We used data from the community-based Norwegian Tracking Opportunities and Problems (TOPP) study sample (n = 921). A Cholesky factorization model was specified to separate stable and emerging risk doses across four developmental periods (infancy, early and middle childhood, and middle adolescence). Children in the High Stable class were characterized by substantially elevated risk levels in multiple domains throughout the study period. Children in the High Childhood Limited class had very high levels of temperamental emotionality, internalizing symptoms, and maternal mental distress, suggesting a substantial intrinsic emotional basis for their externalizing problems. Intrinsic factors seemed less salient for the Adolescent Onset class. These findings emphasize the need for a dynamic perspective on risk factors and support the importance of prevention and intervention efforts across multiple domains from early childhood and throughout adolescence.


Uterine molecular changes for non-invasive embryonic attachment in the marsupials Macropus eugenii (Macropodidae) and Trichosurus vulpecula (Phalangeridae).
Pregnancy in mammals requires remodeling of the uterus to become receptive to the implanting embryo. Remarkably similar morphological changes to the uterine epithelium occur in both eutherian and marsupial mammals, irrespective of placental type. Nevertheless, molecular differences in uterine remodeling indicate that the marsupial uterus employs maternal defences, including molecular reinforcement of the uterine epithelium, to regulate embryonic invasion. Non-invasive (epitheliochorial) embryonic attachment in marsupials likely evolved secondarily from invasive attachment, so uterine defences in these species may prevent embryonic invasion. We tested this hypothesis by identifying localization patterns of Talin, a key basal anchoring molecule, in the uterine epithelium during pregnancy in the tammar wallaby (Macropus eugenii; Macropodidae) and the brush tail possum (Trichosurus vulpecula; Phalangeridae). Embryonic attachment is non-invasive in both species, yet Talin undergoes a clear distributional change during pregnancy in M. eugenii, including recruitment to the base of the uterine epithelium just before attachment, that closely resembles that of invasive implantation in the marsupial species Sminthopsis crassicaudata. Basal localization occurs throughout pregnancy in T. vulpecula, although, as for M. eugenii, this pattern is most specific prior to attachment. Such molecular reinforcement of the uterine epithelium for non-invasive embryonic attachment in marsupials supports the hypothesis that less-invasive and non-invasive embryonic attachment in marsupials may have evolved via accrual of maternal defences. Recruitment of basal molecules, including Talin, to the uterine epithelium may have played a key role in this transition.


Mechanical properties of sensory hair bundles are reflected in their Brownian motion measured with a laser differential interferometer.
By optically probing with a focused, low-power laser beam, we measured the spontaneous deflection fluctuations of the sensory hair bundles on frog saccular hair cells with a sensitivity of about 1 pm/square root of Hz. The preparation was illuminated by two orthogonally polarized laser beams separated by only about 0.2 microns at their foci in the structure under investigation. Slight movement of the object from one beam toward the other caused a change of the phase difference between the transmitted beams and an intensity modulation at the detector where the beams interfered. Maintenance of the health of the cells and function of the transduction mechanism were occasionally confirmed by measuring the intracellular resting potential and the sensitivity of transduction. The root-mean-square (rms) displacement of approximately 3.5 nm at a hair bundle's tip suggests a stiffness of about 350 microN/m, in agreement with measurements made with a probe attached to a bundle's tip. The spectra resemble those of overdamped harmonic oscillators with roll-off frequencies between 200 and 800 Hz. Because the roll-off frequencies depended strongly on the viscosity of the bathing medium, we conclude that hair-bundle motion is mainly damped by the surrounding fluid.


Bilateral trigeminal amyloidoma: an unusual case of trigeminal neuropathy with a review of the literature. Case report.
Isolated amyloidomas may, albeit rarely, involve the central nervous system. There are three previous reports of amyloidomas that involved the gasserian ganglion and caused unilateral trigeminal neuropathies. The authors report the case of a 49-year-old woman with apparently isolated amyloidomas that caused slowly progressive bilateral trigeminal neuropathies. Magnetic resonance imaging of the brain revealed mild swelling of the left trigeminal nerve within the cavernous sinus and uniform enhancement with gadolinium throughout the length of the nerve. At craniotomy, the trigeminal nerve and ganglion were observed to be infiltrated by a tumor-like mass. Biopsy showed extensive infiltration of the nerve and ganglion by amyloid. Immunocytochemical studies of the amyloid were negative for immunoglobulins, kappa and lambda light chains, beta-amyloid A4 protein, transthyretin, beta 2-microglobulin, cystatin C, and gelsolin, but weak focal immunoreactivity with antiamyloid AA antibody was seen in the amyloid in vessels and in some intraneural deposits. Extensive investigations failed to reveal evidence of either systemic amyloidoses or an underlying inflammatory disorder or malignancy.


Unique and redundant roles of Smad3 in TGF-beta-mediated regulation of long bone development in organ culture.
The most well-characterized intracellular signaling molecules for transforming growth factor-beta (TGF-beta) are the Smads. R-Smads interact with and are phosphorylated directly by the TGF-beta type I receptor. Phosphorylated R-Smads can then associate with Smad4, translocate to the nucleus and regulate transcription. Specific R-Smads transduce distinct signals for members of the TGF-beta superfamily. Smad2 and -3 mediate signaling by TGF-beta/activin, whereas Smad1, -5, and -8 mediate bone morphogenetic protein signaling. TGF-beta inhibits proliferation and hypertrophic differentiation in metatarsal organ cultures by a perichondrium-dependent mechanism. To determine the mechanism of TGF-beta signaling in the perichondrium, we tested the hypothesis that TGF-beta-restricted Smad2 and Smad3 regulate chondrocyte proliferation and differentiation in embryonic metatarsal organ cultures. Perichondrium was infected with adenoviruses containing dominant-negative forms of Smad2 (Ad-Smad2-3SA) and Smad3 (Ad-Smad3 Delta C). Proliferation and differentiation were measured in response to treatment with TGF-beta 1. Results were compared with control bones infected with a beta-galactosidase reporter virus (Ad-beta-gal). Infection with Ad-Smad2-3SA completely blocked the effects of TGF-beta 1 on metatarsal development while Ad-Smad3 Delta C only partially blocked TGF-beta 1 effects. To further characterize the role of Smad3 in long bone development, TGF-beta 1 responsiveness in cultures from Smad3(+/+) and Smad3(ex8/ex8) mice were compared. Loss of Smad3 only partially blocked the effects of TGF-beta1 on differentiation. In contrast, the effects of TGF-beta 1 on chondrocyte proliferation were blocked completely. We conclude that Smad2 signaling in the perichondrium can compensate for the loss of Smad3 to regulate inhibition of hypertrophic differentiation; however, Smad3 is required for TGF-beta 1-mediated effects on proliferation.


Traditional Chinese medicine in treatment of opiate addiction.
Traditional Chinese medicine (TCM) includes Chinese medicine and acupuncture. Chinese medicine consists of natural products including plants, animals and minerals. TCM has been practiced in China for more than 2000 years, and for the past 200 years has been used in treatment of drug addiction. Ten Chinese medicines for the treatment of opiate addiction have been approved by the Chinese State Food and Drug Administration (SFDA), and at least 6 are in clinical trials. The general therapeutic principle of Chinese medicine developed was based on its unique theory of " reinforcing healthy Qi and resolving and removing effects of toxicity". Acupuncture, another essential part of TCM, which was developed based on the principle that " functions of the human body are controlled by the ' Jing-Luo' and 'Qi-Xue'system" , has been used not only in China, but also in Europe, the USA and other countries, for controlling opiate addiction. There are some advantages in using TCM for opiate detoxification, including less harmful side effects, high safety and ideal effects in the inhibition of protracted withdrawal symptoms and relapse. Co-administration of TCM with modern medicine shows some synergistic effects in detoxification. Many TCM for detoxification also have efficacy in the rehabilitation of abnormal body functions induced by chronic drug use, including improving immune function, increasing working memory and preventing neurological disorder. Given that TCM is effective in the prevention of relapse and causes fewer side effects, it may be used widely in the treatment of opiate addiction.


Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia.
Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this purpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4+ and CD8+ T cells as measured by the expression of IL-2 receptors (CD25), HLA-DR, and the very late activation antigen VLA-1. Beside the characteristic leukocyte infiltrate in the various lung diseases, all patients demonstrated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine pattern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-gamma in allergic asthma. ABPA patients demonstrated significantly increased levels of IL-4 and IL-5, with low but significantly elevated concentrations of IL-2 and IFN-gamma. In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a cytokine pattern incompatible with a pure Th1 or Th2 cell response, because IL-5, IL-2, and IFN-gamma were found to be significantly increased. The BAL fluid analysis of the other, mainly non-T cell-derived cytokines and soluble receptors showed increased levels in all patients compared with normal individuals and may represent the ongoing inflammatory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The close correlation between IL-5 levels, number of eosinophils, and activated T cells further supports a role for IL-5 in causing tissue eosinophilia.


Exogenous MSCs ameliorate hypoxia/reoxygenation injury in renal tubular epithelial cells through JAK/STAT signaling pathway-mediated regulation of HMGB1.
This study was conducted to investigate the repair mechanism of hypoxia/reoxygenation injury (HRI) in renal tubular epithelial cells (HK-2) by exogenous mesenchymal stem cells (MSCs). The activation of the JAK/STAT pathway in HK-2 cells after HRI and treatment of MSCs, JAK inhibitor WP1066 and STAT inhibitor SOCS3 was investigated using Western blot analysis. HK-2 cells were transfected with siRNA STAT3 and analyzed for expression of STAT3, JAK2 and HMGB1 using fluorescence quantitative PCR and Western blot. Cell viability and apoptosis were analyzed using the MTT assay and flow cytometry. After HRI, the JAK/STAT pathway in HK-2 cells was activated, resulting in the upregulation of JAK1, JAK2, JAK3, p-JAK1, p-JAK2, p-JAK3, STAT1, STAT2, STAT3, p-STAT1, p-STAT2 and p-STAT3. After treatment with MSC conditioned medium (MSCs CM), WP1066, or SOCS, the expression of these proteins was significantly down-regulated. When the cells were transfected with siRNA STAT3, the expression of STAT3 at protein and mRNA levels and JAK2 and HMGB1 at mRNA level was down-regulated; the cell viability was reduced and apoptosis increased. It is concluded that exogenous MSCs reduce HRI of HK-2 cells by suppressing the JAK/STAT signaling pathway and down-regulating the expression of HMGB1.


Intelligent sensing based on active micro/nanomotors.
In the microscopic world, synthetic micro/nanomotors (MNMs) can convert a variety of energy sources into driving forces to help humans perform a number of complex tasks with greater ease and efficiency. These tiny machines have attracted tremendous attention in the field of drug delivery, minimally invasive surgery, in vivo sampling, and environmental management. By modifying their surface materials and functionalizing them with bioactive agents, these MNMs can also be transformed into dynamic micro/nano-biosensors that can detect biomolecules in real-time with high sensitivity. The extensive range of operations and uses combined with their minuscule size have opened up new avenues for tackling intricate analytical difficulties. Here, in this review, various driving methods are briefly introduced, followed by a focus on intelligent detection techniques based on MNMs. And we discuss the distinctive advantages, current issues, and challenges associated with MNM-based intelligent detection. It is believed that the future advancements of MNMs will greatly impact the diagnosis, treatment, and prevention of diseases.


Clinical and pathological aspects of microscopic thymoma with myasthenia gravis and review of published reports.
Microscopic thymomas, defined as epithelial proliferations smaller than 1 mm in diameter, characteristically occur in patients with myasthenia gravis without macroscopic thymic epithelial tumors. However, some clinical and pathological aspects of this entity are still unclear. This retrospective study includes five consecutive patients who had undergone extended thymectomy for myasthenia gravis at our institution from April 2007 to March 2016 and in whom microscopic thymomas were diagnosed by histopathological examination of the resected specimens. During the same period, we performed 32 extended transsternal thymothymectomies/thymectomies in patients with myasthenia gravis, including the above five cases. We here review 18 cases of microscopic thymoma, including our five cases and 13 previously reported cases. The incidence of previously undiagnosed microscopic thymoma in patients undergoing thymectomy for myasthenia gravis in our institution is 15.2%. Serum preoperative anti-acetylcholine receptor antibody (anti-AchR Ab) titers were abnormally high in all of our five cases h (74.4±53.3 nmol/L) and decreased significantly after surgery (11.7±13.5 nmol/L, P=0.037). We divided our cases into the following three groups: microscopic thymoma group (Group M), thymoma group (Group T) and non-thymic tumor group (Group N). The mean preoperative anti-AchR Ab titers of these groups were 74.4, 26.5, and 368 nmol/L, respectively. All these values decreased postoperatively. The mean anti-AchR Ab titer was significantly higher in Group M than in Group T (P=0.034). All five cases in Group M were found by post-operative pathological examination to have multifocal type A thymomas. Microscopic thymomas tend to be multifocal type A thymomas. Anti-AchR Ab titers decreased significantly in all groups. It is very important to both perform complete extended thymectomies in patients with myasthenia gravis and pathological examination of thin slices of thymic tissue to maximize detection of microscopic thymomas.


Asymmetry of the lateral (sylvian) fissures in man.
We compared the courses of right and left lateral (sylvian) fissures by superimposing left lateral and reversed right lateral photographic slide projections and tracing the sulci and fissures of each hemisphere in different colors. A characteristic pattern of divergence of posterior regions of the lateral fissures was noted in 25 of 36 adult brains. After pursuing similar courses, the right lateral fissure angulates sharply upward into the inferior parietal area while the left one continues posteriorly. As a consequence, on the right, there is a smaller parietal operculum, a shorter planum temporale, a higher sylvian point, and compensatory expansion of the inferior parietal region posterior to the lateral fissure.


Oxindole, a sedative tryptophan metabolite, accumulates in blood and brain of rats with acute hepatic failure.
Rats treated with oxindole (10-100 mg/kg i.p.), a putative tryptophan metabolite, showed decreased spontaneous locomotor activity, loss of the righting reflex, hypotension, and reversible coma. Brain oxindole levels were 0.05 +/- 0.01 nmol/g in controls and increased to 8.1 +/- 1.7 or 103 +/- 15 nmol/g after its administration at doses of 10 or 100 mg/kg i.p., respectively. To study the role that oxindole plays in the neurological symptoms associated with acute liver failure, we measured the changes of its concentration in the brain after massive liver damage, and we investigated the possible metabolic pathways leading to its synthesis. Rats treated with either thioacetamide (0.2 and 0.4 g/kg i.p., twice) or galactosamine (1 and 2 g/kg i.p.) showed acute liver failure and a large increase in blood or brain oxindole concentrations (from 0.05 +/- 0.01 nmol/g in brains of controls to 1.8 +/- 0.3 nmol/g in brains of thioacetamide-treated animals). Administration of tryptophan (300-1,000 mg/kg p.o.) caused a twofold increase, whereas administration of indole (10-100 mg/kg p.o.) caused a 200-fold increase, of oxindole content in liver, blood, and brain, thus suggesting that indole formation from tryptophan is a limiting step in oxindole synthesis. Oral administration of neomycin, a broad-spectrum, locally acting antibiotic agent able to reduce intestinal flora, significantly decreased brain oxindole content. Taken together, our data show that oxindole is a neurodepressant tryptophan metabolite and suggest that it may play a significant role in the neurological symptoms associated with acute liver impairment.


Screening adolescents for sexually transmitted infections in the pediatric emergency department.
The objectives of this study were to determine the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infections among adolescents presenting to a pediatric emergency department (PED), to assess the association between these infections and certain risk factors, and to assess the feasibility of routine screening for sexually transmitted infections (STIs) in the PED. This was a prospective, observational cohort study. Three hundred seven adolescents aged 13 to 17 years in an urban PED in Bronx, NY, were enrolled in the study. Subjects provided urine samples for nucleic acid amplification testing for CT and GC and self-completed a confidential questionnaire to assess health care-seeking patterns, high-risk social behaviors, and the presence of abuse, depression, and suicidal ideation. Outcome measures include prevalence of STIs and association of STIs with responses to the confidential questionnaire. Twenty subjects (6.5%) tested positive for an STI. Seventeen (5.5%) were positive for CT, 2 (0.7%) for GC, and 1 (0.3%) for both. Fourteen adolescents (70%) with a positive test were asymptomatic. Logistic regression yielded 4 factors significantly associated with an STI: female sex (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.1-15.2), illicit drug use (OR, 3.3; 95% CI, 1.1-9.3), disclosure of sexual activity (OR, 9.3; 95% CI, 1.1-76.9), and report of a sexual encounter resulting in pregnancy (OR, 3.7; 95% CI, 1.3-10.4). Sexually transmitted infections were common in asymptomatic adolescents presenting to the PED. We identified 4 risk factors that were significantly associated with STIs. Our findings may facilitate identification of adolescents at highest risk for STIs, help prevent further transmission of infection, and decrease morbidity in this marginalized population.


Characterization and localization of an iron-binding 18-kDa glycopeptide isolated from the N-terminal half of human lactotransferrin.
Mild treatment of iron-saturated human lactotransferrin by trypsin at pH 8.2 cleaves the molecule into a N-tryptic (Mr approximately equal to 30000) and a C-tryptic (Mr approximately equal to 50000) fragment, which have been isolated. Each of them carries a glycan moiety and keeps the property to bind reversibly one Fe3+. The N-tryptic fragment has been submitted to a second tryptic digestion which led to an iron-binding glycopeptide fragment with a molecular weight of about 18500. This fragment, the smallest iron-binding peptide isolated up to now from a transferrin, includes the ND2 domain of human lactotransferrin.


Intervening sequences increase efficiency of RNA 3' processing and accumulation of cytoplasmic RNA.
Two expression vectors were constructed that differ only in the presence (+) or absence (-) of an intervening sequence (IVS) in their 5'-untranslated leaders. Transient transfection into four mammalian cell lines resulted in higher levels of the indicator protein (CAT) from the IVS(+) vector (6 to 50-fold). Cytoplasmic RNA concentrations in 293s and HeLa cell lines corresponded directly to resultant protein levels; measurements in 293s cells of transcription initiation and elongation, steady-state total nuclear RNA, and cytoplasmic RNA stability, were equivalent for the two vectors. Surprisingly, the amount of poly(A)+ nuclear RNA was greater from the IVS(+) vector. Since this difference matches the ratio seen with polyadenylated cytoplasmic RNA, our results imply that splicing is coupled to a polyadenylation/transport pathway.


Triple-image encryption based on phase-truncated Fresnel transform and basic vector operation.
A triple-image encryption method is proposed that is based on phase-truncated Fresnel transform (PTFT), basic vector composition, and XOR operation. In the encryption process, two random phase masks, with one each placed at the input plane and the transform plane, are generated by basic vector resolution operations over the first and the second plaintext images, and then a ciphered image in the input plane is fabricated by XOR encoding for the third plaintext image. When the cryptosystem is illuminated by an on-axis plane, assisted by PTFT, the ciphered image is finally encrypted into an amplitude-only noise-like image in the output plane. During decryption, possessing the correct private key, decryption keys, and the assistant geometrical parameter keys, and placing them at the corresponding correct positions, the original three plaintext images can be successfully decrypted by inverse PTFT, basic vector composition, and XOR decoding. Theoretical analysis and numerical simulations both verify the feasibility of the proposed method.


Enteric bacteria isolated from acute diarrheal patients in the Republic of Korea between the year 2004 and 2006.
In an epidemiological survey of human enterobacterial infections in the Republic of Korea during three years from 2004 to 2006, we isolated 1,784 (6.2%, isolation rate of enteropathogens from stool samples) in 2004, 2,547 (9.5%) in 2005 and 3,506 bacteria (12.3%) from people who visited clinics. Among the isolated bacteria, pathogenic Escherichia coli, especially, EAEC was the most frequently identified pathogen in both urban and rural regions followed by Staphylococcus aureus, Salmonella species, Bacillus cereus, Vibrio parahaemolyticus, Campylobacter jejuni, Clostridium perfringens, and Shigella species. Distinct seasonality was found in V. parahaemolyticus species, while this pathogen showed no age-specific patterns. However, other bacteria, i.e., pathogenic E. coli, S. aureus, Salmonella spp., and B. cereus showed similar seasonality throughout the year, showing a slight increase in the infection rate during the summer months and high prevalence among children under 10 years of age and elder-age people. The antibiotic susceptibility patterns of pathogenic E. coli, Salmonella spp., and S. aureus showed high resistance to penicillins. However, both pathogenic E. coli and Salmonella spp. were susceptible to several cephems, imipenem, and amikacin. Moreover, S. aureus strains resistant to vancomycin were not found. In conclusion, these surveillances can play an important role for the control and prevention to the diseases originated by enteritis bacteria.


Prevalence of HIV-positives and hepatitis B surface antigen-positives among donors in the University of Benin Teaching Hospital, Nigeria.
The purpose of this study is to determine the rate of human immunodeficiency virus (HIV) and hepatitis B surface antigen (HBsAg) among commercial blood donors in the University of Benin Teaching Hospital. Five thousand seven hundred and thirty-seven prospective commercial blood donors were screened for both HIVand HBsAg. Three hundred and eighty-three (7%) donors were positive for HIV while 609 donors (11%) were positive for HBsAg. Thirty-seven donors were positive for both HIV and HBsAg. The need to make the screening of blood donors for HIV and HBsAg compulsory in all hospitals is crucial so that the spread of HIV and HBsAg can be prevented.


Characterization of the veiling glare PSF in x-ray image intensified fluoroscopy.
A theoretical derivation for the point spread function (PSF) which describes the veiling glare in x-ray image intensifiers (II) is presented. The PSF is dependent on two parameters which can be determined experimentally for a given II. An experimental investigation of the linearity of veiling glare phenomenon is undertaken. The experimental results indicate that veiling glare could be described as a linear process to a high degree of accuracy.


The relationship between treatment-induced hypertension and efficacy of anlotinib in recurrent or metastatic esophageal squamous cell carcinoma.
In this post-hoc analysis, we evaluated anlotinib treatment-induced hypertension as a potential predictive factor of efficacy in esophageal squamous cell carcinoma (ESCC) patients. A total of 109 patients enrolled in the anlotinib group in a phase 2 trial were included. The tumor response was assessed by computed tomography at week 3, week 6, and then every 6 weeks until progressive disease was observed. The primary endpoint of the study was progression free survival (PFS). The secondary endpoints included overall survival (OS) and objective response rate (ORR). In all patients, the median PFS was 3.02 months [95% confidence interval (CI): 2.63-3.65 months] and the OS was 6.11 months (95% CI: 4.40-7.79 months). The ORR was 7.34% (95% CI: 3.22%-13.95%). A total of 59 (54%) patients were diagnosed with treatment-induced hypertension (Group A), and the remaining patients (n = 50, 46%) were in Group B. Baseline prognostic factors were similar between the 2 groups. Patients in Group A had a longer PFS and OS and higher ORR. When stratifying patients using a previously known history of hypertension, treatment-induced hypertension was a predictor only for patients without previous hypertension, who had longer PFS [hazard ratio (HR): 0.40, 95% CI: 0.24-0.68] and OS (HR: 0.37, 95% CI: 0.21-0.67). We showed, for the first time, a correlation between treatment-induced hypertension and better prognoses in recurrent or metastatic ESCC patients treated with anlotinib, without a previously known history of hypertension. Treatment-induced hypertension may be a simple and low cost predictor for anlotinib antitumor efficacy in these patients, which may also reflect the intended target inhibition.


Covalent modification of ribulose 1,5-bisphosphate carboxylase/oxygenase in Rhodomicrobium vannielii.
The most abundant phosphorus-containing polypeptide in the purple non-sulphur bacterium Rhodomic-robium vannielii has been identified by a combination of immunoprecipitation and sucrose density gradient centrifugation as the large subunit of ribulose 1,5-bisphosphate carboxylase/oxygenase. The covalent modification of the large subunit involves the phosphorylation of one or more tyrosine residues and appears to occur prior to assembly of the large subunit into the mature enzyme. In addition, the phosphorylated form of the large subunit was found to exist in at least two distinct protein complexes of Mr 410,000 and 440,000.


CM352 Reduces Brain Damage and Improves Functional Recovery in a Rat Model of Intracerebral Hemorrhage.
Intracerebral hemorrhage (ICH) is an acute neurological disorder with high mortality and no effective treatment. In addition to the initial bleeding event, rebleeding and hematoma expansion are associated with poor outcome in these patients. We studied the effectiveness of the new antifibrinolytic agent CM352, a short-half-life matrix metalloproteinase inhibitor, for achieving early hemostasis and improving functional recovery in a rat model of collagenase-induced ICH. ICH was induced by striatal injection of collagenase, and 1 hour later, rats received an intravenous injection of saline (n=6) or CM352 (1 mg/kg, n=6). Hematoma (basal and after 3 and 24 hours) and lesion (14 days) volumes were quantified on T2-weighted (T2) magnetic resonance images. Neurological and functional recovery was evaluated by using Bederson score and a cylinder test (basal, 24 hours, and 14 days). Early treatment (1 hour) with CM352 was efficient reducing hematoma expansion at 3 hours (P<0.01) and, more markedly, at 24 hours (P<0.01). Decreased bleeding after antifibrinolytic treatment was accompanied by reduced interleukin-6 levels at 3 hours (P<0.05) and smaller lesion volume at 14 days (P<0.01). CM352 drastically reduced sensorimotor impairment (cylinder test) after ICH in rats at 24 hours (P<0.01) and 14 days (P<0.01). Similarly, it also attenuated neurological deficit (Bederson scale) at 24 hours (P<0.01) and 14 days (P<0.01). Interestingly, late (3 hours) CM352 administration also resulted in reduced lesion size and better functional outcome. CM352, a new antifibrinolytic agent and matrix metalloproteinase inhibitor, effectively prevented hematoma growth and reduced lesion size in ICH in association with improved functional and neurological recovery.


Individualization of treatment for hilar bile duct cancers.
Two cases of hilar bile duct cancer are presented, 1 treated with the preferred technique of left intrahepatic anastomosis, the other with tube drainage. The many factors to be considered before choosing the most appropriate procedure are stressed. A critique of several techniques is offered, with a discussion of the nuances in decision making. The surgeon who embarks upon treatment of such tumors should be thoroughly familiar with the wide range of procedures available; better selection should improve palliation.


[99mTc-HMPAO SPECT in the brain death--a case report].
Brain single photon emission computed tomography (SPECT) with 99mTc-d,l-hexamethyl-propyleneamine oxime (HMPAO) was performed twice in a 78-year-old man clinically diagnosed as brain death according to the standard criteria of the Japanese Ministry of Welfare. The first brain SPECT demonstrated the tracer accumulation in the brain, indicating preserved cerebral blood flow. The second brain SPECT performed 3 days later revealed cessation of the blood flow. In patients with preserved cerebral blood flow, the diagnosis of brain death cannot be made, even if they meet the existing criteria, because previous report noted the recovery in some of those patients. Brain perfusion SPECT plays an important role as a confirmatory test for the diagnosis of the brain death.


Magnetic resonance angiography: the nuts and bolts.
Magnetic resonance angiography (MRA) has matured into an extremely reliable and valuable diagnostic vascular tool. We are now able to acquire clinically diagnostic angiograms in all the major vascular territories by using MRA, thereby replacing invasive angiography. This paradigm shift has enormous clinical and financial ramifications, as MRA is safer, cheaper, and far more convenient for our patients than invasive angiography. Future magnetic resonance imaging research developments that are on the verge of being incorporated into clinical practice include real-time magnetic resonance fluoroscopy and endovascular therapeutic ability. It should therefore be incumbent upon the vascular and interventional community to embrace this powerful technology by collaborating and integrating with those physicians who possess the skills to perform high-quality magnetic resonance imaging. This article provides basic key fundamental concepts and protocol guidelines for state-of-the art MRA performance and elucidates future directions of this technology as it pertains to the interventional and vascular radiologist.


Cloning and characterization of the cDNA for human airway trypsin-like protease.
Previously we isolated a trypsin-like enzyme designated human airway trypsin-like protease from the sputum of patients with chronic airway diseases. This paper describes the cDNA cloning, characterization of the primary protein structure deduced from the cDNA, and gene expression of this enzyme in various human tissues. We obtained an entire 1517-base pair sequence of cDNA with an open reading frame encoding a polypeptide with 418-amino acid residues. The polypeptide consisted of a 232-residue catalytic region and a 186-residue noncatalytic region with a hydrophobic putative transmembrane domain near the NH2 terminus. The polypeptide was suggested to be a type II integral membrane protein in which the COOH-terminal catalytic region is extracellular. Therefore, this protein is thought to be synthesized as a membrane-bound precursor and to mature to a soluble and active protease by limited proteolysis. It showed 29-38% identity in the sequence of the catalytic region with human hepsin, enteropeptidase, acrosin, and mast cell tryptase. The noncatalytic region had little similarity to other known proteins. In Northern blot analysis a transcript of 1.9 kilobases was detectable most prominently in the trachea among 17 human tissues examined.


Combinatorial mixtures of organic solutes for improved liquid/liquid extraction of ions.
Biological systems routinely extract and organize ions in complex yet highly ordered and active systems. Much of this function is attributed to proteins, although recent evidence indicates aggregates of lipids are also capable of molecular recognition. Here we tested the hypothesis that combinatorial mixtures of organic solutes might lead to enhanced liquid/liquid extraction. We started with liquid oleic acid as an organic phase extracting copper ions from water and added a library of additives. By using Bayesian optimization to autonomously direct the combinatorial formulation, we discovered mixtures that enhanced the extraction performance. The main additive that improved the system was octylphosphonic acid. Interestingly, the optimal mixture has a significant improvement compared to this additive alone. This suggests that the combinations of organic solutes are better than using pure components in liquid/liquid extraction. Furthermore, we found that precipitation occurs in the samples showing better extraction efficiency, which has interesting material properties and potential for new types of supramolecular biosensors.


Liver failure after an uncovered TIPS procedure associated with hepatic infarction.
Transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective procedure for the treatment of complications of liver cirrhosis, such as refractory ascites, hepatic hydrothorax and refractory variceal bleeding. The aim of this paper is to describe a rare case of liver failure after a TIPS procedure. A 38-year-old diabetic male with Child-Pugh C liver cirrhosis due to chronic hepatitis C infection who had developed refractory ascites was scheduled for a TIPS procedure. Within 24 h following TIPS placement, the patient developed distributive shock, jaundice, persistentgrade 3 hepatic encephalopathy, severe coagulopathy and acute renal failure. He was treated with lactulose enemas, broad-spectrum antibiotics and blood-derived products. Laboratory data revealed a 100-fold increase in aminotransferases and a non-enhanced computed tomography showed an irregular hypodense area in the right posterior segment of the liver. Despite being initially being in a stable condition, the patient developed progressive liver failure and died 2 mo later. Hepatic infarction is an uncommon phenomenon after a TIPS procedure; however, it can greatly complicate the course of a disease in a patient with an already compromised liver function.


Copper sulfide nanoparticles with phospholipid-PEG coating for in vivo near-infrared photothermal cancer therapy.
In this work, small sizes of hydrophobic copper sulfide nanoparticles (CuS NPs, ∼3.8 nm in diameter) have been successfully prepared from the reaction of copper chloride with sodium diethyldithiocarbamate (SDEDTC) inside a heated oleylamine solution. These CuS NPs displayed strong absorption in the 700-1100 nm near-infrared (NIR) region. By coating CuS NPs with DSPE-PEG2000 on the surface, the as-synthesized CuS@DSPE-PEG NPs exhibited good water solubility, significant stability and biocompatibility, as well as excellent photothermal conversion effects upon exposure to an 808 nm laser. After intravenous administration to mice, the CuS@DSPE-PEG NPs were found to passively target to the tumor site, and tumor tissues could be ablated efficiency under laser irradiation. In addition, CuS@DSPE-PEG NPs do not show significant toxicity by histological and blood chemistry analysis, and can be effectively excreted via metabolism. Our results indicated that CuS@DSPE-PEG NPs can act as an ideal photothermal agent for cancer photothermal therapy.


Collaborative Goal-Setting Beliefs and Practices of Out-Patient Pediatric Physical Therapists Working in Saudi Arabia and the United States.
(1) identify and compare family-centered care (FCC) and collaborative goal-setting (CGS) beliefs and practices of out-patient pediatric physical therapists (PTs) in Saudi Arabia (SA) and the United States (US); (2) describe CGS approaches; and (3) determine the association between CGS practices and educational level, clinical experience, and FCC beliefs and practices. 87 PTs completed an online survey. Ninety percent of PTs believed in FCC to a great extent. PTs in the US rated their organization's family-centeredness and their own FCC application significantly higher than PTs in SA. PTs believed in CGS with parents (86%) and children (66%) to a great extent while 69% of PTs reported applying CGS with parents to a great extent compared to 39% with children. PTs in SA rated the importance of determining therapy goals by PTs significantly higher than PTs in the US. The most selected CGS strategy was asking about concerns and needs. Low to moderate significant positive associations were found between CGS practices and PTs belief of their organization's family-centeredness and their own FCC application. Similarities and differences were found between the two countries in FCC and CGS beliefs and practices. Organizational and individual FCC practices influence CGS practices.


Robotic assisted radical nephrectomy with Inferior vena cava tumor thrombus.
Surgery for renal cell carcinoma (RCC) with an inferior vena cava (IVC) tumor thrombus can be done via a robotic approach. While this approach is thought to minimize blood loss, it may still result in significant losses (1) and current publications indicate that it can require upwards of 3-day hospital stays (1, 2). However, innovative surgical techniques, such as the split and roll, may curtail this. The purpose of this video is to present the case and surgical technique of robotic assisted radical nephrectomy with IVC thrombectomy. The patient was a 77-year-old male found to have a right upper pole renal mass on CT urogram. On MRI (Figure 1), a renal mass and level II thrombus was seen. For this case, the Da Vinci Xi Intuitive robotic system was used, with four robotic 8-millimeter (mm) metallic trocars, two 5 mm assistant trocars, and one 12 mm air seal port. The split and roll technique were utilized to access the IVC and lumbar veins. This surgical method uses the adventitia of the IVC as a plane of dissection and safely identifies all branches/tributaries of the IVC to minimize the chance of vascular injury (3). Robotic console time was 150 minutes. The patient had an excellent outcome, with all tumor thrombus removed, less than 50cc of blood loss, and was discharged within 24 hours of the operation. The tumor pathology came back as papillary, high grade, and was stage pT3bN1. The robotic approach with split and roll technique is a great surgical option for urologists to consider in patients with RCC and a level I or II thrombus, which can minimize blood loss and expedite discharge.


The Use of Triphasic Bone Graft for the Treatment of Pediatric Bone Cysts: Experience at 2 Institutions.
Unicameral/aneurysmal bone cysts can lead to pain, fracture, and limb deformity. In this study, the authors evaluated the outcome of triphasic bone graft to treat unicameral/aneurysmal bone cysts. They retrospectively evaluated 41 immature patients from a prospectively enrolled cohort from 2 institutions treated from May 9, 2007, to November 1, 2014. Medical record review and evaluation of radiographs and computed tomography scans were performed. The authors characterized replacement of the material by normal bone or recurrent cyst at final follow-up. They recorded rates of fractures and complications after treatment. Twenty-nine patients were treated in Wisconsin, and 12 patients were treated in Florida. Average follow-up was 2.8 years. At follow-up, 13 of 41 patients had cyst recurrence. Three patients had fracture after initial treatment; 2 were treated surgically. Two of 9 patients with extraosseous bone graft had soft tissue swelling, and 1 required debridement. Complications did not differ by cyst type, location, sex, age, or use of internal fixation. For 27 patients with at least 2-year follow-up, percent fill of triphasic bone graft at initial surgery correlated with rate of recurrence at final follow-up: 15 of 27 patients with no cyst recurrence at final follow-up had a mean of 100% initial fill, and 12 of 27 with cyst recurrence at final follow-up had a mean of 90% initial fill (P=.048). Using triphasic bone graft for the treatment of unicameral/aneurysmal bone cysts, the authors observed a 7% rate of clinical recurrence (3 of 41 had fracture). Because this material has the potential to be locally inflammatory, efforts are needed to keep it within the bone. [Orthopedics. 2018; 41(5):e705-e712.].


Impact of pulmonary regurgitation and age at surgical repair on textural and functional right ventricular myocardial properties in patients with tetralogy of Fallot.
The aim of this study was to identify non-invasively the potential impact of pulmonary regurgitation and age at surgical repair on the right ventricular (RV) textural and functional myocardial properties in patients operated on for tetralogy of Fallot (TOF). We assessed the average intensity (Int.(1B)) and the cyclic variation (CV(IB)) of the echocardiographic backscatter curve in 30 TOF patients (mean age 16.2 +/- 8.3 years), who had undergone corrective surgery (mean age at repair 3.2 +/- 2.6 years, range 0.2-11 years). They were divided into three age- and body surface area (BSA)-matched subgroups according to the results of the surgical repair: 12 patients had no significant postsurgical sequelae (group I), 12 patients had isolated moderate-severe pulmonary regurgitation (group II), and 6 patients had pulmonary regurgitation associated with significant (> 30 mmHg) RV outflow tract obstruction (group III). In addition, 30 age-, sex- and BSA-matched normal subjects were identified as the control group. In our study population, CV(IB) was lower (7.86 +/- 2.5 vs 10.6 +/- 1.4 dB, p < 0.001) and Int.IB higher (-18.6 +/- 4.1 vs -21 +/- 2.8 dB, p = 0.01) compared to the control group. Comparison between the control group and each subgroup of TOF patients showed: a) comparable values of CV(IB) and Int.(IB) in group I (10.6 +/- 1.4 vs 9.4 +/- 2.3 dB, p = 0.07; and -21 +/- 2.8 vs -21.4 +/- 2.3 dB, p = 0.7, respectively); b) Int.(IB) was significantly different only in group III (-21 +/- 2.8 vs -13.3 +/- 4.6 dB, p < 0.0001), c) CV(IB) was different either in group II or III (10.6 +/- 1.4 vs 7.42 +/- 2, p < 0.001; and 10.6 +/- 1.4 vs 5.56 +/- 1.8, p < 0.001, respectively). In addition, comparison of integrated backscatter indexes among the TOF subgroups revealed significant differences of CV(IB) between group I and II (9.4 +/- 2.4 vs 7.4 +/- 2, p = 0.03) and between group I and III (9.4 +/- 2.4 vs 5.56 +/- 1.8, p = 0.004), and of Int.(IB) between group I and III (-21.4 +/- 2.3 vs -13.3 +/- 4.66, p < 0.001) and between group II and III (-21.4 +/- 2.3 vs -18.6 +/- 2.8, p = 0.006). Group III patients, who had the most significant RV dilation, expressed as the ratio between RV and left ventricular end-diastolic diameter (0.55 +/- 0.8) compared to group II (0.67 +/- 0.11, p = 0.038) and group I (0.55 +/- 0.87, p < 0.001), showed the lowest values of CV(IB) (5.56 +/- 1.8 dB) and the highest values of Int.(IB) (-13.3 +/- 4.6 dB) Finally, in our study population, both the degree of RV dilation and the age at surgical repair significantly correlated with Int.(IB) (r = 0.49 and r = 0.4, p = 0.06 and p = 0.033, respectively) and inversely correlated with CV(IB) (r = -0.55 and r = -0.53, p = 0.002 and p = 0.003, respectively). In patients operated on for TOF: a) integrated backscatter analysis may identify patients with significant RV myocardial abnormalities related to postsurgical sequelae; b) residual pulmonary regurgitation, particularly if associated with pulmonary stenosis, appears to affect RV myocardial properties; c) an earlier repair of TOF may result in better preservation of myocardial characteristics.


Heteroleptic Cu(I) bis-diimine complexes of 6,6'-dimesityl-2,2'-bipyridine: a structural, theoretical and spectroscopic study.
A series of heteroleptic Cu(I) complexes containing 6,6'-dimesityl-2,2'-bipyridine and phenanthroline-, bipyridine-, and biquinoline-based ligands is studied. The HETPHEN strategy is utilized to synthesize the heteroleptic complexes, which are stable in solution. The X-ray crystal structures of the complexes are presented; the solid-state four-coordinate Cu(I) geometries are quantified by using the τ4 parameter. A feature of the crystal structures is the intramolecular π-stacking between the mesityl ring(s) and the diimine ligand; the phen-based complexes exhibit stacking between the phen ligand and one of the mesityl rings, creating a "Pac-Man" motif. On the other hand, the bpy-based complexes show different types of packing interaction, with both mesityl rings "clamping down" on the bpy based ligand to give π-stacking. Cyclic voltammetry is used to examine the redox chemistry of the complexes. The most positive potentials for the oxidation process are observed for the complexes with bulky substituents ortho to the coordination nitrogens atoms, i.e., 2,9-dimethyl-1,10-phenanthroline and 6,6'-dibromo-2,2'-bipyridine. The Cu(I) MLCT transitions of the complexes are investigated by resonance Raman spectroscopy in concert with TD-DFT calculations. The resonance Raman spectra of complexes containing substituted biquinolines are straightforward, in that vibrational bands of the biquinoline-based ligand are selectively enhanced over bpy(Mes)2 bands. This is consistent with the purple color of the complexes, due to the lower energy of the biquinoline-based LUMO compared to the bpy(Mes)2 LUMO. All the phen- and bpy-based complexes show enhancement of bpy(Mes)2 bands.


Wheelchair basketball, health, competitive analysis, and performance advantage: a review of theory and evidence.
The purpose of this study was to review the various risks and benefits of wheelchair basketball (WB) and explore some of the research which outlines factors that influence WB player performance and conditioning. WB offers several physical and psychological advantages. Physically, it can improve muscle strength, endurance, and cardiovascular fitness while decreasing the prevalence of chronic physical disorders. From a psychological standpoint, WB has been shown to alleviate anxiety and feelings of depression while also creating and improving social relationships. Despite the many benefits, WB can cause injuries, particularly in the upper extremities, and preventative measures should be employed. WB necessitates intense intermittent efforts and athletes must maintain excellent cardiovascular fitness, strength, and muscular endurance. Healthy sleeping patterns have also been shown to improve performance in WB players. Wheelchair mobility and biomechanical variables as well as wheelchair size and weight appear to be critical success elements in WB. WB can be a powerful tool for coaches and therapists to boost the physical and emotional health of individuals with disabilities and motivate them to participate in team-based sport.


The impact of workplace risk factors on the occurrence of neck and upper limb pain: a general population study.
Work-related neck and upper limb pain has mainly been studied in specific occupational groups, and little is known about its impact in the general population. The objectives of this study were to estimate the prevalence and population impact of work-related neck and upper limb pain. A cross-sectional survey was conducted of 10,000 adults in North Staffordshire, UK, in which there is a common local manual industry. The primary outcome measure was presence or absence of neck and upper limb pain. Participants were asked to give details of up to five recent jobs, and to report exposure to six work activities involving the neck or upper limbs. Psychosocial measures included job control, demand and support. Odds ratios (ORs) and population attributable fractions were calculated for these risk factors. The age-standardized one-month period prevalence of neck and upper limb pain was 44%. There were significant independent associations between neck and upper limb pain and: repeated lifting of heavy objects (OR = 1.4); prolonged bending of neck (OR = 2.0); working with arms at/above shoulder height (OR = 1.3); little job control (OR = 1.6); and little supervisor support (OR = 1.3). The population attributable fractions were 0.24 (24%) for exposure to work activities and 0.12 (12%) for exposure to psychosocial factors. Neck and upper limb pain is associated with both physical and psychosocial factors in the work environment. Inferences of cause-and-effect from cross-sectional studies must be made with caution; nonetheless, our findings suggest that modification of the work environment might prevent up to one in three of cases of neck and upper limb pain in the general population, depending on current exposures to occupational risk.


Revival of nifedipine, a dihydropyridine-based calcium blocker.
A recent analysis by the Blood Pressure Lowering Treatment Trialists' Collaboration revealed that any commonly-used blood pressure (BP)-lowering regimen reduced the risk of total major cardiovascular events, and larger reductions in BP produced larger reductions in the risk. These observations suggest that most of the differences among treatment regimens in their effects on cardiovascular outcomes could be explained by the differences in achieved BP level. However, it may also be true that some treatment regimen is superior or inferior to others with regard to the risk reduction of cardiovascular events. Indeed, the data from dihydropyridine-based calcium antagonist (DHP) trails are consistent in that they could not protect against new-onset heart failure or progression of renal disease in patients with left-ventricular systolic dysfunction or overt proteinuria, respectively. However, a multicenter, randomized, placebo-controlled, double-blind ACTION trial, which compared the effect of long-acting nifedipine or placebo on mortality and cardiovascular morbidity in patients with stable angina, revealed that nifedipine reduced the risk for new-onset overt heart failure by 29%. Further, an open-label, randomized prospective J-MIND trial, which compared the effect of long-acting nifedipine or enalapril, an angiotensin-converting enzyme inhibitor on onset and progression of nephropathy in hypertensive patients with type 2 diabetes, showed that long-acting nifedipine had an equipotent reoprotective effect on diabetic nephropathy. In this paper, we would like to propose our hypothesis that nifedipine may be unique and superior in its effects on heart failure and proteinuria compared with various DHPs. For ensuring our hypothesis, the following clinical issues would be addressed. Does nifedipine treatment alone decrease the progression of renal disease with overt proteinuria? If these answers are yes, are these beneficial effects of nifedipine superior to that of other DHPs with equihypotensive properties? Does nifedipine treatment also reduce oxidative stress markers? Are these unique effects of nifedipine correlated with its anti-oxidative properties? These prospective studies will provide further valuable information whether nifedipine may be a preferred DHP to achieve BP goals in hypertensive patients with systolic dysfunction or overt proteinuria.


Stress-sensitive dynamics of miRNAs and Elba1 in Drosophila embryogenesis.
Early-life stress can result in life-long effects that impact adult health and disease risk, but little is known about how such programming is established and maintained. Here, we show that such epigenetic memories can be initiated in the Drosophila embryo before the major wave of zygotic transcription, and higher-order chromatin structures are established. An early short heat shock results in elevated levels of maternal miRNA and reduced levels of a subgroup of zygotic genes in stage 5 embryos. Using a Dicer-1 mutant, we show that the stress-induced decrease in one of these genes, the insulator-binding factor Elba1, is dependent on functional miRNA biogenesis. Reduction in Elba1 correlates with the upregulation of early developmental genes and promotes a sustained weakening of heterochromatin in the adult fly as indicated by an increased expression of the PEV wm4h reporter. We propose that maternal miRNAs, retained in response to an early embryonic heat shock, shape the subsequent de novo heterochromatin establishment that occurs during early development via direct or indirect regulation of some of the earliest expressed genes, including Elba1.


Crucial role of macrophages in matrix metalloproteinase-mediated cartilage destruction during experimental osteoarthritis: involvement of matrix metalloproteinase 3.
To explore the involvement of synovial macrophages in early cartilage damage in osteoarthritis (OA), and to identify the role of matrix metalloproteinase 3 (MMP-3) in the pathology of early and late OA. The role of synovial macrophages in MMP-mediated damage in OA was studied by depleting synovial macrophages prior to elicitation of a collagenase-induced instability model of OA. The expression of MMP in synovium and cartilage was monitored using TaqMan analysis. In spontaneous and induced OA, cartilage pathology was scored in MMP-3-knockout mice and control mice, by histologic assessment and VDIPEN staining. On day 14 following induction of OA, MMP-mediated neoepitopes were detected in cartilage from mice with mild experimental OA (mean +/- SD positively stained surface area 20 +/- 3.2%). Remarkably, by depleting synovial macrophages prior to induction of OA, the generation of MMP-induced neoepitopes was largely prevented (mean +/- SD positively stained surface area 5 +/- 1%; P< 0.001), indicating an important role for synovial macrophages in the occurrence of MMP-mediated cartilage damage. We observed a strong decrease in MMP-3 and MMP-9 expression in synovial but not cartilage tissue in macrophage-depleted joints. Among 2-year-old mice, spontaneous OA-like changes in the lining layer were significantly decreased in MMP-3-knockout mice compared with control mice. Even more striking was the 67% reduction in the occurrence of severe cartilage damage in MMP-3-knockout mice. In addition, MMP-mediated VDIPEN expression was significantly decreased, indicating reduced MMP-mediated cartilage breakdown. The results of this study prove that MMP-3 is involved in the generation of severe cartilage damage in murine OA. Synovial macrophages are crucial in early MMP activity and appear to mediate MMP production in synovium rather than cartilage.


Enclosing a pen to improve response rate to postal questionnaire: an embedded randomised controlled trial.
Background: Poor response to questionnaires collecting outcome data in randomised controlled trials (RCTs) can affect the validity of trial results. The aim of this study within a trial (SWAT) was to evaluate the effectiveness of including a pen with a follow-up postal questionnaire on response rate. Methods: A two-armed RCT was embedded within SSHeW (Stopping Slips among Healthcare Workers), a trial of slip-resistant footwear to reduce slips in NHS staff. Participants were randomised 1:1 to receive a pen or no pen with their follow-up questionnaire. The primary outcome was the proportion of participants who returned the questionnaire. Secondary outcomes were: time to response, completeness of response, and whether a postal reminder notice was required. Data were analysed using logistic regression, linear regression and Cox proportional hazards regression. Results: Overall, 1466 SSHEW trial participants were randomised into the SWAT. In total, 13 withdrew from the host trial before they were due to be sent their follow-up questionnaire, 728 participants received a pen with their questionnaire, and 725 did not receive a pen. A questionnaire was returned from 67.7% of the pen group and 64.7% of the group who did not receive a pen. There was no significant difference in return rates between the two groups (OR 1.15, 95% CI 0.92 to 1.43, p=0.22), nor level of completeness of the questionnaires (AMD -0.01, 95% CI 0.06 to 0.05, p=0.77). There was weak evidence of a reduction in the proportion of participants requiring a reminder and in time to response in the pen group. Conclusion: Inclusion of a pen with the follow-up postal questionnaire sent to participants in the SSHeW trial did not statistically significantly increase the response rate. These results add to the body of evidence around improving response rates in trials. Trial registration: ISRCTN 33051393 (for SSHEW). Registered on 14/03/2017.


Indefinite islet allograft survival in mice after a short course of treatment with anti-CD45 monoclonal antibodies.
Although islet cell transplantation is considered an ideal form of endocrine replacement for type I diabetes, clinical application in humans is still not feasible. New immunosuppressive strategies are clearly needed to control inexorable rejection. CD45 is a family of transmembrane protein tyrosine phosphatases critically involved in the regulation of lymphocyte activation signals. Anti-CD45RB monoclonal antibody can prevent rejection of murine renal allografts. Here, we examine the consequences of targeting CD45 in murine islet cell transplantation. Diabetic mice recipients received islet allografts under the kidney capsule and were divided into seven groups. Recipients received no treatment (controls) or anti-CD45RB monoclonal antibody (mAb; MB23G2 or C363.16A) at different dosages and treatment intervals. All untreated control animals lost islet function, becoming hyperglycemic within 10-17 days after transplantation. Animals treated with either anti-CD45RB mAb showed a significant prolongation of islet allograft survival when compared with controls. Anti-CD45RB MB23G2 at 100 microg/day, given on days -1, 0, and 5 was particularly effective, inducing indefinite islet allograft survival in 60% of recipients. These results indicate that anti-CD45 mAbs are potent immunomodulatory agents, able to sustain indefinite islet allograft function after a short treatment course in the highly immunogenic model of islet transplantation.


Chloroquine causes lysosomal dysfunction in neural retina and RPE: implications for retinopathy.
Chronic use of chloroquine has been shown to induce numerous pathophysiological defects in the retina. This drug has the ability to alter pH of intracellular compartments and lysosomal function of the retinal pigment epithelium (RPE) and retinal neurons may constitute the basis of chloroquine retinopathy. The aim of the current study was to investigate pathogenic alterations in retinal cells continuously exposed to chloroquine using appropriate in vivo and in vitro models. Male hooded Lister rats were implanted with osmotic mini pumps which released chloroquine continuously over a period of seven days. The eyes were processed for electron microscopy and ultrastructural abnormalities determined in the neural retina and quantified using stereology in the retinal pigment epithelium (RPE). RPE were also exposed to chloroquine in vitro and lysosomal pH changes were investigated using a pH sensitive probe. Degradative capacity was also analysed using FITC labeled rod outer segments (ROS). Chloroquine-treated animals displayed several ultrastructural abnormalities including numerous membranous cytoplasmic bodies (MCBs) in retinal neurons. Cone photoreceptors displayed numerous MCBs although rods did not. The RPE of the treated groups all showed significantly higher numbers of lysosomal associated organelles (LAO) than the control group (p < 0.001). The in vitro experiments demonstrated chloroquine-mediated rises in lysosomal pH and an increase in lysosome/phagosome accumulation of ROS in the chloroquine treated group (p < 0.01). The current study demonstrates that chloroquine disrupts lysosomal function in retinal neurons and RPE. The evidence presented provides a clear pathogenic basis for the functional defects experienced by patients with chloroquine retinopathy.


Comparative Effects of Energy-Related Saline Wastewaters and Sodium Chloride on Hatching, Survival, and Fitness-Associated Traits of Two Amphibian Species.
Salinity (sodium chloride [NaCl]) is a prevalent and persistent contaminant that negatively affects freshwater ecosystems. Although most studies focus on effects of salinity from road salts (primarily NaCl), high-salinity wastewaters from energy extraction (wastewaters) could be more harmful because they contain NaCl and other toxic components. Many amphibians are sensitive to salinity, and their eggs are thought to be the most sensitive life-history stage. However, there are few investigations with salinity that include eggs and larvae sequentially in long-term exposures. We investigated the relative effects of wastewaters from a large energy reserve, the Williston Basin (USA), and NaCl on northern leopard (Rana pipiens) and boreal chorus (Pseudacris maculata) frogs. We exposed eggs and tracked responses through larval stages (for 24 days). Wastewaters and NaCl caused similar reductions in hatching and larval survival, growth, development, and activity, while also increasing deformities. Chorus frog eggs and larvae were more sensitive to salinity than leopard frogs, suggesting species-specific responses. Contrary to previous studies, eggs of both species were less sensitive to salinity than larvae. Our ecologically relevant exposures suggest that accumulating effects can reduce survival relative to starting experiments with unexposed larvae. Alternatively, egg casings of some species may provide some protection against salinity. Notably, effects of wastewaters on amphibians were predominantly due to NaCl rather than other components. Therefore, findings from studies with other sources of increased salinity (e.g., road salts) could guide management of wastewater-contaminated ecosystems, and vice versa, to mitigate effects of salinization. Environ Toxicol Chem 2021;40:3137-3147. © 2021 SETAC.


Noninvasive prenatal diagnosis for hemoglobin Bart's hydrops fetalis.
Hemoglobin (Hb) Bart's hydrops fetalis, the most severe thalassemic disease, occurs from homozygosity of alpha-thalassemia 1. Deletion of all 4 alpha-globin genes (- -/- -) in this condition results in the absence of alpha-globin chains, and the physiologic dysfunction of Hb Bart's (gamma4) leads to lethality, either in utero or soon after birth. The best strategy for prevention and control of the disease is prenatal diagnosis in the mothers at risk. However, conventional prenatal diagnosis involves invasive procedures that may result in infection or abortion. In this study, a simple technique was developed to identify the presence or absence of alpha-globin chains in fetal nucleated red blood cells (NRBCs) enriched from maternal blood. Mononuclear cells including fetal NRBCs were isolated from maternal blood at 10 to 26 weeks of pregnancy by density-gradient centrifugation. Immunomagnetic separation with anti-CD71 antibody was employed to enrich fetal NRBCs, whose numbers increase with increasing gestational age. For the unaffected fetus, fetal NRBCs were detected by immunofluorescence microscopy after staining with rabbit antihuman alpha-globin antibody. In contrast, fetal red blood cells homozygous for alpha-thalassemia 1, which were identified from their size and morphology, did not stain for alpha-globin antibody. In this study, 3 affected fetuses were detected from 10 pregnancies at risk of Hb Bart's hydrops fetalis, and the results were confirmed by DNA analysis. In the remaining cases, all fetal NRBCs were positive for immunofluorescence staining. DNA analysis revealed that 2 cases were normal, 1 was heterozygous for alpha-thalassemia 2, and the other 4 cases were heterozygous for alpha-thalassemia 1.


Comparison of canine single and sequential bilateral lung transplant model for lung preservation study.
The purpose of this study was to compare canine sequential bilateral lung transplantation (SBLT) with left single lung transplant (LSLT) models. After 24 hours of lung preservation with low potassium/dextran glucose (LPDG) solution, seven SBLT procedures were performed using mongrel dogs. The comparative group including nine cases of LSLT. After completion of each transplant, the dogs were maintained on a ventilator for 3 hours. Thereafter serial hemodynamics were evaluated with recipients with chest X-ray, computed tomography, and lung perfusion scan checked at 2 hours after transplantation. Pathological evaluations were also performed. Five of seven SBLT successfully completed the whole assessment, all LSLT survived. In SBLT, pulmonary arterial pressure and pulmonary vascular resistance were significantly elevated, but recovered 3 hours after reperfusion. The ultrastructural aspects of alveolae and pulmonary artery endothelium showed a reversible mild injury 24 hours after lung preservation and reperfusion. The present study suggests that the canine SBLT model using LPDG solution provides an excellent preservation effect and is more physiological as the dog is completely dependent on the function of the transplanted lung.


Femtosecond Laser-Assisted Keratolimbal Allograft Transplantation for the Treatment of Total Limbal Stem Cell Deficiency.
To investigate the surgical procedure and therapeutic efficacy of femtosecond (FS) laser-assisted keratolimbal allograft (KLAL) transplantation in the treatment of eyes with total limbal stem cell deficiency. Ten eyes from 10 patients who underwent FS laser-assisted KLAL transplantation were enrolled. The best-corrected visual acuity (BCVA), ocular surface stability, corneal transparency, and postoperative complications were recorded. The keratolimbal grafts prepared using the FS laser were even in thickness and width. After the surgery, glucocorticoid and tacrolimus eye drops were administered locally to the eyes with concentration gradients, and a medium dose was prescribed for maintenance. Within the mean follow-up period of 16.8 ± 7.3 months, 9 of 10 eyes (90.0%) maintained a stable ocular surface and showed significant improvements in corneal transparency and BCVA. Persistent corneal edema only occurred in one eye because of repeated epithelial defects, and the BCVA of this eye did not improve. Confocal microscopy revealed activated dendritic cells in the Bowman membrane at the limbus, but they were always low in density with small dendritic processes. No acute immune rejection, cataracts, or elevation of intraocular pressure were detected. The FS laser-assisted KLAL technique can produce ring-shaped grafts with an even depth and width, resulting in a stable ocular surface and good visual prognosis. After surgery, glucocorticoids and potent immunosuppressive eye drops were administered locally with concentration gradients and effectively inhibited acute immune rejection.


Acute diverticulitis in the young adult.
Seven cases of acute diverticulitis in patients 35 years of age or younger are presented. This disease is not rare in young adults. There seems to be a higher incidence in males and an increased need for surgical intervention when younger individuals are affected. The barium enema is useful in confirming the diagnosis.


Calcineurin signaling and PGC-1alpha expression are suppressed during muscle atrophy due to diabetes.
PGC-1alpha is a transcriptional coactivator that controls energy homeostasis through regulation of glucose and oxidative metabolism. Both PGC-1alpha expression and oxidative capacity are decreased in skeletal muscle of patients and animals undergoing atrophy, suggesting that PGC-1alpha participates in the regulation of muscle mass. PGC-1alpha gene expression is controlled by calcium- and cAMP-sensitive pathways. However, the mechanism regulating PGC-1alpha in skeletal muscle during atrophy remains unclear. Therefore, we examined the mechanism responsible for decreased PGC-1alpha expression using a rodent streptozotocin (STZ) model of chronic diabetes and atrophy. After 21days, the levels of PGC-1alpha protein and mRNA were decreased. We examined the activation state of CREB, a potent activator of PGC-1alpha transcription, and found that phospho-CREB was paradoxically high in muscle of STZ-rats, suggesting that the cAMP pathway was not involved in PGC-1alpha regulation. In contrast, expression of calcineurin (Cn), a calcium-dependent phosphatase, was suppressed in the same muscles. PGC-1alpha expression is regulated by two Cn substrates, MEF2 and NFATc. Therefore, we examined MEF2 and NFATc activity in muscles from STZ-rats. Target genes MRF4 and MCIP1.4 mRNAs were both significantly reduced, consistent with reduced Cn signaling. Moreover, levels of MRF4, MCIP1.4, and PGC-1alpha were also decreased in muscles of CnAalpha-/- and CnAbeta-/- mice without diabetes indicating that decreased Cn signaling, rather than changes in other calcium- or cAMP-sensitive pathways, were responsible for decreased PGC-1alpha expression. These findings demonstrate that Cn activity is a major determinant of PGC-1alpha expression in skeletal muscle during diabetes and possibly other conditions associated with loss of muscle mass.


[Spatial epidemiological study on malaria epidemics in Hainan province].
To better understand the characteristics of spatial distribution of malaria epidemics in Hainan province and to explore the relationship between malaria epidemics and environmental factors, as well to develop prediction model on malaria epidemics. Data on Malaria and meteorological factors were collected in all 19 counties in Hainan province from May to Oct., 2000, and the proportion of land use types of these counties in this period were extracted from digital map of land use in Hainan province. Land surface temperatures (LST) were extracted from MODIS images and elevations of these counties were extracted from DEM of Hainan province. The coefficients of correlation of malaria incidences and these environmental factors were then calculated with SPSS 13.0, and negative binomial regression analysis were done using SAS 9.0. The incidence of malaria showed (1) positive correlations to elevation, proportion of forest land area and grassland area; (2) negative correlations to the proportion of cultivated area, urban and rural residents and to industrial enterprise area, LST; (3) no correlations to meteorological factors, proportion of water area, and unemployed land area. The prediction model of malaria which came from negative binomial regression analysis was: I (monthly, unit: 1/1,000,000) = exp (-1.672-0.399xLST). Spatial distribution of malaria epidemics was associated with some environmental factors, and prediction model of malaria epidemic could be developed with indexes which extracted from satellite remote sensing images.


Occurrence of Stolbur Phytoplasma Disease in Spreading Type Petunia hybrida Cultivars in Korea.
In January 2012, spreading type petunia cv. Wave Pink plants showing an abnormal growth habit of sprouting unusual multiple plantlets from the lateral buds were collected from a greenhouse in Gwacheon, Gyeonggi Province, Korea. The presence of phytoplasma was investigated using PCR with the primer pairs P1/P6, and R16F1/R1 for nested-PCR. In the nested PCR, 1,096 bp PCR products were obtained, and through sequencing 12 Pet-Stol isolates were identified. Comparison of the nucleotide sequences of 16S rRNA gene of the 12 Pet-Stol isolates with other phytoplasmas belonging to aster yellows or Stolbur showed that Pet-Stol isolates were members of Stolbur. The presence of phytoplasma in petunia was also confirmed by microscopic observation of the pathogens. In this study, Stolbur phytoplasma was identified from spreading type petunia cultivars by sequence analysis of 16S rRNA gene of phytoplasma and microscopic observation of phytoplasma bodies. This is the first report of Stolbur phytoplasma in commercial Petunia hybrida cultivars.


[Absorption of enzymatic protein hydrolysates and equimolar amino acid mixtures in the perfused small intestine of the rat].
Casein, wheat gluten or field-bean protein isolate (vicia faba) was hydrolyzed enzymatically by trypsin or thermitase (proteinase from Thermoactinomyces vulgaris). The degree of splitting of the protein peptide bounds was, resp., 18% or 30% for casein, 8% or 30% for wheat gluten and 16% or 29% for the field-bean protein isolate. The peptide pattern of the protein hydrolysates was measured by gel chromatography. The absorption of the enzymatic protein hydrolysates was compared with the absorption of the equimolar mixtures of free amino acids by perfusion of the distal or proximal part of the small intestine of nonanaesthesized rats. The absorption was measured on the basis of the amino acid disappearance from the perfused part of the small intestine and expressed as absorption of the total amino acids, of each single amino acid and as coefficient of variation of amino acid absorption. There are no differences in the total amino acid absorption of the tryptic casein hydrolysate and the three thermitatic protein hydrolysates compared with their corresponding mixtures of free amino acids. The absorption is decreased in case of larger oligopeptides. Their preceding mucosal hydrolysis is slower than the absorption of the splitting products. This is true for tryptic hydrolysates of wheat gluten and field-bean protein. The absorption patterns of the single amino acids are different for protein hydrolysates compared with their equimolar mixtures of amino acids in case of a same total absorption, too. The coefficient of variation is low (more equal amino acid absorption) in hydrolysates consisting of a homogeneous mixture of low molecular weight peptides. It is more increased in mixtures of free amino acids or in hydrolysates containing longer-chain peptides.


Medium-chain and long-chain fatty acids have different postabsorptive fates in Atlantic salmon.
An increasingly larger proportion of the oils used in diets for farmed fish are plant derived and rapeseed oil is most commonly used. Despite high dietary lipid levels and a marked change in lipid composition, the transport and metabolic fate of absorbed fatty acids is not fully understood in teleost fish. The main purpose of this study was to trace the postabsorptive metabolic fate of 2 fatty acids of different chain length: oleic acid [(3)H-18:1(n-9)], constituting 70% of fatty acids in rapeseed oil, and the medium-chain decanoic acid [(14)C-10:0], which does not require carrier molecules for membrane passage. The fatty acids and their metabolites were traced in portal and peripheral blood, liver, heart, skeletal muscle, and visceral adipose tissue at time intervals from 3 to 48 h after feeding. The portal vein was the primary transport route for both 10:0 and 18:1(n-9) from the intestine to the liver the first 6 h after feed intake. From 12 to 48 h, the peripheral route became increasingly more important. The study also indicates a possible direct transport route of fatty acids from the intestine to the surrounding viscera. Our data demonstrate that whereas 18:1(n-9) is primarily deposited as TG in skeletal muscle and visceral adipose tissue, 10:0 is used by the heart and skeletal muscle as a source for rapid energy production.


Justice for children: the child as organ donor.
I argue that parents ought to be allowed to authorize their child's participation as an organ donor for another family member. I introduce a model of decisionmaking for children in intimate families which I call Constrained Parental Autonomy. This model permits wide parental discretion which is constrained absolutely by a broadly defined principle of respect for persons. In general, parental authorization alone is sufficient but I argue that the respect for persons constraint prevents certain donations and requires the child's assent for other donations. I also consider two controversial implications of the application of this model: the objection that the model does not respect the child's right to bodily integrity, and the objection that the model does not and is unable to address intrafamilial disagreement.


Endoscopic percutaneous dilatational tracheotomy: a prospective evaluation of 500 consecutive cases.
An evaluation of 500 adult, intubated, intensive care unit patients undergoing endoscopic percutaneous tracheotomy using the multiple and single dilator techniques was conducted to assess the feasibility and safety of the procedure as it compares with surgical tracheotomy. Endoscopy was used in all cases and evaluated as an added safety measure in reducing complications. A prospective evaluation of endoscopic percutaneous dilatational tracheotomy in 500 consecutive adult, intubated intensive care unit patients. Between 1990 and 2003, endoscopically guided percutaneous dilatational tracheotomy (PDT) was performed in 500 consecutive adult, intubated patients in the intensive care units (ICU) of three tertiary care adult hospitals. The first 191 patients underwent PDT using the Ciaglia Percutaneous Tracheostomy Introducer Kit (Cook Critical Care Inc., Bloomington, Indiana) and in the remaining 309 patients the Ciaglia Blue Rhino Single Dilator Kit (Cook Critical Care Inc., Bloomington, Indiana) was used. The procedure was contraindicated in the following situations: 1) children, 2) unprotected airway, 3) emergencies, 4) presence of a midline neck mass, 5) inability to palpate the cricoid cartilage, and 6) uncorrectable coagulopathy. The following parameters were recorded preoperatively: age, sex, diagnosis, American Society of Anesthesia (ASA) class, body mass index (BMI), and number of days intubated. Recorded hematologic parameters included hemoglobin (Hgb), platelets, prothrombin time (PT), partial thromboplastin time (PTT), and the international normalized ratio (INR) since it became available in 1998. All patients were ventilated on 100% oxygen and vital signs were continuously monitored. Tracheotomy was carried out under continuous endoscopic guidance using a series of graduated dilators in the first 191 cases, and a single, tapered dilator in the remaining 309 patients. The preoperative data on each patient, along with the type of dilator used, the size of the tube, the intraoperative and postoperative complications, and blood loss information were recorded prospectively and maintained in a computer spreadsheet. Univariate analyses were used in each group separately for each type of dilator to assess the risks of a complication within subgroups defined by each parameter/characteristic, and the statistical significance assessed with a chi test, or Fisher exact test. The total complication rate was 9.2% (13.6% in the multiple dilator group, and 6.5% in the single dilator group), with more than half of these considered minor. Overall, the two most common complications were oxygen desaturation in 14 cases and bleeding in 12 cases. The absence of serious complications such as pneumothorax and pneumomediastinum are attributable to the use of bronchoscopy. There was no significant association between the rate of complications and age, gender, ASA, weeks intubated, tracheostomy tube size, Hgb levels, platelets, PT, PTT, or INR. There was a statistically significant relationship between experience and the likelihood of complications in the multiple dilator group (P < .0001), with a higher rate of complications in the first 30 patients (40%) compared with 8.7% in the remaining 161 patients. This relationship did not exist for the first 30 patients in the single dilator group. Patients with a BMI of 30 or higher experienced a significantly greater (P < .05) number of complications (15%), compared with an 8% complication rate in patients with a BMI of less than 30. This risk was even more significant for patients with a BMI of 30 or greater who were also in ASA class 4 (11/56 or 20%) (P < .02). Endoscopic PDT is associated with a low complication rate and is at least as safe as surgical tracheotomy in the ICU setting. Bronchoscopy significantly decreases the incidence of complications and should be used routinely. While embraced by critical care physicians, endoscopic PDT has been infrequently performed by otolaryngologists. As the airway experts, otolaryngologists are in the best position to learn and teach the procedure as it should be done.


An antenatal diagnosis: Congenital high airway obstruction.
Congenital high airway obstruction (CHAOS) is a rare lethal fetal malformation characterised by obstruction to the fetal upper airway, which can be partial or complete. Antenatal diagnosis of CHAOS is important due to recent management options. Diagnosis is made with secondary changes such as hyperechoic enlarged lungs resulting in mediastinal compression, ascites, hydrops, flattened or everted diaphragms and dilated distal airways. We reported a case of CHAOS, antenatally on ultrasonography (USG) at 20 weeks of gestation.


Advertising Click-Through Rate Prediction Based on CNN-LSTM Neural Network.
In the era of big data information, how to effectively predict and analyze the click-through rate of information advertising is the key for enterprises in various fields to seek returns. The point rate prediction of advertising is one of the core contents of advertising calculation. The traditional shallow prediction model cannot meet the nonlinear relationship of data processing, and the manual processing of data information extraction method is very resource consuming. To solve the above problems, this paper proposes a CNN-LSTM (convolutional neural network-long short-term memory) convolution hybrid neural network algorithm to predict the click-through rate of advertisements. According to the neural network algorithm, the prediction model is constructed, and the effective features are extracted in the process of model establishment, and the prediction analysis is carried out according to the simplified LSTM neural network time serialization features. CNN convolution neural network is used to train the prediction model. This paper analyzes the characteristics of traditional prediction methods and the corresponding solutions and carries out feature learning and prediction model construction for advertising click-through rate prediction. Then, the unknown behavior of advertising users is judged and predicted. The results show that, compared with the single structure network of traditional prediction model, the prediction effect based on CNN-LSTM neural network algorithm has higher accuracy.


Quantitative evaluation of sensory nerve endings in hypertrophy of labia minora pudendi in women.
The authors studied the types of sensory nerve endings in hypertrophic labia minora pudendi in women aged between 18 and 69. The nervous tissue was impregnated with silver nitrate by Lavrentyev's modification of the Bielschowski-Gross method. The sensory nerve endings were divided into the following groups: free endings and arborizations, spray-like endings, seven types of clew-like nerve endings, and Pacinian corpuscles. It is the clew-like endings that absolutely predominate, they were 2,027 in number. The arborizations and spray-like endings found were 105 in number and only 4 of Pacinian corpuscles were found. As compared with normal labia there are no principal differences among the types of sensory nerve endings. The main difference consists in the rate of occurrence (89.6 as against 57.8) and in the thickness of the capsule, while the nerve clew proper does not grow in diameter. Therefore, we are of theopinion that a more frequent occurrence and larger size of the capsule is associated with local changes in the organ (especially with hypertrophy of the connective tissue). We observed no differences due to age either in the occurrence of the individual types or in the thickness of the capsule. Great individual variability in both directions was seen. The findings corroborated again the rare occurrence of meissner's endings in the labia minora in woman. Therefore it may be assumed that it is rather a random finding and that it is a type of clew-like nerve ending. Finally, we presume that the individually varying rate of occurrence of the nerve endings in the external genitals could also affect general sensitivity in this region, including sexual sensitivity.


Hypoglycemic Bioactivity of Novel Eco-Friendly Carbon Dots Derived from Traditional Chinese Medicine.
Although recent research on intrinsic bioactivities of carbon dots is expanding, it is focused on basic aspects, which creates the need for broadening our knowledge about carbon dots to expand their uses in biomedical sciences and facilitate their application in clinical practice. Jiaosanxian is a charcoal traditional Chinese medicine with a pronounced effect on promoting appetite and digestion that is widely used as dyspepsia therapy in China. To study the underlying mechanism and the material requirements, we investigated carbon dots which was generated in the charcoal processing. In this study, we developed Jiaosanxian-derived carbon dots (JSX-CDs) with an average diameter of 4.4-6.4 nm. No further modifications or external surface passivation agents were required because Jiaosanxian naturally contains carbon, nitrogen, and oxygen. We found that carbon dots derived from different charcoal traditional Chinese medicines had both similarities and differences in their structural features, physicochemical properties, and bioactivities. Due to an abundance of surface groups, JSX-CDs showed a distinct solubility and bioactivity. In this study, we established a modified hyperglycemia model in mice to evaluate the hypoglycemic activity of JSX-CDs. We found that JSX-CDs were effective in regulating blood sugar and appeared to be very safe, indicating its potential use as a hypoglycemic agent. Our results do not only provide guidance for further research on intrinsic bioactivities of CDs but also give new insights into their potential biomedical and healthcare applications.


C3H/HeN mammary tumor-bearing mice develop type-specific neutralizing antibodies and group-specific precipitating antibodies for the mouse mammary tumor virus.
The development of mouse mammary tumor virus (MMTV)-neutralizing antibodies in various strains of mice was measured by their ability to neutralize the focus-forming capacity of a Kirsten sarcoma virus (C3H MMTV) pseudotype containing the MMTV envelope glycoprotein gp52. C3H/HeN, but not GR/N and RIII, mammary tumor-bearing mice were found to develop neutralizing antibodies to this pseudotype. In addition, non-tumor-bearing C3H/HeN, GR/N, RIII, NIH Swiss, C57BL/6, and BALB/c mice and 13 feral mice were also negative for neutralizing antibodies. The neutralization was immunoglobulin G mediated, and the antibodies of C3H/HeN mammary tumor-bearing mice were type specific and capable of distinguishing C3H and GR/N MMTVs from RIII and C3H/HeNf MMTVs. Precipitating antibodies were detected in sera from RIII and GR/N tumor-bearing mice, GR/N non-tumor-bearing mice, and six of the feral mice, although these same sera did not neutralize the Kirsten sarcoma virus (C3H MMTV) pseudotype. The results of this study and of a previous study demonstrate that C3H/HeN mammary tumor-bearing mice develop three functionally distinct antibody populations: (i) group-specific virus-precipitating antibodies; (ii) type-specific virus-neutralizing antibodies; and (iii) type-specific cytotoxic antibodies.


[Evaluation of municipal administration of healthcare actions for the elderly].
Aging individuals can experience frailty and loss of independence and autonomy. Healthcare for the elderly should help them recover their health and maintain their autonomy, in keeping with the Brazilian Statute of the Elderly and underlying policies in the Brazilian Unified National Health System. Based on a multiple case study, the objective was to assess the capacity of municipal administration to provide healthcare for the elderly. The assessment was oriented by an evaluative model validated by experts in administration and evaluation, with 16 indicators analyzing political, organizational, technical, and operational factors. Care f or the elderly was rated fair in all five cases. Health promotion and prevention actions were identified as best practices, and the main challenge was in the intra and inter-sector linkages needed for healthcare for the elderly.


Ploidy and Number of Chromosomes in the Alveolate Alga Chromera velia.
Chromera velia is an alveolate alga which represents the closest known phototrophic relative to apicomplexan parasites. Although the nuclear, mitochondrial, and plastid genomes of this alga have been sequenced, the number of chromosomes and ploidy of C. velia are unknown. We explored ploidy in the vegetative cell, the predominant stage in cultures of Chromera, using the tyramide signal amplification-fluorescence in situ hybridization (TSA-FISH) in isolated nuclei of C. velia. Probes were derived from three single copy genes coding for 4-diphosphocytidyl-2-C-methyl-D-erythritol (CDP-ME) kinase, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (MEcPP) synthase and Topoisomerase II. Our results indicate that the vegetative cell of C. velia is haploid, as each probe produced a single fluorescent signal, although the possibility of diploidy with somatic pairing of homologous chromosomes cannot be completely excluded. Restriction analysis and hybridization with the telomere probe produced eight bands suggesting the presence of four chromosomes in haploid vegetative cells of C. velia. However, when the chromerid-specific telomere probe (TTTAGGG)4 was used for TSA-FISH, we consistently obtained a double signal. This may indicate that the four chromosomes are organized in clusters in interphase nuclei of C. velia, which is a chromosome organization similar to that of their apicomplexan relatives.


Bubble-surface interactions with graphite in the presence of adsorbed carboxymethylcellulose.
The adsorption of carboxymethylcellulose (CMC), and the subsequent effect on bubble-surface interactions, has been studied for a graphite surface. CMC adsorbs on highly oriented pyrolytic graphite (HOPG) in specific patterns: when adsorbed from a solution of low concentration it forms stretched, isolated and sparsely distributed chains, while upon adsorption from a solution of higher concentration, it forms an interconnected network of multilayer features. The amount and topography of the adsorbed CMC affect the electrical properties as well as the wettability of the polymer-modified HOPG surface. Adsorption of CMC onto the HOPG surface causes the zeta potential to be more negative and the modified surface becomes more hydrophilic. This increase in both the absolute value of zeta potential and the surface hydrophilicity originates from the carboxymethyl groups of the CMC polymer. The effect of the adsorbed polymer layer on wetting film drainage and bubble-surface/particle attachment was determined using high speed video microscopy to monitor single bubble-surface collision, and single bubble Hallimond tube flotation experiments. The time of wetting film drainage and the time of three-phase contact line spreading gets significantly longer for polymer-modified HOPG surfaces, indicating that the film rupture and three-phase contact line expansion were inhibited by the presence of polymer. The effect of longer drainage times and slower dewetting correlated with reduced flotation recovery. The molecular kinetic (MK) model was used to quantify the effect of the polymer on dewetting dynamics, and showed an increase in the jump frequency for the polymer adsorbed at the higher concentration.


Case reports: management of intractable upper extremity pain with continuous subarachnoid block at the low cervical level without impairment of upper extremity function.
We present a case of continuous subarachnoid block for the treatment of refractory cancer pain in the shoulder and upper extremity on the right side of the patient. The catheter tip was placed in the subarachnoid space close to the nerve roots on the right side at the height of C5 corresponding to the painful region. Until the patient died, his pain was controlled with infusions of bupivacaine (30-58.7 mg/d) and morphine (2-19.6 mg/d) for 120 days during which upper extremity function was not disturbed and respiratory function and performance status were improved. This case suggests continuous subarachnoid block at the low cervical level is useful for refractory cancer pain in the shoulder and upper extremity.