C. elegans: Sensing the low-frequency profile of amplitude-modulated ultrasound.
Several research groups have demonstrated that C. elegans can respond to pulsed ultrasound stimuli, and elucidating the underlying mechanisms is necessary to develop ultrasound neuromodulation. Here, amplitude-modulated (AM) ultrasound is applied to C. elegans, and its behavioral responses are investigated in detail. By loading surface acoustic waves (SAWs) onto free-moving worms on an agar surface, a carrier wave with a frequency of 8.80 MHz is selected. The signal is modulated by a rectangular or sinusoidal profile. It is demonstrated that sinusoidal modulation can produce similar responses in worms to rectangular modulation, with the strongest responses occurring at modulation frequencies of around 1.00 kHz. Meanwhile, the behavioral response is relatively weak when the ultrasonic signal is unmodulated, that is, when only the carrier wave is applied. At modulation frequencies other than 100.00 Hz to 10.00 kHz, the worms respond weakly, but when a second modulation frequency of 1.00 kHz is introduced, an improvement in response can be observed. These results suggest that C. elegans may sense the low-frequency envelope and respond to amplitude-modulated ultrasonic stimuli like an amplitude demodulator. MEC-4, an ion channel for touch sensing, is involved in the behavioral response of C. elegans to ultrasound in the present setup.


Real-world effectiveness and safety of adalimumab for treatment of ankylosing spondylitis in Japan.
Objective: To evaluate the real-world effectiveness and safety of adalimumab for the treatment of ankylosing spondylitis (AS) in Japan.Methods: All AS patients initiated on adalimumab from 27 October 2010 to 28 May 2015, were enrolled. Patient characteristics at baseline, changes in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores, and adverse drug reactions (ADRs) for 24 weeks from the first adalimumab treatment were evaluated.Results: Of 403 enrolled patients, 396 and 374 comprised the safety and effectiveness analysis sets, respectively. In the safety analysis set, 266/396 (67.2%) were males, with a mean ± standard deviation (SD) age of 46.3 ± 15.6 years and mean ± SD disease duration of 9.8 ± 9.8 years. Of 236 patients examined for human leukocyte antigen (HLA)-B27, 131 (55.5%) were HLA-B27-positive. In the effectiveness analysis set, the mean ± SD BASDAI score was 4.9 ± 2.3 at baseline (n = 292). Overall, 216 patients had BASDAI data pre- and post-baseline. At 24 weeks, 143 patients had BASDAI scores, and the mean ± SD decrease was -2.0 ± 2.6 (p < .0001). Fifteen serious ADRs occurred in 15 (3.79%) patients; 30 (7.58%) ADRs of infections were reported, of which, five (1.26%) were serious.Conclusion: Safety and effectiveness of adalimumab in this postmarketing observational study were similar to that in previous clinical trials.


Molecular regulation of Histoplasma dimorphism.
Temperature serves as a fundamental signal in biological systems. In some microbial pathogens of humans, mammalian body temperature triggers establishment and maintenance of a developmental program that allows the microbe to survive and thrive in the host. Histoplasma capsulatum is one of a group of fungal pathogens called thermally dimorphic fungi, all of which respond to mammalian body temperature by converting from an environmental mold form that inhabits the soil into a parasitic form that causes disease in the host. It has been known for decades that temperature is a key signal that is sufficient to trigger the switch from the soil to host form (and vice versa) in the laboratory. Recent molecular studies have identified a number of key regulators that are required to specify each of the developmental forms in response to temperature. Here we review the regulatory circuits that govern temperature-dependent dimorphism in Histoplasma.


Virus-specific antibodies to Epstein-Barr virus, varicella-zoster virus and rubella virus in renal transplant patients with cytomegalovirus infections.
Renal transplant patients with primary and recurrent cytomegalovirus (CMV) infection had higher antibody titres to Epstein-Barr virus viral capsid antigen (EBV-VCA-IgG) before and after transplantation than healthy blood donors. The geometric mean titres (GMT) of EBV-VCA-IgG were higher in renal transplant patients without CMV infection than in renal transplant patients with CMV infection. Four-fold or greater rises in EBV-VCA-IgG antibody were detected in six patients and a similar rise in antibody to EBV early antigen (EBV-EA-IgG) was detected in one other patient. IgM antibody to EBV-VCA (EBV-VCA-IgM) was detected in only three of these patients. EBV-EA-IgG was present in 39% patients and in 30% control subjects. IgG titres to varicella zoster virus (VZV-IgG) and rubella virus (rubella HI) were higher in patients without CMV infection compared to the patients with CMV infection. Raised titres were detected to VZV in five patients and to rubella virus in three patients. Reductions in antibody titre of four-fold or more were also detected in EBV-EA-IgG (one patient) and to rubella virus (one patient). Raised antibody titres to EBV, VZV, and rubella virus in renal transplant patients may indicate reactivation of these viruses without any symptoms.


[Therapeutic facial surgery possibilities for orbital tumors].
Based on a large experience of more than 400 orbital tumours which were treated operatively, the surgical strategies are described in detail. A surgical approach including the temporary removal of one or more bony orbital walls provided excellent exposure of the intraorbital structures. Using microsurgical techniques for tumour removal the surgical morbidity could be minimized. Subsequent refixation of the osteotomized orbital bones with microplates and screws and skin incisions within the hair bearing parts of the skull resulted in excellent postoperative function and cosmesis. For many malignant orbital tumours definitive cure can only be achieved by an orbital exenteration procedure. An individually tailored surgical and reconstructive strategy (if possible preservation of eyelid skin, tarsal and bulbar conjunctiva) gives a significant benefit, as well with respect to function as to the esthetic outcome of the patient.


Bi incorporation and segregation in the MBE-grown GaAs-(Ga,Al)As-Ga(As,Bi) core-shell nanowires.
Incorporation of Bi into GaAs-(Ga,Al)As-Ga(As,Bi) core-shell nanowires grown by molecular beam epitaxy is studied with transmission electron microscopy. Nanowires are grown on GaAs(111)B substrates with Au-droplet assisted mode. Bi-doped shells are grown at low temperature (300 °C) with a close to stoichiometric Ga/As flux ratio. At low Bi fluxes, the Ga(As,Bi) shells are smooth, with Bi completely incorporated into the shells. Higher Bi fluxes (Bi/As flux ratio ~ 4%) led to partial segregation of Bi as droplets on the nanowires sidewalls, preferentially located at the nanowire segments with wurtzite structure. We demonstrate that such Bi droplets on the sidewalls act as catalysts for the growth of branches perpendicular to the GaAs trunks. Due to the tunability between zinc-blende and wurtzite polytypes by changing the nanowire growth conditions, this effect enables fabrication of branched nanowire architectures with branches generated from selected (wurtzite) nanowire segments.


Filipin-cholesterol binding in CNS axons prior to myelination: evidence for microheterogeneity in premyelinated axolemma.
The distribution of cholesterol in axonal membrane of developing rat optic nerves prior to myelination was studied by freeze-fracture cytochemistry. Binding of the cholesterol-specific probe, filipin, to the axolemma of premyelinated axons was heterogeneous; this suggests the presence of microdomains of axolemma with different membrane composition and/or cytoskeletal/extracellular matrix association. Although the reasons for this binding pattern have not yet been determined, heterogeneity occurs prior to association of glia with the axon, and may reflect regional differences in lipid/sterol composition of the axonal membrane bilayer, or distribution of membrane-associated cytoskeleton. The distribution of intramembranous particles was not obviously associated with the pattern of filipin binding in early developing axons, however, as might have been expected from the attending differences in fluidity of the membrane microdomains. Microheterogeneity in axonal membranes of developing axons could have an influence on several membrane properties, and may be associated with processes important for growth and differentiation of axons.


Canine osteosarcoma: amputation and chemotherapy.
One of the most important advances in veterinary oncology during the past 10 years has been the use of adjuvant chemotherapy for treatment of the micrometastases of canine osteosarcoma. This article reviews the biologic behavior of osteosarcoma and discusses chemotherapy with the two agents known to be effective: cisplatin and doxorubicin.


Electrostatically assembled wound dressings deliver pro-angiogenic anti-miRs preferentially to endothelial cells.
Chronic non-healing wounds occur frequently in individuals affected by diabetes, yet standard-of-care treatment leaves many patients inadequately treated or with recurring wounds. MicroRNA (miR) expression is dysregulated in diabetic wounds and drives an anti-angiogenic phenotype, but miRs can be inhibited with short, chemically-modified RNA oligonucleotides (anti-miRs). Clinical translation of anti-miRs is hindered by delivery challenges such as rapid clearance and uptake by off-target cells, requiring repeated injections, excessively large doses, and bolus dosing mismatched to the dynamics of the wound healing process. To address these limitations, we engineered electrostatically assembled wound dressings that locally release anti-miR-92a, as miR-92a is implicated in angiogenesis and wound repair. In vitro, anti-miR-92a released from these dressings was taken up by cells and inhibited its target. An in vivo cellular biodistribution study in murine diabetic wounds revealed that endothelial cells, which play a critical role in angiogenesis, exhibit higher uptake of anti-miR eluted from coated dressings than other cell types involved in the wound healing process. In a proof-of-concept efficacy study in the same wound model, anti-miR targeting anti-angiogenic miR-92a de-repressed target genes, increased gross wound closure, and induced a sex-dependent increase in vascularization. Overall, this proof-of-concept study demonstrates a facile, translational materials approach for modulating gene expression in ulcer endothelial cells to promote angiogenesis and wound healing. Furthermore, we highlight the importance of probing cellular interactions between the drug delivery system and the target cells to drive therapeutic efficacy.


Reassessment of stiripentol pharmacokinetics in healthy adult volunteers.
Because children who have been receiving stiripentol for the treatment of Dravet syndrome for more than 10 years are now becoming young adults, it is important to accurately characterize stiripentol pharmacokinetics in this age range. A double-blind placebo-controlled dose ranging study was therefore conducted to investigate the pharmacokinetics and tolerability of stiripentol in 12 healthy volunteers. Each subject received 3 single doses of stiripentol (500, 1000, and 2000 mg) separated by a wash-out period of 1 week. Pharmacokinetics of stiripentol was analyzed for each dose by non-compartmental analysis. Median area under the curve (AUC), terminal elimination half-life (t1/2,z) and maximal concentration (Cmax) were calculated for between-dose comparison. Safety was evaluated based on both clinical and biological criteria. Oppositely to previous results, there was no concentration rebounds in the elimination phase, which could be the consequence of the food intake. A more than proportional increase in the AUC was observed, associated with a significant increase in the t1/2,z, for increasing doses (median AUC of 8.3, 31 and 88 mgh/L, and median t1/2,z of 2, 7.7 and 10h for the 500, 1000, and 2000 mg doses respectively), which confirmed the Michaelis-Menten pharmacokinetics of Stiripentol. However, dose-normalized Cmax did not significantly vary between doses. Median Michaelis-Menten parameters were 117 mg/h for Vmax and 1.9 mg/L for Km. No safety concern was observed during the study. The present study allowed a better characterization of the disposition phase of stiripentol and confirmed its non-linear pharmacokinetic behaviour. Further pharmacokinetic/pharmacodynamic studies would be useful to determine the optimal dose of stiripentol for the treatment of Dravet patients in adulthood.


Optical shaping of the polarization anisotropy in a laterally coupled quantum dot dimer.
We find that the emission from laterally coupled quantum dots is strongly polarized along the coupled direction [1 1 ¯ 0], and its polarization anisotropy can be shaped by changing the orientation of the polarized excitation. When the nonresonant excitation is linearly polarized perpendicular to the coupled direction [110], excitons (X1 and X2) and local biexcitons (X1X1 and X2X2) from the two separate quantum dots (QD1 and QD2) show emission anisotropy with a small degree of polarization (10%). On the other hand, when the excitation polarization is parallel to the coupled direction [1 1 ¯ 0], the polarization anisotropy of excitons, local biexcitons, and coupled biexcitons (X1X2) is enhanced with a degree of polarization of 74%. We also observed a consistent anisotropy in the time-resolved photoluminescence. The decay rate of the polarized photoluminescence intensity along the coupled direction is relatively high, but the anisotropic decay rate can be modified by changing the orientation of the polarized excitation. An energy difference is also observed between the polarized emission spectra parallel and perpendicular to the coupled direction, and it increases by up to three times by changing the excitation polarization orientation from [110] to [1 1 ¯ 0]. These results suggest that the dipole-dipole interaction across the two separate quantum dots is mediated and that the anisotropic wavefunctions of the excitons and biexcitons are shaped by the excitation polarization.


A community effort for automatic detection of postictal generalized EEG suppression in epilepsy.
Applying machine learning to healthcare sheds light on evidence-based decision making and has shown promises to improve healthcare by combining clinical knowledge and biomedical data. However, medicine and data science are not synchronized. Oftentimes, researchers with a strong data science background do not understand the clinical challenges, while on the other hand, physicians do not know the capacity and limitation of state-of-the-art machine learning methods. The difficulty boils down to the lack of a common interface between two highly intelligent communities due to the privacy concerns and the disciplinary gap. The School of Biomedical Informatics (SBMI) at UTHealth is a pilot in connecting both worlds to promote interdisciplinary research. Recently, the Center for Secure Artificial Intelligence For hEalthcare (SAFE) at SBMI is organizing a series of machine learning healthcare hackathons for real-world clinical challenges. We hosted our first Hackathon themed centered around Sudden Unexpected Death in Epilepsy and finding ways to recognize the warning signs. This community effort demonstrated that interdisciplinary discussion and productive competition has significantly increased the accuracy of warning sign detection compared to the previous work, and ultimately showing a potential of this hackathon as a platform to connect the two communities of data science and medicine.


Multiphase coalescence mediates Hippo pathway activation.
The function of biomolecular condensates is often restricted by condensate dissolution. Whether condensates can be suppressed without condensate dissolution is unclear. Here, we show that upstream regulators of the Hippo signaling pathway form functionally antagonizing condensates, and their coalescence into a common phase provides a mode of counteracting the function of biomolecular condensates without condensate dissolution. Specifically, the negative regulator SLMAP forms Hippo-inactivating condensates to facilitate pathway inhibition by the STRIPAK complex. In response to cell-cell contact or osmotic stress, the positive regulators AMOT and KIBRA form Hippo-activating condensates to facilitate pathway activation. The functionally antagonizing SLMAP and AMOT/KIBRA condensates further coalesce into a common phase to inhibit STRIPAK function. These findings provide a paradigm for restricting the activity of biomolecular condensates without condensate dissolution, shed light on the molecular principles of multiphase organization, and offer a conceptual framework for understanding upstream regulation of the Hippo signaling pathway.


L-type amino acid transporter 1, LAT1, in growth hormone-producing pituitary tumor cells.
Pituitary tumors (PTs) can cause significant mortality and morbidity due to limited therapeutic options. L-type amino acid transporters (LATs), in particular, the LAT1 isoform, is expressed in a variety of tumor cells. Pharmacological inhibition or genetic ablation of LAT1 can suppress leucine transport into cancer cells, resulting in suppression of cancer cell growth. However, roles of LAT1 in PTs have not been elucidated. Therefore, we assessed LAT1 expression in PTs and evaluated a LAT1-specific inhibitor, JPH203, on rat somatomammotroph tumor cells, GH4 cells. GH4 cells dominantly express LAT1 mRNA rather than other LAT isoforms, whereas LAT2 transcripts were most abundant in normal rat pituitary tissues. JPH203 inhibited leucine uptake and cell growth in GH4 cells in a concentration-dependent manner, and appeared to be independent of the mechanistic target, the rapamycin pathway. Although JPH203 did not induce apoptosis, it suppressed growth hormone production in GH4 cells. Also, genetic downregulation of LAT1 showed similar effects on cell growth and hormone production. These results indicated that restriction of LAT1 substrates by JPH203 modulated both cell growth and hormone production. In conclusion, LAT1 may be a new therapeutic target for PTs because its inhibition leads to suppression of cell growth as well as hormone production. JPH203 may represent a promising drug for clinical use in patients with PTs, with the potential of hormonal control and tumor suppression.


Intertypic modular exchanges of genomic segments by homologous recombination at universally conserved segments in human adenovirus species D.
Human adenovirus species D (HAdV-D), which is composed of clinically and epidemiologically important pathogens worldwide, contains more taxonomic "types" than any other species of the genus Mastadenovirus, although the mechanisms accounting for the high level of diversity remain to be disclosed. Recent studies of known and new types of HAdV-D have indicated that intertypic recombination between distant types contributes to the increasing diversity of the species. However, such findings raise the question as to how homologous recombination events occur between diversified types since homologous recombination is suppressed as nucleotide sequences diverge. In order to address this question, we investigated the distribution of the recombination boundaries in comparison with the landscape of intergenomic sequence conservation assessed according to the synonymous substitution rate (dS). The results revealed that specific genomic segments are conserved between even the most distantly related genomes; we call these segments "universally conserved segments" (UCSs). These findings suggest that UCSs facilitate homologous recombination, resulting in intergenomic segmental exchanges of UCS-flanking genomic regions as recombination modules. With the aid of such a mechanism, the haploid genomes of HAdV-Ds may have been reshuffled, resulting in chimeric genomes out of diversified repertoires in the HAdV-D population analogous to the MHC region reshuffled via crossing over in vertebrates. In addition, some HAdVs with chimeric genomes may have had the opportunity to avoid host immune responses thereby causing epidemics.


Estimation of the avidity of antibodies in polyclonal antisera against Streptococcus pneumoniae type 3 by inhibition ELISA.
The reliability of the determination of antibody avidity in polyclonal sera by indirect sandwich ELISA was studied. Binding of IgM and IgG (sub)classes in unpurified serum to Streptococcus pneumoniae type 3 capsular polysaccharide, which was coated onto ELISA plates, was inhibited with different inhibitors. The inhibitor concn at which 50% inhibition of antibody binding to the ELISA coat was achieved, was used as a measure for antibody avidity. As this 50% inhibition value is dependent upon the dilution of the serum and thus upon the initial amount of free antibody, it is necessary to define (a narrow range of) final ELISA absorbance values to which the dilutions of non-inhibited sera have to be adjusted. The shapes of the serum dilution curves have a good correlation with the numerical 50% inhibition values of the antibody avidity. The inhibition ELISA is suitable to compare the avidity values of the different antibody isotypes, but two remarks should be made: (1) antibody heterogeneity should be considered to influence the results and prevent the accurate measurement of absolute numerical avidity values. Because in the ELISA system merely antibody "activity" is measured, comparison of the efficacy of vaccines by means of the 50% inhibition (avidity) value of various antibody (sub)classes can still be performed in a reliable way; (2) results of the determination of the 50% inhibition values of the different antibody (sub)classes showed them to be dependent on the molecular ratio between antibody (sub)class levels. More aspects of the determination should be taken into account, like shapes of simple dilution curves, influences of various inhibitor concns in the diluent and whole (extended) inhibition curves.


Opacification of the glans penis during cavernosography.
Cavernosography and cavernometry were performed in 150 impotent patients and 10 normal potent volunteers. Opacification of the glans penis was noted in 5 normal volunteers, while among the impotent patients it was noted in 53 per cent of those with venous leakage and in 36 per cent of those without leakage. We believe that opacification of the glans during cavernosography must be regarded as a normal variant rather than as a sign of pathological shunts between the glans and the corpora cavernosa.


Cancer and severe mental illness: Bi-directional problems and potential solutions.
Given the reported increased rates of physical morbidity and higher mortality rates among people with severe mental illness (SMI) (schizophrenia and severe mood disorders), with a life expectancy shorter of 15-20 years with respect to the general population, the aim of this paper was to call attention to the problem of cancer in SMI. We conducted a narrative review of the most significant papers published in the areas of cancer screening, incidence, mortality and palliative care in SMI. Data from the literature confirm disparities in screening (eg, mammography; pap-smear test; colorectal cancer screening) and prevention (eg, clinical breast examination; smoking cessation). The incidence of cancer was found to be variable with a portion of the studies reporting a higher prevalence while others a similar or a lower prevalence of cancer compared to the general population. A lower percentage of patients with SMI received proper cancer treatment resulting in survival after cancer diagnosis significantly worse than people without SMI. Likewise, end-of-life care has been shown to be lacking with poorer levels of physical, psychological and spiritual care. The problems of stigma and discrimination, poorer dignity, poorer health behavior, lack of integration in health-care services for people with SMI needs to be addressed and solved in cancer care. Psycho-oncology has a very specific and mandatory role in integrating the recommendation of the World Health Organization to improve the links between oncology and mental health settings for more specific psycho-oncology programs addressed for this vulnerable segment of the population.


SPONTANEOUS FORMATION AND RESOLUTION OF A LAMELLAR HOLE IN A PATIENT SUCCESSFULLY TREATED FOR DIABETIC MACULAR EDEMA WITH A FLUOCINOLONE ACETONIDE IMPLANT.
The purpose of this study was to report a case of spontaneous formation and resolution of a lamellar macular hole in a patient with diabetic macular edema treated with steroid implants. This study is a case report. A 53-year-old man presented with blurry vision and was found to have diabetic macular edema that remained refractory to treatment despite multiple short-term intravitreal steroid implants. He was eventually treated with an intravitreal fluocinolone acetonide implant and was subsequently noted to have developed a lamellar macular hole that then resolved spontaneously without any additional therapy. There can be spontaneous formation and resolution of lamellar holes in the treatment of diabetic macular edema because of reorganization of the inner retinal layers, without significant impact on visual acuity. To the best of our knowledge, this finding has not been previously reported.


Qualitative analysis of chemical constituents in traditional Chinese medicine analogous formula cheng-Qi decoctions by liquid chromatography-mass spectrometry.
Cheng-Qi decoctions (CQs), a group of analogous formulas, are well-known traditional Chinese preparations used as purgative remedies to treat 'internal heat'-induced symptoms, which manifest as a bloated and painful abdomen, hard stools, fever and other clinical observations. In this study, HPLC-ESI-MS/MS and UPLC-TOF-MS were employed for separation and structural identification of constituents in CQs. As a result, a total of 90 compounds, including seven anthraquinones, 39 flavones, 21 glycosides, 11 stilbene glycosides, six organic acids, five coumarins and one lignans, were detected and tentatively identified in CQs extracts. The characterization results shed some light on the scientific foundation for clinical application of the CQ analogous formulas. Our results also indicate that the HPLC-MS method is useful for the systemic identification of major constituents in traditional Chinese medicine formulas.


Evaluation and operative technique to repair isolated sternal fractures.
A series of 12 patients with traumatic sternal fractures without internal organ injury are reported to have had their fractures repaired with a standard operative technique that has proved to be effective up to 17 years of follow-up. Although sternal fractures are often seen in emergency departments of trauma centers, rarely are they recommended for correction. Often patients experience physical deformity, chronic pain, and abnormal physical habits. A standard operative technique is proposed with highly satisfactory results. Thoracic surgeons should be familiar with this problem and with available standard methods to correct it.


Phylogeny and Redescription of the Testate Amoeba Diaphoropodon archeri (Chlamydophryidae, Thecofilosea, Cercozoa), De Saedeleer 1934, and Annotations on the Polyphyly of Testate Amoebae with Agglutinated Tests in the Cercozoa.
The genus Diaphoropodon, Archer 1869, comprises filose amoebae with agglutinated tests made of quartz grains, diatom frustules and other particulate materials. The key trait of the genus is a hyaline theca covered with numerous 5- to 10-μm-long, hairlike rods. Based on SSU rDNA phylogeny, we show that Diaphoropodon groups closely to Lecythium, a testate amoeba genus with a flexible but naked theca. Electron microscopic images reveal that the rods of Diaphoropodon are not perforating the test but lie randomly distributed on the surface of the amoeba. Comparing fairly naked cells from our cultures with cells from the environment leads to the conclusion that these rods play a role in agglutinating the material on the test.


Antibody responses to Herpesvirus papio antigens in baboons with lymphoma.
An Epstein-Barr virus-related herpesvirus, termed Herpesvirus papio (HVP), was isolated from baboons (Papio hamadryas) at the Institute of Experimental Pathology and Therapy, Sukhumi, USSR, where there is a continuing outbreak of lymphoma. In the present study sera from diseased baboons and from age- and sex-matched control animals were examined for antibodies to HVP antigens. Results showed that animals with lymphoid disease had antibodies to HVP virus capsid, early, soluble, and nuclear antigens at higher frequencies and at higher titers than did control animals. Antibody titers were not age- or sex-related. No concordancy was detected for antibodies to soluble and nuclear antigens. The sera were also examined for antibodies to two other widely distributed viruses of hamadryas baboons, cytomegalovirus and foamy virus. The results of these studies did not indicate a disease-related role for either of these viruses.


Cryopreserved platelets washed with a dialysis machine for dimethyl sulphoxide removal.
Cryopreserved platelets (cPLTs) can be stored for years and are mainly used in military settings. However, the commonly used cryoprotectant dimethyl sulphoxide (DMSO) has toxic side effects when utilized in high quantities. We developed a novel method to aseptically remove DMSO from thawed cPLTs by dialysis. One unit of platelets (N = 6) was mixed with 75 mL of 27% DMSO within 4 days after collection and stored at -80°C for 1 week. The platelet counts, platelet distribution width, mean platelet volume (MPV), platelet activity, platelet release, platelet aggregation, platelet metabolism indicators and platelet ultrastructural features (determined by electron microscopy) of the samples at the pre-freeze, post-thaw wash (post-TW) and 24 h post-thaw wash (24-PTW) stages were determined and compared. The DMSO clearance rate from the post-TW platelets was 95.56 ± 1.3%, and the platelet recovery rate after washing was 74.66 ± 6.34%. The total count, activity, release factors, aggregation and thrombolytic ability of the post-TW platelets were lower, whereas the MPV and apoptosis rates were higher compared with those of the pre-freeze platelets. The lactic acid, glucose and potassium ions released from the platelets during washing were filtered away by the dialyser, which significantly reduced their concentration. However, 24-PTW platelets were metabolically active, resulting in a decrease in pH and glucose content and an increase in lactic acid content. The level of potassium ions remained low after 24 h of storage and washing. The pre-freeze platelets maintained their normal disc shape and exhibited an open canalicular system (OCS) and a dense tubular system. The cPLTs appeared irregular after washing, with protruding pseudopodia and an extensive OCS, which increased the release of their contents. We developed a novel dialysis method to effectively remove DMSO from cPLTs under aseptic conditions and maintain platelet quality. The clinical efficacy of our method remains to be determined. However, the function of the platelets declined 24 h after washing, making them unsuitable for transfusion.


Electrochemical Study and Characterization of an Amperometric Biosensor Based on the Immobilization of Laccase in a Nanostructure of TiO₂ Synthesized by the Sol-Gel Method.
Laccase amperometric biosensors were developed to detect the catechol compound. The laccase enzyme (LAC) immobilization was performed on nanostructures of (a) titania (TiO₂); (b) titania/Nafion (TiO₂/NAF) (both immobilized by the sol-gel method) and a third nanostructure, which consisted of a single biosensor composite of Nafion and laccase enzyme denoted as NAF/LAC. The Nafion was deposited on a graphite electrode and used to avoid "cracking" on the matrix. The TiO₂ particle size was an average of 66 nm. FTIR spectroscopy vibration modes of different composites were determined. The electrochemical behavior of the biosensor was studied using electrochemical spectroscopy (EIS) and cyclic voltammetry (CV). The biosensor based on TiO₂/NAF/LAC presented the best electro-chemical properties with regard to sensitivity, stability and detection limit after a period of 22 days.


Recruitment of the Next Generation of Diverse Hand Surgeons.
Hand surgery encompasses a diaspora of pathology and patients, but the surgeons treating this population are not commensurately diverse. A physician population that reflects the population it treats consistently leads to improved patient outcomes. Despite increasing diversity amongst surgeons entering into pipeline specialties such as General Surgery, Plastic Surgery, and Orthopaedic Surgery, the overall makeup of practicing hand surgeons remains largely homogenous. This article outlines organizations, such as the Perry Initiative, which have increased recruitment of women and underrepresented minorities into pipeline programs. Techniques of minimizing bias and increasing opportunities for underrepresented groups are also discussed.


The Ycf48 accessory factor occupies the site of the oxygen-evolving manganese cluster during photosystem II biogenesis.
Robust oxygenic photosynthesis requires a suite of accessory factors to ensure efficient assembly and repair of the oxygen-evolving photosystem two (PSII) complex. The highly conserved Ycf48 assembly factor binds to the newly synthesized D1 reaction center polypeptide and promotes the initial steps of PSII assembly, but its binding site is unclear. Here we use cryo-electron microscopy to determine the structure of a cyanobacterial PSII D1/D2 reaction center assembly complex with Ycf48 attached. Ycf48, a 7-bladed beta propeller, binds to the amino-acid residues of D1 that ultimately ligate the water-oxidising Mn4CaO5 cluster, thereby preventing the premature binding of Mn2+ and Ca2+ ions and protecting the site from damage. Interactions with D2 help explain how Ycf48 promotes assembly of the D1/D2 complex. Overall, our work provides valuable insights into the early stages of PSII assembly and the structural changes that create the binding site for the Mn4CaO5 cluster.


Ultimate figures of merit broadband self-powered obliquely deposited antimony thin film laser detectors.
Fabrication of a fast and high detectivity infrared detector operating at room temperature represents a big challenge. Due to the small energy gap of the semiconducting materials used for infrared detectors, the noise becomes considerable factor and the possibility of operating the detector at room temperature is very limited. A study of the figures of merit antimony thin films detector grown by oblique angle deposition technique is presented. Polycrystalline antimony thin films were thermally evaporated on the glass substrates at a angles of 0, 10, 30, and70°. The aim was to develop a wideband (0.649-10.6) µm self-powered laser detectors; operating at room temperature. The deposition angle had a decisive role in the detector specifications, namely, its detectivity, responsivity, linearity, and response time. At θ = 70° deposition angle; maximum detectivity and fastest response were achieved. The variation of rise time with deposition angle was linear, and the rise time was around 50 ns at 70°. The antimony detectors showed about the same specific detectivity ~ 109 Jones at 300 k for the wavelength range of 1.064-10.6 µm.


Sleep disorder and behavior problems in children with type 1 diabetes mellitus.
To examine sleep and behavior problems in children with type 1 Diabetes Mellitus (T1DM) compared to nondiabetic controls in a bridging country between east and west and to evaluate the interaction of sleep on behavior problems, maternal sleep, and maternal depressive symptoms. The study included children with T1DM (4-12 years old) and age/sex-matched healthy controls. Parents completed the Children Sleep Habits Questionnaire (CSHQ), Children Behavior Checklist/4-18 (CBCL/4-18), Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory (BDI), and a study-specific sociodemographic questionnaire. Clinical parameters regarding T1DM were collated from medical records. Participants included 75 children with T1DM and 49 controls. Based on CSHQ results 65.3% of all participants in both groups had sleep problems. Children with T1DM slept less and had higher daytime sleepiness problems than controls (p=0.024, p=0.008, respectively). No association was found between CSHQ or sleep duration and mode of diabetes treatment (pump, multiple daily injections) or glycemic control. CSHQ correlated with maternal PSQI (r=0.336 p=0.004) and BDI (r=0.341 p=0.004) in children with T1DM, but there was no association amongst controls. Children with T1DM had higher internalizing problems compared to controls. CSHQ and BDI correlated with internalizing, externalizing, and the total scores of the CBCL/4-18 in children with T1DM (R2=0.260 p<0.001; R2=0.207 p<0.001, R2=0.381 p<0.001 respectively). In controls, only BDI was associated with internalizing, externalizing, and the total scores of the CBCL/4-18. Children with T1DM should be evaluated for sleep pattern and quality at follow-up, to identify those at risk for behavior problems and improve maternal life quality. Large longitudinal studies are necessary to assess the effect of new diabetes treatment modalities on sleep.


Do CSF Biomarkers Predict Progression to Cognitive Impairment in Parkinson's disease patients? A Systematic Review.
Many patients with Parkinson's disease (PD) will develop cognitive impairment. Cross-sectional studies have shown that certain protein levels are altered in the cerebrospinal fluid (CSF) of PD patients with dementia and are thought to represent potential biomarkers of underlying pathogenesis. Recent studies suggest that CSF biomarker levels may be predictive of future risk of cognitive decline in non-demented PD patients. However, the strength of this evidence and difference between specific CSF biomarkers is not well delineated. We therefore performed a systematic review to assess if levels of specific CSF protein biomarkers are predictive of progression to cognitive impairment. Nine articles were identified that met inclusion criteria for the review. Findings from the review suggest a convergence of evidence that a low baseline Aβ42 in the CSF of non-demented PD patients predicts development of cognitive impairment over time. Conversely, there is limited evidence that CSF levels of tau, either total tau or phosphorylated tau, is a useful predictive biomarker. There are mixed results for other CSF biomarkers such as α-synuclein, Neurofilament light chain, and Heart fatty acid-binding protein. Overall the results of this review show that certain CSF biomarkers have better predictive ability to identify PD patients who are at risk for developing cognitive impairment. Given the interest in developing disease-modifying therapies, identifying this group will be important for clinical trials as initiation of therapy prior to the onset of cognitive decline is likely to be more efficacious.


Visualization of arterial grafts on a gastrointestinal bleeding scan.
A case of patent arterial grafts causing an abnormal Tc-99m sulfur colloid bleeding scan is presented. This finding has not been reported previously.


Awareness of the healthcare system and rights to healthcare in the Colombian population.
To analyze changes in users' awareness of the healthcare system and of their rights to healthcare in Colombia in the last 10 years, as well as the factors that influence users' awareness. We carried out a descriptive study to compare the results of two cross-sectional studies based on two surveys of users of the Colombian healthcare system. The first survey was performed in 2000 and the second in 2010. The municipalities of Tuluá (urban area) and Palmira (rural area) were surveyed. In both surveys, a stratified, multistage probability sample was selected. There were 1497 users in the first sample and 1405 in the second. Changes in awareness of the healthcare system and associated factors in each year were assessed through multivariate logistic regressions. Users' awareness of the healthcare system was limited in 2000 and was significantly lower in 2010, except for that relating to health insurers and providers. In contrast, more than 90% of users in both surveys perceived themselves as having healthcare rights. The factors consistently associated with greater awareness were belonging to a high socioeconomic stratum and having higher education. The most underprivileged users were less likely to be aware of the healthcare system, hampering their ability to make informed decisions and to exercise their health rights. To correct this situation, health institutions and the government should act decisively to reduce social inequalities.


[A topical subject in the Lombardy of 1906: the regeneration of nerves].
The author informs about a manuscript containing a communication of Agostino Gemelli's to the Brescia University (1906). He analyzes end compares it with a similar communication given by Gemelli to the Lombard Institute in Milan, concerning the regeneration of peripheral nerves.


Demonstrating Value: A Case Study of Enhanced Recovery.
An enhanced recovery after surgery strategy will be increasingly adopted in the era of value-based care. The various elements in each enhanced recovery after surgery protocol are likely to add value to the overall patient surgical journey. Although the evidence varies considerably based on type of surgery and patient group, the team-based approach of care should be universally applied to patient care. This article provides an overview of up-to-date techniques and methodology for enhanced recovery, including an overview of value-based care, delivery, and the evidence base supporting enhanced recovery after surgery.


Whole-genome sequencing of Bacillus velezensis LS69, a strain with a broad inhibitory spectrum against pathogenic bacteria.
Bacillus velezensis LS69 was found to exhibit antagonistic activity against a diverse spectrum of pathogenic bacteria. It has one circular chromosome of 3,917,761bp with 3,643 open reading frames. Genome analysis identified ten gene clusters involved in nonribosomal synthesis of polyketides (macrolactin, bacillaene and difficidin), lipopeptides (surfactin, fengycin, bacilysin and iturin A) and bacteriocins (amylolysin and amylocyclicin). In addition, B. velezensis LS69 was found to contain a series of genes involved in enhancing plant growth and triggering plant immunity. Whole genome sequencing of Bacillus velezensis LS69 will provide a basis for elucidation of its biocontrol mechanisms and facilitate its applications in the future.


The wear of polished and glazed zirconia against enamel.
The wear of tooth structure opposing anatomically contoured zirconia crowns requires further investigation. The purpose of this in vitro study was to measure the roughness and wear of polished, glazed, and polished then reglazed zirconia against human enamel antagonists and compare the measurements to those of veneering porcelain and natural enamel. Zirconia specimens were divided into polished, glazed, and polished then reglazed groups (n=8). A veneering porcelain (Ceramco3) and enamel were used as controls. The surface roughness of all pretest specimens was measured. Wear testing was performed in the newly designed Alabama wear testing device. The mesiobuccal cusps of extracted molars were standardized and used as antagonists. Three-dimensional (3D) scans of the specimens and antagonists were obtained at baseline and after 200 000 and 400 000 cycles with a profilometer. The baseline scans were superimposed on the posttesting scans to determine volumetric wear. Data were analyzed with a 1-way ANOVA and Tukey Honestly Significant Difference (HSD) post hoc tests (α=.05) Surface roughness ranked in order of least rough to roughest was: polished zirconia, glazed zirconia, polished then reglazed zirconia, veneering porcelain, and enamel. For ceramic, there was no measureable loss on polished zirconia, moderate loss on the surface of enamel, and significant loss on glazed and polished then reglazed zirconia. The highest ceramic wear was exhibited by the veneering ceramic. For enamel antagonists, polished zirconia caused the least wear, and enamel caused moderate wear. Glazed and polished then reglazed zirconia showed significant opposing enamel wear, and veneering porcelain demonstrated the most. Within the limitations of the study, polished zirconia is wear-friendly to the opposing tooth. Glazed zirconia causes more material and antagonist wear than polished zirconia. The surface roughness of the zirconia aided in predicting the wear of the opposing dentition.


The use of low level laser therapy in the treatment of temporomandibular joint disorders. Review of the literature.
The temporomandibular disorders (TMDs) have been identified as the most important cause of pain in the facial region. The low level laser therapy (LLLT) has demonstrated to have an analgesic, anti-inflammatory and biostimulating effects. The LLLT is a noninvasive, quick and safe, non-pharmaceutical intervention that may be beneficial for patients with TMDs. However the clinical efficiency of LLLT in the treatment of this kind of disorders is controversial. Literature review in reference to the use of LLLT in the treatment of TMDs, considering the scientific evidence level of the published studies. A MEDLINE and COCHRANE database search was made for articles. The keywords used were "temporomandibular disorders" and "low level laser therapy" or "phototherapy" and by means of the Boolean operator "AND". The search provided a bank of 35 articles, and 16 relevant articles were selected to this review. These articles were critically analyzed and classified according to their level of scientific evidence. This analysis produced 3 literature review articles and 13 are clinical trials. The SORT criteria (Strength of Recommendation Taxonomy) was used to classify the articles. Only one article presented an evidence level 1, twelve presented an evidence level 2, and three presented an evidence level 3. According to the principle of evidence-based dentistry, currently there is a scientific evidence level B in favor of using LLLT for treatment of TMDs. Publications on the use of LLLT for treatment of TMDs are limited making difficult to compare the different studies due to the great variability of the studied variables and the selected laser parameters. The great majority of the studies concluded that the results should be taken with caution due to the methodological limitations.


Accumulation of activated invariant natural killer T cells in the tumor microenvironment after α-galactosylceramide-pulsed antigen presenting cells.
The intravenous administration of α-Galactosylceramide (α-GalCer)-pulsed antigen presenting cells (APCs) is well tolerated and the increased IFN-γ producing cells in the peripheral blood after the treatment appeared to be associated with prolonged survival. An exploratory study protocol was designed with the preoperative administration of α-GalCer-pulsed APCs to clarify the mechanisms of these findings, while especially focusing on the precise tumor site. Patients with operable advanced lung cancer received an intravenous injection of α-GalCer-pulsed APCs before surgery. The resected lung and tumor infiltrating lymphocytes (TILs) as well as peripheral blood mononuclear cells were collected and the invariant NKT (iNKT) cell-specific immune responses were analyzed. Four patients completed the study protocol. We observed a significant increase in iNKT cell numbers in the TILs and augmented IFN-γ production by the α-GalCer-stimulated TILs. The administration of α-GalCer-pulsed APCs successfully induced the dramatic infiltration and activation of iNKT cells in the tumor microenvironment.


Hepatic resection for minute hepatocellular carcinoma.
Twenty-three patients with minute hepatocellular carcinoma, defined as a solitary lesion less than or equal to 2 cm, underwent hepatectomy at our institute during the 10 years between January, 1979 and December, 1988. Hepatitis B surface antigen was positive in 4 patients and the preoperative serum alpha-fetoprotein level was within the normal range in 7 patients and slightly elevated (20-200 ng/mL) in 14 patients. Liver cirrhosis was present in 16 patients and chronic hepatitis in 6 patients. The diagnosis was first suspected from the results of periodic examinations, including echography and the measurement of alpha-fetoprotein, in all except one patient. Minor hepatic resection was performed in 22 patients, and lobectomy in one patient in whom the tumor was located centrally in the liver. Three patients died of hepatic failure in hospital following surgery, and the survival rates of the other 20 patients at 1, 3, and 5 years were 90, 79, and 61 percent, respectively. The prognostic factors that influenced long-term survival were investigated by comparing the survival curves. The only factor associated with a significant difference in survival was the severity of concomitant liver disease. Thus, severe cirrhosis is the main obstacle against the long-term survival of patients with minute hepatocellular carcinoma.


Evaluation of Chromocult enterococci agar for the isolation and selective enumeration of Enterococcus spp. in broilers.
To investigate the productivity and specificity of a new chromogenic enterococci selective medium (Chromocult enterococci agar) recently developed by Merck. The study was carried out comparing Chromocult enterococci agar with MRS agar (Merck), a basal lactic acid bacteria medium in current use. A total of 216 faecal samples from poultry were collected and enterococci populations were counted. Likewise, 100 randomly selected strains were identified for each medium. The differences found between the two media were analysed and discussed. A good sensitivity of 98% was obtained for Chromocult agar and all false-positive isolates obtained were identified as Leuconostoc spp. However significant differences (P<0.01) were obtained between the enterococci species isolation rates identified from these two media, suggesting the poor growth of some species in Chromocult enterococci agar. Viable counts of Enterococcus spp. obtained with MRS agar were significantly higher than those obtained with Chromocult enterococci agar. The use of chromogenic media for microbiological analysis is increasing. Independent studies are important to evaluate newly developed chromogenic media.


Cardiovascular correlates of insulin resistance in normotensive and hypertensive African Americans.
Insulin resistance (IR) is associated with obesity and predisposes to diabetes mellitus (DM) and cardiovascular disease. The purpose of this study is to determine if IR is related to cardiovascular function independent of DM or hypertension among African Americans (AA). Four hundred sixty-two nondiabetic AA (50% hypertensive and 51% women) were studied on an inpatient General Clinical Research Center. Measurements included anthropometrics and 24-hour blood pressure (BP), heart rate (HR), fasting blood glucose, plasma aldosterone, and insulin. Stroke volume (SV) and cardiac output (CO) were measured by impedance plethysmography; peripheral vascular resistance (PVRI) and vascular compliance indices (VCI) were computed. These measurements were also obtained in response to mental (computerized math testing) and pharmacologic (graded norepinephrine infusion) stress. Insulin resistance was calculated using the homeostasis model assessment (HOMA-IR). SV, CO, and VCI decreased with increasing HOMA-IR, whereas HR and PVRI increased. Overall, BP, HR, and PVRI were positively correlated with HOMA-IR (P < .01); and SV index, cardiac index, and VCI were negatively correlated with HOMA-IR (P < .0001). The correlations persisted after adjustment for BP, age, sex, plasma aldosterone, total cholesterol, or low-density lipoprotein and high-density lipoprotein cholesterol. In addition, multiple linear regression analyses showed that HOMA-IR contributes to the maximum variability of all the hemodynamic variables. Blood pressure responses to math stress and norepinephrine infusion did not correlate with HOMA-IR. Unrelated to DM and BP, IR is associated with increased PVRI and decreased CO in AA. These observations suggest that an exclusive focus on effects of IR on DM or BP may ignore independent pathophysiologic contributions of IR to cardiovascular disease.


Associations between enzyme genotypes and dark respiration in perennial ryegrass, Lolium perenne L.
In this study, we determined whether relationships existed between dark respiration and genotype at five enzyme polymorphisms in perennial ryegrass, Lolium perenne L. Positive correlations were found between Q 10 of dark respiration and genotype at the phosphoglucomutase (PGM) and 6-phosphogluconate dehydrogenase (6PGD) loci. Plants doubly homozygous for the common allele at these loci were found to have Q 10 values 20% higher than those for double heterozygotes. In plants that were heat stressed for five consecutive days, Q 10 was found to be negatively correlated with apparent vigor after stressing. Individuals homozygous for PGM and 6PGD (with higher Q 10 values) exhibited more apparent damage following the stress than heterozygous individuals. Both PGM and 6PGD occupy positions in metabolism with regulatory potential. Although caution must be used in assigning causal relationships, the results suggest that specific forms of these enzymes are directly related to, or are correlated with, the determinants of respiratory efficiency in L. perenne.


Gorilla RH-like genes and antigens.
It has been previously shown that most of the human IgG monoclonal D-specific antibodies define a polymorphism in the gorilla consisting of two phenotypes: Dgor-positive and Dgor-negative. By quantitative indirect immunofluorescence assay and quantitative immunoblotting it was evaluated that the number of Dgor antigenic sites per gorilla red cell varies from a level equivalent to that observed for human RhD-positive cells to a level eight times higher. By immunoblotting with a rabbit reagent specific for the carboxylic end of human Rh-polypeptides it was demonstrated that RBCs from all gorillas, whatever their Dgor phenotype, possess 33000 relative molecular mass Rh-like polypeptides. The expression of the Dgor antigen was shown to be associated with the presence of three polymorphic bands defined by Southern blot using a human exon 4 RHCE probe, and to a length polymorphism of gorilla intron 3 evidenced by polymerase chain reaction. By contrast, the expression of the Dgor antigen was not associated to the length polymorphism of gorilla intron 4 which is related to the presence or absence of an Alu-Sx element in intron 4, paralleling the situation observed in human. These results confirmed the presence in the gorilla genome of at least two RH-like genes, one of which being responsible for Dgor polymorphism. The phylogenesis of the human and gorilla RH genes is discussed in light of the comparison of intron 4 sequences.


Fighting undernutrition: don't forget the bugs.
Severe acute malnutrition is a major cause of child death in developing countries. In a recent study, Smith et al. (2013) monitored a large twin cohort in Malawi to unveil a causal relationship between gut microbiota and weight loss in undernutrition.


Low-dose and oral exposure to SARS-CoV-2 may help us understand and prevent severe COVID-19.
The effectiveness and sustainability of current public health interventions designed to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission remain of great concern in many settings, especially in the absence of a transmission-preventing vaccine. It was hypothesized that a more targeted set of interventions focusing on preventing severe coronavirus disease 2019 (COVID-19), rather than SARS-CoV-2 transmission, would be less disruptive to society. To identify these, it would be helpful to better understand how the infecting dose of SARS-CoV-2 and its route of infection influence the clinical outcome, immunological protection, and likelihood of onward transmission. It is suggested that carefully controlled human infection model (CHIM) studies involving intranasal and oral administration of progressively increasing doses of SARS-CoV-2, starting with low levels, to healthy young adult volunteers may be the most expeditious and definitive way to answer these questions. Such studies would differ in objective from CHIM proposals designed to expedite vaccine development, although the latter might be adapted to address some of the questions raised here. Results from the studies proposed here could help elucidate the relationship of infection to COVID-19 and thereby provide a scientific basis for more targeted and sustainable application of public health control measures, and inform the design of improved immunotherapeutics and more targeted vaccine development.


The relationship between depressive and anxious symptoms and school attendance among adolescents seeking psychological services in a public general hospital in China: a cross-sectional study.
School attendance problems (SAPs), whether absenteeism or dropout, are strongly associated with poor outcomes for adolescents. We examined multiple variables that influence SAPs to identify potential leverage points for improving school attendance. Self-reported SAPs and demographic information was collected from 392 adolescents in adolescents presenting to the general hospital for psychological services. PHQ-9 and GAD-7 were applied to assess the severity of depressive and anxious symptoms. We constructed logistic regression analysis and the Chi-Square Automatic Interaction Detection (CHAID) segmentation analysis via SPSS Decision Tree to identifying risk factors for the development of SAPs in adolescents. SAPs were self-reported by 252 (64.3%) adolescents. The SAPs group and non-SAPs group showed a significant difference in age, PHQ9 total scores, GAD7 total scores, schools, siblings, residence, parental marital quality, general health, regular exercise, and regular diet. A post hoc comparison between the two groups showed that the frequency of SAPs was significantly higher in the moderately-severe and severe depressive groups compared with other three groups (none, mild, moderate). The frequency of SAPs in severe anxious groups was significantly different from the none-anxious group. According to the binary logistic regression analysis, the depressive severity, siblings, residence, marital quality of parents, general health, and regular diet were correlated with the SAPs among adolescents. The adjusted OR of SAPs according to moderately-severe depressive symptoms was 10.84 (95%CI: 1.967-59.742) and severe depressive symptoms was 6.659 (95%CI: 1.147-38.666). In the decision tree model, PHQ-9 severity was extracted as the first splitting variable, with regular exercise and residence as the second, and siblings as the third. The ROC curves for predicting SAPs showed a fair diagnostic accuracy of the model with AUCs of CHAID model (0.705,95%CI:0.652-0.759, P = 0.000) and logistic regression model (0.777,95%CI:0.729-0.824, P = 0.000). Our study provides insights into the associations between depressive symptoms and poor school attendance and identifies a number of risk factors associated with SAPs. Effective intervention by mental health practitioners, more attention by policy makers, and further research in this area are urgently needed for adolescents.


Perfusion-computed tomography for simultaneous bilateral middle cerebral artery occlusion.
Bilateral simultaneous middle cerebral artery occlusion is a rare condition that may lead to severe neurological disability or death, thus requiring rapid intervention in order to restore vessels patency and brain perfusion. Perfusion-computed tomography is demonstrated to be a fundamental tool for selecting stroke patients candidate to mechanical thrombectomy, but its role for guiding the optimal strategy of endovascular treatment in concomitant multivessel cerebral occlusion has never been reported. We describe a case of bilateral middle cerebral artery occlusion in which perfusion-computed tomography was crucial both for addressing to endovascular procedure and planning the sequence treatment of mechanical thrombectomies.


Pectinase hydrolysis of Dendrobium huoshanense polysaccharide and its effect on protein nonenzymatic glycation.
The aim of this study was to investigate the inhibitory effects of molecular weight alteration of Dendrobium huoshanense polysaccharide on protein nonenzymatic glycation. For this purpose, one homogeneous active polysaccharide DHPD1 with molecular weight 3.2 kDa was extracted from D. huoshanense. GC analysis showed that DHPD1 was mainly composed of glucose, arabinose, galactose in a molar ratio of 0.023:1.023:0.021 with a trace of mannose and xylose. In order to get DHPD1-derived fragments with different molecular weight, response surface methodology was employed to optimize the enzymatic degradation conditions. The maximum reducing sugar production (0.399 mg/mL) was obtained under an optimal condition including pectinase dosage 126 U/mL, reaction pH 4.46 and reaction temperature 48 °C. By applying this condition, three DHPD1-derived fragments with different molecular weights were obtained through changing the hydrolysis time. Infrared spectroscopy analysis indicated that the backbone structure of DHPD1 was not destroyed by pectinase hydrolysis. Monosaccharide composition analysis showed that pectinase preferred to liberate glucose from DHPD1. The inhibitory action of DHPD1 on protein nonenzymatic glycation reduced with the decrease of molecular weight.


Do children evaluated for maltreatment have higher subsequent emergency department and inpatient care utilization compared to a general pediatric sample?
Child maltreatment leads to substantial adverse health outcomes, but little is known about acute health care utilization patterns after children are evaluated for a concern of maltreatment at a child abuse and neglect medical evaluation clinic. To quantify the association of having a child maltreatment evaluation with subsequent acute health care utilization among children from birth to age three. Children who received a maltreatment evaluation (N = 367) at a child abuse and neglect subspecialty clinic in an academic health system in the United States and the general pediatric population (N = 21,231). We conducted a retrospective cohort study that compared acute health care utilization over 18 months between the two samples using data from electronic health records. Outcomes were time to first emergency department (ED) visit or inpatient hospitalization, maltreatment-related ED use or inpatient hospitalization, and ED use or inpatient hospitalization for ambulatory care sensitive conditions (ACSCs). Multilevel survival analyses were performed. Children who received a maltreatment evaluation had an increased hazard for a subsequent ED visit or inpatient hospitalization (hazard ratio [HR]: 1.3, 95 % confidence interval [CI]: 1.1, 1.5) and a maltreatment-related visit (HR: 4.4, 95 % CI: 2.3, 8.2) relative to the general pediatric population. A maltreatment evaluation was not associated with a higher hazard of health care use for ACSCs (HR: 1.0, 95 % CI: 0.7, 1.3). This work can inform targeted anticipatory guidance to aid high-risk families in preventing future harm or minimizing complications from previous maltreatment.


Incidence, Persistence, and Factors Associated With HPV Infection Among Male Adolescents With and Without Perinatally Acquired HIV Infection.
Infection with high-risk human papillomavirus (HR-HPV) has been shown to be more prevalent and persistent in female adolescents with HIV. However, data among male adolescents with perinatally acquired HIV (PHIV) are limited. We investigated the incidence and persistence of HR-HPV in anogenital compartments and associated factors among PHIV in comparison to HIV-uninfected (HU) male adolescents in Thailand. PHIV and HU males aged 12-24 years were enrolled. At baseline and 3 subsequent annual visits, specimens from the scrotum, penis, and anal area were obtained for HPV and other testing. From June 2013 to October 2017, 49 PHIV and 47 HU male adolescents with a median age of 18 (interquartile range 17-20) years were enrolled. PHIV had higher incidence of any HR-HPV infection than HU adolescents {33.05 [95% confidence interval (CI): 20.82 to 52.46] vs. 15.73 [95% CI: 8.18 to 30.22] per 100 person-years, P = 0.04}. The persistence of any HR-HPV genotypes (detected at ≥2 annual visits) was not different by group (PHIV 27% vs. HU 23%, P = 0.75). Having ≥3 sex partners in past 6 months (adjusted prevalence ratio 2.39, 95% CI: 1.14 to 5.05; P = 0.02) and co-infection with other sexually transmitted infections (syphilis, chlamydia, and/or gonorrhea) were associated with persistent HR-HPV infection (adjusted prevalence ratio 6.21, 95% CI: 2.87 to 13.41; P < 0.001). Thai PHIV male adolescents had a higher incidence of HR-HPV infection than those without HIV. Having multiple sex partners and co-infection with sexually transmitted infections was associated with persistent HR-HPV infection. These data demonstrate the need to prioritize PHIV male adolescents in routine and catch-up HPV vaccination programs.


Increase in plasma homocysteine levels induced by drug treatments in neurologic patients.
Homocysteine (Hcy) is a thyol amino acid resulting from de-methylation of methionine, an essential amino acid derived from dietary proteins. It is metabolized through two pathways: re-methylation and transsulfuration, which use as cofactors folate, vitamin B6 and vitamin B12. Hyperhomocysteinemia has been identified as a risk factor for cerebrovascular disease, dementia, impaired cognitive function and depression. Several drugs may interfere with metabolic pathways of Hcy, leading to an alteration of plasma Hcy levels. Lipid-lowering agents, used to reduce the risk of cerebral venous thrombosis or occlusive vascular disease in patients with high levels of plasmatic lipids, can increase plasma Hcy levels. Hyperhomocysteinemia has been also documented in Parkinson disease patients treated with levodopa and in epileptic patients after chronic treatment with antiepileptic drugs. In contrast, vitamins supplementations may be warranted in patients treated with lipid-lowering agents, levodopa and antiepileptic drugs in order to maintain normal plasma Hcy values. In contrast, higher doses of vitamins can induce dysfunctions in central and peripheral nervous system; therefore excessive supplements should be avoided.


Clinical phenotypes of five patients with psychotic disorders carrying rare schizophrenia-associated loss-of-function variants.
The Schizophrenia Exome Meta-Analysis (SCHEMA) consortium identified 10 genes in which loss-of-function (LoF) variants are highly associated with schizophrenia (SZ). In a well-characterized sample of 988 patients with psychotic disorders, we investigated whether patients bearing a SCHEMA variant presented with unusual or unique signs, symptoms, or course of illness. We identified 5 patients who carried a LoF variant in a SCHEMA gene, each in a different gene. None of the patients with a SCHEMA variant had unique symptoms. However, compared to the average of patients in the sample, all of the patients with a SCHEMA variant had earlier onset of any mental illness and more hospitalizations. Also, among SCHEMA carriers, 80 % were treated with clozapine, 60 % with ECT, all with either clozapine or ECT and 40 % with both clozapine and ECT, compared to only 2 % treated with clozapine and 18 % treated with ECT in the comparison group of patients without SCHEMA variants. All 5 patients with a SCHEMA variant had polysubstance abuse, and all had attempted suicide. Fewer than half had such presentations in the group without SCHEMA variants. In this small sample, SCHEMA variants appear to be associated with earlier onset, less favorable response to standard first-line treatments, and more severe illness, but not unique presentations of illness.


Laparoscopic surgery for rectal cancer with a coexisting Retzius shunt and inferior mesenteric arteriovenous malformation: A case report.
A coexisting short-circuit from the inferior mesenteric vein (IMV) to the inferior vena cava, known as a Retzius shunt, and arteriovenous malformation (AVM) of the inferior mesentery are extremely rare conditions. We encountered a case of rectal cancer with coexisting Retzius shunt and inferior mesenteric AVM successfully treated with laparoscopic surgery. Contrast computed tomography (CT) in a 62-year-old man with rectal cancer showed multiple dilated veins at the mesenterium of the descending sigmoid colon. These dilated veins were connected between the IMV and the left renal vein. A diagnosis of Retzius shunt was made, and laparoscopic low anterior resection with lymph node dissection was performed. A pathological examination of the colonic mesenterium revealed AVM communicating with the dilated IMV and Retzius shunt. The preoperative evaluation of aberrant vessels by three-dimensional CT is particularly useful for patients with vascular malformations to ensure safe laparoscopic surgery.


Functional alginate nanoparticles for efficient intracellular release of doxorubicin and hepatoma carcinoma cell targeting therapy.
In order to efficiently deliver chemotherapy drugs into hepatoma cells, a pH-sensitive and liver-targeted drug delivery system (glycyrrhetinic acid-modified alginate/doxorubicin-modified alginate complex nanoparticles), termed GA-ALG/DOX-ALG NPs, was prepared. First, GA-ALG and DOX-ALG were synthesized, and then GA-ALG/DOX-ALG NPs self-assembled by mixing GA-ALG and DOX-ALG via dialysis. Properties of pH-sensitivity, biodistribution in mice, and antitumor activity against ectopic hepatoma tumors in the NPs were evaluated. DOX release from GA-ALG/DOX-ALG NPs showed pH-sensitivity; less than 10% of drugs were liberated at pH 7.4 within 9 d while 58.7% of DOX released at pH 4.0. The confocal laser scanning microscope (CLSM) experiment showed that GA-ALG/DOX-ALG NPs can respond to the endosomal/lysosomal environment and had pH-triggered intracellular releasing property. The area under the curve (AUC(0-∞)) and half-life (t(½)) in the liver of GA-ALG/DOX-ALG NPs were 1156.7 μg h/g and 34.3 h, respectively, which was 11.8- and 3.2-fold higher than that of the DOX·HCl group. Furthermore, the inhibition rate of tumor growth was 79.3% after treatment with GA-ALG/DOX-ALG NPs, which was much higher than that of the DOX·HCl (48.5%) and DOX-ALG NPs groups (62.7%). Importantly, no mice died in the GA-ALG/DOX-ALG NPs group, while the mortality rate was 40% in the DOX·HCl group.


Simultaneous optical and electrical in vivo analysis of the enteric nervous system.
The enteric nervous system (ENS) is a major division of the nervous system and vital to the gastrointestinal (GI) tract and its communication with the rest of the body. Unlike the brain and spinal cord, relatively little is known about the ENS in part because of the inability to directly monitor its activity in live animals. Here, we integrate a transparent graphene sensor with a customized abdominal window for simultaneous optical and electrical recording of the ENS in vivo. The implanted device captures ENS responses to neurotransmitters, drugs and optogenetic manipulation in real time.


Endogenous levels of tryptophan, serotonin and 5-hydroxyindole acetic acid in the developing brain of the cat.
Using spectrofluorimetric methods, endogenous levels of tryptophan (TRP), serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) were determined in various structures of the growing brain of cats. After one month, 5-HT metabolism is comparable to that observed in adult cats. The third week after birth is marked by increasing levels of TRP and 5-HIAA and seems to be a critical period for the maturation of serotoninergic neurons.


Morphometric aspects and proposal of a new classification of genial tubercles in cone-beam computed tomography in a Brazilian population.
This study evaluated epidemiological and morphological aspects of genial tubercles (GTs) using cone-beam computed tomography (CBCT). This retrospective, observational and cross-sectional study evaluated 276 tomographs of adult dentate individuals (18-69 years). The presence and absence of GTs were evaluated, and in cases in which this structure was observed, linear measurements (length, height, and width), and anatomical distances. In addition, a GT classification was proposed based on the presence, number, and location of the tubercles. Of the 276 CT scans, 28 (10.14%) had absence of GTs and in 248 CT scans GTs were present, of which 42 (57.5%) were from females and 106 (42.5%) from males. Regarding the number of GTS, the most prevalent variant was the two-tubercle-variant (143, 57.7%), followed by the presence of a single tubercle (n = 62, 25.0%), 3 tubercles (n = 40, 16.1%) and 4 tubercles (n = 3, 1.2%). The most prevalent classification was IIIA (n = 96, 38.7%), followed by IIIB (n = 60, 36.3%), IIA (n = 53, 21.4%) and IIB (n = 9, 3.6%). A prevalence of GT of approximately 90% was observed, with two GTs per exam as the most frequent finding. Men had a longer mean GT length compared to women. Female individuals exhibited a shorter distance from the base of the GT to the base of the mandible.


Parathyroidectomy for the attainment of NKF-K/DOQI™ and KDIGO recommended values for bone and mineral metabolism in dialysis patients with uncontrollable secondary hyperparathyroidism.
The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI™) 2003 and Kidney Disease: Improving Global Outcomes (KDIGO) 2009 have established guidelines for the treatement of secondary hyperparathyroidism. This study evaluated the impact of parathyroidectomy to achieve recommended values for parathyroid hormone, calcium, phosphorus and CaxPO(4) product in dialysis patients with severe secondary hyperparathyroidism that is resistant to medical treatment. This study included 43 consecutive patients who underwent parathyroidectomy for a severe form of secondary hyperparathyroidism (SHPT) that is unresponsive to medical treatment. The serum iPTH, calcium and phosphorus levels were measured prior to surgery, every morning after surgery for 5 days and on the first, sixth and eighth postoperative months. Following parathyroidectomy, a significant decline in iPTH values was observed in all patients; however, after the 8-month study period, only one of these patients achieved a serum iPTH concentration within the K/DOQI recommended target range. Unlike iPTH, targeting for calcium, phosphorus and CaxPO(4) at the last follow-up were 55.8%, 60.5% and 93%, respectively. These values indicated a significant improvement in comparison to preoperative percentages. In regards to the KDIGO recommended guidelines, the iPTH levels did not significantly change at the end of our study compared to preoperative values; however, calcium levels significantly declined and phosphorus levels significantly improved compared to preoperative values. Although the majority of patients fail to reach recommended iPTH values, parathyroidectomy remains a valuable tool to attain these NKF-K/DOQI recommendations for serum calcium, phosphorus and CaxPO(4) in dialysis patients with secondary hyperparathyroidism resistant to medical therapy. Parathyroidectomy was shown to be an inadequate intervention for achieving KDIGO recommendations.


Comparison of postpolypectomy bleeding events between cold snare polypectomy and hot snare polypectomy for small colorectal lesions: a large-scale propensity score-matched analysis.
Cold snare polypectomy (CSP), a safe procedure for removing colon polyps, has a low prevalence of postpolypectomy bleeding (PPB). Previous studies have failed to demonstrate differences in PPB rates between CSP and hot snare polypectomy (HSP), possibly because of their small sample sizes. This study analyzed PPB rates after CSP and HSP. This was a retrospective analysis of colorectal lesions (diameter <10 mm) treated using endoscopic resection at our institution between January 2015 and December 2019. Resections were performed using CSP or HSP, depending on the endoscopist's preference. Endoscopic and histologic findings were recorded in the endoscopic database at our institution. Propensity score (PS) matching was performed to match patient age, lesion size, macroscopic features, location of the lesions, clipping after resection, and antithrombotic agent use. The CSP and HSP groups were compared to determine the adverse event (PPB) rates. The CSP and HSP groups included 12,928 and 2408 lesions (total of 5371 patients), respectively. Univariate analysis revealed that the overall prevalence of PPB after HSP was higher than that after CSP (odds ratio [OR], 5.39; 95% confidence interval [CI], 2.50-11.60). After PS matching (2135 lesions per group), the prevalence of PPB after HSP remained higher than that after CSP (OR, 6.0; 95% CI, 1.34-26.8). For colorectal lesions <10 mm in diameter, the risk of PPB after CSP is significantly lower than that after HSP, after PS matching. CSP for lesions <10 mm could be safely performed compared with HSP.


The relationship between calcium flux and beating in hyperpermeable heart muscle cells.
Beating hyperpermeable myocardial fragments, suspended in fresh medium, show a Ca uptake rate which greatly exceeds the release rate. Under these conditions, Ca influx and contraction frequency co-vary with temperature. Ca efflux, however, is not temperature responsive. In addition, influx, but not efflux, is ATP-dependent. This implies that influx, but not efflux, is a controlled process, the activity of which has the same determinants as does contraction. However, under conditions approximating the steady state, the Ca influx rate was found to decrease, while the efflux rate increased. This suggests the possibility, at least, that the source of contraction-activating Ca can vary with the prevailing conditions.


[Blood microfilters].
In preserved blood and during extracorporeal circulation there become formed micro-aggregates which fail to be entrapped by standard filters. The emerging there-from microembolisms provoke functional disorders in vital organs and account for unfavourable outcomes of the treatment. Basic trends in the microfiltration of the blood are analyzed, a classification of microfilters according to their design features and purpose is given, along with the medico-technical requirements they have also to meet the performance characteristics of the most wildly used microfilter models, are listed.


Non-White Race/Ethnicity and Female Sex Are Associated with Increased Allogeneic Red Blood Cell Transfusion in Cardiac Surgery Patients: 2007-2018.
To evaluate racial and/or ethnic and sex disparities in allogeneic and autologous red blood cell (RBC) transfusions in cardiac surgery. A retrospective observational study. 2007 to 2018 data from FL, MD, KY, WA, NY, and CA from the State Inpatient Databases (SID), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality. A total of 710,296 inpatients who underwent elective or emergency coronary artery bypass grafting (CABG), cardiac valve surgery,or combination CABG and/or valve surgery. None. Patients were cohorted by race and/or ethnicity and sex, as defined by SID-HCUP. Demographic characteristics and comorbidities were compared. Rates and risk-adjusted odds ratios (aOR) were calculated for allogeneic and autologous RBC transfusion (primary outcomes). Additional secondary analyses were conducted for in-hospital mortality, 30-day readmission, 90-day readmission, hospital length of stay, and total charges to examine the effect of RBC transfusion status. Effect modification between race and sex was assessed. When controlling for patient demographics, comorbidities, and hospital characteristics, non-White patients were more likely to receive an allogeneic RBC transfusion during cardiac surgery than White patients (Black: aOR 1.17, 99% CI 1.13-1.20, p < 0.001, Hispanic: aOR 1.22, 99% CI 1.19-1.22, p < 0.001). Women were more likely to receive allogeneic RBC than men (aOR 1.69, 99% CI 1.66-1.72, p < 0.001). In interaction models, non-White women had the highest odds of allogeneic blood transfusion as compared to White men (reference category; Black women: aOR 2.04, 99% CI 1.91-2.17, p < 0.001, Hispanic women: aOR 2.03, 99% CI 1.90-2.16, p < 0.001). These findings highlighted the differences in the rates of allogeneic RBC transfusion for non-White and female patients undergoing cardiac surgery, which is a well-established marker of poorer outcomes.


β-Amyloid peptide (1-40) in the brain reaches the nasal cavity via a non-blood pathway.
We examined the distribution patterns of human β-amyloid (1-40) peptide labeled with iodine 125 ((125)I-Aβ40) after injections into the cerebral ventricle or tail vein of rats. In rats receiving an intravenous injection, the radioactive concentration of (125)I-Aβ40 in the nasal area was similar to other extracranial organs. In contrast, the caudal part of the nasal area in rats receiving an intracerebroventricular injection displayed a high level of (125)I-Aβ40 radioactivity. These results suggest that Aβ reaches the nasal cavity from the brain via a non-blood pathway.


Effect of luteinizing hormone on RNA synthesis in Leydig cells of immature rats.
Luteotrophic hormone acts on testicular interstitial cells, promoting the activation of several cellular events that culminate in steroids synthesis. Since the interstitial tissue include several cell types, purified Leydig cells were used in this work. Isolated interstitial cells from immature rats were purified through a 0-40% metrizamide gradient. Either LH, HCG or Bt2-cAMP significantly stimulated the incorporation of [3H]uridine into RNA, when compared to control. The effect of HCG on RNA synthesis was developed within 30 min after the addition of the hormone and was dose-dependent. The maximum effect was attained with 10 mIU/ml of HCG. These results indicate that HCG/LH or Bt2-cAMP but not FSH, promote an acute stimulation of RNA synthesis by Leydig cells from immature rats.


Radionuclide monitoring in environmental water body using an in situ gamma probe.
An HPGe gamma probe designed to monitor radioactive nuclides in environmental water in situ is described. The probe is equipped with a 15% HPGe detector and an associated spectrum analyzer. Laboratory tests were performed to evaluate its operating depth, detecting sensitivity, detecting volume and the detection limits of radionuclides. A field operation was conducted to measure in situ radionuclide concentrations in a nuclear reactor pool, and the feasibility as well as the disadvantages of this rapid survey are discussed.


Low-dose fish oil supplementation increases serum adiponectin without affecting inflammatory markers in overweight subjects.
Obesity is associated with an increased risk of cardiovascular disease, whereas long-chain n-3 polyunsaturated fatty acids (PUFAs) from fish may have cardioprotective and anti-inflammatory effects. This study aimed to investigate the hypothesis that acute and short-term supplementation with a low dose of marine n-3 PUFA exerts an anti-inflammatory effect in overweight subjects. In a double-blind, placebo-controlled trial with 2 parallel groups, 50 overweight subjects were randomized to receive daily supplementation with 2 capsules containing either 2 g of fish oil (1.1 g marine n-3 PUFA) or 2 g of olive oil. Blood samples and adipose tissue biopsies were collected at baseline, after 1 day (acute effect), and after 6 weeks (short-term effect) of supplementation. No significant effects were seen after supplementation for 1 day, but after 6 weeks, subjects receiving fish oil had a significant increase in the n-3 PUFA content of granulocytes and adipose tissue (P < .01). Serum adiponectin levels were increased by 0.55 μg/mL (95% confidence interval, 0.02-1.08) in the fish oil group compared with the control group (P = .04) after 6 weeks of supplementation. Levels of interleukin 6 were inversely correlated to the marine n-3 PUFA content of granulocytes and adipose tissue at baseline (excluding α-linolenic acid). In conclusion, daily supplementation with 1.1 g of marine n-3 PUFA significantly increased serum adiponectin, but the effect was small, and no overall anti-inflammatory effect of the supplement could be demonstrated.


Endometritis: the clinical-pathologic syndrome.
The purpose of this study was to evaluate histologically proved endometritis as a clinical syndrome that is distinct from laparoscopically confirmed salpingitis. This was a cross-sectional study of 152 women in an urban hospital with a suspected pelvic inflammatory disease. All women provided a standardized medical history and underwent physical examination, endometrial biopsy, and laparoscopy. We defined endometritis by the presence of plasma cells in endometrial stroma and neutrophils in the endometrial epithelium. Of 152 women who were enrolled, 43 women had neither endometritis nor salpingitis; 26 women had endometritis alone without salpingitis, and 83 women had salpingitis. Those women with endometritis alone more often had douched recently, had a current intrauterine device, and were in menstrual cycle day 1 to 7, compared with women with no endometritis or salpingitis (P =.007,.04,.005, respectively) or women with acute salpingitis (P =.03,.01,.02, respectively). Infection with Neisseria gonorrhoeae and/or Chlamydia trachomatis was found more frequently in women with endometritis alone than in women with no endometritis or salpingitis (P <.001) and less frequently than in women with salpingitis (P =.05). Lower quadrant, adnexal, cervical motion, rebound tenderness, peritonitis, tenderness score, fever, and laboratory abnormalities that indicated inflammation and detection of gonorrheal or chlamydial infection were significantly less common in women with endometritis alone than in women with salpingitis but were somewhat more common in women with endometritis alone than among women with no salpingitis or endometritis. Among women with suspected pelvic inflammatory disease, the histopathologic manifestations of endometritis were associated with clinical manifestations, infection, and specific risk factors that were intermediate in frequency between women with salpingitis and women with neither endometritis nor salpingitis.


Berry By-Products in Combination with Antimicrobial Lactic Acid Bacteria Strains for the Sustainable Formulation of Chewing Candies.
The purpose of this research was to develop formulations of chewing candies (CCs) in a sustainable manner by using berry by-products in combination with antimicrobial lactic acid bacteria (LAB) strains. To implement this aim, the optimal quantities of by-products from lyophilised raspberry (Rasp) and blackcurrant (Bcur) from the juice production industry were selected. Prior to use, Lactiplantibacillus plantarum LUHS135, Liquorilactobacillusuvarum LUHS245, Lacticaseibacillusparacasei LUHS244, and Pediococcus acidilactici LUHS29 strains were multiplied in a dairy industry by-product-milk permeate (MP). The antimicrobial activity of the selected ingredients (berry by-products and LAB) was evaluated. Two texture-forming agents were tested for the CC formulations: gelatin (Gl) and agar (Ag). In addition, sugar was replaced with xylitol. The most appropriate formulation of the developed CCs according to the product's texture, colour, total phenolic compound (TPC) content, antioxidant activity, viable LAB count during storage, overall acceptability (OA), and emotions (EMs) induced in consumers was selected. It was established that the tested LAB inhibited three pathogens out of the 11 tested, while the blackcurrant by-products inhibited all 11 tested pathogens. The highest OA was shown for the CC prepared with gelatin in addition to 5 g of Rasp and 5 g of Bcur by-products. The Rasp and LUHS135 formulation showed the highest TPC content (147.16 mg 100 g-1 d.m.), antioxidant activity (88.2%), and LAB count after 24 days of storage (6.79 log10 CFU g-1). Finally, it was concluded that Gl, Rasp and Bcur by-products, and L. plantarum LUHS135 multiplied in MP are promising ingredients for preparing CCs in a sustainable manner; the best CC formula consisted of Gl, Rasp by-products, and LUHS135 and showed the highest OA (score 9.52) and induced the highest intensity of the EM 'happy' (0.231).


The reaching movement in breast cancer survivors: Attention to the principles of rehabilitation.
Breast-cancer is leading cause of morbidity and mortality in women. The prognosis and survival rate of women with breast-cancer have significantly improved worldwide; more attention needs to be paid to rehabilitative interventions after surgery. This paper describes use of reaching movement to assess upper limb motorcontrol and functional ability after breast-cancer surgery (BC). We conducted a cross-sectional observational study consisting of biomechanical evaluation of upper limb limitations in women BC, versus a controlgroup (CG). Thirty breast-cancer survivors and thirty healthy women participated in this study. Both groups were subjected to clinical evaluation of the shoulder joint ROM on the operated side, as an assessment of the muscular-strength of the shoulder with the MRC-scale. The Functional-Assessment was evaluated by the DASH and Constant-Murley-Score. The EORTC QLQ-C30 and VAS were used to measure the quality of life assessment and pain respectively. A Biomechanical evaluation was performed, using Reaching-Task and Surface-EMG. Normal Jerk for BC was higher than CG. Target approaching velocity and movement duration BC was lower than CG. Synergy Anterior Deltoid/Triceps Brachii muscles in CG was higher than BC.


Fortified gelatin-based hydrogel scaffold with simvastatin-mixed nanomicelles and platelet rich plasma as a promising bioimplant for tissue regeneration.
Treatment of intervertebral disc (IVD) degeneration includes conservative and surgical strategies that have a high risk of recurrence. Consequently, tissue engineering represents a promising alternative treatment. This study aimed at healing damaged IVD with a bioimplant that can maintain the function of defected IVD. The developed IVD scaffold is composed of a fortified biocompatible gelatin-based hydrogel to mimic the ECM mechanical properties of IVD and to allow a sustained release of loaded bioactive agents. The hydrogel is laden with platelet-rich plasma (PRP) and simvastatin (SIM)-loaded mixed pluronics nanomicelles because of their regenerative ability and anti-inflammatory effect, respectively. The gelatin-based hydrogel attained swelling of 508.9 ± 7.9 % to 543.1 ± 5.9 % after 24 h. Increasing crosslinking degree of the hydrogel improved its mechanical elasticity up to 0.3 ± 0.1 N/mm2, and retarded its degradation. The optimum mixed nanomicelles had particle size of 84 ± 0.5 nm, a surface charge of -10 ± 7.1 mv, EE% of 84.9 %, and released 88.4 % of SIM after 21 days. Cytotoxicity of IVD components was evaluated using human skin fibroblast for 3 days. WST-test results proved biocompatibility of IVD scaffold. Subcutaneous implantation of the IVD scaffold was performed for 28 days to test in-vivo biocompatibility. Histological and histochemical micrographs depicted normal healing signs such as macrophages, T-cells, angiogenesis and granulation reactions. Introducing PRP in IVD improved healing process and decreased inflammation reactions. The developed multicomponent implant could be used as potential IVD scaffold with desirable mechanical properties, biocompatibility and healing process.


Synthesis and evaluation of the molluscicidal activity of the 5,6-dimethyl-dihydro-pyran-2,4-dione and 6-substituted analogous.
Five dihydro-piran-2,4-diones, including 5,6-dimethyl-dihydro-piran-2,4-dione one of the intermediates of the synthesis of caloverticilic acid, were synthesized and submitted to molluscicidal bioassay. The compound's yields varied from moderate to good (42%- 80%) and were achieved through the preparation of the dianion of ethyl acetoacetate, reaction with and aldehyde followed by hydrolysis of the ester (NaOH, H(2)O, 2 h, T.A.) and lactonization in acidic medium (HCl, 0 degrees C). The 5,6-dimethyl-dihydro-piran-2,4-dione and three analogous dihydro-piran-2,4-diones 6-substituted,-phenyl, (4-methoxy-phenyl), and -propenyl, showed significant activities against the Biomphalaria glabrata egg masses, while the analogous 6-(3,4-dimethoxy-phenyl) was inactive as molluscicide. This activity is reported for the first time, extending the range of biological activities of this group.


Norovirus genotype IIb associated acute gastroenteritis in India.
In India the role of noroviruses in causing gastroenteritis is not well defined. To determine the norovirus prevalence in sporadic cases of acute gastroenteritis in western India. A total of 236 fecal specimens consisting 192 specimens from hospitalized and 44 from OPD (outpatient department) children < or = 5 years of age were tested for the presence of norovirus genogroup (G)I and GII by RT-PCR followed by sequencing. Multiple alignment and phylogenetic analysis were carried out to determine the norovirus genetic types. Norovirus GII infection was detected in 11.9% (28/236) specimens. These included 24 of 192 (12.5%) specimens from hospitalized and 4 of 44 (9.0%) specimens from OPD cases. Nucleotide sequence based analysis of norovirus GII strains indicated circulation of GIIb strains at a significant level in hospitalized (12.5%) and OPD (75%) children. This study demonstrates the predominance of GII/4 (genogroup II/genotype 4) along with co-circulation of GII/1, GII/2, GII/3 and GIIb revealing the possibility of norovirus as the second most common cause of non-bacterial acute gastroenteritis after rotavirus in western India. It also documents for the first time occurrence of norovirus GIIb infections in India.


Ultrastructure of acinar cell injuries in experimental acute pancreatitis created by common bile duct ligation.
Morphogenesis of acute pancreatitis induced by ligation of the common bile duct and the ultrastructure of autolytic transformations of acinar cells were studied. Autolytic changes in acinar cells started from the basal zones and then involved the apical zones. Violation of the zymogen granules integrity, interactions of their contents with the adjacent ultrastructures, destruction (melting) of ultrastructures, and formation of huge autophagosomes play an important role in the development of autolysis. Disordered secretion of zymogen granules (foci of their accumulation in the apical zone), hyperplasia and hypertrophy of centroacinar cells and ductal epitheliocytes aimed at restoration of the pancreatic secretion discharge pathways were seen in the retained acini.


Homologous RuO2-Ru heterostructures for tandem catalytic upgrading of ethanol.
The homologous RuO2-Ru heterostructure was demonstrated as an efficient tandem catalyst for upgrading ethanol. The adjacent RuO2 and Ru separately serve as aldol condensation/dehydration and dehydrogenation/hydrogenation sites for ethanol conversion.


Spatial learning/memory and social and nonsocial behaviors in the spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rat strains.
The Spontaneously Hypertensive rat (SHR) is often described as less behaviorally reactive than its normotensive strain, the Wistar-Kyoto (WKY), although results are somewhat inconsistent across studies. In part, this may be due to the lack of a definitive characterization of "reactivity." Still, results from identical behavioral tests of SHR and WKY across studies are sometimes conflicting. Further, few comparisons with other rodent strains are available and these might provide guidance in outlining the meaning of reactivity. Here, social and nonsocial behaviors and spatial learning and memory were measured in male and female SHR, WKY, and Sprague-Dawley (SD) rats. Systolic blood pressure measurements at adulthood confirmed hypertension in the SHR. Juvenile play behavior indicated that SHRs were more sensitive to the strain of their play partner than were the WKY or SD, playing less with different strain partners than with same strain partners. However, adult dominance behavior (restricted access in a water competition test) indicated no strain differences. The SHR appeared to exhibit attenuated acoustic startle relative to the WKY and SD and their prepulse inhibition was substantially less at higher prepulse decibel intensities; however, this decreased prepulse inhibition was not the result of decreased startle during the test. Anxiety-related behavior in the elevated plus maze was most prominent in the SD strain, possibly as a result of poorer motor coordination as measured by rotarod performance. Elevated plus maze behavior as well as motor coordination did not differ between the SHR and WKY strains. Performance in the NCTR complex maze and the Morris water maze was significantly better in the SHR. These results do not support hypotheses of decreased behavioral reactivity in the SHR strain. Rather, they suggest complex interactions between social and nonsocial environments and the behavioral capabilities and requirements of the rat strain.


Change in general and central adiposity measures in prediction of incident dysglycemia; Tehran Lipid and Glucose Study.
To examine the change in general and central adiposity measures as a predictor of incident dysglycemia during a 6-year follow-up. A total of 4029 (2333 women and 1696 men) non-dysglycemic Iranians aged ≥ 20 years, underwent standard fasting and 2-h post-challenge plasma glucose tests at baseline and follow-up. During follow-up, 458 new cases of dysglycemia occurred. In multivariable models including baseline values of each anthropometric measure, odds ratios (ORs) for dysglycemia incidence corresponding to a 1-SD increase in changes of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and hip circumference (HC), were 1.32, 1.56, 1.39, 1.51 and 1.39 for men and 1.59, 1.50, 1.37, 1.47, and 1.38, for women, respectively (all P<0.05). After controlling for weight change and WC change among men and women, respectively, HC change did not remain as a predictor. Using the paired homogeneity test, there was no superiority for changes in central obesity measures compared to changes in BMI to predict dysglycemia. The association between HC changes and incident dysglycemia was dependent upon changes in central and general adiposity measures, where the former did not have higher predictability than the latter in prediction of dysglycemia.