Transcriptome sequencing reveals core regulation modules and gene signatures of Zusanli acupoints in response to different moxibustion warm stimulation in adjuvant arthritis rat.
The efficacy of moxibustion in treating rheumatoid arthritis is recognized, but its molecular mechanism is still unclear. This study aimed to characterize the molecular map and potential key genes in the process of different moxibustion warm at Zusanli acupoint treatment of adjuvant arthritis (AA) model. AA rat model was induced by complete Freund's adjuvant (CFA) and then accessed by foot swelling and thermal hyperalgesia test. Transcriptome sequencing, series test of cluster (STC) and weighted gene co-expression network analysis (WGCNA) were used in this study. CFA-induced inflammation, foot swelling, and pain in AA rats were significantly improved by moxibustion warm. Differentially expressed genes (DEGs) were screened in nine different comparison groups and a total of 4535 DEGs were identified, and these DEGs were preferentially clustered in inflammatory and immune-related pathways, such as MAPK signaling pathway. Only 1 DEG of heat shock protein 90, alpha (cytosolic), class A member 1 (Hsp90aa1) was shared in comparison groups of model with moxibustion treatment. STC analysis also revealed that Hsp90aa1 was increased in AA model, but decreased after 37 °C moxibustion intervention, and constantly decreased after 42 °C moxibustion treatment. GO and KEGG pathway analysis revealed that these genes enriched in inflammatory and immune-related pathways. Moreover, WGCNA identified that violet module was positively correlated with model temperature while negatively correlated with control, and the paleturquoise module was positively correlated with model. The violet and paleturquoise module gene were significantly enriched in MAPK signaling pathway. Importantly, Hsp90aa1 also played a central role in the violet module by interacting with multiple proteins. Moxibustion warm improved AA in rat, and we obtained the transcriptome profile and excavate a critical gene of Hsp90aa1, and provided insight into gene signatures for moxibustion warm at Zusanli acupoint in AA rat.


Pharmacokinetic and pharmacodynamic population modeling of orally administered rabeprazole in healthy Chinese volunteers by the NONMEM method.
The pharmacokinetic-pharmacodynamic (PK-PD) relationship of the proton pump inhibitor rabeprazole in healthy Chinese volunteers was characterized via a population approach. Healthy Chinese male volunteers were enrolled in the clinical trial. Subjects were divided into three groups by their CYP2C19 genotype. Serum concentrations of rabeprazole were determined using high performance liquid chromatography (HPLC). The intragastric pH values were monitored simultaneously. Data analysis was performed using nonlinear mixed-effects modeling as implemented in the NONMEM software package. The final PK-PD model incorporated a one-compartment PK model with one-order absorption from the gastroenteric trace, first-order elimination pathway with one fixed-effect genotype modeling, and a full sigmoidal Emax PD model (X +/- SE: E0 = 2.30 +/- 0.189; Emax = 7.32 +/- 0.662; EC50 = 51.3 +/- 2.142 ng/ml; Hill coefficient = 5.00 +/- 0.556). The time profiles for concentration and pH value, as well as the concentration-pH value relationship of rabeprazole in healthy Chinese volunteers were well described by the developed population PK-PD model.


Arthroscopic staple capsulorrhaphy: a long-term follow-up.
Fifty-four shoulders with recurrent anterior shoulder instability were evaluated following arthroscopic staple capsulorrhaphy. Average follow-up for those with only the index surgery was 39 months. Eighteen patients (33%) experienced at least one episode of postoperative instability. Ten underwent an open reconstructive procedure. Routine radiographs at time of follow-up demonstrated loose staples in 15% of asymptomatic patients. Range of motion was preserved following surgery. There was no loss of forward elevation. An average of 5 degrees of external rotation and one spinal segment in internal rotation were lost following surgery. Forty-three percent of overhead athletes were able to return to their preinjury level of activity. Caution should be taken when considering arthroscopic staple capsulorrhaphy as recurrence rates are higher than those following open reconstruction. However, range of motion and functional level are well-maintained. When capsulorrhaphy is performed, consideration should be given to routine staple removal following adequate capsular healing.


Photochemical switching of luminescence and singlet oxygen generation by chemical signal communication.
Photoluminescence in the far red spectral region and photosensitised generation of singlet oxygen, with associated near-IR emission, are reversibly controlled by near-UV or violet light in a communicating ensemble of molecular switches.


Effect Analysis of Different Environmental Disinfection Methods on Reducing Contamination of Surfaces by the Omicron BA.2.2 Variant of SARS-CoV-2 and the Characteristics of Fomite Contamination in the Fever Clinic in the Out-Broken of Shanghai.
This study aimed to investigate the effect of different environmental disinfection methods on reducing contaminated surfaces (CSs) by the Omicron BA.2.2 variant of SARS-CoV-2 in the fever clinic between March 20 and May 30, 2022, and to analyze the influences and related factors of CSs. This study includes survey data from 389 positive patients (SPPs) and 204 CSs in the fever clinic, including the CS type, disinfection method, length of time spent in the clinic, cycle threshold (CT) value, name, age, weight, mask type, mask-wearing compliance, hand-mouth touch frequency and sex. Associations between study variables and specified outcomes were explored using univariate regression analyses. Mask-wearing compliance had a significant negative correlation with CSs (r = - 0.446, P = 0.037). Among the 389 SPPs, 22 SPPs (CRP, 5.66%) caused CSs in the separate isolation room. A total of 219 SPPs (56.30%) were male. The mean age of SPPs was 4.34 ± 3.92 years old, and the mean CT value was 12.44 ± 5.11. In total, 9952 samples with exposure history were taken, including 204 (2.05%) CSs. Among the CSs, the positive rate of flat surfaces was the highest in public areas (2.52%) and separate isolation rooms (4.75%). Disinfection methods of ultraviolet radiation + chemical irradiation significantly reduced the CSs in both the public area (0% vs. 4.56%) and the separate isolation room (0.76% vs. 2.64%) compared with the chemical method alone (P < 0.05). Compared with ordinary SPPs, CRPs were older (6.04 year vs. 4.23 year), and the male proportion was higher (72.73% vs. 55.31%). In particular, it was found that SPPs contaminated their surroundings and therefore imposed risks on other people. Environmental disinfection with ultraviolet radiation + chemical treatment should be emphasized. The findings may be useful to guide infection control practices for the Omicron BA.2.2 variant of SARS-CoV-2.


Is waist circumference associated with fear of falling in community-dwelling older adults? A cross-sectional study.
Fear of falling (FOF) is a prevalent condition among older adults and several variables have been pointed out as risk factors. To identify the cut-off point on waist circumference (WC), capable of discriminating between older adults with and without FOF, and to test the association between WC and FOF. A cross-sectional observational study was carried out with older adults of both sexes from Balneário Arroio do Silva, Brazil. We used Receiver Operating Characteristic (ROC) curves to determine the cut-off point on WC and logistic regression adjusted for potential confounding variables to test the association. Older women with WC >93.5 cm [area under the curve: 0.61 (95%CI 0.53; 0.68)] had 3.30 (95%CI 1.53; 7.14) greater chances of having FOF compared with older women with WC ≤93.5 cm. WC was not able to discriminate FOF in older men. WC values >93.5 cm are associated with higher chances of FOF in older women.


Alveolar soft part sarcoma.
Alveolar soft part sarcoma is a neoplasm that usually presents as a slow-growing mass located in an extremity and is most often initially discovered by the patient, who then seeks medical evaluation (1, 2). Local pain or symptoms produced by metastases as the initial manifestations of this neoplasm are unusual (2). A case is presented in which CT demonstrated multiple metastases to the central nervous system that produced headaches as the first symptoms in a patient with alveolar soft part sarcoma.


Monoclonal antibodies to baculovirus structural proteins: determination of specificities by Western blot analysis.
Conventional mouse hybridoma technology was utilized to produce a panel of monoclonal antibodies which reacted with baculovirus proteins. Using an enzyme-linked immunosorbent assay (ELISA), the hybridomas which were raised against polyhedrin from Autographa californica nuclear polyhedrosis virus (AcNPV) and Choristoeura fumiferana nuclear polyhedrosis virus (CfNPV) were found to cross-react differentially with polyhedrins and granulins from several species of baculoviruses. Hybridoma antibodies which reacted against the nonoccluded form (NOV) of AcNPV in an ELISA test expressed different specificities for the occluded form of the virus (OV), a mutant strain of AcNPV, and CfNPV. Four hybridoma clones produced antibody which neutralized the infectivity of AcNPV NOV. One hybridoma antibody reacted strongly with the uninfected Spodoptera frugiperda host cell line. Using Western blot analysis, it was shown that hybridoma antibodies against polyhedrin reacted differentially with the complete polypeptide and protease-generated fragments of polyhedrin. The polypeptide specificity of 19 of 28 hybridoma antibodies which reacted with OV and NOV of AcNPV was assigned using Western blot analysis.


Estrogen receptors in breast carcinogenesis and endocrine therapy.
Excessive exposure to estrogen has long been associated with an increased risk for developing breast cancer and anti-estrogen therapy is the gold standard of care in the treatment of estrogen receptor (ER) α-positive breast cancers. However, there are several mysteries concerning both anti-estrogen, tamoxifen, and estrogen. The most important of these are: (1) some ERα-positive breast cancers do not respond to tamoxifen; (2) some ERα-negative breast cancers do respond to tamoxifen; (3) initial or acquired resistance to tamoxifen occurs with recurrent tumors; (4) estrogen can cause marked tumor regression in long-term tamoxifen-resistant ERα-positive breast cancer. These mysteries indicate that we do not know enough about estrogen signaling to understand the effects of targeting these receptors in cancer. The discovery of ERβ, the second estrogen receptor, has added another level of complexity to estrogen signaling. This review summarizes recent publications and makes an updated portrait of ERα and ERβ in breast carcinogenesis and endocrine cancer therapy.


A simple and reliable method for obtaining Entomosporium monoconidial isolates.
Monoconidial isolates of Entomosporium mespili were successfully cultured using a simple isolation procedure. A detailed description of the steps required for isolating E. mespili is provided. The characteristic pattern of conidial germination and growth on potato dextrose agar is also described. The process that was successful in obtaining pure isolates involved collecting material in the morning, picking a glistening white mass of conidia under dissecting microscope magnification, depositing a mass of conidia onto a drop of water on a glass slide, streaking the conidial mass onto potato dextrose agar, incubating the plate for 48 h, and transferring the characteristic fan-shaped colonies to fresh medium.


Colon cancer and polyps in acromegaly: increased risk associated with family history of colon cancer.
A cohort of 52 subjects diagnosed with acromegaly in southeastern Michigan and northern Ohio between 1935 and 1985 were followed to determine the incidence of colon cancer and polyps. Medical records were reviewed, subjects or their next-of-kin were interviewed, and screening examinations of the colon were offered to the living patients who were located. Data on demographics, personal histories of cancer and colon polyps, family history of colon cancer, and cure from acromegaly were obtained for both living and deceased subjects. The risk for colon cancer compared to the general population was estimated using standardized incidence ratios (SIRs). The expected number of cases was determined utilizing age, sex and race-specific rates provided by the cancer registry in southeastern Michigan. Among the 52 subjects, one could not be located and nine were deceased, none from colon cancer, with one known to have a history of colon polyps. Of 13 (31%) who declined the screening physical, one had a history of polyps and none reported a history of colon cancer. Two of 29 screened patients were found to have right-sided adenocarcinoma of the colon. Of the entire cohort, eight people (including one deceased) had a current or previous diagnosis of polyps, with five known to be histologically adenomatous. The SIR for colon cancer was 4.7 (95% confidence interval 0.6-17.1). Seven subjects, including the two with detected adenocarcinoma and four of the six living subjects with polyps only, reported a family history of colon cancer. The SIR for the subset of subjects with a family history of colon cancer was 29.1 (95% confidence interval of 3.5-104.6).(ABSTRACT TRUNCATED AT 250 WORDS)


Rapid, low cost prototyping of transdermal devices for personal healthcare monitoring.
The next generation of devices for personal healthcare monitoring will comprise molecular sensors to monitor analytes of interest in the skin compartment. Transdermal devices based on microneedles offer an excellent opportunity to explore the dynamics of molecular markers in the interstitial fluid, however good acceptability of these next generation devices will require several technical problems associated with current commercially available wearable sensors to be overcome. These particularly include reliability, comfort and cost. An essential pre-requisite for transdermal molecular sensing devices is that they can be fabricated using scalable technologies which are cost effective. We present here a minimally invasive microneedle array as a continuous monitoring platform technology. Method for scalable fabrication of these structures is presented. The microneedle arrays were characterised mechanically and were shown to penetrate human skin under moderate thumb pressure. They were then functionalised and evaluated as glucose, lactate and theophylline biosensors. The results suggest that this technology can be employed in the measurement of metabolites, therapeutic drugs and biomarkers and could have an important role to play in the management of chronic diseases.


First reported case of Steel syndrome in the European population: A novel homozygous mutation in COL27A1 and review of the literature.
Steel syndrome is an autosomal recessive disorder that primarily affects the skeletal system causing a variety of manifestations. Sixteen individuals with Steel syndrome, mainly Puerto Ricans (11/16), were previously reported to carry bi-allelic mutations in the COL27A1 gene. Here, we present the first patient with Steel syndrome in Europe and the sixth non-Puerto Rican carrying a novel homozygous mutation in COL27A1. The patient is a 4-year-old boy born to non-consanguineous healthy parents, with dysmorphic facial features, absent hip ossification centres, external rotation of both feet, relatively short stature, mild skin syndactyly, short mid phalanges and bilateral sensorineural hearing loss. Whole exome sequencing (WES) revealed a novel homozygous missense variant p.(Gly802Glu) in COL27A1. The homozygous mutation was confirmed by Sanger sequencing in the proband and carrier status was confirmed in both parents and his unaffected sibling. According to online and in-house minor allele frequency (MAF) databases, this is the first COL27A1 mutation reported in the European population. Additional screening of healthy Greek-Cypriot individuals was thus performed, which did not reveal any additional carriers in the population for the variant in question.


"Neuro-cardiovascular" surgery: innovations for the treatment and prevention of cardiovascular disease.
The concept of performing surgery on the conduction system and the nervous system of the heart with the use of peripheral nervous tissue, Purkinje fibers or biophysical means, may solve many enigmas concerning the treatment of arrythmias. More importantly, a correlation is suggested between coronary artery disease, the state of depolarization of the myocardial cells, local electrical and magnetic fields, the state of local innervation of coronary blood vessels, the activity of the specialized conducting system, and higher central nervous system centers. This suggested correlation may contribute significantly in the treatment, and eventually, in the prevention of coronary artery disease.


AAV-S: A versatile capsid variant for transduction of mouse and primate inner ear.
Gene therapy strategies using adeno-associated virus (AAV) vectors to treat hereditary deafnesses have shown remarkable efficacy in some mouse models of hearing loss. Even so, there are few AAV capsids that transduce both inner and outer hair cells-the cells that express most deafness genes-and fewer still shown to transduce hair cells efficiently in primates. AAV capsids with robust transduction of inner and outer hair cells in primate cochlea will be needed for most clinical trials. Here, we test a capsid that we previously isolated from a random capsid library, AAV-S, for transduction in mouse and non-human primate inner ear. In both mice and cynomolgus macaques, AAV-S mediates highly efficient reporter gene expression in a variety of cochlear cells, including inner and outer hair cells, fibrocytes, and supporting cells. In a mouse model of Usher syndrome type 3A, AAV-S encoding CLRN1 robustly and durably rescues hearing. Overall, our data indicate that AAV-S is a promising candidate for therapeutic gene delivery to the human inner ear.


Dual-band and dual-polarized reflective Fresnel zone plate design based on Fractal shape.
In this study, a dual-polarized and dual band reflective Fresnel zone plate with reconfigurable beam is proposed on the basis of fractal frequency selective surface (FSS) unit with nearly 360° phase tunability. Firstly, a new phase distribution calculation strategy based on Fresnel diffraction theory is proposed to improve the performance under certain scenarios like sparse arrays. Then, a novel fractal shape is put forward and applied to the design of the Fresnel zone plate. The introduction of the fractal structure makes the unit cell perform dual band, dual polarization and 309° phase tunability characteristics. Due to the self-symmetry of the unit cell, the proposed fractal Fresnel zone plate (FFZP) is capable of beam steering in ± 45° in both TE and TM incident waves. Besides, the proposed structure shows small performance degradation when it comes to oblique incidence up to 45°, which decreases the focal diameter ratio and profile of the proposed FFZP. The operating bandwidth of the FFZP can reach up to 700 MHz at X and Ku bands. It is applicable in a wide range of RF and microwave settings such as satellite and base station.


Common structural features of cholesterol binding sites in crystallized soluble proteins.
Cholesterol-protein interactions are essential for the architectural organization of cell membranes and for lipid metabolism. While cholesterol-sensing motifs in transmembrane proteins have been identified, little is known about cholesterol recognition by soluble proteins. We reviewed the structural characteristics of binding sites for cholesterol and cholesterol sulfate from crystallographic structures available in the Protein Data Bank. This analysis unveiled key features of cholesterol-binding sites that are present in either all or the majority of sites: i) the cholesterol molecule is generally positioned between protein domains that have an organized secondary structure; ii) the cholesterol hydroxyl/sulfo group is often partnered by Asn, Gln, and/or Tyr, while the hydrophobic part of cholesterol interacts with Leu, Ile, Val, and/or Phe; iii) cholesterol hydrogen-bonding partners are often found on α-helices, while amino acids that interact with cholesterol's hydrophobic core have a slight preference for β-strands and secondary structure-lacking protein areas; iv) the steroid's C21 and C26 constitute the "hot spots" most often seen for steroid-protein hydrophobic interactions; v) common "cold spots" are C8-C10, C13, and C17, at which contacts with the proteins were not detected. Several common features we identified for soluble protein-steroid interaction appear evolutionarily conserved.


Endometrial carcinoma complicated by malignant pericardial effusion: A case report on the therapeutic regimen.
High-stage endometrial carcinoma is an aggressive tumor with a high propensity for distant spread. However, metastases to the pericardium are rare in gynecological cancer, and are usually fatal. A 69-year-old woman was diagnosed with endometrial carcinoma with pericardium metastasis. The symptoms at presentation were panic and shortness of breath. The cytologic examination of pericardial fluid obtained by pericardiocentesis confirmed metastasis. In addition to cisplatin instilled into the pericardial space, for systemic chemotherapy, we chose that gemcitabine and lobaplatin regimen be preferred. The patient has been participating in telephone follow-up for 8 months and has generally remained in a good condition. Endometrial carcinoma can have pericardial metastases. When this happens, we recommend ultrasound-guided pericardial puncture and the pericardial injection of cisplatin, in combination with systemic chemotherapy that consists of gemcitabine and lobaplatin.


Worries About COVID-19 Infection and Psychological Distress at Work and While Commuting.
This study examined the relationship between worry about COVID-19 infection in the workplace and while commuting to work and psychological distress in Japan. An internet monitor study was conducted. Out of a total of 33,302 participants, 26,841 people were included. The subjects were asked single-item questions about whether they were worried about COVID-19 infection in general, at work and while commuting to work. K6 was used to assess psychological distress. The OR was significantly higher in association with worry about infection in the workplace at 1.71 (95%CI 1.53 to 1.92) and worry about infection while commuting at 1.49 (95%CI 1.32 to 1.67). This study suggests the need for psychological intervention to reduce worry about infection in response to public mental health challenges associated with the COVID-19 pandemic.


Enhancement of single-walled carbon nanotube accumulation in glioma cells exposed to low-strength electric field: Promising approach in cancer nanotherapy.
The objective of the study is to determine the patterns of regulation of single-walled carbon nanotube accumulation, distribution, and agglomeration in glioma cells exposed to an external electric field. C6 glioma cells were treated with 5 μg/ml DNA wrapped single-walled carbon nanotubes and exposed to bi-phasic electric pulses (6.6 V/m, 200 Hz, pulse duration 1 ms). Nanotube accumulation was determined by Raman microspectroscopy and their intracellular local concentration was evaluated using the G-band intensity in Raman spectra of single-walled carbon nanotubes. It was revealed that the low-frequency and low-strength electric field stimulation of glioma cells exposed to single-walled carbon nanotubes led to facilitation and, thus, to amplification of nanotube accumulation inside the cells. The number of nanotubes in intracellular agglomerates increased from (28.8 ± 13.1) un./agglom. and (84.0 ± 28.7) un./agglom. in control samples to (60.6 ± 21.4) un./agglom. and (184.2 ± 53.4) un./agglom. for 1 h and 2 h stimulation, respectively. Thus, the tumor exposure to an external electric field makes it possible to more effectively regulate the accumulation and distribution of carbon nanotubes inside glioma cells allowing to reduce the applied therapeutic doses of carbon nanomaterial delivered anticancer drugs.


Time-varying closed-loop modeling of autonomic control in pediatric obstructive sleep apnea syndrome during cold face stimulation.
Adults with obstructive sleep apnea syndrome (OSAS) are known to have impaired autonomic function but the corresponding effects in children appear to be more subtle. Model-based analysis of the cardiovascular response to cold face test (CFT) was used to quantify daytime autonomic dysfunction. The increase in transfer gain between respiration and RRI was not different between controls and OSAS. However, the transfer gain between "surrogate cardiac output" (pulse pressure+R-R interval) and systolic blood pressure (SBP) and the transfer gain between cardiac output and SBP both increased significantly in controls but not in OSAS during CFT. These findings suggest that the parasympathetic function remains relatively normal in pediatric OSAS, but cardiovascular sympathetic reactivity is impaired.


Pentaphosphaferrocene-mediated synthesis of asymmetric organo-phosphines starting from white phosphorus.
The synthesis of phosphines is based on white phosphorus, which is usually converted to PCl3, to be afterwards substituted step by step in a non-atomic efficient manner. Herein, we describe an alternative efficient transition metal-mediated process to form asymmetrically substituted phosphines directly from white phosphorus (P4). Thereby, P4 is converted to [Cp*Fe(η5-P5)] (1) (Cp* = η5-C5(CH3)5) in which one of the phosphorus atoms is selectively functionalized to the 1,1-diorgano-substituted complex [Cp*Fe(η4-P5R'R″)] (3). In a subsequent step, the phosphine PR'R″R‴ (R' ≠ R″ ≠ R‴ = alky, aryl) (4) is released by reacting it with a nucleophile R‴M (M = alkali metal) as racemates. The starting material 1 can be regenerated with P4 and can be reused in multiple reaction cycles without isolation of the intermediates, and only the phosphine is distilled off.


Nitrogen Fixation and Diazotrophic Community in Plastic-Eating Mealworms Tenebrio molitor L.
Mealworms, the larvae of a coleopteran insect Tenebrio molitor L., are capable of eating, living on, and degrading non-hydrolyzable vinyl plastics as sole diet. However, vinyl plastics are carbon-rich but nitrogen-deficient. It remains puzzling how plastic-eating mealworms overcome the nutritional obstacle of nitrogen limitation. Here, we provide the evidence for nitrogen fixation activity within plastic-eating mealworms. Acetylene reduction assays illustrate that the nitrogen-fixing activity ranges from 12.3 ± 0.7 to 32.9 ± 9.3 nmol ethylene·h-1·gut-1 and the corresponding fixed nitrogen equivalents of protein are estimated as 8.6 to 23.0 µg per day per mealworm. Nature nitrogen isotopic analyses of plastic-eating mealworms provide further evidence for the assimilation of fixed nitrogen as a new nitrogen source. Eliminating the gut microbial microbiota with antibiotics impairs the mealworm's ability to fix nitrogen from the atmosphere, indicating the contribution of gut microbiota to nitrogen fixation. By using the traditional culture-dependent technique, PCR and RT-PCR of nifH gene, nitrogen-fixing bacteria diversity within the gut was detected, and the genus Klebsiella was demonstrated to be an important nitrogen-fixing symbiont. These findings first build the relationship between plastic degradation (carbon metabolism) and nitrogen fixation (nitrogen metabolism) within mealworms. Combined with previously reported plastic-degrading capability and nitrogen-fixing activity, mealworms may be potential candidates for up-recycling of plastic waste to produce protein sources.


Dynamic mechanical analysis to assess viscoelasticity of liver tissue in a rat model of nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in both developed and developing countries. A noninvasive method of detecting early stage NAFLD and distinguishing non-alcoholic steatohepatitis (NASH) from simple steatosis (SS) would be useful. The over-accumulation of fat in hepatocytes alters the physical microstructure and chemical contents of the liver tissue. This study included dynamic mechanical analysis (DMA) testing on liver samples from a rat model of NAFLD to determine whether the tissue shows any significant changes in viscoelasticity due to the histological changes. Liver steatosis was induced in 57 rats by gavage feeding of a high fat emulsion; 12 rats received a standard diet only and served as controls. Each rat provided 2 or 3 samples for DMA tests. The shear modulus and loss modulus were measured at 9 frequency points evenly-spaced in the range from 1Hz to 41Hz. The phase velocity of shear wave was calculated from the measured modulus. Multivariate T2 test was used to assess the significance of intra-group difference. The results showed significant changes (p < 0.05) in storage modulus in livers with moderate to severe (S2 to S4) steatosis in comparison with livers without steatosis (S0), while the loss modulus demonstrated significant changes earlier in stage S1, indicating that fat accumulation affects the mechanical properties of liver, particularly viscosity. However, no significant differences were observed between the steatosis grades. These results also suggest that mild inflammation may affect the mechanical properties, which requires further verification. These findings provide new information about the mechanical properties of livers with NAFLD in low frequency range and suggest that it is possible to distinguish normal livers from livers with NAFLD.


Preventing packaging of translatable P5-associated DNA contaminants in recombinant AAV vector preps.
Recombinant adeno-associated virus (rAAV) vectors are increasingly being used for clinical gene transfer and have shown great potential for the treatment of several monogenic disorders. However, contaminant DNA from producer plasmids can be packaged into rAAV alongside the intended expression cassette-containing vector genome. The consequences of this are unknown. Our analysis of rAAV preps revealed abundant contaminant sequences upstream of the AAV replication (Rep) protein driving promoter, P5, on the Rep-Cap producer plasmid. Characterization of P5-associated contaminants after infection showed transfer, persistence, and transcriptional activity in AAV-transduced murine hepatocytes, in addition to in vitro evidence suggestive of integration. These contaminants can also be efficiently translated and immunogenic, revealing previously unrecognized side effects of rAAV-mediated gene transfer. P5-associated contaminant packaging and activity were independent of an inverted terminal repeat (ITR)-flanked vector genome. To prevent incorporation of these potentially harmful sequences, we constructed a modified P5-promoter (P5-HS), inserting a DNA spacer between an Rep binding site and an Rep nicking site in P5. This prevented upstream DNA contamination regardless of transgene or AAV serotype, while maintaining vector yield. Thus, we have constructed an rAAV production plasmid that improves vector purity and can be implemented across clinical rAAV applications. These findings represent new vector safety and production considerations for rAAV gene therapy.


[Magnetic resonance tomography in the staging of uterine neoplasms].
Diagnostic significance of MR imaging used for cervical carcinoma staging was established during the examination of 71 patients with verified tumors stage I-III. These findings were compared with the clinical and surgical data. MRI procedure proved highly effective in detecting uterine body involvement, identification of hydroureter caused by the ureters being squeezed by parametrial infiltrates as well as reliable exclusion of parametrial infiltration of bladder wall invasion. It is instrumental in assessing involvement of tissues around the uterus and regional lymph node condition.


An easily constructed durable chronic intracerebral cannula system.
A simple, inexpensive, and rugged intracerebral cannula system is described and construction details are provided for both guide and injection cannula assemblies. The guide cannula assembly is easily and quickly molded from dental acrylic cement and has a protective acrylic collar surrounding the end of the actual guide cannula. This system is believed to offer some advantage over current methodologies in terms of expense, durability and ease of construction and is well suited to use in rodents.


Proteasome inhibitors induce auditory hair cell death through peroxisome dysfunction.
Even though bortezomib, a proteasome inhibitor, is a powerful chemotherapeutic agent used to treat multiple myeloma (MM) and other lymphoma cells, recent clinical reports suggest that the proteasome inhibitor therapy may be associated with severe bilateral hearing loss. We herein investigated the adverse effect of proteasome inhibitor on auditory hair cells. Treatment of a proteasome inhibitor destroys stereocilia bundles of hair cells resulting in the disarray of stereocilia in the organ of Corti explants. Since proteasome activity may be potentially important for biogenesis and function of the peroxisome, we tested whether proteasome activity is necessary for maintaining functional peroxisomes. Our results showed that treatment of a proteasome inhibitor significantly decreases both the number of peroxisomes and expression of peroxisomal proteins such as PMP70 and Catalase. In addition, we also found that proteasome inhibitor impairs the import pathway of PTS1-peroxisome matrix proteins. Taken together, our findings support recent clinical reports of hearing loss associated with proteasome inhibition. Mechanistically, peroxisome dysfunction may contribute to hair cell damage and hearing loss in response to the treatment of a proteasome inhibitor.


Lumbar interbody fusion with utilization of recombinant human bone morphogenetic protein: a retrospective real-life study about 277 patients.
The purpose of this study was to report an independent real-life experience about the use of recombinant human bone morphogenetic protein 2 in lumbar interbody fusion with a special focus on complications. This is a retrospective single-center cohort study between 2007 and 2013 including 277 patients treated for anterior or posterior lumbar fusion with recombinant human bone morphogenetic protein 2. We report the complications occurring during the 12 first postoperative months and analyze the fusion rate on X-rays. There are 58 cases (22.8%) of clinical complications. In 15 cases (5.9%), these complications were related to the use of recombinant human bone morphogenetic protein 2. Only one patient (0.4%) required a new intervention due to recombinant human bone morphogenetic protein 2. Fusion rate at 1 year was 98%. The low rate of specific complication suggests that recombinant human bone morphogenetic protein 2 can be safe and effective in anterior and posterior interbody fusion when used with simple precautions.


Symptomatic mucoid degeneration of the anterior cruciate ligament.
Mucoid degeneration of the anterior cruciate ligament (ACL) is a little-known entity. The aim of this study was to detail the clinical, radiological, arthroscopic and pathological findings of this condition and to report clinical outcomes following arthroscopic partial excision of the ACL. Between 1999 and 2009, 80 knees in 78 patients were diagnosed as having mucoid degeneration of the ACL based on MRI and clinical findings, and subsequently underwent arthroscopic treatment. Of these, 68 knees in 66 patients, with a median age of 51 years (range, 35-75 years), were followed-up for at least one year. All patients had insidious onset of knee pain, while 56 knees (82 %) had associated extension deficits and 36 knees (53 %) had restricted flexion. MRI findings typically showed diffuse thickening and increased signal intensity of the ACL. Arthroscopic examination revealed notch impingement and bulging of hypertrophied ACL into lateral compartments. Associated lesions included meniscal tears in 33 knees and chondral lesions of at least Outerbridge grade 2 in 56 knees. All knees underwent arthroscopic partial excision of the hypertrophied ACL, with three undergoing preoperative and 30 undergoing concomitant meniscectomies. Pain relief was achieved in 58 of 62 knees (94 %) following partial excision of the ACL. Extension deficits were normalized in 49 of 56 knees (88 %), and restricted flexion was normalized in 33 of 36 affected knees (92 %). Four knees of four patients had postoperative symptoms of anterior instability. Pain and limitation of motion due to mucoid degeneration of the ACL can be improved by arthroscopic partial excision of the ACL with or without notchplasty. However, one potential complication is the development of postoperative symptoms of anterior instability. Retrospective study, Level IV.


Novel insights into the aetiology and pathophysiology of increased airway inflammation during COPD exacerbations.
Airway inflammation increases during acute exacerbations of COPD. Extrinsic factors, such as airway infections, increased air pollution, and intrinsic factors, such as increased oxidative stress and altered immunity may contribute to this increase. The evidence for this and the potential mechanisms by which various aetiological agents increase inflammation during COPD exacerbations is reviewed. The pathophysiologic consequences of increased airway inflammation during COPD exacerbations are also discussed. This review aims to establish a cause and effect relationship between etiological factors of increased airway inflammation and COPD exacerbations based on recently published data. Although it can be speculated that reducing inflammation may prevent and/or treat COPD exacerbations, the existing anti-inflammatory treatments are modestly effective.


Predictive macroscopic modeling of cell growth, metabolism and monoclonal antibody production: Case study of a CHO fed-batch production.
We describe a systematic approach to establish predictive models of CHO cell growth, cell metabolism and monoclonal antibody (mAb) formation during biopharmaceutical production. The prediction is based on a combination of an empirical metabolic model connecting extracellular metabolic fluxes with cellular growth and product formation with mixed Monod-inhibition type kinetics that we generalized to every possible external metabolite. We describe the maximum specific growth rate as a function of the integral viable cell density (IVCD). Moreover, we also take into account the accumulation of metabolites in intracellular pools that can influence cell growth. This is possible even without identification and quantification of these metabolites as illustrated with fed-batch cultures of Chinese Hamster Ovary (CHO) cells producing a mAb. The impact of cysteine and tryptophan on cell growth and cell productivity was assessed, and the resulting macroscopic model was successfully used to predict the impact of new, untested feeding strategies on cell growth and mAb production. This model combining piecewise linear relationships between metabolic rates, growth rate and production rate together with Monod-inhibition type models for cell growth did well in predicting cell culture performance in fed-batch cultures even outside the range of experimental data used for establishing the model. It could therefore also successfully be applied for in silico prediction of optimal operating conditions.


The development of fluorescent protein tracing vectors for multicolor imaging of clinically isolated Staphylococcus aureus.
Recent advances in fluorescent protein technology provide a wide variety of biological imaging applications; however current tools for bio-imaging in the Gram-positive bacterium Staphylococcus aureus has necessitated further developments for fluorescence intensity and for a multicolor palette of fluorescent proteins. To enhance the expression of multicolor fluorescent proteins in clinical S. aureus strains, we developed new fluorescent protein expression vectors, containing the blaZ/sodp promoter consisting of the β-lactamase gene (blaZ) promoter and the ribosome binding site (RBS) of superoxide dismutase gene (sod). We found S. aureus-adapted GFP (GFPsa) driven by the blaZ/sodp promoter was highly expressed in the S. aureus laboratory strain RN4220, but not in the clinical strains, MW2 and N315, harboring the endogenous blaI gene, a repressor of the blaZ gene promoter. We therefore constructed a constitutively induced blaZ/sodp promoter (blaZ/sodp(Con)) by introducing substitution mutations into the BlaI binding motif, and this modification allowed enhanced expression of the multicolor GFP variants (GFPsa, EGFP, mEmerald, Citrine, Cerulean, and BFP) as well as codon-optimized reef coral fluorescent proteins (mCherry and AmCyan) in the S. aureus clinical strains. These new fluorescent probes provide new tools to enhance expression of multicolor fluorescent proteins and facilitate clear visualization of clinical S. aureus strains.


Application of self-expanding stents in prostate cancer with rectal involvement. Report of two cases and review of the literature.
Rectal involvement due to local spread from prostate cancer is an uncommon finding. When this condition occurs, prognosis is ominous. Our objective is to report our experience in the use of self-expanding endorectal stents in the management of rectal invasion from prostate cancer. Two cases are presented and a review of the literature is carried out. In both cases, self-expanding Wallstent devices were placed (under fluoroscopic control), in order to solve their episodes of bowel obstruction. It was successfully performed in both patients. Therefore, an open surgery procedure was avoided. When facing the evidence of a tumor that invades the rectal wall, it is important to rule out the existence of prostate cancer (the surgical option in these patients carries an ominous prognosis). Therefore, we propose this new procedure whose results could be very satisfactory in certain settings.


Cortical gyrification in children with attention deficit-hyperactivity disorder and prenatal alcohol exposure.
An improved understanding of the neurodevelopmental differences between attention deficit hyperactivity disorder with and without prenatal alcohol exposure (ADHD + PAE and ADHD-PAE, respectively) is needed. Herein, we evaluated gyrification (cortical folding) in children with ADHD + PAE compared to that in children with familial ADHD-PAE and typically developing (TD) children. ADHD + PAE (n = 37), ADHD-PAE (n = 25), and TD children (n = 27), aged 8-13 years, were compared on facial morphological, neurobehavioral, and neuroimaging assessments. Local gyrification index (LGI) maps were compared between groups using general linear modelling. Relationships between LGI and clincobehavioral parameters in children with ADHD ± PAE were evaluated using multivariate partial least squares. ADHD + PAE and ADHD-PAE groups showed significantly lower LGI (relative to TD) in numerous regions, overlapping in medial prefrontal, parietal, and temporo-occipital cortices (p < 0.001). However, LGI in left mid-dorsolateral prefrontal cortex was uniquely lower in the ADHD + PAE group (p < 0.001). Partial least squares analysis identified one significant latent variable (accounting for 59.3 % of the crossblock correlation, p < 0.001), reflecting a significant relationship between a profile of lower LGI in prefrontal (including left mid-dorsolateral), insular, cingulate, temporal, and parietal cortices and a clinicobehavioral profile of PAE, including a flat philtrum and upper vermillion border, lower IQ, poorer behavioral regulation scores, and greater hyperactivity/impulsivity. Children with ADHD + PAE uniquely demonstrate lower mid-dorsolateral LGI, with widespread lower LGI related to more severe facial dysmorphia and neurobehavioral impairments. These findings add insight into the brain bases of PAE symptoms, potentially informing more targeted ADHD treatments based on an objective differential diagnosis of ADHD + PAE vs. ADHD-PAE.


Building the Connectivity Map of epigenetics: chromatin profiling by quantitative targeted mass spectrometry.
Epigenetic control of genome function is an important regulatory mechanism in diverse processes such as lineage commitment and environmental sensing, and in disease etiologies ranging from neuropsychiatric disorders to cancer. Here we report a robust, high-throughput targeted, quantitative mass spectrometry (MS) method to rapidly profile modifications of the core histones of chromatin that compose the epigenetic landscape, enabling comparisons among cells with differing genetic backgrounds, genomic perturbations, and drug treatments.


The introduction of treatment and the cultural adaptability of western psychotherapies for eating disorders in China.
In the past 40 years, the prevalence of eating disorders (ED) in China has shown an increasing trend, leading to an urgent need to develop efficient treatment modes and methods. Since the beginning of the new century, the diagnosis, treatment, and research of ED in China have been under development. This article gives an introduction and commentary on the treatment modes, treatment methods and their applications in ED in China. There are two main treatment forms for ED until now, that is, inpatient treatment and outpatient treatment. Inpatient treatment is recommended as the first choice. Since 2008, clinical psychotherapies such as cognitive behavioral therapy (CBT), dialectical behavioral therapy (DBT), and family-based treatment (FBT), which are effective for pathological symptoms of ED, have been introduced into China and developed clinically. Group CBT and group DBT for patients with ED and group FBT for caregivers might be the most efficient psychotherapy in China nowadays. A multi-family FBT support group could be developed as the basic treatment of ED patients. Although these new types of psychotherapy have observed effectiveness in clinical application, the Randomized Controlled Trials (RCT) are rare and need to be developed.


Chromosome homeologies and high variation in heterochromatin distribution between Citrus L. and Poncirus Raf. as evidenced by comparative cytogenetic mapping.
The genus Citrus is well-known for its economic importance and complex taxonomy. Only three to six Citrus taxa are considered true biological species, among them is Citrus medica, the citron. Previous studies based on chromomycin A3 (CMA)/4',6-diamidino-2-phenylindole staining showed that the citron has a homomorphic karyotype, consisting of four distinct chromosome types according to the CMA(+) heterochromatin distribution. Based on the pattern of CMA(+) bands and the hybridization of 25 bacterial artificial chromosomes (BACs) from a genomic library of Poncirus trifoliata, a closely related species to the genus Citrus, we were able to identify each chromosome pair and build a comparative cytogenetic map for C. medica. The data showed a high degree of sequence conservation between these genera, enabling heterologous hybridization of BACs, and the establishment of chromosomal homeologies. It was thus possible to visualize changes in the position of some BACs in relation to CMA(+) bands. Since no breakdown of synteny was observed between these species, expansions and contractions in repetitive DNA sequences seem to be the major driving force of chromosomal evolution since the separation of these two genera.


A framework for evaluating predictive models.
Predictive models provide estimates on an individual's probability of having a disease or developing a disease/disease outcome. Clinicians often use them to support clinical decision-making. Many prediction models are published annually; online versions of models (such as MDCalc and QxMD) facilitate their use at the point of care. However, before using a model, the clinician should first establish that the model has undergone external validation demonstrating satisfactory predictive performance. Ideally, the model should also demonstrate improved outcomes from an impact analysis. This article summarizes the basic steps of predictive model evaluation, and is followed by an application example.


Improving the frying performance of RBD palm olein oil using NaturFORT™ TRLG 101 liquid as on-top of TBHQ in deep-fat frying of potato chips.
Improvement in the frying performance of palmolein oil with NaturFORT™ TRLG 101 (TRLG 101) liquid in addition to tert-butyl hydroquinone (TBHQ) has been evaluated. Four treatment groups (Negative control, 200 ppm TBHQ, 200 ppm TBHQ + 400 ppm TRLG 101 liquid and 200 ppm TBHQ + 750 ppm TRLG 101 liquid) were added to RBD (Refined, Bleached and Deodorized) palm olein oil which was used to produce potato chips. Frying trials were conducted for 120th frying cycles. The oil samples were analyzed for peroxide value, free fatty acid, p-anisidine value, oxidative stability index, %total polar compounds and Chroma (C*) values after every 20 frying cycles. Potato chips were analyzed for Chroma (C*) values after every 20 frying cycles. The results of oxidative stability index, total polar compounds and p-anisidine value showed that the addition of NaturFORT™ TRLG 101 liquid at 750 ppm had showed significantly better performance followed by the addition of NaturFORT™ TRLG 101 liquid at 400 ppm. Thus, the addition of NaturFORT™ TRLG 101 liquid as on top of TBHQ contributes to the improvement in the frying performance of palm olein oil with subject to their dosage and this could be a better solution for frying industries which would like to get extra frying cycles for their products without encountering the regulatory hurdles posed by the limitations of using such additives.


Predictors of emotional distress in patients with head and neck cancer.
Patients with head and neck cancer are known to be more commonly emotionally distressed than patients with other tumors. This study investigates reasons for this difference. Patients in this prospective cohort study included those with head and neck cancer (n = 113) and those with other cancers (n = 1690). The Hospital Anxiety and Depression Scale, measuring emotional distress, along with additional questions regarding emotional support wished and provided were administered. Patients with head and neck tumors were 1.5-fold (at the time of admission), 1.2-fold (before discharge), and 2.7-fold (half a year after admission) more frequently distressed than the other patients with cancer. This association was confounded by perceived social support and sociodemographic factors. Patients with head and neck cancer expressed less frequently the wish for and received less support by psycho-oncologists. Emotional distress is more common in patients with head and neck tumors; this is largely a result of the psychosocial context the patients live in, especially the amount of social support received.


Effects of chronic vagal nerve stimulation in the treatment of β-amyloid-induced neuropsychiatric symptoms.
Alzheimer's Disease (AD) is the leading cause of dementia and, at the time of diagnosis, half of AD patients display at least one neuropsychiatric symptom (NPS). However, there is no effective therapy for NPSs; furthermore, current treatments of NPSs accelerate cognitive decline. Due to the ineffectiveness and negative consequences of current treatments for NPSs, new approaches are strongly needed. Currently, indications for vagal nerve stimulation (VNS) include epilepsy, stroke rehabilitation and major depression but not NPSs or AD. Therefore, we investigated whether chronic VNS can treat NPSs in a rat model of AD. Here, we report the intracerebroventricular injection of amyloid-β (Aβ) results in depression-like behaviors and memory impairment in rats. Chronic VNS (0.8 mA, 500 μs, 30 Hz, 5 min/day) showed strong antidepressant and anxiolytic effects, and improved memory performance. Additionally, the anxiolytic effect of VNS was retained in the non-Aβ-treated rats. VNS also decreased aggressiveness and increased locomotor activity in both Aβ-treated and non-Aβ-treated rats. Recent studies showed VNS alters glutamatergic receptor levels, thus levels of GluA1, GluN2A, and GluN2B were determined. A significant reduction in GluN2B levels was seen in the hippocampus of VNS-treated groups which may relate to the anxiolytic effects and increased locomotor activity of VNS. In conclusion, VNS could be an effective treatment of NPSs, especially depression and anxiety, in AD patients without impairing cognition.


Quality Criteria for Studies on Dietary Glycation Compounds and Human Health.
Current reports increasingly associate dietary "advanced glycation end products" ("AGEs") resulting from the Maillard reaction (glycation) between reducing sugars and amino compounds in foods with pathophysiological consequences, such as chronic inflammation, atherosclerosis, and metabolic syndrome. Heated foods are therefore suggested to pose a potential risk for human health. However, studies in this field are very often based on questionable quantitative data and inadequate structural characterization. To improve the situation, the present perspective suggests quality criteria for future studies and the assessment of the currently available literature.


Perioperative management of patients with hypothyroidism.
Hypothyroidism is a common disorder affecting the cardiovascular, respiratory, hematopoietic, and renal organ systems--each of which is particularly germane in the management of the surgical patient. In general, treatment of recognized hypothyroidism is recommended before any surgical procedure whenever possible and euthyroidism should be documented by measurement of serum TSH as part of the preoperative evaluation. Such a strategy is likely to result in better surgical outcomes with improved morbidity and mortality. One exception to treating first with thyroid hormone is the patient with angina or coronary artery disease requiring bypass grafting, angioplasty or stenting. In this setting, preoperative thyroid hormone therapy could tax the ischemic myocardium. The coronary blood flow should be addressed first, and thyroid hormone therapy initiated afterwards. The authors have emphasized the need for caution in the interpretation of low serum thyroid hormones in sick or surgical patients because of the importance of distinguishing between hypothyroidism and the "euthyroid sick syndrome." There is no clear evidence at this point to support thyroid hormone replacement in the latter patients, and it may be potentially harmful. Rather, we hold that T3 treatment of various surgical and other patients with nonthyroidal illness should be deferred until proof of its therapeutic efficacy is demonstrated.


Lung inflammatory responses and hyperinflation induced by an intratracheal exposure to lipopolysaccharide in rats.
Exposure of the respiratory tract to lipopolysaccharide (LPS) induces acute local inflammation and tissue injury associated with the various deliveries of LPS. To determine potential association of local inflammatory responses with respiratory tract dysfunction, infiltration of inflammatory cells, production of inflammatory mediators, lung hyperinflation and edema were measured in Wister rats 2, 4, and 24 h after an intratracheal administration of LPS at different doses (5, 50, 500 and 5000 microg/ml/kg). Lung hyperinflation determined by an increased excised lung gas volume was significantly increased 2 and 4 h after LPS instillation and lung edema occurred from 2 h onward. Peak BAL levels of TNFalpha appeared at 2 h, MCP-1 at 4 h, and IL-6 at 2 and 4 h, while BAL levels of IL-1beta were increased during 24 h after the intratracheal instillation of LPS. Neutrophilia in BAL fluid was noted from 2 h post-challenge. Our results demonstrate a clear dose-related change in the lung weight at 4 and 24 h, in the BAL levels of MCP-1 at 4 h, and IL-6 and IL-1beta at 2 and 4 h. It seems important to understand polymorphisms of LPS-induced lung hyperinflation and inflammation. Lung hyperinflation and inflammation may be independent during the development of acute lung injury.


Effects of a local single dose administration of growth hormone on the osseointegration of titanium implants.
The aim of the present study was to evaluate the effect of different concentrations of growth hormone (GH) on endosteal implant's surface at the early stages of osseointegration. Sixty tapered acid-etched titanium implants were divided into four groups: i) Collagen, used as a control group; and three experimental groups, where after collagen coating, GH was administered directly to the surface in varying concentrations: ii) 0.265 mg, iii) 0.53 mg, and iv) 1 mg. Implants were placed in an interpolated fashion in the anterior flange of C3, C4 or C5 of 15 sheep with minimum distance of 6 mm between implants. After 3-, 6- and 12-weeks of healing samples were harvested, histologically processed, qualitatively and quantitatively assessed for bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO). Statistical analysis as a function of time in vivo and coating resulted in no significant differences for BIC and BAFO at any evaluation time point. Histological evaluation demonstrated similar osseointegration features for all groups with woven bone formation at 3 weeks and progressive replacement of woven for lamellar bone in close contact with the implant surface and within the implant's threads. A single local application of growth hormone to the surface of titanium implants did not yield improved implant osseointegration independent of healing time.


Biological determinants of health: Genes, microbes, and metabolism exemplars of nursing science.
Increasingly, nurse scientists are incorporating "omics" measures (e.g., genomics, transcriptomics, proteomics, and metabolomics) in studies of biologic determinants of health and behavior. The role of omics in nursing science can be conceptualized in several ways: (a) as a portfolio of biological measures (biomarkers) to monitor individual risk, (b) as a set of combined data elements that can generate new knowledge based on large and complex patient data sets, (c) as baseline information that promotes health education and potentially personalized interventions, and (d) as a platform to understand how environmental parameters (e.g., diet) interact with the individual's physiology. In this article, we provide exemplars of nursing scientists who use omics to better understand specific health conditions. We highlight various ongoing nursing research investigations incorporating omics technologies to study chronic pain vulnerability, risk for a pain-related condition, cardiometabolic complications associated with pregnancy, and as biomarkers of response to a dietary intervention. Omics technologies add an important dimension to nursing science across many foci of investigation. However, there are also challenges and opportunities for nurse scientists who consider using omics in their research. The integration of omics holds promise for increasing the impact of nursing research and practice on population health outcomes.


The anatomical basis of the osteo-musculo-cutaneous trapezius flap in mandibular reconstruction.
The osteo-musculo-cutaneous trapezius flap has seen its indications in mandibular reconstruction reduced since the appearance of micro-anastomotic flaps. However, it may still be useful when the patient has marked atheroma contraindicating a free flap. While the arterial supply of this flap is well known, the same is not true for its venous drainage. The preservation of the accessory nerve and its limits in mandibular reconstruction has been little studied. We carried out a study on 30 subjects (60 cadaveric dissections of trapezius flaps) in order to address these questions. The study has been completed by a surgical series of five patients. The cadaveric study allowed demonstration of the variability of venous drainage of this flap, which depended on the external jugular vein in 80% of cases, the subclavian vein in 12% of cases and on both veins in about 8% of cases. The accessory nerve in one third of cases passed through the middle of the arteriovenous pedicle making its preservation impossible. The segment of the scapular spine allowed reconstruction of about 9 cm of mandible including the mental protuberance in 95% of cases. The surgical study confirmed the data of the cadaveric study and showed the value of this flap when free flaps are contraindicated.


Endometriosis is not detrimental to embryo implantation in oocyte recipients.
Our purpose was to determine the effects of endometriosis on implantation and pregnancy rates in ovum recipients. The medical records of 239 consecutive oocyte recipient patients who were treated between January 1, 1991, and June 30, 1995, were analyzed retrospectively. Recipients with endometriosis (group 1; n = 55) were compared to recipients without endometriosis (group II; n = 184). Patients in group I had active endometriotic disease confirmed by laparoscopy and were subdivided into mild (Stages I and II; n = 18) and moderate to severe (Stages III and IV; n = 37) endometriosis. No difference was found in recipient age, endometrial thickness, donor age, and embryos transferred. The pregnancy rates (28 versus 29%) and implantation rates (12 and 13%) were also comparable between group I and group II, as well as between patients with mild and patients with moderate to severe endometriosis. The presence of endometriosis in oocyte recipients does not lower implantation or pregnancy rates. We conclude that the adverse effect of endometriosis on reproductive outcome is not related to implantation but, in fact, is most likely an effect on oocyte or embryo quality.


The codon usage model of the context flanking each cleavage site in the polyprotein of foot-and-mouth disease virus.
To investigate the codon usage pattern of the contexts flanking 11 cleavage sites of foot-and-mouth disease virus (FMDV) polyprotein, the codon usage model of the corresponding codon position and the synonymous codon usage in the target contexts of 66 strains were characterized by two simple methods based on the relative synonymous codon usage value. The synonymous codons usage pattern was also compared between this virus and two species of hosts (cattle and domestic pig). It is indicated that FMDV bore a general resemblance to the hosts in terms of the synonymous codon usage pattern. This feature may help FMDV to utilize translational resources of host efficiently. The two amino acid residues constituting each cleavage site contain at least one conserved residue. It was noticed that the codon usage model with the strong bias appeared in some specific positions in the target contexts, and the under-represented synonymous codons, AUA for Ile, CUA for Leu, UUA for Leu and GUA for Val, are preferentially used in these positions. These under-represented synonymous codons likely play role in regulating the translation rate and influencing the secondary structure of the contexts flanking the cleavage sites.


Khaya grandifoliola C. DC. (Meliaceae: Sapindales): Ethnobotany, phytochemistry, pharmacological properties, and toxicology.
Khaya grandifoliola is a well-known tree species in Africa with a conservation status of 'vulnerable' due to its overexploitation by the wood industry. Several studies have recorded numerous ethnobotanical uses of this plant, as well as the scientific validation of the efficacy of extracts from different plant parts used for the treatment of various ailments. However, this useful information is scattered throughout the literature and thus there is no opportunity to identify the existing knowledge gaps. This review aims to highlight the medicinal importance of Khaya grandifoliola including its known phytochemistry, biological activities and toxicology, to encourage a refocused conservation strategy since all current efforts are geared towards maintaining its continuous supply to the wood industry. Articles on K. grandifoliola were sourced from online databases such as Google Scholar, Medicine, PubMed, Science Direct, Scopus, SciFinder and other science journal websites up to May 2020. The search was conducted using various combinations of keywords such as biotechnological uses, biological activity, ethnobotany, ethnomedicine, indigenous uses, pharmacological activity, phytochemistry, proximate composition, toxicity, and traditional uses of K. grandifoliola. All downloaded articles were screened to determine their relevance to the scope of the review and the selected papers were included. The review revealed a host of ethnomedicinal uses such as anticancer, antidiabetic, antimicrobial, anti-sickling, anti-ulcerogenic, and hepatoprotective, many of which are supported by scientific data. More importantly, toxicity tests revealed that many of the extracts are safe at various therapeutic doses. Important knowledge gaps that should be explored include phytochemical characterization and validation of some ethnobotanical claims on the folkloric usage of the plant. Notwithstanding the importance of K. grandifoliola in the wood industry, this review reveals that its use as a medicine is equally important. Its medicinal uses are also well supported with scientific studies as well as favourable toxicological studies though some scientific knowledge gaps require further studies.


Laparoscopic resection for low rectal cancer: evaluation of oncological efficacy.
Laparoscopic resection of low rectal cancer poses significant technical difficulties for the surgeon. There is a lack of published follow-up data in relation to the surgical, oncological and survival outcomes in these patients. The aim of this study is to evaluate the surgical, oncological and survival outcomes in all patients undergoing laparoscopic resection for low rectal cancer. Consecutive patients undergoing laparoscopic resection for low rectal cancers were included in the study. Clinical, pathological and follow-up data were recorded over a 4-year period. The mean follow-up was 25 months A total of 53 patients were included in the study, 30 of whom were males. The mean age was 64.14 years (range, 34-86 years). The mean hospital stay was 8.2 days (range, 4-42 days). Fifty were completed laparoscopically and three were converted to an open procedure. Thirty-eight were anterior resections and 15 were abdominoperineal resections. Twenty-four patients received neoadjuvant chemoradiotherapy. The total mesorectal excision was optimal in 51 (98%) cases. There were no anastomotic sequelae and no surgical mortality. There was no local recurrence detected. The overall survival (mean follow-up, 25 months) was 93.5%. Laparoscopic resection for low rectal cancers permits optimum oncological control. In our series, this technical approach is associated with excellent 4-year survival and clinical outcomes.


Prevalence and predictors of timely initiation of breastfeeding in Ghana: an analysis of 2017-2018 multiple indicator cluster survey.
Timely initiation of breastfeeding is putting the newborn baby to the breast within 1 h of birth. Its practice can prevent neonatal and under-5 mortality. This study aims to assess the prevalence and factors associated with timely initiation of breastfeeding among mothers in Ghana. We used data from the 2017-2018 Ghana multiple indicator cluster survey and our analysis was restricted to 3466 mothers who had a live birth within 2 years. Multivariable logistic regression was used to estimate the factors associated with timely initiation of breastfeeding whilst adjusting for potential confounders, and accounted for clustering, stratification, and sample weights. The prevalence of timely initiation of breastfeeding was 52.3% (95% CI 49.7%, 54.9%). Mothers who were assisted by a skilled attendant at birth had 65% higher odds of timely initiation of breastfeeding compared to mothers who were not assisted by a skilled attendant (adjusted prevalence odds ratio [aPOR] 1.65; 95% CI 1.28, 2.13). Mothers who delivered by Caesarean section had 74% lower odds of timely initiation of breastfeeding compared to mothers who had vaginal delivery (aPOR 0.26; 95% CI 0.18, 0.36). Mothers who had planned their pregnancy had 31% higher odds of timely initiation of breastfeeding compared to mothers who had an unplanned pregnancy (aPOR 1.31; 95% CI 1.05, 1.63). There were also 74% and 51% higher odds of timely initiation of breastfeeding among mothers who perceived their baby was large (aPOR 1.74; 95% CI 1.34, 2.26), and of average size (aPOR 1.51, 95% CI 1.16, 1.97) at birth respectively, compared to mothers who perceived their baby was small. Interventions to increase timely initiation of breastfeeding should provide breastfeeding support to mothers who have had a Caesarean section, small sized babies and unplanned pregnancies, and to promote birthing by skilled birth attendants.


SYP-3343 drives abnormal vascularization in zebrafish through regulating endothelial cell behavior.
SYP-3343 is a novel strobilurin fungicide with excellent and broad-spectrum antifungal activity, and its potential toxicity raises public health concerns. However, the vascular toxicity of SYP-3343 to zebrafish embryos is still not well understood. In the present study, we investigated the effects of SYP-3343 on vascular growth and its potential mechanism of action. SYP-3343 inhibited zebrafish endothelial cell (zEC) migration, altered nuclear morphology, and triggered abnormal vasculogenesis and zEC sprouting angiogenesis, resulting in angiodysplasia. RNA sequencing showed that SYP-3343 exposure altered the transcriptional levels of vascular development-related biological processes in zebrafish embryos including angiogenesis, sprouting angiogenesis, blood vessel morphogenesis, blood vessel development, and vasculature development. Whereas, the addition of NAC exerted an improvement effect on zebrafish vascular defects owing to SYP-3343 exposure. Additionally, SYP-3343 altered cell cytoskeleton and morphology, obstructed migration and viability, disrupted cell cycle progression, and depolarized mitochondrial membrane potential, as well as promoted apoptosis and reactive oxygen species (ROS) in HUVEC. SYP-3343 also caused an imbalance of the oxidation and antioxidant systems and irritated the alterations in the cell cycle- and apoptosis-related genes in HUVECs. Collectively, SYP-3343 has high cytotoxicity, possibly by up-regulating p53 and caspase3 expressions and bax/bcl-2 ratio via ROS, leading to malformed vascular development.


Potentiated thrombolysis in a Chandler system using rtPA and lys-plasminogen.
The effect of glu/lys-plasminogen on rtPA induced thrombolysis was studied in a Chandler model using rabbit blood. Glu/lys-plasminogen in various concentrations was added to the Chandler loop before or after thrombi were formed from 2 ml of rabbit blood containing 125I-labelled rabbit fibrinogen. The thrombolysis was estimated as radioactivity in the supernatant/total radioactivity. Thrombi formed in the presence of extra lys-plasminogen (conc greater than or equal to 0.025 mg/ml blood) lysed spontaneously to a significantly higher extent than thrombi formed in the presence of glu-plasminogen or saline. If the glu/lys-plasminogen was added to a preformed thrombus no thrombolysis occurred. When added together with single-chain rtPA (s.c. rtPA) or two-chain rtPA (t.c.rtPA) the thrombolysis was similar to the one obtained by s.c./t.c.rtPA alone. If on the other hand s.c./t.c.rtPA was added to lys-plasminogen enriched thrombi (greater than 0.01 mg/ml blood) a significantly enhanced thrombolysis as compared to the one achieved by s.c./t.c.rtPA alone was obtained. Based on the observation that lys-plasminogen potentiates the lysis of thrombi in a Chandler model a bolus dose administered preoperatively may enhance spontaneous lysis of thrombi formed during surgery.


Potential role of endothelin 1 in ischaemia-induced angiogenesis in critical leg ischaemia.
Ischaemia-induced angiogenesis occurs in critical leg ischaemia (CLI) and endothelin (ET) 1 may be involved in this process. The aim of this study was to quantify microvessels and study ET receptor expression and distribution in critically ischaemic leg muscle. Leg muscle biopsies were taken from 12 patients with CLI and 12 patients with no leg ischaemia. Microvessels were identified immunohistochemically on muscle sections, and the number of immunopositive cells was quantified. ETA and ETB receptor messenger RNA (mRNA) expression was studied using real-time quantitative reverse transcriptase-polymerase chain reaction, and receptor binding was localized and assessed by in vitro autoradiography. The number of microvessels in CLI muscle biopsies was 2.6 times higher than that in controls (P < 0.01). ETB receptor mRNA expression and binding were significantly increased in CLI tissue (P < 0.05), while ETA receptor levels were not significantly raised. High-resolution autoradiography showed that ET receptor binding was associated with microvessels. Angiogenesis occurs in CLI and raised ETB receptors within the muscle were associated with microvessels, suggesting that ET-1 may mediate angiogenesis via these receptors in critically ischaemic muscle.


Antiviral effects of interferon-β are enhanced in the absence of the translational suppressor 4E-BP1 in myocarditis induced by Coxsackievirus B3.
Viral myocarditis is most frequently associated with infection by Coxsackievirus B3 (CVB3). Interferon (IFN)-β therapy has been studied and could reduce virally induced tissue damage and improve heart function. In the present study we have investigated the role of translational suppression in the context of an IFN-α/β-mediated antiviral immune response to CVB3 infection. Specifically, we examined the effects of IFN-α/β treatment of CVB3-infected mouse embryonic fibroblast cells and splenocytes lacking eukaryotic initiation factor 4E binding protein-1 (4E-BP1), a suppressor of 5'-capped mRNA translation. Extending these in vitro studies, we examined the effects of CVB3 infection and IFN-β treatment in 4E-BP1(-/-) mice. Our data show that 4E-BP1(-/-) cells are more -sensitive to the antiviral effects of IFN-α4 and IFN-β treatment than 4E-BP1(+/+) cells when infected with CVB3. Similarly, 4E-BP1(-/-) mice are more sensitive to treatment with IFN-β, exhibiting lower viral titres in heart tissue than 4E-BP1(+/+) mice during the course of infection. Additionally, we demonstrate that treatment with IFN-β reduces inflammatory infiltrates into the hearts of infected mice. These data identify 4E-BP1 as a novel drug target to augment responsiveness to IFN-β therapy in CVB3-induced myocarditis.


Cooperative behaviour of the elementary sarcomere units and the cross-bridge step size.
We present a model of muscle contraction based on purely physical grounds and modulated by a parameter, k, related to the visco-elastic hindrances of the contractile apparatus. The model predicts a strong cooperation among sarcomere units and proposes that viscous hindrance is a fundamental component of the economy of the contraction. The concept of cross-bridge step size is also discussed and it is concluded that the step size is of various and probably undeterminable length.


Testing the Accuracy of Pont's Index in Diagnosing Maxillary Transverse Discrepancy as Compared to the University of Pennsylvania CBCT Analysis.
Introduction: Assessment of maxillary transverse discrepancy requires an accurate tool in order to implement the appropriate treatment plan. Aim: To evaluate the accuracy of Pont's Index in confirming a transverse maxillary deficiency by comparing its results with the corresponding results yielded by the University of Pennsylvania CBCT analysis. Material and methods: The study was performed on dental casts and CBCT's of 60 randomly selected patients by adopting a cluster sampling method. The results of Pont's Index and University of Pennsylvania CBCT analysis were analyzed through McNemar's test using Excel Data Analysis, and the accuracy indicators for Pont's Index were computed using MedCalc Ltd. Results: Mc Nemar's test revealed a p-value of 0.85. The accuracy indicators of Pont's Index were: sensitivity: 69%; specificity: 16.6%; positive predictive value: 65%; negative predictive value: 18.75%; positive likelihood ratio: 0.83; negative likelihood ratio: 1.86; and accuracy: 53.28%. Conclusion: Due to the fact that CBCT is not used on a daily basis and Pont's Index has a relatively high sensitivity (69%) making it suitable to detect patients with a narrow maxilla, assessment of the maxillary deficiency on CBCT can be recommended for cases were the midpalatal suture maturation should be evaluated.


Left paratesticular fibrous pseudotumor on the single testis and contribution of imaging in therapeutic management, a case report.
Paratesticular fibrous pseudotumor is a rare benign tumor. Clinically, it can mimic testicular malignancy, but this lesion results from a reactive proliferation of inflammatory and fibrous tissue. A 62-year-old man presented with left scrotal swelling dating back years. A left paratesticular mass is palpated, firm and painless. Ultrasound showed a heterogeneous and hypoechoic lesion in a single left testicle; the right testicle was not found in the scrotum or at the inguinal level. CT scan showed a hypodense left scrotal mass. The scrotal MRI showed the presence of a paraliquid left intrascrotal formation pushing back the left testicle. We performed a scrotal exploration with excision of the paratesticular mass, sparing the left testicle. The definitive pathological diagnosis was reported as paratesticular fibrous pseudotumor. Paratesticular Fibrous pseudotumors are a rare tumor with approximately 200 cases reported to date. These lesions constitute 6 % of all paratesticular lesions. Magnetic resonance imaging can give additional information when an ultrasound is inconclusive. The treatment of choice is a scrotal exploration of the mass and frozen section biopsy to avoid unnecessary orchiectomy. The diagnosis of paratesticular Fibrous pseudotumor is challenging. The contribution of scrotal MRI and intra-operative frozen section is essential for therapeutic management.


Postoperative endophthalmitis: a comparison of methods for treatment and prophlaxis with gentamicin.
Toxicity of gentamicin and its use in the treatment of experimentally induced Pseudomonas aeruginosa endophthalmitis were studied in the postoperative aphakic eye. The retinal toxicity of intravitreal gentamicin was different from toxicity in the intact eye and varied with the method of injection. Successful prophylaxis of induced postoperative infection was obtained with an intravitreal injection of 30 mu-g of gentamicin but not with sub-Tenon's administration of gentamicin. Treatment for progressive endophthalmitis was effective with high dose (200 mu-g) gentamicin alone, or a combination of low-dose (30 mu-g) gentamicin with topical and systemic gentamicin. Either sub-conjunctival and systemic gentamicin or low-dose gentamicin alone was ineffective once endophthalmitis was in progress. Although vitrectomy removed abscess products, it failed in this experiment to provide better results than the other modes of therapy.


Identification of a Patient Acceptable Symptomatic State Score for the International Hip Outcome Tool in People Undergoing Hip Arthroscopy.
To determine a Patient Acceptable Symptomatic State (PASS) score for the 33-item International Hip Outcome Tool (iHOT-33) in people undergoing hip arthroscopy for primary diagnoses of femoroacetabular impingement syndrome, acetabular labral tears, and/or ligamentum teres pathology. Consecutive participants underwent hip arthroscopy by a single surgeon between August 2011 and May 2016. Participants were included if they were between ages 18 and 60 years and underwent hip arthroscopy for femoroacetabular impingement syndrome, acetabular labral tears, or ligamentum teres pathology. Participants were excluded if they did not speak sufficient English to complete the iHOT-33, had evidence of hip dysplasia, had less than 2 mm of joint space on anteroposterior radiograph, or underwent subsequent total hip replacement surgery. Participants completed the iHOT-33 preoperatively and at a minimum of 1 to a maximum of 5 years postoperatively. Participants were also asked to answer yes or no to the external anchor question of "Taking into account all the activities you do during your daily life, your level of pain and also your functional impairment, are you satisfied with your current state following your surgery?" A receiver operating characteristic (ROC) curve was used to identify the PASS score. Multiple logistic regression was performed to determine if patient factors, primary preoperative diagnosis, or intraoperative findings predicted achievement of the PASS score. A total of 117 participants undergoing hip arthroscopy were included: 72 women (61.1%) and 45 men (38.5%) with mean age of 36.81 years (18-59). Forty-two (35.9%) had cam morphology, 18 (15.4%) had pincer morphology, 78 (67.2%) had labral tears, and 97 (82.9%) had ligamentum teres tears. Mean time to final follow-up was 2.25 years (range, 1-5). The PASS score at a mean of 2.25 years postoperatively was 58 as determined by the cutoff threshold on the ROC curve with the lowest difference between sensitivity and specificity (area under the ROC curve 0.88; P < .01; 95% confidence interval [CI], 0.81-0.95). No factors were predictors of achievement of the PASS score in this study (P > .05), including age (odds ratio [OR], 0.71; 95% CI, 0.32-1.56), sex (OR, 1.02; 95%, CI 0.98-1.06), preoperative iHOT-33 score (OR, 1.002; 95% CI, 0.98-1.03), primary preoperative diagnosis (OR, 0.86; 95% CI, 0.53-1.40), cam morphology (OR, 1.19; 95% CI, 0.54-2.64), Pincer morphology (OR, 0.50; 95%, CI 0.18-1.38), acetabular labral tears (OR, 1.93; 95% CI, 0.88-4.26), Outerbridge grade 3-4 chondral damage (OR, 0.97; 95% CI, 0.42-2.25), and ligamentum teres pathology (OR, 0.95; 95% CI, 0.35-2.61). This study reports a PASS score of 58 for the iHOT-33 at 2 years following hip arthroscopy. The PASS score will assist in assessing response to hip arthroscopy in research and clinical settings. Level II, retrospective prognostic study.


Changes in Treatment-Naive Pigment Epithelial Detachments Associated With the Initial Anti-Vascular Endothelial Growth Factor Injection: A Post Hoc Analysis From the HARBOR Trial.
Pigment epithelial detachment (PED) is a feature commonly associated with neovascular age-related macular degeneration (nAMD) and may be perceived as being difficult to treat. Therefore, this investigation explored changes in PEDs and visual acuity outcomes following an initial anti-vascular endothelial growth factor (VEGF) injection and identified factors associated with positive response. To describe changes in treatment-naive pigment epithelial detachments associated with the initial anti-VEGF injection. Post hoc analysis of patients from the Phase III, Double-masked, Multicenter, Randomized, Active Treatment-controlled Study of the Efficacy and Safety of 0.5 mg and 2.0 mg Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-Related Macular Degeneration (HARBOR) trial (NCT00891735) with PED at baseline. The HARBOR trial was a phase 3, randomized, multicenter, double-masked, active treatment-controlled trial. Participants included treatment-naive patients with subfoveal nAMD and PEDs at baseline; intervention arms were pooled for analysis (n = 586). The HARBOR study began in July 2009 and was completed in August 2012, and the post hoc analyses were conducted between October 2016 and May 2018. Intravitreal injections of ranibizumab, 0.5 mg and 2.0 mg, administered monthly or on an as-needed basis over 24 months. Post hoc analyses of flattened PED frequency at month 1, univariate and multivariable analysis of patient and ocular characteristics at baseline and PED status at month 1, and total number of ranibizumab injections received stratified by PED status at month 1. A total of 35.5% of patients (208 of 586) with PED at baseline achieved a flattened PED after a single ranibizumab injection. An additional 17.3% subsequently achieved a flattened PED at month 2. Univariate analysis identified an association between older age, lower PED height, and lower subretinal fluid thickness with PED flattening after a single injection. Multivariable analysis identified PED height as a factor associated with this anatomical outcome. Best-corrected visual acuity scores were not superior based on PED flattening at month 1. On average, patients in the as-needed arm who achieved a flattened PED after a single ranibizumab injection required fewer injections by month 24 vs patients whose PED remained present at month 1 (11.0 vs 14.2; difference, 3.3; 95% CI, 1.9-4.6; P < .001). In this group of treatment-naive patients with PED from nAMD, after the initial ranibizumab injection approximately one-third and after the second injection approximately one-half had flattened PEDS, although visual outcomes were not superior among those that did vs did not have flattening. The findings suggest flattening may serve as a marker for less intensive as-needed injection frequencies. ClinicalTrials.gov Identifier: NCT00891735.


Impact of right ventricular side branch occlusion during percutaneous coronary intervention of chronic total occlusions on right ventricular function.
To determine the impact of right ventricular side branch (RVB) occlusion, during percutaneous coronary interventions (PCIs) of chronic total occlusions (CTOs) of the right coronary artery (RCA), on right ventricular (RV) function. Developments in PCI techniques have expanded PCI CTO feasibility. However, the utilization of dissection and reentry techniques and extensive stent implantation increases the risk of coronary side branch occlusion. Fifty-four patients (80% male, 63±10years) evaluated with cardiac magnetic resonance imaging (CMR) prior and three months after successful PCI CTO RCA (median: 99days, IQR: 92-105days) were included. Right ventricular end-diastolic volume (RVEDV), end-systolic volume (RVESV), and ejection fraction (RVEF) were quantified on CMR images. Occurrence of RVB occlusion and/or RVB recruitment was assessed using procedural angiograms. RVB occlusion was observed in 12 patients (22%), while RVB recruitment occurred in seven patients (13%). Overall, RVEF was comparable between baseline and follow-up (53.8±5.8 vs. 53.9±5.8%, p=0.95). RVB occlusion was not associated with a significant change in RVEDV or RVEF (156.9±36.3 vs. 162.1±35.5mL, p=0.30 and 54.2±3.9 vs. 52.7±4.4%, p=0.19, respectively); however a trend was observed for an increase of RVESV (72.5±20.0 vs. 77.4±20.7mL, p=0.05) at follow-up. RVB recruitment did not result in a significant improvement of RVEF (55.4±4.6 vs. 56.1±5.3%, p=0.75). RVB occlusion was not associated with a significant decreased RVEF at follow-up, although the results suggested a limited increase of RVESV.


Nanofibers of cellulose bagasse from Agave tequilana Weber var. azul by electrospinning: preparation and characterization.
In this study, cellulose of bagasse from Agave tequilana Weber var. azul was extracted to elaborate nanofibers by the electrospinning technique. Fiber characterization was performed using Transmission Electron Microscopy (TEM), x-ray, Fournier Transform-InfraRed (FT-IR) spectroscopy, and thermal analysis by Differential Scanning Calorimetry-Thermogravimetric Analysis (DSC-TGA). Different diameters (ranging from 54.57 ± 0.02 to 171 ± 0.01 nm) of nanofibers were obtained. Cellulose nanofibers were analyzed by means of x-ray diffraction, where we observed a total loss of crystallinity in comparison with the cellulose, while FT-IR spectroscopy revealed that the hemicellulose and lignin present in the agave bagasse were removed. Thermal analysis showed that nanofibers exhibit enhanced thermal properties, and the zeta potential value (-32.5 mV) demonstrated moderate stability in the sample. In conclusion, the nanofibers obtained provide other alternatives-of-use for this agro-industrial residue and could have potential in various industrial applications, among these encapsulation of bioactive compounds and reinforcing material, to mention a few.


Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity.
We have performed a double-blind, placebo-controlled injection immunotherapy study with genetically modified derivatives of the major birch pollen allergen, Bet v 1 (Bet v 1-trimer, Bet v 1-fragments). To investigate whether vaccination with genetically modified allergens induces allergen-specific antibodies in nasal secretions and to study whether these antibodies affect nasal allergen sensitivity. A randomly picked subgroup of patients (n = 23; placebo, n = 10; trimer, n = 10; fragments, n = 3) was subjected to an extensive analysis of serum samples and nasal lavage fluids and to nasal provocation testing. Bet v 1-specific IgG(1-4) and IgA antibodies were determined in serum samples obtained before and after vaccination, after the birch pollen season, and 1 year after start of vaccination as well as in nasal lavage fluids obtained after the birch pollen season and 1 year after start of vaccination by ELISA. Nasal sensitivity to natural, birch pollen-derived Bet v 1 was determined by active anterior rhinomanometry after the birch pollen season and 1 year after start of vaccination. Vaccination with genetically modified Bet v 1 derivatives, but not with placebo, induced Bet v 1-specific IgG1, IgG2, and IgG4, and low IgA antibodies in serum, which also appeared in nasal secretions, but no IgG3 antibodies. The levels of therapy-induced Bet v 1-specific IgG4 antibodies in nasal secretions were significantly (P < .05) associated with reduced nasal sensitivity to natural, birch pollen-derived Bet v 1 as objectively determined by controlled nasal provocation experiments. Our data demonstrate that vaccination with genetically modified allergens induces IgG antibody responses against the corresponding natural allergen not only in serum but also in mucosal fluids, where they may protect against allergen-induced inflammation.


PRC2 Facilitates the Regulatory Topology Required for Poised Enhancer Function during Pluripotent Stem Cell Differentiation.
Poised enhancers marked by H3K27me3 in pluripotent stem cells have been implicated in the establishment of somatic expression programs during embryonic stem cell (ESC) differentiation. However, the functional relevance and mechanism of action of poised enhancers remain unknown. Using CRISPR/Cas9 technology to engineer precise genetic deletions, we demonstrate that poised enhancers are necessary for the induction of major anterior neural regulators. Interestingly, circularized chromosome conformation capture sequencing (4C-seq) shows that poised enhancers already establish physical interactions with their target genes in ESCs in a polycomb repressive complex 2 (PRC2)-dependent manner. Loss of PRC2 does not activate poised enhancers or induce their putative target genes in undifferentiated ESCs; however, loss of PRC2 in differentiating ESCs severely and specifically compromises the induction of major anterior neural genes representing poised enhancer targets. Overall, our work illuminates an unexpected function for polycomb proteins in facilitating neural induction by endowing major anterior neural loci with a permissive regulatory topology.


Epidemiological correlates of overweight and obesity in the Northern Cape Province, South Africa.
In the past several decades, obesity has become a major public health issue worldwide, associated with increased rates of chronic disease and death. Like many developing nations, South Africa is experiencing rapid increases in BMI, and as a result, evidence-based preventive strategies are needed to reduce the increasing burden of overweight and obesity. This study aimed to determine the prevalence and predictors of overweight and obesity among a multi-ethnic cohort from the rural Northern Cape of South Africa. These data were collected as part of a tuberculosis (TB) case-control study, with 395 healthy control participants included in the final analysis. Overweight and obesity were defined according to WHO classification. Multivariate linear models of BMI were generated using sex, age, education level, smoking, alcohol consumption, and diabetes as predictor variables. We also used multivariable logistic regression analysis to assess the relationship of these factors with overweight and obesity. The average BMI in our study cohort was 25.2. The prevalence of overweight was 18.0% and the prevalence of obesity was 25.0%. We find that female sex, being older, having more years of formal education, having diabetes, and being in a rural area are all positively associated with BMI in our dataset. Women (OR = 5.6, 95% CI [3.3-9.8]), rural individuals (OR = 3.3, 95% CI [1.9-6.0]), older individuals (OR = 1.02, 95% CI [1-1.04]), and those with more years of education (OR = 1.2, 95% CI [1.09-1.32]) were all more likely to be overweight or obese. Alternatively, being a smoker is negatively associated with BMI and decreases one's odds of being overweight or obese (OR = 0.28, 95% CI [0.16-0.46]). We observed a high prevalence of overweight and obesity in this study. The odds of being overweight and obese were higher in women, those living in rural areas, and those with more education, and increases with age. Community-based interventions to control obesity in this region should pay special attention to these groups.


The complete chloroplast genome sequence of Vitis davidii Foex strain 'SJTU003'.
In the present study, the complete chloroplast genome of Vitis davidii Foex strain 'SJTU003' was assembled and subjected to phylogenetic analysis. This chloroplast genome of 'SJTU003' was 161,335 bp in length, including two inverted repeat regions (IRa and IRb) that were separated by a large single-copy region (89,570 bp) and a small single-copy region (19,059 bp). The genome contained 133 genes, including 88 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis indicated that V. davidii is most closely related to Vitis flexuosa and Vitis amurensis.


Omega-3 fatty acid intake during pregnancy and risk of infant maltreatment: a nationwide birth cohort - the Japan Environment and Children's Study.
Intake of omega-3 polyunsaturated fatty acids (PUFAs) has favorable effects, including reducing violent and aggressive behaviors, but its association with infant maltreatment is unknown. We therefore tested the hypothesis that maternal intake of omega-3 PUFAs is associated with a lower risk of infant maltreatment. Participants were 92 191 mothers involved in the ongoing Japan Environment and Children's Study. Omega-3 PUFA intake during pregnancy was measured using a food frequency questionnaire. Infant maltreatment was assessed using a self-reported questionnaire administered at 1 and 6 months postpartum. Analysis using the lowest quintile of intake as a reference revealed that the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for cases of 'hitting' decreased as quintiles increased, with values for the second to fifth quintiles of 0.93 (95% CI 0.77-1.13), 0.79 (95% CI 0.64-0.97), 0.78 (95% CI 0.64-0.96), and 0.72 (95% CI 0.59-0.89), respectively. Adjusted ORs (95% CIs) for 'shaking very hard' at 6 months were 0.87 (0.73-1.04), 0.81 (0.67-0.97), 0.73 (0.61-0.89), and 0.78 (0.65-0.94), respectively. Adjusted ORs for 'leaving alone at home' for the second to fifth quintiles were 0.92 (0.87-0.98), 0.91 (0.86-0.97), 0.94 (0.88-0.99), and 0.85 (0.80-0.90), respectively. Higher maternal intake of omega-3 PUFAs during pregnancy was associated with fewer cases of hitting and violent shaking and leaving the child alone at home, implying a lower risk of infant maltreatment. Our results indicate the potential applicability of omega-3 PUFAs in reducing infant maltreatment.


Primary hyperparathyroidism presenting as a massive maxillary swelling.
A patient with primary hyperparathyroidism is reported, in which the sole presenting feature was an orofacial swelling. Untreated, the disease is life-threatening and its early recognition will reduce the risk of morbidity. Recent figures suggest that the incidence of the condition tends to be underestimated.


Biosynthetic relationship between C₂₈-brassinosteroids and C₂₉-brassinosteroids in rice (Oryza sativa) seedlings.
A crude enzyme solution was prepared from young rice seedlings, and the metabolism of C29-brassinosteroids identified from the seedlings was examined. When 28-homoteasterone was added as a substrate, 28-homotyphasterol, teasterone, and 26-nor-28-homoteasterone were characterized as enzyme products by GC-MS/SIM analysis. With 28-homotyphasterol, 28-homoteasterone, typhasterol, 28-homocastasterone, and 26-nor-28-homotyphasterol were formed and identified as products. When 28-homocastasterone was used, castasterone and 26-nor-28-homocastasterone were identified as products. Together with the reduced biological activity of C29-brassinosteroids and their metabolites in the rice lamina inclination assay, these metabolic studies suggest a biosynthetic sequence, 28-homoteasterone↔28-homotyphasterol→28-homocastasterone for C29-brassinosteroid biosynthesis is connected to the biosynthetic sequence teasterone↔typhasterol→castasterone for C28-brassinosteroids by C-28 demethylation, i.e., in order to increase biological activity in the rice plant. Additionally, the C29-brassinosteroids seem to bio-degrade their C-26 demethylated C28-brassinosteroid analogs to reduce brassinosteroid activity in planta. In conclusion, the biosynthesis of C29-brassinosteroids is a likely alternative route to the biologically-active brassinosteroid, castasterone, in rice.