Comparison of the effectiveness of Tokuyama and GC II metal primer on the bond strength of acrylic resins to Ti-6Al-7Nb.
Because of the toxicity of vanadium in Ti-6Al-4V alloy, next generation of titanium alloys is proposed to focus on niobium-containing alloy, but for clinical applications, it is crucial for this alloy to bond with acrylic resins with or without the use of primers. However, literature was lacking about the effect of primers on bonding of autopolymerizing resins to Ti-6Al-7Nb. To evaluate the effect of different metal primers on the shear bond strength of acrylic resin to Ti-6Al-7Nb. A total of 30 dis-shaped wax patterns (10 mm in diameter and 2 mm thickness) were prepared and casted using Ti-6Al-7Nb. After casting, the disk surfaces were finished with abrasive paper under water. Specimens were equally divided into three groups on the basis of the use of primer: metal primer (GC II metal primer) (Group 1), Universal Tokuyama primer (Group 2), no primer (Group 3). Tape of 50 μm thickness was applied on each of the specimens. Then, self-cure acrylic resin was mixed and applied on the center part of the tape, on which Bernouilles tube was placed. The tensile bond strength was measured with a universal testing machine. The data were obtained for all the specimens and analyzed using Statistical Package for Social Sciences version 17.0 at a statistically significance level of <0.05. Mean tensile force was maximum for Group 2 (28.58 ± 39.40 N) and minimum for control Group 3 (6.24 ± 10.97 N), thereby showing a significant inter-group difference (P < 0.001). On applying post hoc test (Tukey HSD), both the Group 1 and Group 2 showed a statistically significant difference as compared to control Group 3; however, the difference between two experimental groups was not statistically significant (P > 0.05). Tokuyama primer and GC II metal primer had a significant effect on improving the bond strength between autopolymerizing denture base resin and Ti-6Al-7Nb.


[Perforation in the primary T-cell lymphoma of the small intestine due to effective chemotherapy-a case report].
A 71-year-old man presented at a clinic with fever and melena. Capsule endoscopy revealed ulcers accompanied by bleeding in the central part of the jejunum. Blood tests revealed a high level of soluble interleukin-2 receptor( sIL-2R). A malignant lymphoma of the small intestine was suspected. A biopsy was performed using double-balloon enteroscopy. We diagnosed a malignant lymphoma, peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a large amount of ascites and we determined that it was stage IIE according to the Lugano International Conference classification. The patient was hospitalized to receive pirarubicin hydrochloride, cyclophosphamide, vincristine sulfate, and prednisolone (THP-COP) therapy. One day after the fourth chemotherapy cycle, the patient complained of abdominal pain. Perforative peritonitis was diagnosed by abdominal computed tomography and emergency laparotomy was performed. A 3.5×2.0 cm perforation was detected in the jejunum, 180 cm from the ligament of Treitz. Approximately 20 cm of the small intestine was resected, and functional end-to-end anastomosis was performed. Histology showed that there were no malignant cells around the perforation site. We believe that the malignant lymphoma had disappeared rapidly because of the effective chemotherapy, and fibrosis could not adequately cover the space from which the tumor had disappeared. Although pancytopenia was observed and granulocyte colony-stimulating factor (G-CSF) was administered to the patient, the postoperative course was uneventful. He received the fifth course of chemotherapy on postoperative day 21.


Associations between HLA-A, -B, and -C alleles and iodinated contrast media-induced hypersensitivity in Koreans.
A common cause of drug hypersensitivity reactions is iodinated contrast media (ICM). ICM-induced hypersensitivity had been considered to be a non-immunological reaction, but evidence for an immunological mechanism has increased recently. Thus, we evaluated whether HLA-A, -B, and -C alleles were associated with ICM-induced hypersensitivity. In total, 126 patients who underwent contrast-enhanced computed tomography studies through outpatient clinics at a tertiary referral hospital between 2008 and 2012 were assessed. Sixty-one patients experienced ICM-induced hypersensitivity and the remainder, 65, were ICM-tolerant patients (control). ICM-induced hypersensitivity patients showed 51 with immediate, 7 with non-immediate, 3 with both or mixed type. HLA-A, -B, and -C genotyping was performed using a PCR sequence-based typing method. Four kinds of ICM were used: iopromide, iohexol, iobitridol, and iodixanol. The most used ICM among the hypersensitivity patients was iopromide. Significant difference in the frequency of HLA-B*58:01 (odds ratios [OR], 3.90; p = 0.0200, 95% confidence interval [CI], 1.16-13.07) was observed between ICM-induced immediate hypersensitivity and control. There were statistically significant differences in the frequencies of the HLA-B*38:02 (OR, 10.24; p = 0.0145; 95% CI, 1.09-96.14) and HLA-B*58:01 (OR, 3.98; p = 0.0348; 95% CI, 1.03-15.39) between iopromide-induced immediate hypersensitivity and control. The mechanism of ICM-induced hypersensitivity remains unknown, but this study showed associations, although weak, with HLA-B*58:01 alleles for ICM-induced immediate hypersensitivity and HLA-B*38:02 and HLA-B*58:01 for iopromide-induced immediate hypersensitivity as risk predictors. Further studies are needed to validate the associations in larger samples and to identify the functional mechanism behind these results.


Spontaneous resolution of vesicoureteral reflux in a renal transplant recipient.
Vesicoureteral reflux has been considered as a predisposing factor to the development of urinary infection in adults. In renal transplant patients, it has been suggested as a risk factor for graft failure. We report a patient with a normal voiding cystourethrogram after renal transplantation who was demonstrated to have mild reflux during an acute infection. Following treatment of the infection, the reflux disappeared. This patient's course suggests that reversible reflux in renal transplant recipients may be a result of infection and is not necessarily a harbinger of graft failure.


Risk factor meta-analysis and Bayesian estimation of genetic parameters and breeding values for hypersensibility to cutaneous habronematidosis in donkeys.
Cutaneous habronematidosis (CH) is a highly prevalent seasonally recurrent skin disease that affects donkeys as a result from the action of spirurid stomach worm larvae. Carrier flies mistakenly deposit these larvae on previous skin lesions or on the moisture of natural orifices, causing distress and inflicting relapsing wounds to the animals. First, we carried out a meta-analysis of the predisposing factors that could condition the development of CH in Andalusian donkeys. Second, basing on the empirical existence of an inter and intrafamilial variation previously addressed by owners, we isolated the genetic background behind the hypersensibility to this parasitological disease. To this aim, we designed a Bayesian linear model (BLM) to estimate the breeding values and genetic parameters for the hypersensibility to CH as a way to infer the potential selection suitability of this trait, seeking the improvement of donkey conservation programs. We studied the historical record of the cases of CH of 765 donkeys from 1984 to 2017. Fixed effects included birth year, birth season, sex, farm/owner, and husbandry system. Age was included as a linear and quadratic covariate. Although the effects of birth season and birth year were statistically non-significant (P > 0.05), their respective interactions with sex and farm/owner were statistically significant (P < 0.01), what translated into an increase of 40.5% in the specificity and of 0.6% of the sensibility of the model designed, when such interactions were included. Our BLM reported highly accurate genetic parameters as suggested by the low error of around 0.005, and the 95% credible interval for the heritability of ±0.0012. The CH hypersensibility heritability was 0.0346. The value of 0.1232 for additive genetic variance addresses a relatively low genetic variation in the Andalusian donkey breed. Our results suggest that farms managed under extensive husbandry conditions are the most protective ones against developing CH. Furthermore, these results provide evidence of the lack of repercussion of other factors such as age or sex. Potentially considering CH hypersensibility as a negative selection aimed goal in donkey breeding programs, may turn into a measure to improve animal welfare indirectly. However, the low heritability value makes it compulsory to control environmental factors to ensure the effectiveness of the breeding measures implemented to obtain individuals that may genetically be less prone to develop the condition.


Thermal energy requirement for strand separation during transcription initiation: the effect of supercoiling and extended protein DNA contacts.
We have studied the role of extended protein DNA contacts and DNA topology on the ability of Escherichia coli RNA polymerase to form open complexes at several related promoters. The -35 region of several Escherichia coli promoters do not have homology with the consensus sequence, but still drive activator independent transcription initiation. This is due to the presence of a TG motif upstream from the -10 hexamer creating an 'extended -10' promoter. We have previously shown that two 'extended -10' promoters, galP1 and pBla, can form open complexes at lower temperatures than the galP1 derivative, galPcon6, which has a consensus -35 hexamer. Here we report further investigations into the mechanism of open complex formation by RNA polymerase, in particular the thermal energy requirement. A single base pair change in galPcon6 creating an 'extended -10' sequence, results in a 20 degrees C reduction in the temperature requirement for open complex formation. The DNA topology has also been shown to effect the thermal energy requirement for strand separation. Promoters carried on supercoiled plasmids form open complexes at lower temperatures than when present on linear DNA templates. We have also shown that in vivo, RNA polymerase can form open complexes at lower temperatures than those observed for linear templates in vitro, but requires slightly higher temperatures than supercoiled templates in vitro, however the promoter hierachy remains the same.


[Surgical instruments (II). An introduction to surgical instruments].
In clinical practice, there are many diverse ways to name each instrument. Some names consist of local terms related to the shape or the use of an instrument; others have their origin in confusing references; few of these names tend to be related to known nomenclature. This causes a serious inconvenience for someone who wishes to learn about the intra-surgical medium in an organized manner. Undoubtedly this is an inconvenience for the untrained person who discovers he/she is incapable of retaining an enormous volume of names, often presented without any logic whatsoever This also causes an inconvenience for the trained professional; it is difficult to understand terms since, depending on which surgical ward one refers to, the name for the same instrument changes.


Characterization of occult hepatitis B virus infection among HIV positive patients in Cameroon.
Occult hepatitis B infection (OBI) among HIV positive patients varies widely in different geographic regions. We undertook a study to determine the prevalence of occult hepatitis B infection among HIV infected individuals visiting a health facility in South West Cameroon and characterized occult HBV strains based on sequence analyses. Plasma samples (n = 337), which previously tested negative for hepatitis B surface antigen (HBsAg), were screened for antibodies against hepatitis B core (anti-HBc) and surface (anti-HBs) antigens followed by DNA extraction. A 366 bp region covering the overlapping surface/polymerase gene of HBV was then amplified in a nested PCR and the amplicons sequenced using Sanger sequencing. The resulting sequences were then analyzed for genotypes and for escape and drug resistance mutations. Twenty samples were HBV DNA positive and were classified as OBI giving a prevalence of 5.9%. Out of these, 9 (45%) were anti-HBs positive, while 10 (52.6%) were anti-HBc positive. Additionally, 2 had dual anti-HBs and anti-HBc reactivity, while 6 had no detectable HBV antibodies. Out of the ten samples that were successfully sequenced, nine were classified as genotype E and one as genotype A. Three sequences possessed mutations associated with lamivudine resistance. We detected a number of mutations within the major hydrophilic region of the surface gene where most immune escape mutations occur. Findings from this study show the presence of hepatitis B in patients without any of the HBV serological markers. Further prospective studies are required to determine the risk factors and markers of OBI.


Scaling analysis for electrospinning.
Electrospinning refers to the process of generating nanofibers from electrified viscous polymeric jets. Though relatively easy to perform, this process is quite complex in its nature, given the large number of parameters that are involved. This study attempts to derive a relation between the final fiber diameter and the major process parameters. Two new dimensionless numbers describing viscous and surface charge repulsion effects are identified from the scaling analysis of governing equation for the motion of a bent jet. Experimental data for a wide range of polymer solutions exhibit a common slope, when expressed in terms of these new dimensionless numbers. This correlation is used to derive a new scaling expression for the final fiber diameter.


Differential gene expression downstream of Toll-like receptors (TLRs): role of c-Src and activating transcription factor 3 (ATF3).
Interferon regulatory factors (IRFs) are crucial for transcription during innate immune responses. We have previously shown that the tyrosine kinase c-Src enhances IRF-3-dependent transcription in response to viral double-stranded RNA. In this study, we show that c-Src has distinct roles in Toll-like receptor (TLR)-mediated activation of IRF-5 and IRF-3. Surprisingly, c-Src inhibition markedly enhanced IRF-5 activation after treatment with unmethylated CpG, while suppressing IRF-3 activation. Also, CpG-elicited interleukin-6 mRNA production was increased, whereas IP10 mRNA synthesis was reduced in cells deficient in c-Src. Interestingly, c-Src regulated TLR-stimulated induction of activating transcription factor 3 (ATF3), a transcriptional repressor. Depletion of ATF3 by small interfering RNA markedly enhanced interleukin-6 production after CpG treatment, whereas IP10 production was reduced. These results demonstrate functional specificity for c-Src in TLR-stimulated responses and suggest that c-Src modulation and ATF3 activity may contribute to differential regulation of IRF-3- versus IRF-5-mediated gene expression.


Effects of dietary vitamin levels on physiological responses, blood profiles, and reproductive performance in gestating sows.
This study was performed to evaluate the effects of dietary vitamin levels on physiological responses, blood profiles, and reproductive performance in gestating sows. A total of 52 F1 multiparous sows (Yorkshire × Landrace) with an average body weight of 223.5 ± 31.7 kg, an average parity of 6.4 ± 2.7, and an average backfat thickness of 18.5 ± 4.9 mm were divided into four treatment groups considering body weight, backfat thickness, and parity in a completely randomized design with 13 replicates. The treatments were 100% (V1), 300% (V3), 600% (V6) and 900% (V9) of the National Research Council (NRC) Nutrient Requirements of Swine. The gestation diet was formulated based on corn-soybean meal (SBM) and contained 3,265 kcal of metabolizable energy (ME)/kg and 12.00% crude protein. During the lactation period, all sows were fed the same commercial lactation diet. There was no significant difference in body weight of gestating sows. However backfat thickness tended to increase when higher levels of vitamins were provided to gestating sows (p < 0.10). When high levels of dietary vitamins were provided, the body weight change of lactating sows increased (p < 0.01). When sows were fed higher levels of vitamins, the feed intake of lactating sows tended to decrease (p = 0.06). There were no treatment differences in the number of total born, born alive, stillbirth piglets, or the body weight of piglets according to different dietary vitamin level. As dietary vitamin level increased, the serum concentration of 25(OH)D3 in sows at 90 days of gestation linearly increased (p < 0.01). Furthermore, the serum vitamin E level of gestating sows was linearly increased with increasing dietary vitamin level (p < 0.05). The current NRC vitamin requirements are sufficient for gestating sows and higher levels of vitamins in the gestation diet did not show any beneficial effects for gestating and lactating sows.


Liquid ingress into intermediate siderails of Hill-Ram TotalCare beds may cause contamination.
Liquids--potentially including infectious body fluids such as blood--may enter the compartments within the intermediate siderails of Hill-Rom TotalCare beds, which could cause contamination of interior surfaces. This can potentially expose staff servicing the intermediate siderails to infectious materials. When performing service on these siderails, staff should follow their facility's safety procedures for handling and disinfecting potentially contaminated equipment. Additionally, to reduce the risk of liquid ingress, service staff should replace the foam gasket used in the siderail assembly each time the siderail is opened.


An Overview of Systemic Health Factors Related to Rapid Oral Health Deterioration among Older People.
The oral health of older individuals can be negatively impacted by various systemic health factors, leading to rapid oral health deterioration. This paper aims to present an overview of the published evidence on systemic health factors that contribute to rapid oral health deterioration in older individuals, and to explore the implications of these factors for both general healthcare and oral healthcare provision. Older people are at risk of experiencing adverse reactions to medications due to multimorbidity, polypharmacy, and changes in pharmacokinetics and pharmacodynamics. Hyposalivation, a significant side effect of some medications, can be induced by both the type and number of medications used. Frailty, disability, sarcopenia, care dependency, and limited access to professional oral healthcare can also compromise the oral health of older people. To prevent rapid oral health deterioration, a comprehensive approach is required that involves effective communication between oral healthcare providers, other healthcare providers, and informal caregivers. Oral healthcare providers have a responsibility to advocate for the importance of maintaining adequate oral health and to raise awareness of the serious consequences of weakened oral health. By doing so, we can prevent weakened oral health from becoming a geriatric syndrome.


[Post-crisis elevation of adrenocorticotropic hormone and prolactin in epileptic children].
In six children, aged from 8 to 12 years, presenting with primary generalized epilepsy a significant rise in plasma ACTH and prolactin levels (as compared with levels measured 5 days later) was observed either during a generalized seizure demonstrated by EEG (3 cases) or within 1 hour of a generalized seizure (3 cases). The neurophysiological basis for these post-epileptic endocrine disturbances is a sudden depression of dopaminergic and GABA-ergic pathways. As a result, these endocrine changes, already well documented in adults, may be regarded as a good biological marker of the epileptic origin of a paroxysmal attack.


Nuclear reprogramming of somatic cells by embryonic stem cells is affected by cell cycle stage.
Hybrid embryonic stem (ES)-like clones were generated by fusion of murine ES cells with somatic cells that carried a neo resistance gene under the transcriptional control of the Oct-4 promoter. The Oct-4 promoter was reactivated in hybrid ES cells formed by fusion with fetal fibroblasts, and all hybrid colonies were of ES rather than fibroblast phenotype, suggesting efficient reprogramming of fibroblast chromosomes. Like normal diploid murine ES cells, hybrid lines expressed alkaline phosphatase activity and formed differentiated cells derived from the three embryonic germ layers both in vitro and in vivo. Treatments thought to affect nuclear transfer efficiency (ES cell confluence and serum starvation of primary embryonic fibroblasts) were investigated to determine whether they had an effect on reprogramming in cell hybrids. Serum starvation of primary embryonic fibroblasts increased hybrid colony number 50-fold. ES cells were most effective at reprogramming when they contained a high proportion of cells in the S and G2/M phases of the cell cycle. These data suggest that nuclear reprogramming requires an initial round of somatic DNA replication of quiescent chromatin in the presence of ES-derived factors produced during S and G2/M phases.


Prevalence of Babesia microti in Ixodes ricinus ticks from Lublin region (eastern Poland).
A total of 1,367 Ixodes ricinus ticks collected from 5 districts of the Lublin region (eastern Poland) were examined for the presence of Babesia microti DNA by PCR and nested-PCR. As many as 74 ticks (5.4 %) were found to be infected with Babesia microti. The infection rate varied significantly with stage/sex of ticks (chi (2) =16.48543, df=2, p < 0.000264). The infection rates in females and males amounted to 6.4 % and 8.8 % respectively and were significantly higher (p=0.006 and p=0.0001 respectively) compared to minimum infection rate in nymphs that was equal to 2.8 %. The prevalence of infection showed also a significant variability depending on geographic location within the Lublin region (chi(2) =18.62812, df=4, p < 0.000932). The highest rates of infection with Babesia microti were noted in ticks collected from the areas of Puławy district situated in the northern part of region and the suburban Lublin district situated in the central part of the region (8.0 % and 7.3 % respectively). Mediocre infection rates (respectively 3.4 % and 3.3 %) were found in ticks from the Parczew and Włodawa districts situated in eastern part of the region and covered with humid lakeland forests. The lowest infection rate (0.5 %) was noted in ticks from the Zamość district situated in southern part of the region. In conclusion, the infection rate of Ixodes ricinus ticks with Babesia microti found in this study is higher compared to the majority of data reported by Polish and other European authors, and indicates a potential risk of human infection during occupational or recreational exposure to tick bite.


Paediatric tonsillectomy: parental experience and outcomes.
To evaluate parental experience, satisfaction and outcomes following their child's tonsillectomy surgery. Structured postal questionnaire sent to the parents or guardians of 77 sequential children undergoing elective day-case tonsillectomy. Seventy-seven children with a mean age of 6.25 years (range three to 17 years) undergoing day-case tonsillectomy predominantly for recurrent acute tonsillitis, upper airway obstruction or a combination of these symptoms; 63.6 per cent of the parents or guardians of these children responded to the questionnaire. There was overall satisfaction with the operation, and positive health outcomes. Despite the current public health agenda to limit access to routine high volume operations such as childhood tonsillectomy on economic grounds, the users of this service rated the outcomes and benefits of the procedure highly.


Cosmid mapping of the human chorionic gonadotropin beta subunit genes by field-inversion gel electrophoresis.
A cosmid clone containing the entire hCG beta gene cluster has been isolated. The restriction map of this clone has been determined by an indirect-end-label FIGE (field inversion gel electrophoresis) method. Analysis of this cosmid clone shows that there are 6 hCG beta genes in human genomic DNA. A previously uncloned portion of the hCG beta cluster, termed the "gap" region, has been shown not to contain any sequences homologous to the hCG beta cDNA. The restriction mapping method employed in this study takes advantage of the superior resolution of FIGE for high molecular weight DNA fragments in the size range 15-50 kb. This method is broadly applicable and permits rapid and accurate restriction mapping for extended regions of genomic DNA that have been cloned into cosmid or lambda vectors.


The Relationship Between Reading Strategy and Reading Comprehension: A Meta-Analysis.
This study synthesized the correlation between reading strategy and reading comprehension of four categories based on Weinstein and Mayer's reading strategy model. The current meta-analysis obtained 57 effect sizes that represented 21,548 readers, and all selected materials came from empirical studies published from 1998 to 2019. Results showed that reading strategies in all the four categories had a similar correlation effect size with reading comprehension. The correlation between monitoring strategy and reading comprehension was significantly larger in first language scripts than second language scripts. Affective strategy and elaboration strategy had an independent effect on reading comprehension, which was not significantly moderated by selected moderators. Results suggested that the reading strategies of all the four categories may have a similar contribution to text comprehension activities.


Sun Safety: Knowledge and Behavior among Egyptian Farmers-a Multicomponent Intervention Study.
The purpose of study was to screen for health hazards related to sun exposure and to examine the effectiveness of a sun safety multicomponent intervention designed specifically for the Egyptian farmers. A multicomponent interventional study was conducted among 128 farmers from three villages in Zagazig district, Sharkia Governorate, Egypt, from January to July 2022. It passed through three phases: phase 1: assessment of participants' risk of skin cancer and vision screening; phase 2: filling a semi-structured questionnaire assessing sun exposure hazards and sun safety knowledge, behavior, and barriers; and phase 3: conducting multicomponent intervention composed of education session, providing sun safety supplies and reminders then evaluate the effect of this intervention after one month. Most of participants had moderate risk for skin cancer (69.0%), history of photokeratitis (77.3%), cataract (15.6%), and bad/very bad self-reported overall eyesight (43.0%). After intervention, there was a statistically significant improvement in the participants' awareness regarding sun exposure-related hazards, all knowledge items about sun safety measures (p < 0.01) and some sun safety behaviors (p < 0.05) including wearing protective clothing, minimization of direct sunlight exposure, taking breaks, plentiful water intake, regular self-checking of skin, wearing wide brimmed hats, and job rotation. Furthermore, there was a statistically significant improvement in all sun protection barriers (p < 0.01) except sunscreen and sunglasses related barriers (p ˃ 0.05). The multicomponent intervention composed of education session, providing sun safety supplies and reminders was effective in increasing awareness of farmers with sun exposure hazards and improving their knowledge and behavior towards sun safety measures.


Influence of histidine beta81 of HLA-DR101 on peptide binding and presentation to T-cell receptor.
HA(306-318) is an immunodominant peptide of the hemagglutinin of influenza virus that binds to most human leukocyte antigen (HLA-DR) alleles, while p18(73-85) is a HIV peptide characterized as a DR101 binding peptide. Our results demonstrate that crystal relaxation leads to the loss of a hydrogen bond between the beta81 histidine and the HA(306-318) peptide. This histidine is also involved in the binding of superantigens like SEA via a coordination of a zinc atom. To monitor the interaction of these peptides with this histidine of HLA-DR molecules, chemical modification, peptide binding on HLA-DR101 wild type and mutated molecules, and proliferation experiments were conducted, together with molecular simulation of HLA-DR/peptide molecular complexes. Our data suggest a different binding peptide pattern, depending of whether the peptide is HLA-DR101 allele specific or a shared one. Furthermore, tyrosine substitution at position beta81 does not affect either peptide binding or HA(306-318) clone-specific T-cell proliferation. On the contrary, the alanine substitution at position HLA-DR101 beta81 abrogated both peptide binding and T-cell proliferation. These results suggest that the histidine 81 on the DRbeta chain plays an important role in the HLA-DR peptide binding, more likely by polar interactions of the amino acid side chain ring with the peptide.


Acetic acid is key for synergetic hydrogen production in Chlamydomonas-bacteria co-cultures.
This study is a proof of concept for the synergetic biohydrogen production in alga-bacteria co-cultures. Algal hydrogen photoproduction was obtained in sugar-containing media only when the green alga Chlamydomonas reinhardtii was co-cultured with Pseudomonas putida (40.8 ml H2·L-1), Escherichia coli (35.1 ml H2·L-1) and Rhizobium etli (16.1 ml H2·L-1). Hydrogen photo-production in these co-cultures was not only linked to the induction of hypoxia, but to the ability of the bacteria to produce acetic acid from sugars. Synergetic hydrogen production was achieved by integrating the photobiological and fermentative production in Chlamydomonas and Escherichia coli co-cultures supplemented with glucose, which resulted in 60% more H2 production than the sum of the respective monocultures. This cooperation relied on the ability of the alga to consume the excreted bacterial acetic acid, which benefited both bacterial and algal hydrogen production. This knowledge may open new possibilities for the biohydrogen production from industrial wastes.


Prenatal dance activity enhances foetal and postnatal cognitive and motor development.
No research has examined the impact of any physical-artistic-cognitive activity on foetal neurodevelopment. The aim of the study was to investigate the efficacy of a unique prenatal dance activity in pre- and postnatal cognitive and motor development as a complementary health care practice. 26 clinically uncomplicated primiparas and multiparas with singleton pregnancies and their later born children were examined in this prospective study at the University of Pécs, Hungary. The activity group participated in supervised, 60-min, twice-weekly, moderate-intensity prenatal dance classes for 19.56 ± 3.97 weeks, whereas the control group did not. We determined the developmental ages of their children with the Bayley Scales of Infant and Toddler Development in both groups at 5 weeks of age and in the activity group at 33 months of age. Prenatal dance activity did not cause any adverse outcomes. Infants in the activity group had significantly higher mean developmental ages than the control group regarding cognitive skills (P < 0.001), receptive (P < 0.001) and expressive communication (P = 0.007), fine (P < 0.001) and gross motor (P = 0.001). As toddlers their mean developmental ages were significantly higher than their mean calendar age regarding cognitive skills (P = 0.001), receptive (P = 0.001) and expressive communication (P = 0.001), fine (P = 0.002) and gross motor (P = 0.001). Our results confirm the safe implementation of this prenatal dance activity and the more advanced cognitive and motor development of children in the activity group as infants compared to the control group and as toddlers compared to the norm. These results offer a novel approach to dance in pre- and postnatal clinical practice.


The Effectiveness and Safety of Direct-Acting Antivirals in the Treatment of Hepatitis C Virus in Saudi Arabia: A Nationwide Study Based on the Saudi Ministry of Health Surveillance Data From 2017 to 2021.
Background and objective While the Kingdom of Saudi Arabia (KSA) has had a hepatitis C virus (HCV) elimination program in place since 2015, there have been limited studies investigating the effectiveness and safety of direct-acting antivirals (DAAS) based on the Ministry of Health (MOH) surveillance data. In light of this, this study was conducted to assess the effectiveness and safety of DAAS (glecaprevir/pibrentasvir, daclatasvir/sofosbuvir, or other combinations) in treating HCV cases in Saudi Arabia as per the MOH data from 2017 to 2021. Methods This was a retrospective cohort study involving recorded HCV cases in the national hepatitis surveillance database of MOH across all regions of KSA from 2017 to 2021. Statistical analyses were performed using IBM SPSS Statistics software (IBM Corp., Armonk, NY). Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables were presented as numbers (percentages). An independent t-test was used for continuous variables, and a Chi-square analysis was used for categorical variables. A confidence interval of 95%, a margin of error of 0.05, a precision of 2%, and a 5% level of significance were employed. Results Regarding demographic characteristics, age was significantly associated with HCV infection (p=0.002). Similarly, nationality had a highly significant association with HCV infection (p=0.004). Regarding clinical characteristics, creatinine levels were significantly associated with HCV infection (p=0.009). As for effectiveness, all participants had a positive polymerase chain reaction (PCR) for HCV at enrolment (n=4806) and were DAAS-naïve. After the completion of the first DAAS course, 99.5% (4781) had negative PCRs 12 weeks post-treatment completion; however, the PCR remained positive for some patients (0.5%, n=25), which became negative after receiving the second DAAS course, resulting in complete cure of HCV infection and a 100% negative PCR among all participants. With regard to safety, no side effects were recorded in the cohort and hence the safety aspect was not analyzed. Conclusion Univariate analysis revealed that nationality (non-Saudi), age, and creatinine levels were significantly associated with HCV infection. However, only nationality showed a significant association with HCV infection following multivariate logistic regression adjustment. We believe that these insights will help guide the creation of clinical guidelines and promote evidence-based decision-making in the management of HCV in Saudi Arabia.


On the concept of frustrated Lewis pairs.
In this concept article, we consider the notion of 'frustrated Lewis pairs' (FLPs). While the original use of the term referred to steric inhibition of dative bond formation in a Lewis pair, work in the intervening decade demonstrates the limitation of this simplistic view. Analogies to known transition metal chemistry and the applications in other areas of chemistry are considered. In the light of these findings, we present reflections on the criteria for a definition of the term 'frustrated Lewis pair'. Segregation of the Lewis acid and base and the kinetic nature of FLP reactivity are discussed. We are led to the conclusion that, while an all-inclusive definition of FLP is challenging, the notion of 'FLP chemistry' is more readily recognized.This article is part of the themed issue 'Frustrated Lewis pair chemistry'.


Neonatal lupus erythematosus and maternal lupus erythematosus mimicking HELLP syndrome.
A 4-month-old boy had a faint, confluent, macular erythema involving the forehead, nose, and philtrum, and matlike telangiectases over the forehead and eyelids. The clinical features, course, and laboratory studies were characteristic of neonatal lupus erythematosus. He was otherwise healthy and the product of a preterm twin pregnancy complicated by the development of maternal HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome. The patient had elevated Ro(SSA) and La(SSB) antibody titers, and studies performed on maternal blood disclosed positive antinuclear antibodies and elevated Ro and La antibody titers.


Effects of Pulsatile Cupping on Body Pain and Quality of Life in People with Suboptimal Health:A Randomized Controlled Exploratory Trial.
Objective: The curative effect of pneumatic pulsatile cupping on pain has been shown. This study was conducted to investigate effects of the pulsating frequency of pneumatic pulsatile cupping, compared with traditional cupping (TC), on body pain and quality of life (QoL) in people with suboptimal health status (SHS). Materials and Methods: Ninety-six participants with SHS were randomized to low-frequency (LF; n = 24) or high-frequency (HF; n = 24) pulsating cupping, traditional cupping (TC; n = 24), or wait-list (WL; n = 24) groups. The LF, HF, and TC groups received 4 sessions of cupping over 2 weeks. Visual analogue scale (VAS; 0-100 mm) pain level and Short-Form-36 (SF-36) QoL measurements were taken before and after the intervention. Results: Both LF and HF reduced pain significantly (VAS: -28.26; 95% confidence interval [CI] -36.18 to -20.34; and -31.88, 95% CI -39.81 to -23.96; both P = 0.000) and improved QoL more than WL (SF-36, Bodily Pain dimension: 1.46, 95% CI: 0.85 to 2.07; and 1.75, 95% CI: 1.14 to 2.36, both P = 0.000). Compared to TC, LF and HF significantly reduced pain (VAS: -7.92, 95% CI: -15.75 to -0.08, P LT = 0.048; and -11.54, 95% CI: -19.38 to -3.70, P HT = 0.004) and improved QoL (SF-36, Bodily Pain dimension: 0.61, 95% CI: 0.01 to 1.21, P LT = 0.046; and 0.90, 95% CI: 0.30 to 1.50, P HT = 0.004). There was no significant difference between LF and HF. Conclusions: This study showed that, in patients with SHS, pulsatile cupping therapy could have a more-favorable effect to relieve body pain, compared to TC. LF and HF pulsation produced equivalent pain relief. Further studies investigating the underlying mechanism are needed. Trial registration: This trial was registered in the Chinese Clinical Trial Registry (ChiCTR-INR-16009345).


Radiolabeled amino acids for tumor imaging with PET: radiosynthesis and biological evaluation of 2-amino-3-[18F]fluoro-2-methylpropanoic acid and 3-[18F]fluoro-2-methyl-2-(methylamino)propanoic acid.
Novel radiopharmaceuticals, including amino acids, that target neoplasms through their altered metabolic states have shown promising results in preclinical and clinical studies. Two fluorinated analogues of alpha-aminoisobutyric acid, 2-amino-3-fluoro-2-methylpropanoic acid (FAMP) and 3-fluoro-2-methyl-2-(methylamino)propanoic acid (N-MeFAMP), have been radiolabeled with fluorine-18, characterized in amino acid uptake assays, and evaluated in vivo in normal rats and a rodent tumor model. The key steps in the syntheses of both radiotracers involved the preparation of cyclic sulfamidate precursors. Radiosyntheses of both [18F]FAMP and [18F]N-MeFAMP via no-carrier-added nucleophilic substitution provided high yields (>78% decay-corrected) in high radiochemical purity (>99%). Amino acid transport assays using 9L gliosarcoma cells demonstrated that both compounds are substrates for the A type amino acid transport system, with [18F]N-MeFAMP showing higher specificity than [18F]FAMP for A type transport. Tissue distribution studies in normal Fischer rats and Fischer rats implanted intracranially with 9L gliosarcoma tumor cells were also performed. At 60 min postinjection, the tumor vs normal brain ratio of radioactivity was 36:1 in animals receiving [18F]FAMP and 104:1 in animals receiving [18F]N-MeFAMP. On the basis of these studies, both [18F]FAMP and [18F]N-MeFAMP are promising imaging agents for the detection of intracranial neoplasms via positron emission tomography.


Staphylococcal scalded skin syndrome in a preterm newborn presenting within first 24 h of life.
A preterm neonate was noted to have diffuse blanching erythema around the mouth followed by appearance of bullous lesions on the upper back, lower neck and right scapular areas at 23 h of life. The bullae subsequently ruptured leaving an extremely tender, erythematous, denuded area of the skin, which extended over next few hours to involve most of the upper back and right shoulder regions. Nikolsky sign was positive. Clinical diagnosis of staphylococcal scalded skin syndrome was made. The throat, blood, urine and cerebrospinal fluid cultures did not yield any growth, but wound culture was positive for Staphylococcus aureus. Treatment included administration of intravenous fluids and vancomycin for 10 days. The wound area was covered with vaseline and sterile gauge dressings. On day 5 of life, epithelialisation began and was complete on the seventh day of life. She was discharged home with intact skin, without scars, on day 12 of life.


Blood volume and hemoglobin concentration as determinants of maximal aerobic power.
Changes in blood volume (BV) and hemoglobin concentration ( [Hb] ) were induced in five healthy young men. After acute hypovolemic anemia was achieved by blood withdrawal, VO2max values decreased, while the same [Hb] due to acute plasma volume expansion (6% dextran) did not alter VO2max. After reinfusion of red blood cells, leading to hypervolemia and increased [Hb], VO2max increased. Plasma volume expansion in this situation, leading to hypervolemia at normal [Hb], resulted in a slight reduction in VO2max, which, however, remained elevated (approximately 4%) above control values. Physical performance, measured as time to exhaustion, corresponded to the changes in VO2max except for the hypervolemic anemic situation, where it decreased. Changes in peak heart rate were inversely related to BV changes, but were also influenced by [Hb]. The results point to a significant influence of the total amount of Hb rather than the blood hemoglobin concentration for obtaining a high maximal aerobic power. Thus, a reduced [Hb], concomitantly with an elevated blood volume (plasma volume), may result in an unchanged VO2max, but reduced performance time.


Classification of peripheral blood neutrophils using deep learning.
Deep learning has been used to classify the while blood cells in peripheral blood smears. However, the classification of developing neutrophils is rarely studied. Moreover, it is still unknown whether deep learning can work well on the data coming from different sources. In this study, we therefore investigate the classification performance of deep learning for immature and mature neutrophils. In particular, we used three open-access datasets obtained from different imaging systems: CellaVision DM 96, CellaVision DM 100, and iCELL ME-150. A total of 26,050 images identified by one laboratory technologist were randomly split into training, validation, and testing datasets. A total of 10 convolutional neural networks were trained to classify six blood cell types: myeloblast, promyelocyte, myelocyte, metamyelocyte, banded neutrophil, and segmented neutrophil. The experimental results showed that compared to any single model, the average ensemble model could achieve a better classification performance and provide a testing accuracy of 90.1%. The sensitivity and specificity of the average ensemble model for the six blood cell types were above 83.5% and 96.9%, respectively. Our results suggest that deep learning is a promising tool for the classification of developing neutrophils, but further improvement is required.


Determination of optimal replicate number for validation of imprecision using fluorescence cell based assays: Proposed practical method.
Background: Assay validation includes determination of inherent imprecision across the reportable range. However specific practical guidelines for determinations of precision for cell based fluorescence assays performed on flow cytometers are currently lacking. Methods: Replicates of 10 or 20 measurements were obtained for flow cytometric assays developed for clinical IVD use, including neutrophil CD64 expression for infection/sepsis detection, fetal red cell enumeration for fetomaternal hemorrhage detection, human equilibrative nucleoside transporter 1 (hENT1) quantitation in leukocytes for possible correlation with drug responsiveness, and CD34+ hematopoietic stem cell (HSC) enumeration of apheresis products, using up to three different instrument platforms for each assay. For each assay, the mean, 95% confidence intervals of the mean (95%CI), standard deviation and coefficient of variation (CV) of sequential replicates were determined. Results: For all assays and most instrument platforms <5 replicates were found adequate to validate assay imprecision levels below the 5-10% CV for repeatability claimed by the manufacturers of these assays. Results plotted as a novel parameter derived from the 95%CI and the cumulative mean for replicates, termed variance factor (VF), provide a data driven means for determining optimal replicate numbers. Conclusions: The novel VF can provide information to guide the practical selection of optimal replicate numbers for validation of imprecision in flow cytometric assays. The optimal number of replicates was assay and instrument platform dependent. Our findings indicate 3-4 replicates are sufficient for most flow cytometric assays and instrument combinations, rather than the higher numbers suggested by CLSI guidelines for soluble analytes. © 2013 Clinical Cytometry Society.


Binding of antiphospholipid antibodies to discontinuous epitopes on domain I of human beta(2)-glycoprotein I: mutation studies including residues R39 to R43.
Pathogenic antiphospholipid antibodies (aPL) bind the self antigen N-terminal domain (domain I) of beta(2)-glycoprotein I (beta(2)GPI), with residues G40-R43 being important. However, peptides homologous to other regions of domain I have also been shown to bind aPL. Furthermore, there are no published reports of the effects of altering R39, which has greater surface exposure than the G40-R43 residues. We used a novel, efficient method of production and purification of human domain I by Escherichia coli to create multiple mutants of domain I. These domain I mutants were then screened for binding to a range of polyclonal IgG purified from patients with antiphospholipid syndrome, using both solid-phase and fluid-phase assays. E coli-expressed purified domain I selectively bound IgG derived from patients with antiphospholipid syndrome. In region R39-R43, the R39S mutation had the greatest effect in terms of reducing binding to a panel of aPL in the fluid phase (mean +/- SD inhibition 14 +/- 18.5% versus 44.1 +/- 31.7% for G40E and 62.9 +/- 25.7% for wild-type domain I). Conversely, altering both D8 and D9 to S8 and G9, respectively, had the effect of enhancing binding to aPL in the fluid phase. Adding the remainder of the domain I-II interlinker resulted in enhanced binding over wild-type in the solid phase but not the fluid phase. The binding of aPL to beta(2)GPI domain I is complex and likely to involve discontinuous epitopes that include R39 in addition to G40-R43, the domain I-II interlinker, and possibly D8 and D9. Domain I variants with enhanced binding to aPL compared with wild-type domain I may aid in the development of novel therapies.


Acute thrombotic obstruction of a mitral valve prosthesis: the role of thrombolytic therapy.
An acute thrombotic occlusion of a mitral prosthesis in a hemodynamically compromised patient was successfully lysed with intravenous streptokinase. Unfortunately, the patient had a major cerebral embolus, from which she died several days later. A review of the current literature reveals that thrombolytic therapy successfully relieves the obstructing thrombus in 73% of cases, while it is partially successful in another 16% allowing deferral of surgical repair to a more optimal time. Mortality from thrombolytic therapy is 14% while hemorrhage or cerebral emboli occur in a further 11%. Reports of surgical intervention have shown an operative mortality rate of 25%, in those fit to undergo surgery. If hemodynamically unstable patients unfit for surgery are included on an intention to treat basis, overall mortality is 42%. Thus, thrombolytic therapy should be considered primarily in those compromised patients who have a thrombotic occlusion of a valvular prosthesis with a greater risk of operative mortality. Low dose, prolonged infusions should be favoured over rapid, high concentration infusions currently employed for coronary thrombolysis, as the latter regime could have contributed to the fatal cerebral embolus in our patient.


Aortic root compliance influences hemolysis in mechanical heart valve prostheses: an in-vitro study.
Mechanical heart valve prostheses are known to activate coagulation and cause hemolysis. Both are particularly dependent on the leaflet dynamics, which in turn depends on the flow field in the aortic root influenced by the aortic root geometry and its compliance. Compliance reduction of large vessels occurs in aging patients, both in those who have atherosclerotic diseases and those who do not. In this study we investigated the correlation between hemolysis and the compliance of the proximal aorta in a novel, pulsatile in vitro blood tester using porcine blood. Two mechanical heart valves, the St Jude Medical (SJM) bileaflet valve and a trileaflet valve prototype (Triflo) were tested for hemolysis under physiological conditions (120/80 mm Hg, 4.5 l/min, 70 bpm) and using two different tester setups: with a stiff aorta and with a compliant aorta. Valve dynamics were subsequently analyzed via high-speed videos. In the tests with the Triflo valve, the free plasma hemoglobin increased by 13.4 mg/dl for the flexible and by 19.3 mg/dl for the stiff setup during the 3-hour test. The FFT spectra and closing speed showed slight differences for both setups. Free plasma hemoglobin for the SJM valve was up by 22.2 mg/dl in the flexible and 42.7 mg/dl in the stiff setup. Cavitation induced by the higher closing speed might be responsible for this, which is also indicated by the sound spectrum elevation above 16 kHz.


Contraceptive patterns of religious and racial groups in the United States, 1955-76: convergence and distinctiveness.
A number of studies have reported data on contraceptive use among white Protestant and white Catholic couples in the United States, but this paper is the first to study a large sample of couples with other or no religious affiliation, as well as black couples by religion, using multivariate controls. Using a nationally representative sample of 14,000 married women aged 15-44, we find convergence among white Protestant, Catholic, and Jewish couples in contraceptive patterns between 1955 and the mid-1970s, but large differences remained at the latter date, even after multivariate controls. Among black couples, differences by religious affiliation are smaller, but differences between white and black couples within religion categories are substantial. We conclude that religious differences are not artifacts of an incomplete demographic transition, and that religious affiliation is an indispensable datum for understanding contraceptive choice in the United States.


Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells.
How the development of antibacterial T helper 17 (Th17) cells is selectively promoted by antigen-presenting dendritic cells (DCs) is unclear. We showed that bacteria, but not viruses, primed human DCs to promote IL-17 production in memory Th cells through the nucleotide oligomerization domain 2 (NOD2)-ligand muramyldipeptide (MDP), a derivative of bacterial peptidoglycan. MDP enhanced obligate bacterial Toll-like receptor (TLR) agonist induction of IL-23 and IL-1, which promoted IL-17 expression in T cells. The role of NOD2 in this IL-23-IL-1-IL-17 axis could be confirmed in NOD2-deficient DCs, such as DCs from selected Crohn's disease patients. Thus, antibacterial Th17-mediated immunity in humans is orchestrated by DCs upon sensing bacterial NOD2-ligand MDP.


Effect of Silicon on Micronutrient Content in New Potato Tubers.
Since silicon can improve nutrient uptake in plants, the effect of foliar silicon (sodium metasilicate) application on micronutrient content in early crop potato tuber was investigated. Silicon was applied at dosages of 23.25 g Si∙ha-1 or 46.50 g Si∙ha-1 (0.25 L∙ha-1 or 0.50 L∙ha-1 of Optysil) once at the leaf development stage (BBCH 14-16), or at the tuber initiation stage (BBCH 40-1), and twice, at the leaf development and tuber initiation stages. Potatoes were harvested 75 days after planting (the end of June). Foliar-applied silicon reduced the Fe concentration and increased Cu and Mn concentrations in early crop potato tubers under water deficit conditions but did not affect the Zn, B, or Si concentrations. The dosage and time of silicon application slightly affected the Fe and Cu concentration in the tubers. Under drought conditions, the highest Mn content in the tuber was observed when 46.50 g Si∙ha-1 was applied at the leaf development stage, whereas under periodic water deficits, it was highest with the application of the same silicon dosage at the tuber initiation stage (BBCH 40-41). The Si content in tubers was negatively correlated with the Fe and B content, and positively correlated with the Cu and Mn content.


Hydration of the calcium dication: direct evidence for second shell formation from infrared spectroscopy.
Infrared laser action spectroscopy in a Fourier-transform ion cyclotron resonance mass spectrometer is used in conjunction with ab initio calculations to investigate doubly charged, hydrated clusters of calcium formed by electrospray ionization. Six water molecules coordinate directly to the calcium dication, whereas the seventh water molecule is incorporated into a second solvation shell. Spectral features indicate the presence of multiple structures of Ca(H2O)(7)2+ in which outer-shell water molecules accept either one (single acceptor) or two (double acceptor) hydrogen bonds from inner-shell water molecules. Double-acceptor water molecules are predominantly observed in the second solvent shells of clusters containing eight or nine water molecules. Increased hydration results in spectroscopic signatures consistent with additional second-shell water molecules, particularly the appearance of inner-shell water molecules that donate two hydrogen bonds (double donor) to the second solvent shell. This is the first reported use of infrared spectroscopy to investigate shell structure of a hydrated multiply charged cation in the gas phase and illustrates the effectiveness of this method to probe the structures of hydrated ions.


A mathematical theory of relational generalization in transitive inference.
Humans and animals routinely infer relations between different items or events and generalize these relations to novel combinations of items ("compositional generalization"). This allows them to respond appropriately to radically novel circumstances and is fundamental to advanced cognition. However, how learning systems (including the brain) can implement the necessary inductive biases has been unclear. Here we investigated transitive inference (TI), a classic relational task paradigm in which subjects must learn a relation (A > B and B > C) and generalize it to new combinations of items (A > C). Through mathematical analysis, we found that a broad range of biologically relevant learning models (e.g. gradient flow or ridge regression) perform TI successfully and recapitulate signature behavioral patterns long observed in living subjects. First, we found that models with item-wise additive representations automatically encode transitive relations. Second, for more general representations, a single scalar "conjunctivity factor" determines model behavior on TI and, further, the principle of norm minimization (a standard statistical inductive bias) enables models with fixed, partly conjunctive representations to generalize transitively. Finally, neural networks in the "rich regime," which enables representation learning and often leads to better generalization, deviate in task behavior from living subjects and can make generalization errors. Our findings show systematically how minimal statistical learning principles can explain the rich behaviors empirically observed in TI in living subjects, uncover the mechanistic basis of transitive generalization in standard learning models, and lay out a formally tractable approach to understanding the neural basis of relational generalization.


Efficacy of antimicrobial photodynamic therapy for root canals infected with Enterococcus faecalis.
Effective decontamination of root canal systems is a constant concern in clinical practice. In this article, we compare the performance of photodynamic therapy (PDT) and sodium hypochlorite (NaOCl) in reducing the amount of Enterococcus faecalis in root canals. Relevant studies were identified by searching electronic databases, including Web of Science, PubMed, BVS (Medline, Scielo, Lilacs and BBO), Scopus, and Cochrane, and by manually searching the references of identified studies. The terms used in the literature search were "photodynamic therapy" and "Enterococcus faecalis". We selected 13 experimental studies that exclusively assessed the performance of PDT in reducing E. faecalis in root canals of human teeth. In an evaluation of methodological quality, 12 articles were classified as moderate-quality reports and 1 as a high-quality report. No article needed to be excluded because of low-quality methodology. The results showed that PDT had a better antimicrobial effect when used as an adjuvant endodontic treatment to NaOCl. However, this finding should be carefully interpreted, as there are few relevant studies and the methods of the selected studies varied.


Nuclear pore clustering is a consistent feature of apoptosis in vitro.
Two cell lines which show different patterns of DNA fragmentation have been examined for variations of their nuclear morphology during apoptosis. FDCP-Mix, a pluripotent murine haemopoietic stem cell line which undergoes typical internucleosomal cleavage of DNA when induced to apoptosis either by drugs or withdrawal of growth factor (IL-3) was compared with the human lymphoid leukemia cell line MOLT-4, a cell line which undergoes apoptosis without production of a typical DNA 'ladder'. The nuclear morphology of FDCP-Mix cells was consistent after apoptotic induction by drug or by growth factor withdrawal. Apoptotic nuclear morphology for MOLT-4 and FDCP-Mix showed variations in the distribution, density and texture of the electron dense nuclear marginations. Despite these differences, clustering of nuclear pore complexes (NPCs) after treatment with the topoisomerase II inhibitor etoposide was a common phenomenon for both cell lines. Moreover, pore clustering for FDCP-Mix nuclei occurred independently from the way in which apoptosis was induced, either by growth factor withdrawal or etoposide treatment. In a novel approach, we visualised the clustering of NPCs three-dimensionally by field emission in-lens scanning electron microscopy (FEISEM).


miR-205-5p downregulation decreases gemcitabine sensitivity of breast cancer cells via ERp29 upregulation.
Breast cancer is the most common cancer in women worldwide, and the incidence and mortality rates are increasing every year. Dysregulation of microRNAs (miRNAs or miRs) is an important step in the initiation and development of breast cancer. Previous studies demonstrated that miR-205-5p is closely associated with occurrence and development of breast cancer; however, underlying mechanisms remain unclear. In the present study, reverse transcription-quantitative polymerase chain reaction assays were used to analyze miR-195-5p and endoplasmic reticulum protein 29 (ERp29) levels in breast cancer and matched normal tissues. Western blot analysis was performed to analyze ERp29 and heat shock protein 27 (HSP27) protein expression levels. Cell viability, flow cytometry and luciferase reporter assay were used to examine cell proliferation, apoptosis and direct miRNA-mRNA binding, respectively. The results revealed that miR-205-5p expression in breast cancer tissues and cell lines was decreased compared with normal tissues and a normal cell line. Overexpression of miR-205-5p significantly augmented cytotoxicity effects of gemcitabine treatment in MDA-MB-231 and BT549 cells. It was observed that miR-205-5p negatively regulated ERp29 expression in breast cancer cells. Dual luciferase assays confirmed that ERp29 was a target of miR-205-5p in breast cancer cells. Additionally, following the established gemcitabine-resistant MDA-MB-231 cells (MDA-MB-231/GEM), ERp29 and HSP27 expression was upregulated and miR-205-5p was downregulated compared with parental cells. Overexpression of miR-205-5p reversed gemcitabine resistance in MDA-MB-231/GEM cells. In conclusion, the present study indicated that miR-205-5p may inhibit gemcitabine resistance in breast cancer cells via inhibition of ERp29 expression.


Possible mechanisms for the anticonvulsant activity of fructose-1,6-diphosphate.
Fructose-1,6-diphosphate (FDP), an intracellular metabolite of glucose, has anticonvulsant activity in several models of acute seizures in laboratory animals. The anticonvulsant effect of FDP is most likely due to a direct effect since intraperitoneal and oral administration results in significant increases in brain levels. A number of mechanisms have been proposed for this action of FDP. One possibility is that peripheral administration of FDP results in changes in brain metabolism that are anticonvulsant. Glucose can be metabolized through the glycolytic or pentose phosphate pathway. There is evidence that the pentose phosphate pathway is more active in the brain than in other tissues, and that, in the presence of elevated levels of FDP, the majority of glucose is metabolized by the pentose phosphate pathway. The pentose phosphate pathway generates NADPH, which is used to reduce glutathione. The reduced form of endogenous glutathione has been shown to have anticonvulsant activity. Taken together, the data suggest a hypothesis that exogenously administered FDP gets into the brain and astrocytes where it increases the flux of glucose through the pentose phosphate pathway, generating additional NADPH for the reduction of glutathione.


Angiotensinogen and AT1R expression in cerebral and femoral arteries during hindlimb unloading in rats.
Studies aimed at elucidating the role of the vascular renin-angiotensin system (RAS) in the mechanism of vascular adaptation to microgravity will also lead to a better understanding of vascular health issues of astronauts during future long-duration spaceflight. The aim of the present study was to elucidate whether the expression of the key components of vascular RAS, angiotensinogen (Ao), and angiotensin II receptor type 1 (AT1R) is differentially regulated in cerebral and hindquarter arteries during simulated microgravity. Tail-suspended hind limb unloading (HLU) for 1 and 4 wk were used to simulate the cardiovascular effect of microgravity. Changes of gene and protein expression of Ao and AT1R in cerebral and femoral arterial tissues were examined by conventional and real-time reverse transcription polymerase chain reaction and Western blot analysis. After 1 wk of simulated microgravity, there were no significant differences in gene [normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH)] and protein (normalized to beta-actin) expressions of Ao and AT1R in cerebral and femoral arterial tissues between control and HLU rats. However, after a 4-wk simulated microgravity, as compared with control, the mRNA expressions of Ao, and AT1a and AT1b in cerebral arterial tissue were significantly increased (1.45 +/- 0.14, 1.30 +/- 0.11, and 1.63 +/- 0.22-fold, respectively), and Ao mRNA expression (real-time PCR) and AT1a mRNA expression in femoral arterial tissue were significantly decreased (0.56 +/- 0.05 and 0.71 +/- 0.09-fold, respectively) in HLU rats. After a 4-wk simulated microgravity, protein expressions of Ao and AT1R in cerebral arterial tissue were significantly increased (2.09 +/- 0.55 and 1.38 +/- 0.14-fold, respectively). Whereas in femoral arterial tissue, AT1 protein expression decreased significantly (0.62 +/- 0.06-fold), but that of Ao just showed a trend of decrease. Our findings have demonstrated that a mid-term simulated microgravity might up- and down-regulate the gene and protein expressions of Ao and AT1R in cerebral and femoral arterial tissues of rats, suggesting the important role of the vascular RAS in mediating and modulating vascular adaptation during microgravity exposure.


The impact of fragmented QRS on clinical findings and outcomes in children with dilated cardiomyopathy with or without left ventricular non-compaction.
The aim of this study is to investigate the frequency of fragmented QRS and its associations with clinical findings and prognosis in children diagnosed with dilated cardiomyopathy with or without left ventricular non-compaction. This retrospective study was conducted between 2010 and 2020. Patients with dilated cardiomyopathy were classified into two groups according to the presence of left ventricular non-compaction: Dilated cardiomyopathy with left ventricular non-compaction and dilated cardiomyopathy without left ventricular non-compaction. Patients were also divided into two groups according to the presence of fragmented QRS (fragmented QRS group and non-fragmented QRS group). Twenty-three of 44 patients (52.3%) were male. Among left ventricular non-compaction patients, the fragmented QRS group had more complex ventricular arrhythmias (p = 0.003). Patients with fragmented QRS had a significantly higher rate of major adverse cardiac events and/or cardiac death in both cardiomyopathy groups (p = 0.003 and p = 0.005). However, the rate of major adverse cardiac events and/or cardiac death was similar between dilated cardiomyopathy patients with and without left ventricular non-compaction. Multivariate logistic regression analysis showed that the presence of fragmented QRS strongly predicts major adverse cardiac events and/or cardiac death (odds ratio, 31.186; 95% confidence interval, 2.347-414.307). Although the survival rates between cardiomyopathy groups were similar, patients with fragmented QRS had a markedly lower survival rate during the follow-up period, as mean of 15 months (p = 0.001). Our study showed that the presence of fragmented QRS may be an important ECG sign predicting an major adverse cardiac event and/or cardiac death in patients with dilated cardiomyopathy. We believe that recognising fragmented QRS could be valuable in forecasting patient prognosis and identifying high-risk patients who require additional support.


[Advances in the study of vasovasostomy under the microscope].
Approximately 10-15% of the cases of male infertility worldwide are caused by obstructive azoospermia. Vasovasostomy (VV) is a gold-standard treatment of this disease, but the success rate of conventional VV remains low for failure to anastomose the vas deferens accurately. Fortunately, microscopy makes the field of vision clearer and greatly increases the success rate of vas deferens recanalization and pregnancy. VV under the microscope, including microsurgical VV, robot-assisted microsurgical VV, and laparoscope-assisted microsurgical VV, is of great importance for the treatment of male infertility. This article reviews the progress in the study of VV under the microscope.


Relationship between Divergent Thinking and Intelligence: An Empirical Study of the Threshold Hypothesis with Chinese Children.
The threshold hypothesis is a classical and notable explanation for the relationship between creativity and intelligence. However, few empirical examinations of this theory exist, and the results are inconsistent. To test this hypothesis, this study investigated the relationship between divergent thinking (DT) and intelligence with a sample of 568 Chinese children aged between 11 and 13 years old using testing and questionnaire methods. The study focused on the breakpoint of intelligence and the moderation effect of openness on the relationship between intelligence and DT. The findings were as follows: (1) a breakpoint at the intelligence quotient (IQ) of 109.20 when investigating the relationship between either DT fluency or DT flexibility and intelligence. Another breakpoint was detected at the IQ of 116.80 concerning the correlation between originality and intelligence. The breakpoint of the relation between the composite score of creativity and intelligence occurred at the IQ of 110.10. (2) Openness to experience had a moderating effect on the correlation between the indicators of creativity and intelligence under the breakpoint. Above this point, however, the effect was not significant. The results suggested a relationship between DT and intelligence among Chinese children, which conforms to the threshold hypothesis. Besides, it remains necessary to explore the personality factors accounting for individual differences in the relationship between DT and intelligence.


Brachypodium distachyon-Cochliobolus sativus Pathosystem is a New Model for Studying Plant-Fungal Interactions in Cereal Crops.
Cochliobolus sativus (anamorph: Bipolaris sorokiniana) causes spot blotch, common root rot, and kernel blight or black point in barley and wheat. However, little is known about the molecular mechanisms underlying the pathogenicity of C. sativus or the molecular basis of resistance and susceptibility in the hosts. This study aims to establish the model grass Brachypodium distachyon as a new model for studying plant-fungus interactions in cereal crops. Six B. distachyon lines were inoculated with five C. sativus isolates. The results indicated that all six B. distachyon lines were infected by the C. sativus isolates, with their levels of resistance varying depending on the fungal isolates used. Responses ranging from hypersensitive response-mediated resistance to complete susceptibility were observed in a large collection of B. distachyon (2n=2x=10) and B. hybridum (2n=4x=30) accessions inoculated with four of the C. sativus isolates. Evaluation of an F2 population derived from the cross between two of the B. distachyon lines, Bd1-1 and Bd3-1, with isolate Cs07-47-1 showed quantitative and transgressive segregation for resistance to C. sativus, suggesting that the resistance may be governed by quantitative trait loci from both parents. The availability of whole-genome sequences of both the host (B. distachyon) and the pathogen (C. sativus) makes this pathosystem an attractive model for studying this important disease of cereal crops.


microRNAs and Molecular Pathogenesis of Microcephaly.
Microcephaly is a clinical condition defined as a reduction in head circumference and brain volume. The abnormal brain size may result from pathological neural stem cell (NSC) proliferation, survival, differentiation and migration during the development of the cerebral cortex. This process is controlled by many factors, including microRNAs that normally silence target genes at the posttranscriptional level. In this review, we will discuss the roles of microRNAs involved in different stages of the cortical development to shed light on the pathogenesis of microcephaly. Understanding the molecular mechanisms of microRNA-mediated cortical development may help develop a means of microRNA-based diagnosis and treatment for microcephaly in humans.


Role of the Inserted α-Helical Domain in E. coli ATP-Dependent Lon Protease Function.
Multidomain ATP-dependent Lon protease of E. coli (Ec-Lon) is one of the key enzymes of the quality control system of the cellular proteome. A recombinant form of Ec-Lon with deletion of the inserted characteristic α-helical HI(CC) domain (Lon-dHI(CC)) has been prepared and investigated to understand the role of this domain. A comparative study of the ATPase, proteolytic, and peptidase activities of the intact Lon protease and Lon-dHI(CC) has been carried out. The ability of the enzymes to undergo autolysis and their ability to bind DNA have been studied as well. It has been shown that the HI(CC) domain of Ec-Lon protease is required for the formation of a functionally active enzyme structure and for the implementation of protein-protein interactions.


Dental students' perceptions about the endodontic treatments performed using NiTi rotary instruments and hand stainless steel files.
This study evaluated the perceptions of Brazilian undergraduate dental students about the endodontic treatments performed using NiTi rotary instruments and hand stainless steel. Data were collected using a questionnaire administered to undergraduate dental students enrolled in endodontic disciplines. The students were divided into 3 groups: G1, students who had treated straight canals with SS hand instruments; G2, students who had treated curved canals with SS hand instruments; and G3, students who had treated both straight and curved canals with NiTi rotary instruments. The number of endodontic treatments performed, types of treated teeth, students' learning, time spent, encountered difficulties, quality of endodontic treatment and characteristics of the employed technique were analyzed. There was a 91.3% rate of return for the questionnaires. Mandibular molars were the most frequently treated teeth, followed by maxillary incisors. The Kruskal-Wallis test showed no differences in learning (p=0.528) or in the characteristics of the technique employed (p=0.560) among the three groups. G3 students performed a greater number of endodontic treatments (p<0.001) in a smaller time (p<0.001) than did G1 and G2 students. Difficulties were reported primarily by students in G2 and G3 compared with G1 (p=0.048). The quality of endodontic treatments differed only between G1 and G2 (p=0.045). The use of NiTi rotary instruments should be included in undergraduate dental curriculum, contributing to the increase of patients assisted and consequently to improve the clinical experience of the students.


Self-care problems of adolescents with type 1 diabetes in southern Taiwan.
The purpose of this study was to explore problems encountered in self-care of adolescents with type 1 diabetes (type 1 + insulin-dependent diabetes mellitus) from a patient-oriented perspective in Taiwan. Thirteen girls and six boys were recruited for participation. An open-ended, in-depth interview method was used for data collection. Findings revealed that 26.3% to 42.1% of the subjects' self-care activities were administered by parents, 36.8% did not use any meal plan, 10% could not manage their hypoglycemia well, and 36.8% had difficulties following prescribed regimens and tried alternative therapies such as herbal medicines or nutrient supplements. Results indicate the importance of parents encouraging their children to take on self-care responsibilities. Professional staffs also need to help modify contents and schedules of regimens for each adolescent patient.


Telemedicine Assessment for the Mental Health of Rural Residents Based on the Safety Degree of Housing in Seismically Active Regions.
Earthquakes inevitably affect the mental health of local residents. In seismically active regions of Southwest China, local rural residents' dilapidated housing with poor seismic performance aggravates the impacts of earthquakes on their mental health. These residents' mental health is difficult to recognize because of the lack of appropriate assessment methods. In addition, rural residents in the area have a low socioeconomic status and cannot access adequate mental treatment. Thus, telemedicine could be an effective approach to assist mental health practice in such areas. However, the lack of telemedicine assessment factors in these areas makes it difficult to complete the correct triage and prioritization of rural residents' mental health quickly and effectively. To provide a foundation for applying telemedicine to assess the risk of mental health problems that rural residents in seismically active regions experience, this paper studied whether the degree of safety of housing can affect mental health. In this study, nine villages near the epicenter of the 2019 6.0-magnitude earthquake in Changning County, China were randomly selected, and 162 valid questionnaires were completed. SPSS statistical software was used to analyze the collected data. First, the satisfaction of rural residents with the degree of safety of housing significantly affected the K6 score and whether they suffered from mental problems. Second, the mental health of rural residents living in reinforced concrete frame structure housing was obviously superior to that of those living in other types of housing. Next, the most significant factor affecting mental health was the degree of wall cracks. Finally, a new approach was developed to assess and prioritize the mental health of rural residents by using degrees of housing safety and smart technology in seismically active regions. The telemedicine assessment approach is expected to be used in the future for mental health evaluation and the large-scale data scoring of rural residents.


[Hypersensitization of alpha-adrenoreceptor of artery smooth muscle in hypertensive rats and hypertensive patients].
To investigate the hypersensitization of alpha-adrenoreceptor of artery smooth muscle in hypertensive patients and rats and the mechanisms concerned. Isometric tension of artery ring segments was recorded by a sensitive myograph system in vitro and the relative amount of alpha-adrenoreceptor mRNA was quantified by a real-time PCR. Noradrenaline (NA)-induced concentration-contraction curve of mesenteric artery segments in spontaneously hypertensive rats (SHR) was more potent than that in Wistar-Kyoto (WKY) rats. The E(max) of NA in SHR was 1.82 times of that of WKY. The concentration-contractile curve induced by NA in great omental arteries of hypertensives significantly shifted toward left and the pD2 value of NA was larger than that of normotensives. After organ culture, the concentration-contractile curves of SD rat mesenteric artery induced by NA shifted toward left with significantly increased E(max). The relative amounts of mRNA for alpha1-adrenoreceptor was increased, but mRNA level for alpha2-adrenoreceptor did not change. The sensitivity of alpha1-adrenoreceptor of artery smooth muscle in hypertensive man and rat is enhanced, suggesting alpha1-adrenoreceptor is upregulated.


Sonographic features of benign papillary neoplasms of the breast: review of 22 patients.
The sonographic features of 22 patients with histologically benign intraductal papillomas are presented, with clinical, mammographic, galactographic, and histopathologic correlation. The most common presenting feature in this series is a palpable central breast mass in an elderly woman. Sonography was abnormal in all 22 patients. The typical sonographic features include a well-defined, smooth-walled, solid, hypoechoic nodule or a lobulated, smooth-walled, cystic lesion with solid components. Dilated ducts are a common feature, often with visible solid intraluminal echoes. These findings suggest the diagnosis of an intraductal papilloma. The differential diagnosis includes fibroadenoma and phyllodes tumor (for large solid lesions) and intracystic carcinoma (for complex cystic lesions). Mammograms are frequently normal (36% of patients). When abnormal, the mammographic features are of a smooth-walled, well-defined mass or increased retroareolar opacity. Contrary to the reported literature, calcification was seen infrequently. We conclude that ultrasonography is useful in the detection and delineation of intraductal papillomas.


Comparison of allergic aspermatogenesis with that induced by vasectomy. I. In vivo studies in the guinea-pig.
Groups of male and female guinea-pigs were immunized with homologous epdidymal sperm in Freund's complete adjuvant (FCA) and skin tested at weekly intervals with a heat-treated extract of the sperm or with PPD. In females, the skin response to both antigens was similar to that to any standard protein antigen. In males, the response to sperm extract varied with the induced auto-immune orchitis, reaching a maximum immediately after testis lesion was most severe and as recovery was beginning (shown histologically): the response to PPD was decreased at 1 week after immunization, but subsequently was similar to that in females. Skin tests on guinea-pigs 8 months after bilateral vasectomy (when both ends of vasa were ligated), showed no evidence of delayed hypersensitivity to sperm, although there was marked histological evidence of reduced spermatognesis, due to back pressure atrophy.


Membrane filtration enzyme immunoassay, a novel, rapid method for measurement of virus-specific immunoglobulins G and M and detection of viral antigens.
A novel membrane filtration enzyme immunoassay (MF EIA) is described in which virus-antibody complexes formed are trapped onto the surface of membranes with low protein-binding affinity by vacuum filtration. Class-specific immunoglobulin G (IgG) or IgM antibody was measured by adding enzyme-conjugated antiimmunoglobulin and incubating prior to the final wash and addition of enzyme substrate. Influenza A virus-specific IgG antibodies measured by MF EIA showed similar sensitivity for detecting seroconversion in volunteers administered influenza virus subunit vaccines and subtype specificity comparable to that observed by the hemagglutination inhibition technique. Cytomegalovirus-specific IgG antibodies measured by MF EIA with commercially available complement fixation antigens gave results similar to those of conventional enzyme-linked immunosorbent assay and complement fixation tests. The MF EIA method is also suitable for detection of rotavirus antigen in feces.


Cylindromatosis Tumor Suppressor Protein (CYLD) Deubiquitinase is Necessary for Proper Ubiquitination and Degradation of the Epidermal Growth Factor Receptor.
Cylindromatosis tumor suppressor protein (CYLD) is a deubiquitinase, best known as an essential negative regulator of the NFkB pathway. Previous studies have suggested an involvement of CYLD in epidermal growth factor (EGF)-dependent signal transduction as well, as it was found enriched within the tyrosine-phosphorylated complexes in cells stimulated with the growth factor. EGF receptor (EGFR) signaling participates in central cellular processes and its tight regulation, partly through ubiquitination cascades, is decisive for a balanced cellular homeostasis. Here, using a combination of mass spectrometry-based quantitative proteomic approaches with biochemical and immunofluorescence strategies, we demonstrate the involvement of CYLD in the regulation of the ubiquitination events triggered by EGF. Our data show that CYLD regulates the magnitude of ubiquitination of several major effectors of the EGFR pathway by assisting the recruitment of the ubiquitin ligase Cbl-b to the activated EGFR complex. Notably, CYLD facilitates the interaction of EGFR with Cbl-b through its Tyr15 phosphorylation in response to EGF, which leads to fine-tuning of the receptor's ubiquitination and subsequent degradation. This represents a previously uncharacterized strategy exerted by this deubiquitinase and tumors suppressor for the negative regulation of a tumorigenic signaling pathway.


Insights into remodeling events during eukaryotic large ribosomal subunit assembly provided by high resolution cryo-EM structures.
Ribosomes are responsible for translating the genome, in the form of mRNA, into the proteome in all organisms. Biogenesis of ribosomes in eukaryotes is a complex process involving numerous remodeling events driven in part by the concerted actions of hundreds of protein assembly factors. A major challenge in studying eukaryotic ribosome assembly has, until recently, been a lack of structural data to facilitate understanding of the conformational and compositional changes the pre-ribosome undergoes during its construction. Cryo-electron microscopy (cryo-EM) has begun filling these gaps; recent advances in cryo-EM have enabled the determination of several high resolution pre-ribosome structures. This review focuses mainly on lessons learned from the study of pre-60S particles purified from yeast using the assembly factor Nog2 as bait. These Nog2 particles provide insight into many aspects of nuclear stages of 60S subunit assembly, including construction of major 60S subunit functional centers and processing of the ITS2 spacer RNA.


Are spatial frequency cues used for whisker-based active discrimination?
Rats are highly skilled in discriminating objects and textures by palpatory movements of their whiskers. If they used spatial frequency cues, they would be able to optimize performance in a stimulus dependent way-by moving their whisker faster or slower across the texture surface, thereby shifting the frequency content of the neuronal signal toward an optimal working range for perception. We tested this idea by measuring discrimination performance of head-fixed rats that were trained to actively sample from virtual grids. The virtual grid mimicked discrete and repetitive whisker deflections generated by real objects (e.g., grove patterns) with single electrical microstimulation pulses delivered directly to the barrel cortex, and provided the critical advantage that stimuli could be controlled at highest precision. Surprisingly, rats failed to use the spatial frequency cue for discrimination as a matter of course, and also failed to adapt whisking patterns in order to optimally exploit frequency differences. In striking contrast they could be easily trained to discriminate stimuli differing in electrical pulse amplitudes, a stimulus property that is not malleable by whisking. Intermingling these "easy-to-discriminate" discriminanda with others that solely offered frequency/positional cues, rats could be guided to base discrimination on frequency and/or position, albeit on a lower level of performance. Following this training, abolishment of electrical amplitude cues and reducing positional cues led to initial good performance which, however, was unstable and ran down to very low levels over the course of hundreds of trials. These results clearly demonstrate that frequency cues, while definitely perceived by rats, are of minor importance and they are not able to support consistent modulation of whisking patterns to optimize performance.


Role of tight junctions in establishing and maintaining cell polarity.
The tight junction (TJ) is not randomly located on the cell membrane, but occupies a precise position at the outermost edge of the intercellular space and, therefore, is itself considered a polarized structure. This article reviews the most common experimental approaches for studying this relationship. We then discuss three main topics. (a) The mechanisms of polarization that operate regardless of the presence of TJs: We explore a variety of polarization mechanisms that operate at stages of the cell cycle in which TJs may be already established. (b) TJs and polarity as partners in highly dynamic processes: Polarity and TJs are steady state situations that may be drastically changed by a variety of signaling events. (c) Polarized distribution of membrane molecules that depend on TJs: This refers to molecules (mainly lipids) whose polarized distribution, although not the direct result of TJs, depends on these structures to maintain such distribution.


Comparison of pulse wave velocity derived from accelerometer and reflective photo-plethysmography signals placed at the carotid and femoral artery.
Carotid - femoral pulse wave velocity is an established measure to assess cardiovascular risk and an interesting surrogate parameter towards non-invasive continuous blood pressure inference. Due to progress in sensing technologies for wearable wrist worn sensors, there are low cost sensor combinations of photo-plethysmography and high fidelity accelerometers available offering access to pulse information from larger arteries complemented by blood volume changes in the superficial tissue. In this work we compare pulse wave velocities derived from accelerometer and reflective photo-plethysmography signals placed at the carotid and femoral artery. We discuss the different underlying physiological processes for the two sensing principles and present experimental results obtained in a study with healthy subjects.


A Sequential Dual Functional Supramolecular Hydrogel with Promoted Drug Release to Scavenge ROS and Stabilize HIF-1α for Myocardial Infarction Treatment.
Myocardial infarction (MI) has a characteristic inflammatory microenvironment due to the overproduction of reactive oxygen species (ROS) and causes the extraordinary deposition of collagen and thereby fibrosis. An on-demand adaptive drug releasing hydrogel is designed to modulate the inflammatory microenvironment and inhibit cardiac fibroblasts (CFs) proliferation post MI by scavenging the overproduced ROS and releasing 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (DPCA) to maintain the expression of hypoxia-inducible factor 1α (HIF-1α). DPCA is prefabricated to a prodrug linked with disulfide bond (DPCA-S-S-OH). The DPCA-S-S-OH and carboxylated calixarene (CSAC4A) are grafted onto the backbone of methacrylated hyaluronic acid (HAMA) to obtain HAMA-S-S-DPCA and HAMA-CA, respectively, which are further reacted to form a dual network hydrogel (R+ /DPCA(CA)) with covalent linking and host-guest interaction between DPCA and CSAC4A. The ROS-triggered hydrolysis of ester bond and subsequently sustaining release of DPCA from the cavity of CSAC4A jointly cause the constant expression of HIF-1α, which significantly restricts the CFs proliferation, leading to suppressed fibrosis and promoted heart repair.


Rapid detection of Pneumocystis carinii in bronchoalveolar lavage samples by using Cellufluor staining.
Cellufluor (Calcofluor white) has been found to be a useful, rapid chemofluorescent stain for detection of Pneumocystis carinii cysts in bronchoalveolar lavage samples. When compared with toluidine blue O and Giemsa stains on 45 specimens (22 positive and 23 negative), the sensitivity and specificity of the Cellufluor stain were 95 and 100%, respectively.


Epidermal inclusion cyst in the foot of a Vietnam Veteran.
Epidermal inclusion cysts are soft-tissue lesions that result from traumatic implantation of epidermal cells into the dermis. A case report is presented involving a large recurrent plantar inclusion cyst secondary to trauma sustained in the Vietnam War. The patient reported that the initiating trauma was the result of stepping on a punji stake in Vietnam. Punji stakes, sharpened spikes typically made of bamboo and dipped in poison or excrement, were used by the Vietnamese soldiers to wound enemy soldiers. Careful excision of the lesion is imperative to prevent recurrence.


Helicobacter pylori: an underestimated factor in acute anterior uveitis and spondyloarthropathies?
Acute anterior uveitis (AAU) is the most common form of intraocular inflammation, but its aetiology is still unclear. Fifty percent of AAU patients are HLA-B27-positive, and half of these also have spondyloarthropathies (SpA). Numerous serological studies have shown elevated levels of serum antibodies to various Gram-negative bacteria in HLA-B27-positive AAU and SpA patients. Antigenic similarities between these bacteria and host components (HLA-B27) have already been shown. Still, the mechanism underlying these diseases has not been clarified. Among the Gram-negative bacteria, Helicobacter pylori has not been screened in AAU patients. The purpose of our study was to see if this common human pathogen somehow interferes with AAU. In addition Chlamydia trachomatis, Yersinia enterocolitica 03 and 09, Salmonella sp. and Proteus OX19 were also examined. A total of 60 patients consisting of 4 groups (15 patients with AAU, 15 with SpA, 15 with AAU+SpA and 15 healthy control persons) were examined. A high percentage of the serological results of all investigated bacteria was positive: 80% in the AAU, 93.3% in the SpA and 100% in the AAU+SpA group, while it amounted to 66.7% in the control group (p < 0.05). H. pylori showed the highest percentage of positivity in all 3 patient groups (66.7% in the AAU, 73.3% in the SpA and 80% in the AAU+SpA group). In contrast, 26.7% of the controls were anti-H.-pylori-positive, thus showing a statistically significant difference between the patients and the control group (p < 0.05). HLA-B27/B7-CREG positivity was detected in 53.3% of the AAU, 66.7% of the SpA and 93.3% of the AAU+SpA patients and in none of the controls. Our results suggest that H. pylori might be a candidate participating in the development of AAU and SpA. They also support the theory of genetic (HLA-B27) and exogenous factors (Gram-negative bacteria) as probable background of these diseases.


Healthcare interventions for the prevention and control of gestational diabetes mellitus in China: a scoping review.
Gestational Diabetes Mellitus (GDM) is a type of diabetes which occurs during pregnancy. Women with GDM are at greater risk of complications during pregnancy and delivery, while babies born from mothers with GDM are at greater risk of post-natal complications. Using the most updated diagnosis criteria, the GDM prevalence is estimated at 9.3-25.5% worldwide and 9.3-18.9% in China. Our objective was to identify healthcare interventions aimed at GDM prevention and control in China. A best-evidence synthesis was performed based on a systematic search of literature published between 1997 and October 2015 in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan-fang databases using keywords "Gestational Diabetes Mellitus", "GDM", "Intervention" "Medical Intervention" "Early Medical Intervention", "Dietary Intervention", "Exercise Intervention", "Lifestyle Intervention", "Therapy", "Treatment" and "China". Inclusion criteria were studies conducted in China, reporting GDM healthcare interventions, and published in either Chinese or English. Two reviewers independently assessed eligibility and quality of the studies and extracted the data. Treatment efficacy was examined with weighted pooled odds ratio (OR) meta-analyses. The search resulted in 5961 articles (published in 276 different Chinese language journals and 6 English language journals), of which 802 were included in this synthesis. While 39.4% (n = 316) failed to report the GDM diagnostic criteria used, the remaining studies classified GDM with various international (n = 5) or Chinese (n = 7) diagnostic standards. Treatment interventions were categorized into 6 types: dietary (18.6%), exercise (1.6%), medication (20.7%), health education (9.0%), psychological (2.6%) and combination (47.4%). No interventions aimed at GDM prevention were identified. Meta-analyses demonstrated a statistically significant overall benefit of GDM treatment strategies in reducing the odds of maternal and infant adverse outcomes (ORs range 0.20-0.34, 95% CI 0.17-0.49, P < 0.05 for all). Dietary, western medication, and combined interventions were the most effective inteventions. An increasing number of healthcare interventions were found in China aimed at controlling GDM while no interventions were intended for GDM prevention. Well-designed clinical trials are needed to determine the comparative and cost effectiveness of GDM prevention and treatment strategies.


A randomized controlled trial comparing two educational booklets on prostate cancer.
To compare the helpfulness of two educational aids or booklets on early-stage prostate cancer. Participating consecutive patients and a family member, in three centres, received one of two booklets, one produced by AstraZeneca (AZ), the other produced by us (CCE); the patient and family shared a booklet but were separate study participants. The primary outcome was the Purpose-based Information Assessment completed after participants read their booklet; they rated the importance (4-point Likert scale) of six potential purposes for the information: to help organize their thoughts, understand their situations, decide on treatment, plan, provide emotional support to others, and discuss issues. Each participant then rated how helpful their booklet was (4-point Likert scale) in addressing each purpose they had rated above the lowest importance category. Participants mailed in their responses. Complete data were received from 308 (81%) of those who consented to the study: 152 in the CCE group and 156 in the AZ group. The CCE booklet was read for a longer time [chi(2) = 28.61, p = 0.00] but was easier to find information in chi(2) = 7.6, p = 0.05]. Although for each purpose, most readers rated each booklet in one of the top two (of four) helpfulness categories, the CCE booklet was rated more helpful for: organizing [chi(2) = 30.49, p = 0.00], understanding [chi(2) = 12.07, p = .007], deciding [chi(2) = 9.96, p = 0.02] and planning [chi(2) = 18.67, p = 0.00]. High helpfulness ratings of both booklets suggest that patients benefit from education aids while differences in the booklet ratings suggest that aids are not equally helpful. The CCE booklet, the more helpful booklet of this study, is a systematically developed education aid available to urologists in Canada.


Safety and efficiency of dexmedetomidine as adjuvant to local anesthetics.
To review the current knowledge of dexmedetomidine as an additive drug to local anesthetics in peripheral and neuraxial regional anesthesia. Recent studies show a perineural mode of action of dexmedetomidine. Pharmacodynamic characteristics of peripheral and neuraxial regional anesthetic techniques are optimized by the addition of dexmedetomidine to long-acting local anesthetics. Bradycardia and sedation are the main systemic side-effects of dexmedetomidine for regional anesthesia purposes. A dose of approximately 100 μg dexmedetomidine for peripheral techniques may represent the optimal balance between optimization of block characteristics and side-effects. Doses between 3 and 10 μg are described to be sufficient for spinal administration. Dexmedetomidine has a potency to ameliorate pharmacodynamic characteristics of peripheral and neuraxial regional anesthetic techniques and is therefore currently the most promising additive drug in regional anesthesia. Future scientific efforts should focus on dose finding studies for particular regional anesthetic techniques. Approval of dexmedetomidine for regional anesthetic indications should be the final target.