Perovskite-based solar cells fabricated from TiO2 nanoparticles hybridized with biomaterials from mollusc and diatoms.
Perovskite solar cells (PVSCs) convert solar energy into electrical energy. Current study employs fabrication of PVSCs using calcium titanate (CaTiO3) prepared by co-precipitation of TiO2 nanoparticle (NP) and CaCO3 NP with later synthesized from mollusc shell. Furthermore, frustules of diatom, Nitzschia palea were used to prepare silica doped CaTiO3 (Si-CaTiO3) nanocomposite. CaTiO3 NP and Si-CaTiO3 nanocomposites film were made on fluorine doped tin oxide (FTO) glass plate using spin coater separately for two different kinds of PVSCs tested at different intensities of light. The perovskite materials were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM) and energy dispersive X-ray (EDX) spectroscopy. Thickness of the film was measured by profilometer. The maximum power density (PDmax) of CaTiO3 made PVSCs was 0.235 mW/m2 under white LED light and 0.041 mW/m2 in broad spectrum light. Whereas, PDmax of PVSCs with Si-CaTiO3 was higher about 0.0083 mW/m2 in broad spectrum light and was 0.0039 mW/m2 in white LED light. This is due to the fact that CaTiO3 allowed blue and red light in broad spectrum to pass through it without being absorbed compared to white LED light which gets reflected. On the offset, in PVSC made of Si-CaTiO3 since diatoms frustules are made up of nanoporous architecture it increases the overall porosity of PVSC making them potentially more efficient in broad spectrum of light compared to white LED light.


Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study.
Patients with metastatic castration-resistant prostate cancer (mCRPC) frequently receive docetaxel after they develop resistance to abiraterone or enzalutamide and need more efficacious treatments. To evaluate the efficacy and safety of pembrolizumab plus docetaxel and prednisone in patients with mCRPC. The trial included patients with mCRPC in the phase 1b/2 KEYNOTE-365 cohort B study who were chemotherapy naïve and who experienced failure of or were intolerant to ≥4 wk of abiraterone or enzalutamide for mCRPC with progressive disease within 6 mo of screening. Pembrolizumab 200 mg intravenously (IV) every 3 wk (Q3W), docetaxel 75 mg/m2 IV Q3W, and prednisone 5 mg orally twice daily. The primary endpoints were safety, the prostate-specific antigen (PSA) response rate, and the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included time to PSA progression; the disease control rate (DCR) and duration of response (DOR) according to RECIST v1.1 by BICR; ORR, DCR, DOR, and radiographic progression-free survival (rPFS) according to Prostate Cancer Working Group 3-modified RECIST v1.1 by BICR; and overall survival (OS). Among 104 treated patients, 52 had measurable disease. The median time from allocation to data cutoff (July 9, 2020) was 32.4 mo, during which 101 patients discontinued treatment, 81 (78%) for disease progression. The confirmed PSA response rate was 34% and the confirmed ORR (RECIST v1.1) was 23%. Median rPFS and OS were 8.5 mo and 20.2 mo, respectively. Treatment-related adverse events (TRAEs) occurred in 100 patients (96%). Grade 3-5 TRAEs occurred in 46 patients (44%). Seven AE-related deaths (6.7%) occurred (2 due to treatment-related pneumonitis). Limitations of the study include the single-arm design and small sample size. Pembrolizumab plus docetaxel and prednisone demonstrated antitumor activity in chemotherapy-naïve patients with mCRPC treated with abiraterone or enzalutamide for mCRPC. Safety was consistent with profiles for the individual agents. Further investigation is warranted. We evaluated the efficacy and safety of the anti-PD-1 antibody pembrolizumab combined with the chemotherapy drug docetaxel and the steroid prednisone for patients with metastatic prostate cancer resistant to androgen deprivation therapy , and who never received chemotherapy. The combination showed antitumor activity and manageable safety in this patient population. This trial is registered on ClinicalTrials.gov as NCT02861573.


Zipper protein, a newly described tropomyosin-like protein of the intestinal brush border.
We have cloned and sequenced from a chick intestinal library the cDNA for a new tropomyosin-like protein with an extensive leucine zipper motif. The cDNA recognized a 2.5-kilobase transcript with highest levels in the intestine. The open reading frame encoded a protein with 239 residues (28 kDa), the deduced sequence of which forms 27 heptad repeats, 21 of which begin with leucine and the other 6 with conservative substitutions (methionine, valine, threonine). This sequence predicts a coiled coil dimer similar to that of tropomyosin with which it has 34% homology. We have named this newly described protein zipper protein. The protein was expressed in bacteria. Antibodies were made to peptides representing different regions of the deduced sequence and tested for their ability to recognize the recombinant zipper protein on immunoblots. Such antibodies were used to immunolocalize zipper protein to the intestinal brush border. A radioimmunoassay was then established using recombinant zipper protein as standard and tracer and one of the affinity-purified antisera as primary antibody. Extracts from intestine, kidney, and liver displaced tracer zipper protein in parallel with that of the standard curve, and zipper protein levels were readily measured in those tissues to be 2.5 +/- 0.4, 0.34 +/- 0.03, and 0.15 +/- 0.03 micrograms/mg of protein, respectively. Brain contained no detectable zipper protein. We conclude that zipper protein is a tropomyosin-like protein found predominantly in the intestinal brush border; its location and structural similarity to tropomyosin suggest a possible role in regulating the interaction of brush border myosin 1 with the actin core of the microvillus.


Dorsal plating for distal radius fractures.
A dorsal approach to the distal radius for comminuted intra-articular fractures affords excellent exposure of the joint surface. Dorsal plating can reliably buttress the joint, leading to low rates of arthrosis, but at the expense of wrist stiffness and high rates of extensor tendon problems. New, smaller implants may prove capable of supporting the joint with lower rates of extensor irritation.


Open in Case of SOAP Emergency: Preparation for and Recovery after Failing to Match.
Failing to secure an internship is an extremely stressful event. In this manuscript we describe a process to prepare students for success, should they fail to match. This process involves an assessment of individual vulnerability, implementing mitigation strategies, developing a comprehensive plan in the event of failing to match, that is executed if the student needs to enter the Supplemental Offer Acceptance Program (SOAP) or the "scramble".


Microwave ablation of a solitary colorectal liver metastasis complicated by stomach perforation and gastrocutaneous fistula - a case report.
Organ perforation secondary to thermal ablation is a rare but severe complication that can occur in certain patients, in whom tissue dissection and preservation cannot be adequately achieved. A 69-year-old man presented with a gastrocutaneous fistula 20 days after a microwave ablation of liver metastases from colorectal cancer. Besides skin rash, local tenderness, and gastric content discharge from a wound where the probe had been placed, no other signs or symptoms were present. The patient was treated surgically, and a wedge-shaped gastric resection was performed. His postoperative course was uneventful. After 8 months, the patient underwent the same procedure for local progression of the same lesion, using a pulsed MW antenna and a dedicated hydrodissection needle, without complications. A gastrocutaneous fistula is a rare complication of microwave ablation. However, adequate hydrodissection can minimize the risk for the development of these complications. Proper treatment of these complications does not preclude repeated usage of microwave ablation in the future.


Corneal hysteresis and axial length among Chinese secondary school children: the Xichang Pediatric Refractive Error Study (X-PRES) report no. 4.
To evaluate the association between corneal hysteresis and axial length/refractive error among rural Chinese secondary school children. Cross-sectional cohort study. Refractive error (cycloplegic auto-refraction with subjective refinement), central corneal thickness (CCT) and axial length (ultrasonic measurement), intraocular pressure (IOP), and corneal hysteresis (Reichert Ocular Response Analyzer) were measured on a rural school-based cohort of children. Among 1,233 examined children, the mean age was 14.7 +/- 0.8 years and 699 (56.7%) were girls. The mean spherical equivalent (n = 1,232) was -2.2 +/- 1.6 diopters (D), axial length (n = 643) was 23.7 +/- 1.1 mm, corneal hysteresis (n = 1,153) was 10.7 +/- 1.6 mm Hg, IOP (n = 1,153) was 17.0 +/- 3.4 mm Hg, and CCT (n = 1,226) was 553 +/- 33 microns. In linear regression models, longer axial length was significantly (P < .001 for both) associated with lower corneal hysteresis and higher IOP. Hysteresis in this population was significantly (P < .001) lower than has previously been reported for normal White children (n = 42, 12.3 +/- 1.3 mm Hg), when adjusting for age and gender. This difference did not appear to depend on differences in axial length between the populations, as it persists when only Chinese children with normal uncorrected vision are included. Prospective studies will be needed to determine if low hysteresis places eyes at risk for axial elongation secondary or if primary elongation results in lower hysteresis.


Improved mortality and rehabilitation of transplant candidates treated with a long-term implantable left ventricular assist system.
This nonrandomized study using concurrent controls was performed to determine whether the HeartMate implantable pneumatic (IP) left ventricular assist system (LVAS) could provide sufficient hemodynamic support to allow rehabilitation of severely debilitated transplant candidates and to evaluate whether such support reduced mortality before and after transplantation. Outcomes of 75 LVAS patients were compared with outcomes of 33 control patients (not treated with an LVAS) at 17 centers in the United States. All patients were transplant candidates who met the following hemodynamic criteria: pulmonary capillary wedge pressure > or = 20 mm Hg with a systolic blood pressure < or = 80 mm Hg or a cardiac index < or = 2.0 L/minute/m2. In addition, none of the patients met predetermined exclusion criteria. More LVAS patients than control patients survived to transplantation: 53 (71%) versus 12 (36%) (p = 0.001); and more LVAS patients were alive at 1 year: 48 (91%) versus 8 (67%) (p = 0.0001). The time to transplantation was longer in the group supported with the LVAS (average, 76 days; range, < 1-344 days) than in the control group (average, 12 days; range, 1-72 days). In the LVAS group, the average pump index (2.77 L/minute/m2) throughout support was 50% greater than the corresponding cardiac index (1.86 L/minute/m2) at implantation (p = 0.0001). In addition, 58% of LVAS patients with renal dysfunction survived, compared with 16% of the control patients (p < 0.001). The LVAS provided adequate hemodynamic support and was effective in rehabilitating patients based on improved renal, hepatic, and physical capacity assessments over time. In the LVAS group, pretransplant mortality decreased by 55%, and the probability of surviving 1 year after transplant was significantly greater than in the control group (90% vs. 67%, p = 0.03). Thus, the HeartMate IP LVAS proved safe and effective as a bridge to transplant and decreased the risk of death for patients waiting for transplantation.


Perissodactyla (Rhinocerotidae and Equidae) from Kanapoi.
The Kanapoi collection of Rhinocerotidae, first studied by Hooijer and Patterson (1972), now consists of 25 specimens and substantial reinterpretation of their affinities is made here. Kanapoi post-dates the extinction of Brachypotherium and the whole collection belongs to the Dicerotini. It is important because it includes the type-specimen of Diceros praecox, a species that remains poorly known, but looks slightly larger and more primitive than the modern 'black' rhino, Diceros bicornis. A second species is probably ancestral to the modern 'white' rhino, Ceratotherium simum; it looks identical to the Pleistocene North African Ceratotherium mauritanicum, of which Ceratotherium efficax is probably a synonym. The evolution of the Dicerotini in Africa can be regarded as an increasing divergence in diet and related morphofunctional adaptations in the two lineages. The co-occurrence at Kanapoi of both Diceros and Ceratotherium, with distinct dietary preferences, suggests some habitat heterogeneity, although the low sample size prevents robust paleoecological conclusions. The Equidae are also rare and consist mostly of isolated teeth. I take the most parsimonious option of tentatively including all of them in a single species, whose identification is left open. Dental features of eastern African Pliocene to Pleistocene hipparions may reflect increasing adaptation to grazing.


A simple technique for blood collection in the pig.
A simple technique for blood collection in pigs of body weight 15-40 kg is described. The subcutaneous abdominal vein was used for rapid collection of 5-20 ml of blood samples. The animals were premedicated with 10 mg/kg of ketamine and 600 micrograms of atropine given intramuscularly prior to blood collection.


Seroma formation following abdominal liposuction.
Liposuction of the abdominal region is a common procedure performed in the United States. A variety of complications can occur when performing this procedure. To present a case of a patient with a seroma as a complication of abdominal liposuction and its management. The patient had a recurring seroma of the right lower quadrant of the abdomen that necessitated ultrasound-guided drainage. This case provided a valuable lesson. Clinicians should be conscious of the potential for this complication to occur. They must select patients appropriately to limit the risk of adverse events.


Local production of interleukins and growth factors in external genital endometriosis.
Secretion of some IL and growth factors (VEGF, IGF-I, TGFbeta) by endometrial tissues and endometrioid heterotopies was studied in vitro in patients with external genital endometriosis of different severity. The production of IL-1beta, IL-2, IL-6, and VEGF in the endometrium increased in severe external genital endometriosis, while the secretion of TGFbeta decreased; hyperproduction of IL-2, IL-6, VEGF and decreased production of TGFbeta were detected in endometrioid foci. Presumably, local cytokine imbalance and increased proliferative activity of endometrial cells are involved in the mechanisms of formation and functioning of endometrioid foci.


Novel mutations in the SPAST gene cause hereditary spastic paraplegia.
Mutations in the SPAST gene are the most frequent cause of hereditary spastic paraplegia (HSP). We aim to extend the mutation spectrum of spastic paraplegia 4 (SPG4) and carried out experiment in vitro to explore the influence of the SPAST gene mutation on the function of corresponding protein. Whole-exome sequencing (WES) combined with multiplex ligation-dependent probe amplification (MLPA) were performed in a cohort of 150 patients clinically diagnosed with HSP. We focus on screening for mutations in SPAST gene and carrying out functional experiments to assess the effects of the novel variants. A total of 34 different mutations in the SPAST gene were identified, of which 10 were novel, including 1 missense (c.1479T > A), 1 nonsense (c.766G > T), 3 splicing (c.1413 + 1_1413+4delGTAA, c.1729-1G > A and c.1536+2T > G) and 5 frameshift mutations (c.1094delC, c.885dupA, c.517_518delAG, c.280delG and c.908dupC). For 7 novel non-splicing mutations, functional study showed that accumulated M1 spastin colcocalized with microtubules which was different from a uniformly diffused M87 spastin. While an impairment in severing activity was observed in both mutant M1 and mutant M87, except for c.280delG. All 3 novel splicing variants w ere predicted to affect splicing by using bioinformatic programs. However, only c.1536+2T > G had no influence on splice site in vitro, which conflicts with the in-silico analysis. We genetically diagnosed 40 SPG4 patients. All the novel non-splicing mutations except for c.280delG were certified to exert an effect on the microtubule-severing and all the novel splicing mutations other than c.1536+2T > G would cause abnormal splicing of the spastin.


Studies on 4 C stored frozen-reconstituted red blood cells. III. Changes occurring in units which have been repeatedly frozen and thawed.
Units of frozen red blood cells were thawed, stored at 4 C for varying amounts of time up to five days, and then subsequently refrozen. This procedure was repeated for two or three cycles. Chemical and cytological studies showed that only a moderate number of red blood cells were lost and that the red blood cells would be transfusable with minimal danger to the patient. The units retained their sterility despite all of the manipulations. The ability to refreeze a unit of blood would extend the value of frozen blood greatly by preventing the loss of very rare units.


Automated thermochemolysis reactor for detection of Bacillus anthracis endospores by gas chromatography-mass spectrometry.
An automated sample preparation system was developed and tested for the rapid detection of Bacillus anthracis endospores by gas chromatography-mass spectrometry (GC-MS) for eventual use in the field. This reactor is capable of automatically processing suspected bio-threat agents to release and derivatize unique chemical biomarkers by thermochemolysis (TCM). The system automatically controls the movement of sample vials from one position to another, crimping of septum caps onto the vials, precise delivery of reagents, and TCM reaction times and temperatures. The specific operations of introduction of sample vials, solid phase microextraction (SPME) sampling, injection into the GC-MS system, and ejection of used vials from the system were performed manually in this study, although they can be integrated into the automated system. Manual SPME sampling is performed by following visual and audible signal prompts for inserting the fiber into and retracting it from the sampling port. A rotating carousel design allows for simultaneous sample collection, reaction, biomarker extraction and analysis of sequential samples. Dipicolinic acid methyl ester (DPAME), 3-methyl-2-butenoic acid methyl ester (a fragment of anthrose) and two methylated sugars were used to compare the performance of the autoreactor with manual TCM. Statistical algorithms were used to construct reliable bacterial endospore signatures, and 24 out of 25 (96%) endospore-forming Bacillus species were correctly identified in a statistically designed test.


St. Valentine--patron saint of epilepsy: illustrating the semiology of seizures over the course of six centuries.
From the 15th century to the present day, Christian art has portrayed people who suffer from epilepsy as attributes in illustrations of Saint Valentine (SV). The objective of our study was to interpret the works of art from a modern epileptological perspective on the basis of a collection of portrayals of SV in Europe that was as comprehensive as possible. The people depicted as attributes were analyzed with respect to their age, gender, social status, and possible seizure semiology. Three hundred forty-one illustrations of SV from Austria, Belgium, Croatia, Czech Republic, France, Germany, Hungary, Ireland, Italy, Luxembourg, Poland, Scotland, Slovakia, and Switzerland were systematically analyzed. Irrespective of the age of the work of art, among the 143 pictures of people with possible epilepsy characteristics, there were more males than females from various levels of society. As far as could be interpreted, there were 17 infants, 35 children, 7 adolescents, and 84 adults. With respect to possible seizure semiology, infantile spasms (n=10), atonic seizures (n=13), tonic seizures (n=53), absences (n=2), psychogenic seizures (n=4), and postictal or undefinable states (n=61) were differentiated in a subjective assessment. Despite the fact that from a modern perspective, the 15th to 20th centuries in Europe seemed to be dominated by a rather superstitious attitude toward epilepsy, there is striking accuracy in the detail of the semiology in many of the historic portrayals, and a well-founded knowledge of epilepsy is apparent.


Highly accurate method for ligand-binding site prediction in unbound state (apo) protein structures.
This article describes a new method for predicting ligand-binding sites of proteins. The method involves calculating the van der Waals interaction energy between a protein and probes placed on the protein surface, and then clustering the probes with attractive interaction to find the energetically most favorable locus. In 80% (28/35) of the test cases, the ligand-binding site was successfully predicted on a ligand-bound protein structure, and in 77% (27/35) was successfully predicted on an unbound structure. Our method was used to successfully predict ligand-binding sites unaffected by induced-fit as long as its scales were not very large, and it contributed to a significant improvement in prediction with unbound state protein structures. This represents a significant advance over conventional methods in detecting ligand-binding sites on uncharacterized proteins. Moreover, our method can predict ligand-binding sites with a narrower locus than those achieved using conventional methods.


Heterogeneity of estrogen binding sites in mammary tumors.
This paper provides a brief summary of our recent work on the heterogeneity of estradiol binding sites in mammary tumors of the mouse and human. Mammary tumors from both species contain the classical estrogen receptor and a second site(s) which we call type II. These type II sites are found in the cytoplasmic and nuclear compartments of both tumors, and can interfere with the measurement of estrogen receptors. The function of type II sites is not known; however, an assessment of these sites in conjunction with an accurate measurement of the estrogen receptor may provide a clearer picture of the true hormone dependence of breast tumors.


The effect of topical doxycycline on corneal neovascularization.
To examine the effect of topical doxycycline on human corneal neovascularization (CONV). Six eyes of six patients with CONV received topical 1% doxycycline four times per day for three weeks and monitored for a total of one year. Ophthalmic evaluations included visual acuity, tonometry, slit-lamp examination, conjunctival swabs, quantification of CONV and photography. CONV either disappeared or was attenuated, shortened and less dense in five of six patients. There were no adverse effects. Topical doxycycline was effective in reducing CONV and healing of the ocular surface.


Oil production by the yeast Trichosporon dermatis cultured in enzymatic hydrolysates of corncobs.
Corncob was hydrolyzed with Trichoderma reesei cellulase and used as substrate for growth by the oleaginous yeast Trichosporon dermatis without detoxification or addition of a nitrogen source or trace elements. A total biomass of 24.4g/L with a lipid content of 40.1% (corresponding to a lipid yield of 9.8g/L), and a high lipid coefficient (lipid yield per mass of sugar, %g/g) of 16.7 could be achieved after cultivation for 7days. Therefore, T. dermatis is a promising strain for microbial oil production from lignocellulosic biomass.


Drosophila melanogaster innate immunity: an emerging role for peptidoglycan recognition proteins in bacteria detection.
Over the past years, parallel studies conducted in mammals and flies have emphasized the existence of common mechanisms regulating the vertebrate and invertebrate innate immune systems. This culminated in the discovery of the central role of the Toll pathway in Drosophila immunity and in the implication of Toll-like receptors (TLRs)/interleukin-1(IL-1) in the mammalian innate immune response. In spite of clear similarities, such as shared intracellular pathway components, important divergences are expected between the two groups, whose last common ancestor lived more than half a billion years ago. The most obvious discrepancies lie in the mode of activation of the signalling receptors by microorganisms. In mammals, TLRs are part of protein complexes which directly recognize microbe-associated patterns, whereas Drosophila Toll functions like a classical cytokine receptor rather than a pattern recognition receptor. Recent studies demonstrate that members of the evolutionarily conserved peptidoglycan recognition protein family play an essential role in microbial sensing during immune response of Drosophila.


Can whole-body magnetic resonance imaging with diffusion-weighted imaging replace Tc 99m bone scanning and computed tomography for single-step detection of metastases in patients with high-risk prostate cancer?
Technetium Tc 99m bone scintigraphy (BS) and contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of the pelvis and abdomen are universally recommended for detecting prostate cancer (PCa) metastases in cancer of all stages. However, this two-step approach has limited sensitivity and specificity. Evaluate the diagnostic accuracy of whole-body MRI (WBMRI) as a one-step screening test for PCa metastases. One hundred consecutive PCa patients at high risk for metastases prospectively underwent WBMRI, CT, and BS completed with targeted x-rays (BS/TXR) in case of equivocal BS. Four independent reviewers reviewed the images. This study compares the diagnostic performance of WBMRI, CT, BS, and BS/TXR in detecting PCa metastases using area under the curve (AUC) receiver operator characteristics. A best valuable comparator (BVC) approach was used to adjudicate final metastatic status in the absence of pathologic evaluation. Based on the BVC, 68 patients had metastases. The sensitivity of BS/TXR and WBMRI for detecting bone metastases was 86% and 98-100%, respectively (p<0.04), and specificity was 98% and 98-100%, respectively. The first and second WBMRI readers respectively identified bone metastases in 7 and 8 of 55 patients with negative BS/TXR. The sensitivity of CT and WBMRI for detecting enlarged lymph nodes was similar, at 77-82% for both; specificity was 95-96% and 96-98%, respectively. The sensitivity of the combination of BS/TXR plus CT and WBMRI for detecting bone metastases and/or enlarged lymph nodes was 84% and 91-94%, respectively (p=0.03-0.10); specificities were 94-97% and 91-96%, respectively. The 95% confidence interval of the difference between the AUC of the worst WBMRI reading and the AUC of any of the BS/TXR plus CT lay within the noninferiority margin of ±10% AUC. WBMRI outperforms BS/TXR in detecting bone metastases and performs as well as CT for enlarged lymph node evaluation. WBMRI can replace the current multimodality metastatic work-up for the concurrent evaluation of bones and lymph nodes in high-risk PCa patients.


Advances in brain tumor surgery.
Advances in the fields of molecular and translational research, oncology, and surgery have emboldened the medical community to believe that intrinsic brain tumors may be treatable. Intraoperative imaging and brain mapping allow operations adjacent to eloquent cortex and more radical resection of tumors with increased confidence and safety. Despite these advances, the infiltrating edge of a neoplasm and distant microscopic satellite lesions will never be amendable to a surgical cure. Indeed, it is continued research into the delivery of an efficacious chemobiologic agent that will eventually allows us to manage this primary cause of treatment failure.


Effects of zinc supplementation on physical growth in 2-5-year-old children.
Physical growth disorders in under 5-year-old children are a common health problem in many countries including Iran. The aim of this study was to determine effects of supplemental zinc on physical growth in preschool children with retarded linear growth. This study was a community-based randomized controlled trial on 2-5-year-old children with height-for-age below 25th percentile of National Center for Health Statistics growth chart. Ninety children were randomly assigned in zinc group (ZG) or placebo group (PG). After 6 months of zinc or placebo supplementation, we followed up the children for another 6 months. Anthropometric indicators were measured before the intervention and then monthly for 11 months. Forty children in ZG and 45 in PG concluded the study. Zinc supplementation increased weight gain in boys (P = 0.04) and girls (P = 0.05) compared to placebo but had no significant effect on mid-upper arm circumference increment in either sexes. The most significant (P = 0.001) effect of Zinc supplementation was seen in boys' height increment at the end of follow-up period. Stunted growth rate in ZG changed significantly (P = 0.01) from 26.7% to 2.5% throughout the study. This study showed that daily supplementation of 5 mg elemental zinc for 6 months improves physical growth in terms of height increment and weight gain in children with undesirable linear growth, especially in boys.


Cloning technologies for protein expression and purification.
Detailed knowledge of the biochemistry and structure of individual proteins is fundamental to biomedical research. To further our understanding, however, proteins need to be purified in sufficient quantities, usually from recombinant sources. Although the sequences of genomes are now produced in automated factories purified proteins are not, because their behavior is much more variable. The construction of plasmids and viruses to overexpress proteins for their purification is often tedious. Alternatives to traditional methods that are faster, easier and more flexible are needed and are becoming available.


An inducible lambdoid prophage encoding cytolethal distending toxin (Cdt-I) and a type III effector protein in enteropathogenic Escherichia coli.
Cytolethal distending toxins (CDTs) are inhibitory cyclomodulins, which block eukaryotic cell proliferation and are produced by a diverse group of Gram-negative bacteria, including Escherichia coli strains associated with intestinal and extraintestinal infections. However, the mode of transmission of the toxin gene clusters among diverse bacterial pathogens is unclear. We found that Cdt-I produced by enteropathogenic E. coli strains associated with diarrhea is encoded by a lambdoid prophage, which is inducible and infectious. The genome of Cdt-I converting phage (CDT-1Phi) comprises 47,021 nucleotides with 60 predicted ORFs organized into six genomic regions encoding the head and tail, virulence, integrase, unknown functions, regulation, and lysis. The genomic organization of CDT-1Phi is similar to those of SfV, a serotype-converting phage of Shigella flexneri, and UTI89, a prophage identified in uropathogenic E. coli. Besides the cdtI gene cluster, the virulence region of CDT-1Phi genome contains sequences homologous to a truncated cycle inhibiting factor and a type 3 effector protein. Mutation analysis of susceptible E. coli strain C600 suggested that the outer membrane protein OmpC is a putative receptor for CDT-1Phi. CDT-1Phi genome was also found to integrate into the host bacterial chromosome forming lysogens, which produced biologically active Cdt-I. Furthermore, phage induction appeared to cause enhanced toxigenicity of the E. coli strains carrying lysogenic CDT-1Phi. Our results suggest that CDT-1Phi is the latest member of a growing family of lambdoid phages encoding bacterial cyclomodulins and that the phage may have a role in horizontal transfer of these virulence genes.


Fitness consequences of alternative life histories in water striders, Aquarius remigis (Heteroptera: Gerridae).
Using field and laboratory observations and experiments over 3 years, I investigated whether reproductive trade-offs shape individual life histories in two natural populations of the water strider, Aquarius remigis, in which univoltine and bivoltine life cycles coexist. Both later eclosion dates and food shortages, even after adult eclosion, induced diapause in females, thus deferring reproduction to the following spring. Adult body size was positively affected by food availability during juvenile development. Higher food levels also increased the reproductive output of females, but not their longevity or oviposition period. When compared to spring breeders (univoltine life cycle), direct (summer) breeders (bivoltine life cycle) experienced reduced lifetime egg numbers and longevity, as well as reduced survivorship of their second-summer-generation offspring; these reproductive costs offset, at least in part, the advantage in non-decreasing populations of having two generations per year. Fecundity was correlated with body size, and among summer-generation females direct breeders were larger than non-breeders. The time remaining before the onset of winter and/or the time since adult eclosion augmented cumulative energy uptake, and consequently the lipid reserves and winter survival probability of non-breeding (diapausing) summer adults approaching hibernation. Overwintered spring reproductives died at faster rates than non-reproductive summer individuals despite greater food availability in spring, indicating a mortality cost of reproduction. Body length correlated with absolute and not with proportional lipid content but showed no consistent relationship with survivorship in the field. These results are in agreement with current theory on the evolution of insect voltinism patterns, and further indicate high degrees of life history flexibility (phenotypic plasticity) in the study populations in response to variable environmental factors (notably photoperiod and food availability). This may be related to their location in a geographic transition zone from uni- to bivoltine life cycles.


Toluidine Blue Staining in Identification of a Biopsy Site in Potentially Malignant Lesions: A Case-control Study.
Oral cancer is a significant threat to public health all over the world, especially in Southeast Asia. At the present time, screening of oral cancer, its premalignant stages as well as its early detection, is still largely based on visual examination of the mouth. Visual examination is highly subjective and hence lacks the specificity and sensitivity. The objective of this study was to determine the usefulness of toluidine blue in marking a biopsy site in potentially malignant disorders. In this study, a total of 500 patients were screened. The study was a case-control study which included 17 lesion cases and 23 normal controls. Toluidine blue staining was taken into consideration to identify clinically doubtful oral potentially malignant lesions and to compare the clinical evaluation with toluidine blue stain followed by a punch biopsy and histological evaluation. SPSS Statistics version 16.0 and Chi-square test were used for statistical analyses. The most common site for potentially malignant lesions was found to be the buccal mucosa. The sensitivity of toluidine blue was found to be 88.89%, while specificity was found to be 74.19%. The positive predictive and negative predictive values were 50% and 97.83%, respectively. P = 0.000672 was considered statistically significant. The results seem to be promising, but many such studies have to be done at larger scales to exactly help us in identifying the capability of toluidine blue in the long run.


Effects of prostaglandins and nitric oxide on rat macrophage lipid metabolism in culture: implications for arterial wall-leukocyte interplay in atherosclerosis.
Macrophages/foam cells have a pivotal role in atherogenesis although little is known about the way lipid imbalance, a hallmark of atherosclerosis, leads to lipid accumulation in these cells. Modified low-density lipoproteins are associated with macrophage lipid dysfunction in atherosclerosis, but a possible role for altered lipogenesis leading to lipid accumulation remains to be elucidated. Since endothelium-derived nitric oxide (NO) and prostaglandins (PGs) are physiological autacoids whose production may be impaired in atherosclerosis, the effects of these mediators on de novo lipid synthesis in 24-h cultured rat peritoneal macrophages is investigated. In resident (unstimulated) cells, 1 microM PGE2 and the stable analog of PGI2 carbaprostacyclin (cPGI2, 1 microM) deviated the overall [1-14C]acetate from incorporation into cholesterol, free fatty acids and triacylglycerols favoring the formation of phospholipids. In inflammatory (thioglycollate-elicited) macrophages, these eicosanoids likewise reduced 14C-incorporations into all the lipid fractions tested. Also, cPGI2 and PGE2 reduced [4-14C]cholesterol uptake from inflammatory cells but did not interfere in 14C-cholesterol export. The PGE2-derivative PGA2 (10-20 microM) reduced 14C-incorporations into all the lipids in resident cells while it enhanced phospholipid synthesis by up to 129% at the expense of reduced incorporations into the other test lipids. The NO donor S-nitroso-N-acetylpenicillamine (SNAP, 1-10 microM), when added to macrophages in the presence of superoxide dismutase (SOD, to avoid the reaction of superoxide with NO), significantly reduced lipogenesis especially in inflammatory cells. These findings suggest that endothelium-derived NO and PGs may be associated with macrophage lipid accumulation by modulating lipogenesis and cholesterol uptake within these cells.


The use of tracheal stoma stents in high spinal cord injury: a patient-friendly alternative to long-term tracheostomy tubes.
Case series. North West Regional Spinal Injuries Unit, Southport and Formby District General Hospital, UK. To identify a novel type of tracheal stents for use in patients with high spinal cord injury. Patients with high spinal cord injury (above C4) frequently have significant respiratory impairment and may require long-term access to the trachea for respiratory support. For the most part, tracheostomy tubes are used for this purpose but a tracheal stoma stent can offer a suitable alternative in selected cases and deserves wider recognition. Following completion of a patient questionnaire survey, the authors describe the use of stoma stents in nine patients, five of whom had full-time diaphragm pacing. The stent in these cases is for retention of access for positive pressure ventilation, and for the prevention of obstructive sleep apnoea. This was also the indication in one self-ventilating patient with tetraplegia and sleep apnoea. Two patients with recurrent chest infections, in whom chest physiotherapy was difficult, benefited from the stoma stents. One patient, after ventilator weaning, required a further 4 months of tracheal access on account of episodic hypoventilation and temporarily had a tracheal stent as an inpatient. Patients who have had the benefit of tracheal stents report significant improvement in relation to local discomfort, tracheobronchial secretions and vocalization. With suitable training, the stents can be changed and cleaned easily in the home setting.


Cervical necrotizing fasciitis: 8-years' experience of microbiology.
Cervical necrotizing fasciitis (CNF) is a life-threatening complication of pharyngeal or dental infections. The aim of this paper was to investigate whether dental or pharyngeal source result from different pathogen(s) in CNF and whether antibiotics, given before admission, influence the antimicrobial resistance of pathogens. In 152 CNF patients, Streptococcus milleri group and Prevotella species were the predominant isolates, frequently copathogens, mostly in dental CNF samples. Penicillin and clindamycin resistance were observed in 39% and 37% of cases, respectively, independently of any previous antibiotic therapy. Thus, a combined aerobe-anaerobe infection may have a synergistic effect, which allows the infection to spread in cervical tissues.


Defining structural homology between the mammalian and avian hippocampus through conserved gene expression patterns observed in the chick embryo.
The mammalian hippocampus, a center of neurogenesis in the adult brain, is involved in critical functions such as learning and memory processing. Although there is an overall functional conservation between birds and mammals in the hippocampal region of the brain, there are several morphological differences. A few different models have been proposed for identifying regional and structural homology between the avian and mammalian hippocampus however a consensus is yet to be reached. In this study we have systematically and comprehensively characterized the developing chicken hippocampus at the molecular level. We have identified the time window of neurogenesis and apoptosis during hippocampal development as well as the likely origin and migration path of neurons of the ventral v-shaped region of chick hippocampus. In addition to this we have identified several genes with expression patterns that are conserved between the hippocampus of chicken and mice. Our study provides molecular data that partially supports one of the models reported in literature for structural homology between the avian and mammalian hippocampus. Functional characterization of the genes found in this study to be specifically expressed in the developing chicken hippocampus is likely to provide valuable information on the mechanisms regulating hippocampus development of birds and perhaps could be extrapolated to mammalian hippocampus development as well.


Positive prostate biopsy laterality and implications for staging.
To examine the effect of including positive prostate biopsy information in palpation staging (2002 system) and the influence of this information on freedom from biochemical failure (bNED). Prostate biopsy laterality status (unilateral versus bilateral positive) is part of clinical staging using American Joint Commission on Cancer criteria, but is rarely used. From April 1, 1989 to September 30, 1999, 1038 patients with palpable T1-T3Nx-0M0 prostate cancer were treated with three-dimensional conformal radiotherapy alone. Kaplan-Meier bNED curves were compared using the log-rank test. The Cox proportional hazards regression model of bNED was used for multivariate analysis. The median follow-up was 46 months. The proportion of patients with bilateral positive biopsies by palpation category T1c was 24%, by T2a was 17%, by T2b was 26%, by T2c was 65%, and by T3 was 53%. No statistically significant difference was noted in bNED on the basis of biopsy laterality status for the palpation T stages T1c, T2a, T2b, or T3. A statistically significant difference in the 5-year bNED in the T2c stage was found; those with unilateral positive biopsies fared worse (46% versus 74%, respectively, P = 0.04). Inclusion of positive biopsy laterality status into clinical staging causes stage migration without reflecting a change in outcome and should not be used.


Effect of deficiency in excision repair and umuC function on the mutagenicity with ethylene oxide in the lacI gene of E. coli.
The influence of uvrB and umuC genes on the induction of lacI- mutants and nonsense mutants by ethylene oxide (EtO) in the lacI gene of E. coli was studied. The uvrB mutation was characterized by much higher mutation frequencies. In contrast the umuC mutation does not significantly affect the induction kinetics. Thus mutation by EtO is enhanced by the lack of excision repair but not influenced by error-prone repair.


The anatomy of the umbilical, portal and hepatic venous systems in the human fetus at 14-19 weeks of gestation.
Ultrasound imaging of the fetal ductus venosus is becoming increasingly commonplace in clinical practice. The true anatomical relationships of the fetal umbilical and portal venous systems have not been clearly defined due to paucity of published data on the relevant anatomy. This has led to confusing terminology when describing the fetal umbilical, portal and hepatic circulations. The aim of the present study was to examine and document the anatomy of the umbilical, portal and hepatic venous systems and to propose a standardized nomenclature. This was a prospective study on 11 fetuses obtained from medical termination of pregnancies between 14 and 19 weeks of gestation. The liver was microdissected to expose the branching pattern and anatomical relations of the umbilical, portal and hepatic venous systems. A wide L-shaped venous confluence at the terminal end of the umbilical vein, termed the portal sinus, was identified. The portal sinus was connected to the right and left hepatic lobes, by the right and left intrahepatic portal veins, respectively. The extrahepatic portal vein drained into the portal sinus just before the origin of the right intrahepatic portal vein. The ductus venosus, a branchless straight vessel, originated from the portal sinus and ascended steeply in the direction of the diaphragm. Numerous small vessels draining the liver converged into three main hepatic veins, which open into the subdiaphragmatic vestibulum. Based on detailed sequential anatomical dissection and clear illustrations, the present study documents the anatomy of the umbilical, portal and hepatic venous systems. Taking into account the embryological origin of the vessels, a new anatomically appropriate and simplified nomenclature of these venous systems is proposed. In clinical practice, the consistent use of the suggested terminology would allow collection of comparable data between units and enable operators to be confident of which vessels they are sampling by Doppler ultrasound.


Phase I study of methylacetylenic putrescine, an inhibitor of polyamine biosynthesis.
In a phase I clinical trial, nine patients with advanced malignancies not amenable to alternative therapy received alpha-methyl-delta-acetylenic putrescine (MAP), an enzyme-activated, irreversible inhibitor of ornithine decarboxylase (ODC). MAP was given orally in increasing doses to successive groups of three patients as follows: 375 mg, 750 mg and 1500 mg/day, given as three equally divided doses for 4 weeks. Doses of 375 and 750 mg/day were well tolerated, with no detectable toxicity. Of three patients receiving 1500 mg/day, two experienced moderate to severe myelosuppression; one of these also became anuric, requiring the discontinuation of therapy after 9 days. Both effects were reversible after treatment was stopped. No objective responses were observed, with five patients having stable disease and four, progressive disease during the study period. In the seven patients in whom it could be calculated, the plasma elimination half-life t1/2 of MAP measured on the last day of treatment was between 3.9 and 9.2 h in six patients (mean, 5.6 h) and 26.1 h in the seventh. Mean steady-state trough concentrations of MAP were 2.3 mumol after the 375 mg/day dose, 7.1 mumol after 750 mg/day and 16.6 mumol after dosing with 1500 mg/day for 4 weeks, the levels after each treatment schedule being sufficient to inhibit ODC as demonstrated by increases in the urinary excretion of decarboxylated S-adenosylmethionine (dc-SAM). MAP treatment was associated with mean maximal increases in the urinary excretion of dc-SAM of 2.6-, 9.3- and 17.9-fold after 375, 750 and 1500 mg/day for 4 weeks, respectively, but no consistent changes in the urinary excretion of the polyamines, putrescine, spermidine or spermine were observed. Thus, the 24-h urinary excretion of dc-SAM may be used as a conveniently accessible marker of ODC inhibition in cancer patients.


Dysregulation of Ruminococcaceae and Megamonas could be predictive markers for rapid progression of mild cognitive impairment.
Intestinal flora dysregulation may affect the development of Alzheimer's disease (AD). However, the correlation between intestinal flora and rapid progression of mild cognitive impairment (MCI) is rarely reported. Our aim was to investigate the features of the intestinal flora in patients with rapidly progressive MCI. A total of 1013 participants were screened, in which 87 patients with MCI were followed up for two years. At the baseline time point, fecal samples of the patients were sequenced via the microbial diversity high-throughput 16 s-rDNA. After a two-year follow-up, 30 patients with MCI presented rapidly progressive cognitive impairment, whereas the 57 patients remained unprogressive. Analyses of their fecal samples showed that the abundance of 11 intestinal microflora were significantly different between the two groups at the baseline time point. Further analyses revealed that the decrease of Ruminococcaceae abundance and the increase of Megamonas abundance were significantly correlated with the progression of MCI. Also, the decreased Ruminococcaceae was independently associated with several factors such as P-tau181, and the increased Megamonas was independently associated with diabetes, low-density lipoprotein, median cell count. The decrease of Ruminococcaceae and the increase of Megamonas could act as predictive markers for the rapidly progressive MCI.


GABA release by basket cells onto Purkinje cells, in rat cerebellar slices, is directly controlled by presynaptic purinergic receptors, modulating Ca2+ influx.
In many brain regions, Ca(2+) influx through presynaptic P2X receptors influences GABA release from interneurones. In patch-clamp recordings of Purkinje cells (PCs) in rat cerebellar slices, broad spectrum P2 receptor antagonists, PPADS (30microM) or suramin (12microM), result in a decreased amplitude and increased failure rate of minimal evoked GABAergic synaptic currents from basket cells. The effect is mimicked by desensitizing P2X1/3-containing receptors with alpha,beta-methylene ATP. This suggests presynaptic facilitation of GABA release via P2XR-mediated Ca(2+) influx activated by endogenously released ATP. In contrast, activation of P2Y4 receptors (using UTP, 30microM, but not P2Y1 or P2Y6 receptor ligands) results in inhibition of GABA release. Immunological studies reveal the presence of most known P2Rs in >or=20% of GABAergic terminals in the cerebellum. P2X3 receptors and P2Y4 receptors occur in approximately 60% and 50% of GABAergic synaptosomes respectively and are localized presynaptically. Previous studies report that PC output is also influenced by postsynaptic purinergic receptors located on both PCs and interneurones. The high Ca(2+) permeability of the P2X receptor and the ability of ATP to influence intracellular Ca(2+) levels via P2Y receptor-mediated intracellular pathways make ATP the ideal transmitter for the multisite bidirectional modulation of the cerebellar cortical neuronal network.


Synthesis and biological evaluation of thiophene [3,2-b] pyrrole derivatives as potential anti-inflammatory agents.
A series of thiophene [3,2-b] pyrrole derivatives were synthesized and evaluated their abilities to inhibit anti-inflammatory activity. In this series, substituent effects at the N-1, 2 and 5 positions of thiophene [3,2-b] pyrrole were examined. The results obtained are compared to those previously reported anti-inflammatory drugs like Tenidap sodium, Diclofenac sodium and Piroxicam. The results indicated the critical role of the group linked in the N-1 position and 2, 5 positions of thiophene [3,2-b] pyrrole with different functional groups.


Diversity and plasticity of microglial cells in psychiatric and neurological disorders.
Recent advanced immunological analyses have revealed that the diversity and plasticity of macrophages lead to the identification of functional polarization states (classically activated M1 type and alternatively activated M2 type) which are dependent on the extracellular environment. M1 and M2 polarization states of macrophages play an important role in controlling the balance between pro-inflammatory and anti-inflammatory conditions. Microglial cells are resident mononuclear phagocytes in the central nervous system (CNS), express several macrophage-associated markers, and appear to display functional polarization states similar to macrophages. Like M1 macrophages, M1 polarized microglia can produce pro-inflammatory cytokines and mediators such as interleukin (IL) 1β, IL-6, tumor necrosis factor-α, CC-chemokine ligand 2, nitric oxide, and reactive oxygen species, suggesting that these molecules contribute to dysfunction of neural network in the CNS. On the other hand, M2 polarized microglia can produce anti-inflammatory cytokine, IL-10 and express several receptors that are implicated in inhibiting inflammation and restoring homeostasis. In this review, we summarize the diversity, plasticity, and immunoregulatory functions of M1 and M2 microglia in psychiatric and neurological disorders. Based on these aspects, we propose a contribution of imbalance between M1 and M2 polarization of microglia in bipolar disorder, obesity, amyotrophic lateral sclerosis, and Rett syndrome. Consequently, molecules that normalize the imbalance between M1 and M2 microglial polarization states may provide a beneficial therapeutic target for the treatment of these disorders.


Management and outcomes of haemorrhage after pancreatogastrostomy versus pancreatojejunostomy.
Postpancreatectomy haemorrhage (PPH) is a major cause of morbidity and mortality after pancreaticoduodenectomy (PD). It remains unclear whether performance of a pancreatogastrostomy (PG) instead of a pancreatojejunostomy (PJ) improves outcomes owing to better endoscopic accessibility. A large retrospective analysis was undertaken to compare outcomes of PPH, depending on whether a PG or PJ was performed. The primary outcome was the rate of successful endoscopy. A secondary outcome was the therapeutic success after adding surgery. Of 944 patients who had a PD, 8·4 per cent developed PPH. Endoscopy was the primary intervention in 21 (81 per cent) of 26 patients with a PG and 34 (64 per cent) of 53 with a PJ; it identified the bleeding site in 35 and 25 per cent respectively (P = 0·347). Successful endoscopic treatment was more common in the PG group (31 versus 9 per cent; P = 0·026). Surgery was performed for PPH in 15 patients (58 per cent) with a PG and 35 (66 per cent) with a PJ (P = 0·470). The majority of haemorrhages that required surgery were non-anastomotic intra-abdominal haemorrhages (12 of 15 versus 21 of 35; P = 0·171). Endoscopic or conservative treatment for PPH was successful in 42 per cent of patients with a PG and 32 per cent with a PJ (P = 0·520). The success rate increased to 85 and 91 per cent respectively when surgery was included in the algorithm (P = 0·467). The type of pancreatic anastomosis and its inherent effect on endoscopic accessibility had very little impact on the outcome of PPH. This was because haemorrhage frequently occurred from intra-abdominal or non-anastomotic intraluminal lesions.


[Immunological diagnosis of cutaneous lymphomas. II. Membrane receptor for Helix pomatia lectin on lymphocytes: a new immunohistological marker for T-lymphocytes and Sezary cells].
Lymphocytes carrying the receptor for helix pomatia lectin on their cytomembranes can be detected in lymphatic tissue and cutaneous T-cell lymphoma by means of peroxidase-labelled helix pomatia lectin. Cells positive for the HPL-receptor are identical with the population of T-lymphocytes, including their pathological variants, i.e. lymphoma cells and Sezary's cells.


Quantitative chemical mapping of plagioclase as a tool for the interpretation of volcanic stratigraphy: an example from Saint Kitts, Lesser Antilles.
Establishing a quantitative link between magmatic processes occurring at depth and volcanic eruption dynamics is essential to forecast the future behaviour of volcanoes, and to correctly interpret monitoring signals at active centres. Chemical zoning in minerals, which captures successive events or states within a magmatic system, can be exploited for such a purpose. However, to develop a quantitative understanding of magmatic systems requires an unbiased, reproducible method for characterising zoned crystals. We use image segmentation on thin section scale chemical maps to segment textural zones in plagioclase phenocrysts. These zones are then correlated throughout a stratigraphic sequence from Saint Kitts (Lesser Antilles), composed of a basal pyroclastic flow deposit and a series of fall deposits. Both segmented phenocrysts and unsegmented matrix plagioclase are chemically decoupled from whole rock geochemical trends, with the latter showing a systematic temporal progression towards less chemically evolved magma (more anorthitic plagioclase). By working on a stratigraphic sequence, it is possible to track the chemical and textural complexity of segmented plagioclase in time, in this case on the order of millennia. In doing so, we find a relationship between the number of crystal populations, deposit thickness and time. Thicker deposits contain a larger number of crystal populations, alongside an overall reduction in this number towards the top of the deposit. Our approach provides quantitative textural parameters for volcanic and plutonic rocks, including the ability to measure the amount of crystal fracturing. In combination with mineral chemistry, these parameters can strengthen the link between petrology and volcanology, paving the way towards a deeper understanding of the magmatic processes controlling eruptive dynamics. The online version contains supplementary material available at 10.1007/s00445-021-01476-x.


Violence Related Behaviors and Weapon Carrying Among Hispanic Adolescents: Results from the National Youth Risk Behavior Survey, 2001-2015.
Hispanic youths are disproportionately represented in gangs in the United States, are more likely to drink alcohol at younger ages, and to live in poverty; all are risks for violence and weapon carrying. No studies to date have assessed violence related behaviors and weapon carrying in Hispanic youth over an extended period. This study utilized the national Youth Risk Behavior Surveys from 2001 to 2015 to assess trends in violence related behaviors and weapon carrying of Hispanic adolescents. Our analyses found both physical fighting and fighting on school property had statistically significant reductions from 2001 to 2015 for Hispanic females and their suicide attempts increased from 2009 to 2015. Hispanic males had statistically significant decreasing trends for: being in a physical fight in the past year, being bullied on school property, being in a physical fight on school property within the past year; threatened or injured with a weapon on school property in the past year; and having attempted suicide in the past year. Hispanic females and males had two groups of items highly predictive of weapon carrying behaviors: alcohol, tobacco, and other drug use and violent risk behaviors. Both female and male students who made mostly A's or B's in school were significantly less likely (about half as likely) to carry weapons. This data could be used to identify Hispanic adolescents at higher risk for weapon carrying and used as a basis for enriching programs to improve academic success of Hispanic adolescents.


Carpal radiographs in orthodontic treatment.
The pubescent period offers the best opportunity to accomplish the objectives of orthodontic treatment in the shortest time. Treatment during the period of maximum growth activity reduces some of the uncertainties associated with early treatment. Carpal radiographs can be used as a guide to determine the onset of the adolescent growth spurt and hence provide the clinician with a diagnostic and planning aid to optimize treatment efficiency.


Innate lymphoid cells: NK and cytotoxic ILC3 subsets infiltrate metastatic breast cancer lymph nodes.
Innate lymphoid cells (ILCs) - which include cytotoxic Natural Killer (NK) cells and helper-type ILC - are important regulators of tissue immune homeostasis, with possible roles in tumor surveillance. We analyzed ILC and their functionality in human lymph nodes (LN). In LN, NK cells and ILC3 were the prominent subpopulations. Among the ILC3s, we identified a CD56+/ILC3 subset with a phenotype close to ILC3 but also expressing cytotoxicity genes shared with NK. In tumor-draining LNs (TD-LNs) and tumor samples from breast cancer (BC) patients, NK cells were prominent, and proportions of ILC3 subsets were low. In tumors and TD-LN, NK cells display reduced levels of NCR (Natural cytotoxicity receptors), despite high transcript levels and included a small subset CD127- CD56- NK cells with reduced function. Activated by cytokines CD56+/ILC3 cells from donor and patients LN acquired cytotoxic capacity and produced IFNg. In TD-LN, all cytokine activated ILC populations produced TNFα in response to BC cell line. Analyses of cytotoxic and helper ILC indicate a switch toward NK cells in TD-LN. The local tumor microenvironment inhibited NK cell functions through downregulation of NCR, but cytokine stimulation restored their functionality.


Behavioral health conditions and potentially preventable diabetes-related hospitalizations in the United States: Findings from a national sample of commercial claims data.
To characterize the relationship between potentially preventable hospitalizations (PPHs) for diabetes and behavioral health conditions in commercially insured working-age persons with diabetes in the United States. We retrospectively analyzed medical and pharmacy claims from services rendered between 2011 and 2013 for 229,039 adults with diabetes. Diabetes PPHs were identified using the Agency for Healthcare Research and Quality's Prevention Quality Indicators v6.0 logic. We used negative binomial-logit hurdle regression models to explore the adjusted relationships between diabetes PPHs and schizophrenia, bipolar, depression, anxiety, adjustment disorder, alcohol use disorder, and drug use disorder. A total of 4,521 diabetes PPHs were experienced by 3,246 of the persons in the sample. The 20.83% of persons with one or more behavioral health conditions experienced 43.62% (1,972/4,521; 95% CI 42.18%-45.07%) of all diabetes PPHs, and the 7.14% of persons with more than one diagnosed behavioral health condition experienced 24.77% (1,120/4,521; 95% CI 23.54%-26.05%) of all diabetes PPHs. After adjusting for sociodemographic and physical health covariates, patients with depression, schizophrenia, drug or alcohol use disorders, or multiple behavioral health conditions were at significantly increased risk of experiencing at least one diabetes PPH, while patients with depression, drug use disorder, or multiple behavioral health conditions were at significantly increased risk of experiencing recurring diabetes PPHs over time. A number of behavioral health conditions are associated with diabetes PPHs, which are often preventable with timely, high-quality outpatient care. The results of this study will enable clinicians, payers, and policy-makers to better focus outpatient care interventions and resources within the population of persons with diabetes.


Pain and interference of pain with function and mood in elderly adults involved in a motor vehicle collision: a pilot study.
BACKGROUND/STUDY CONTEXT: Musculoskeletal pain after motor vehicle collision is a substantial public health problem. The number of elderly individuals experiencing motor vehicle collision is increasing. The authors conducted analyses of data collected as part of a prospective observational study of outcomes after motor vehicle collision to estimates rates of persistent pain, pain interference, and change in physical function in patients 65 or older. Adults presenting to one of four emergency departments following motor vehicle collision without severe or life-threatening injury were recruited. Outcomes were assessed using 1-month follow-up surveys. The frequencies of persistent moderate or severe pain resulting from the motor vehicle collision were similar among elderly and nonelderly participants, both in the neck region (27% vs. 30%) and in any region (60% vs. 56%). For both elderly and nonelderly patients, persistent pain was associated with high levels of interference with physical activity and mood. Further studies of this vulnerable and rapidly increasing injury population are needed.


[The use of the macrophage disappearance reaction for detecting delayed hypersensitivity to Yersinia pestis antigens].
The possibility of using the reaction of macrophage disappearance (RMD) for the detection of delayed hypersensitivity (DH) to Y. pestis has been studied. As the result of these studies, RMD has been found suitable, in principle, for use in the quantitative evaluation of DH to Y. pestis. High sensitivity and specificity of this reaction have been established. The presence of DH in the process of the formation of immunity after immunization with Y. pestis antigen FIA has been shown. RMD can be observed during 28 days after immunization (the term of observation).


Skin effects of trichothecenes and their amelioration by decontamination.
The ability of trichothecenes, in particular T2 toxin (T2), to cause irritant effects on the skin has been investigated in laboratory rodents and rabbits. Quantitatively, T2 was found to be highly potent in this respect, causing irritant reactions on rat skin at contamination densities of less than 1 microgram.cm-2. The first appearance of skin effects was delayed for approximately 6 h after application, irrespective of the dose applied. Similarly, variation in solvent or injection into or beneath the skin failed to accelerate the onset of the irritant reaction. An aqueous soap solution was largely effective in removing low doses of T2 from the skin, but was ineffective in removing larger doses. However, washing the contaminated skin with polyethylene glycol 300 was very effective at removing even large doses of T2 from the skin. The macrocyclic trichothecene verrucarin A was of comparable irritancy to T2 on rat skin. Diacetoxyscirpenol and nivalenol were less potent.


Implementation of a sugar-sweetened beverage tax in low- and middle-income countries: recommendations for policymakers.
Longitudinal and observational studies have found a link between the consumption of sugar-sweetened beverages (SSBs) and non-communicable diseases (NCDs) including obesity and diabetes. Following World Health Organization (WHO) recommendations, SSB taxes have been implemented in over 40 countries and cities to reduce sugar consumption. Despite continuing battles with communicable diseases in low- and middle-income countries (LMICs), an epidemiological transition towards NCDs warrants SSB tax implementation. However, LMICs face challenges when implementing SSB taxes including a lack of resources and opposing arguments from industry. Sharing experiences among countries can help to improve the likelihood of successful SSB tax implementation. We review experiences of tobacco, alcohol, and SSB tax implementation in LMICs. We discuss potential pitfalls for policymakers and how they might be overcome. We provide recommendations based on implementation experiences in LMICs to help governments improve implementation capacity and advance public health.


Insulin sensitivity and beta-cell responsivity are not decreased in elderly subjects with normal OGTT.
Glucose intolerance has been observed often in elderly subjects, but it is not yet clear whether this impaired metabolic state is due to the aging process itself or is secondary to the appearance of other age-related variables. This study attempts to elucidate the effect of age in itself on factors controlling glucose tolerance. Several metabolic parameters were measured in 10 young male controls (23-29 yr) and 17 nonhospitalized, healthy, nonobese, old (60-80 yr) male subjects. Insulin binding to circulating cells was performed along with the intravenous glucose tolerance test, and the data were analyzed by the minimal model method. This approach yields the following measures: tissue insulin sensitivity (SI), fractional glucose disappearance at basal insulin (glucose effectiveness, SG), and first (phi 1) and second (phi 2) phase beta-cell responsiveness to glucose. Insulin-binding capacity to monocytes and erythrocytes was respectively 6.03% +/- 0.57% and 5.96% +/- 0.53% (elderly), 5.97% +/- 0.39% and 5.36% +/- 0.57% (young); SI was 6.20 +/- 0.59 X 10(4) min-1/(microU/mL) (elderly) and 6.35 +/- 0.30 (young); SG was 0.016 +/- 0.002 min-1 (elderly) and 0.019 +/- 0.003 (young); phi 1 was 1.84 +/- 0.29 min-1 (microU/mL)/(mg/dL) (elderly) and 3.37 +/- 0.84 (young); phi 2 was 13.80 +/- 1.78 X 10(4) min-2 (microU/mL)/(mg/dL) (elderly) and 9.59 +/- 2.65 (young). These results show no change with aging of tissue insulin sensitivity and an intact beta-cell activity, suggesting that age per se does not contribute to the deterioration of glucose tolerance when the effect of other age-related variables, eg, obesity and physical inactivity, is precluded.


Google search volume predicts the emergence of COVID-19 outbreaks.
Digital epidemiology is increasingly used for supporting traditional epidemiology. This study was hence aimed to explore whether the Google search volume may have been useful to predict the trajectory of coronavirus disease 2019 (COVID-19) outbreak in Italy. We accessed Google Trends for collecting data on weekly Google searches for the keywords "tosse" (i.e., cough), "febbre" (i.e., fever) and "dispnea" (dyspnea) in Italy, between February and May 2020. The number of new weekly cases of COVID-19 in Italy was also obtained from the website of the National Institute of Health. The peaks of Google searches for the three terms predicted by 3 weeks that of newly diagnosed COVID-19 cases. The peaks of weekly Google searches for "febbre" (fever), "tosse"( cough) and "dispnea" (dyspnea) were 1.7-, 2.2- and 7.7-fold higher compared to the week before the diagnosis of the first national case. No significant correlation was found between the number of newly diagnosed COVID-19 cases and Google search volumes of "tosse" (cough) and "febbre" (fever), whilst "dyspnea" (dyspnea) was significantly correlated (r= 0.50; p=0.034). The correlation between newly diagnosed COVID-19 cases and "tosse" (cough; r=0.65; p=0.008) or "febbre" (fever; 0.69; p=0.004) become statistically significant with a 3-week delay. All symptoms were also significantly inter-correlated. Conclusions; Continuously monitoring the volume of Google searches and mapping their origin can be a potentially valuable instrument to help predicting and identifying local recrudescence of COVID-19.


Double replica electroblotting for the simultaneous phenotyping of C6 and C7, and its application to the examination of bloodstains.
A new reliable and reproducible technique for the simultaneous determination of C6 and C7 types is presented, which employs double replica electroblotting after isoelectric focusing. It permitted clear discrimination of both C6 and C7 components, and the patterns were nearly comparable to those demonstrated separately. The population data obtained by this new technique fitted the genetic hypothesis. The present double replica electroblotting method was successfully applied to the combined phenotyping of C6 and C7 from bloodstains which were stored at room temperature for up to 4 weeks. The method is quite suitable for medicolegal examination of bloodstains particularly for the saving in the amount of sample.


The validity of the French version of the GHQ-28 and PSYDIS in a community sample of 20 year olds in Switzerland.
The 28-item GHQ (General Health Questionnaire) and the 43-item PSYDIS (Psychic Distress) were translated into French and administered to a community sample of 233 young adults. Of the two tests, the GHQ was shown to have the better correlation with the clinical assessment. For PSYDIS, specificity was 72.8, sensitivity was 64.2, but the misclassification rate rose to 29.2. The GHQ misclassified 18.5% of the respondents at the best cut-off point (5/6), with a specificity of 91.1 and a sensitivity of 49.1. The corrections C-GHQ (Goodchild and Duncan-Jones method of scoring) and simple Likert scoring improved sensitivity, although this was still unsatisfactory with males. Considering the lability of troubles in a young population, the GHQ should be applied with caution for epidemiological purposes.


Subdermal norethindrone pellets -- a method for contraception?
The mode of action of compressed pellets containing 85 per cent norethindrone (NET) and 15 per cent cholesterol was studied. Four pellets were inserted subcutaneously, in each of five healthy volunteers and left in place for 200--229 days. The NET content of the pellets varied between 23.9 mg and 25.6 mg; and the cholesterol content between 4.2 mg and 4.5 mg. Plasma levels of NET, estradiol and progesterone were determined by radioimmunoassays. Plasma levels of NET varied mostly between 1--2 ng/ml the first month after insertion. After two months plasma levels of NET ranged between 0.5 ng/ml and 1 ng/ml in all volunteers and there was a gradual decrease of the plasma NET levels throughout treatment. Pronounced day-to-day variations in plasma NET levels were recorded. The release rates of NET was calculated to be between 187 micrograms/day and 243 micrograms/day among the five volunteers. Ovulations occurred in four out of five subjects during treatment. This study indicates that the release of gestagen from four NET pellets was only initially high enough to completely inhibit ovulation and that to accomplish full contraceptive efficacy, a higher dose, i.e. more pellets, would have to be inserted.


[Distal, metaphyseal compression fractures of the radius. Results of open reposition, stable defect replacement with cortico-cancellous iliac crest bone and plate osteosynthesis].
Conservative treated distal radius fractures with extended metaphyseal void and missing cortical support resulted in loss of reduction. From 1988 till 1994 117 fractures of the distal radius were treated by open reduction, filling the metaphyseal void with a corticocancellous iliac bone graft and plate fixation. In this retrospective study results after surgical reconstruction were evaluated radiologically and clinically and were discussed to conservative treatment. 30 patients suffering from extraarticular metaphyseal distal radius fracture were evaluated after a mean of 42 months (minimum 20, maximum 68 months) after surgery. Ulnar variance was restored in 70% to the uninvolved side. Ulnar minus variance up to 2 mm persisted in 30%. Radial joint angles were restored to normal in 53%. In 40% of the patients a loss of reduction up to 10 degrees and in 7% up to 25 degrees occured. Active range of motion in the sagittal and frontal plane was equivalent to the non involved side in 30%. 70% of the patients showed reduced range of motion up to 20%. Rotation was unlimited in 77%, reduced up to 10% in 23%. Subjective results were excellent in 90%, good in 10%. Compared to conservative therapie, surgery showed superior results.


Comparison of a pump-around, a diffusion-driven, and a shear-driven system for the hybridization of mouse lung and testis total RNA on microarrays.
In the present study, we demonstrate the benefits of a shear-driven rotating microchamber system for the enhancement of microarray hybridizations, by comparing the system with two commonly used hybridization techniques: purely diffusion-driven hybridization under coverslip and hybridization using a fully automated hybridization station, in which the sample is pumped in an oscillating manner. Starting from the same amount of DNA for the three different methods, a series of hybridization experiments using mouse lung and testis DNA is presented to demonstrate these benefits. The gain observed using the rotating microchamber is large: both in terms of analysis speed (up to tenfold increase) and in final spot intensity (up to sixfold increase). The gain is due to the combined effect of the hybridization chamber miniaturization (leading to a sample concentration increase if comparing iso-mass conditions) and the transport enhancement originating from the rotational shear-driven flow induced by the rotation of the chamber bottom wall.


The roles of isomers of phytoene, phytofluene and zeta-carotene in carotenoid biosynthesis by a mutant strain of Scenedesmus obliquus.
Considerable changes in pigment composition occur during a period of 10 h when dark-grown cultures of PG1, a zeta-carotenic strain of Scenedesmus obliquus, are illuminated. These changes are consistent with a biosynthetic pathway in which 15-cis-phytoene is converted via 15-cis-phytofluene and 15-cis-zeta-carotene into all-trans-zeta-carotene and trans-bicyclic carotenoids. The findings also support the view that the xanthophylls lutein and zeaxanthin are formed from the corresponding carotenes and are especially important in the development of a normal chloroplast structure.


Biofunctionalization of silica microspheres for protein separation.
Mercapto-silica (SiO2-SH) microspheres were prepared via direct hydrolysis of 3-mercaptopropyltrimethoxysilane (MPS) in a basic aqueous solution. The content of surface thiol group (SH) of SiO2-SH microspheres was measured by Ellman's reagent method and X-ray photoelectron spectroscopy (XPS) and the content of surface thiol group of SiO2-SH microspheres is strongly dependent on the reaction conditions. The thermal stability of SiO2-SH microspheres was evaluated by thermogravimetric (TG) analysis, which tended to reduce with the increase of content of surface thiol groups. SiO2-SH microspheres can be easily modified with reduced glutathione (GSH) to generate SiO2-GSH microspheres for the affinity separation of Glutathione S-transferase (GST). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to examine the validity of the separation procedure. The results showed that SiO2-GSH microspheres were efficient in GST affinity separation from mixed proteins.


Purification of diphtheria toxin by chromatography on Cibacron Blue-Sepharose.
Diphtheria toxin binds to Cibacron Blue-Agarose and may be eluted by increasing the ionic strength of the elution buffer. Experiments using difference spectroscopy showed that the interaction between toxin and dye is ionic rather than hydrophobic, and therefore it is of a different nature with respect to that usually found in nucleotide-requiring enzymes.


Ambient Electrosynthesis of Ammonia Using Core-Shell Structured Au@C Catalyst Fabricated by One-Step Laser Ablation Technique.
This work reports the synthesis of core-shell structured Au@C composite through a simple one-step laser ablation technique. The results demonstrate that the Au@C with a mean nanosphere size of ∼8.0 nm is composed of a spherical shaped Au core and 1-2 layered graphitic carbon shell with abundant defects. As a nitrogen reduction reaction (NRR) electrocatalyst, the Au@C gives a large NH3 yield rate of 241.9 μg h-1 mgcat.-1 with a high faradaic efficiency of 40.5% at -0.45 V versus reversible hydrogen electrode in a 0.1 M Na2SO4 electrolyte (pH = 6.3) under ambient conditions, surpassing the performances of most aqueous-based NRR electrocatalysts recently reported. The 15N labeling experimental results demonstrate that the produced NH3 is undoubtedly originated from the NRR process catalyzed by Au@C. The superior NRR performance of Au@C can be ascribed to the ultrathin carbon layer, effectively inhibiting the aggregation of Au nanospheres during the NRR, and the abundant defects such as carbon vacancies existed in the ultrathin carbon layer, providing additional NRR catalytic active sites. Our theoretical calculation results further confirm the role of carbon vacancies in the electrocatalytic NRR.


First bite syndrome: Our experience with intraparotid injections with botulinum toxin type A.
First bite syndrome is the sudden onset of acute and severe pain in the parotid region at the initiation of mastication. Although it generally lasts less than a minute, it is disabling for these individuals and leads to a fear of oral intake. It is typically seen after parapharyngeal or deep parotid space surgery. Intraparotid injection of botulinum toxin A (BTA) has been suggested as a treatment for this condition, but there is little supporting literature to this effect. The purpose of this study is to document our experience using this treatment method for first bite syndrome. Retrospective case review. Five patients with first bite syndrome, developed after parapharyngeal space surgery, were treated by multisite injection of BTA into the parotid gland. Between 17.5 and 50 total U of BTA were injected into four or more sites in the parotid region. The patients were then followed up every 4 months. Three of five patients reported a significant improvement in symptoms at the 4-month follow-up visit, although complete resolution was not reported. One patient reported only moderate improvement, and despite two series of injections there was no improvement in one patient, leading us to question our initial diagnosis. Unilateral BTA injection into the affected parotid gland produces a decrease in the severity of symptoms. It is a safe and viable noninvasive treatment for this difficult to treat condition and may lead to permanent resolution of symptoms in some patients.


Feasibility of robot-assisted submandibular gland resection via retroauricular approach: preliminary results.
To present the surgical technique and feasibility of robot-assisted submandibular gland (SMG) resection via retroauricular approach. Feasibility study of case series. We performed robot-assisted SMG resection on five patients with benign SMG tumors. The surgical complications, operation time, amount of bleeding, amount and duration of drainage, and duration of hospital stay were reviewed. The surgery was successful in all patients without any significant complications. The mean operation time was 62.4 ± 6.3 minutes, amount of bleeding was 10.4 ± 3.2 mL, amount of drainage was 149.8 ± 114.7 mL (3.2 ± 1.6 days), and duration of hospital stay was 4.2 ± 1.8 days. All patients showed excellent cosmetic satisfaction because the postoperative scar was hidden by the auricle and hair. Robot-assisted SMG resection was feasible without any significant complications and satisfactory cosmetic results. The safety and oncologic outcome of the procedure should be verified with larger number of patients and longer follow up period.


Absorption of Cr(VI) onto amino-modified titanate nanotubes using 2-bromoethylamine hydrobromide through SN2 reaction.
Unlike the complex reaction of grafting amino groups using harmful organic solvents, we proposed an environmental friendly method for effective amino grafting on titanate nanotubes (TNTs) with 2-Bromoethylamine hydrobromide (2-Bh) through a two-step SN2 reaction in pure water solution. The amino-modified titanate nanotubes (TNTs-RNH2) were characterized by Transmission electron microscope, X-ray diffraction, X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Under optimal conditions, the molar ratio of NaOH/2-Bh was 1.2 for step 1 and 1.3 for step 2 with corresponding reaction time of 12h and 24h, respectively. The adsorption isotherm of Cr(VI) onto TNTs-RNH2 well fits Langmuir model with maximal adsorption capacity of 69.1 mg/g, which is almost five times larger than that of fresh TNTs. The slight decrease in adsorption capacity with NO3(-) concentration was attributed to competition from ions, suppression of electric double layer and changes of Cr(VI) speciation. The wide adsorption pH range was due to much larger point of zero charge (8.2) and electrostatic attraction between positively charged TNTs-RNH2 and Cr(VI) with different speciations. The products could be well reused due to simple desorption at pH 10 with about 20% loss of the adsorption capacity after three recycles without any regeneration treatment.


Identification and quantification of six major α-dicarbonyl process contaminants in high-fructose corn syrup.
High-fructose corn syrup (HFCS) is a widely used liquid sweetener produced from corn starch by hydrolysis and partial isomerization of glucose to fructose. During these processing steps, sugars can be considerably degraded, leading, for example, to the formation of reactive α-dicarbonyl compounds (α-DCs). The present study performed targeted screening to identify the major α-DCs in HFCS. For this purpose, α-DCs were selectively converted with o-phenylendiamine to the corresponding quinoxaline derivatives, which were analyzed by liquid chromatography with hyphenated diode array-tandem mass spectrometry (LC-DAD-MS/MS) detection. 3-Deoxy-D-erythro-hexos-2-ulose (3-deoxyglucosone), D-lyxo-hexos-2-ulose (glucosone), 3-deoxy-D-threo-hexos-2-ulose (3-deoxygalactosone), 1-deoxy-D-erythro-hexos-2,3-diulose (1-deoxyglucosone), 3,4-dideoxyglucosone-3-ene, methylglyoxal, and glyoxal were identified by enhanced mass spectra as well as MS/MS product ion spectra using the synthesized standards as reference. Addition of diethylene triamine pentaacetic acid and adjustment of the derivatization conditions ensured complete derivatization without de novo formation for all identified α-DCs in HFCS matrix except for glyoxal. Subsequently, a ultra-high performance LC-DAD-MS/MS method was established to quantify 3-deoxyglucosone, glucosone, 3-deoxygalactosone, 1-deoxyglucosone, 3,4-dideoxyglucosone-3-ene, and methylglyoxal in HFCS. Depending on the α-DC compound and concentration, the recovery ranged between 89.2% and 105.8% with a relative standard deviation between 1.9% and 6.5%. Subsequently, the α-DC profiles of 14 commercial HFCS samples were recorded. 3-Deoxyglucosone was identified as the major α-DC with concentrations up to 730 μg/mL HFCS. The total α-DC content ranged from 293 μg/mL to 1,130 μg/mL HFCS. Significantly different α-DC levels were not detected between different HFCS specifications, but between samples of various manufacturers indicating that the α-DC load is influenced by the production procedures.


Other methods of laparoendoscopic hernia repair: mini-hernia--inguinal hernia repair through a 2-cm incision.
Mini-hernia repair is an endoscopic modification of the Lichtenstein tension-free repair. Clinical trials are warranted to determine the efficacy of this procedure and any advantages it may have over the original operation.


Deep learning approach for bubble segmentation from hysteroscopic images.
Gas embolism is a potentially serious complication of hysteroscopic surgery. It is particularly necessary to monitor bubble parameters in hysteroscopic images by computer vision method for helping develop automatic bubble removal devices. In this work, a framework combining a deep edge-aware network and marker-controlled watershed algorithm is presented to extract bubble parameters from hysteroscopy images. The proposed edge-aware network consists of an encoder-decoder architecture for bubble segmentation and a contour branch which is supervised by edge losses. The post-processing method based on marker-controlled watershed algorithm is used to further separate bubble instances and calculate size distribution. Extensive experiments substantiate that the proposed model achieves better performance than some typical segmentation methods. Accuracy, sensitivity, precision, Dice score, and mean intersection over union (mean IoU) obtained for the proposed edge-aware network are observed as 0.859 ± 0.017, 0.868 ± 0.019, 0.955 ± 0.005, 0.862 ± 0.005, and 0.758 ± 0.007, respectively. This work provides a valuable reference for automatic bubble removal devices in hysteroscopic surgery.


Switching from Warfarin to rivaroxaban induces sufficiency of vitamin K and reduction of arterial stiffness in patients with atrial fibrillation.
Use of chronic vitamin K antagonist (VKA) induces a long-term deficiency of vitamin K, which may cause arterial stiffness and bone-related disease. Switching from VKA to rivaroxaban could induce rapid sufficiency of vitamin K and improvement of arterial stiffness. The K2 SUMMIT-3 study is a multicenter, open-label, prospective, and randomized design. Patients with atrial fibrillation who have been taking VKA for more than 6 months but less than 10 years were randomly assigned to two groups; those switching from VKA to rivaroxaban and those continuing with VKA medication. The primary endpoint was the percentage difference of brachial-ankle pulse wave velocity (baPWV) in 3 months. A total of 77 patients were randomly assigned to receive rivaroxaban (n = 38) or VKA (n = 39). The average age was 74 ± 9 years. The duration for which VKA was prescribed prior to randomization was 90 ± 87 months.Abnormally high levels of Des-gamma carboxyprothrombin (PIVKA-II) or uncarboxylated osteocalcin (ucOC) indicating vitamin K insufficiency were observed in 100% or 82% of the patients at baseline but it reduced to 2% (p < 0.0001) or 55% (p = 0.01) at 3 months in the rivaroxaban group. To the contrary, theses data had no changes in the VKA group. The percentage difference in baPWV was - 1.4 ± 10.0% vs. 3.5 ± 14.7% in the rivaroxaban and the VKA groups, respectively. (p = 0.02). Switching from VKA to rivaroxaban resulted in rapid sufficiency of vitamin K and reduction of arterial stiffness in 3 months.


Engineering Coupled NiSx -WO2.9 Heterostructure as pH-Universal Electrocatalyst for Hydrogen Evolution Reaction.
Exploiting highly active and low-cost materials as pH-universal electrocatalysts for the hydrogen evolution reaction (HER) and achieving high-purity hydrogen fuel is highly desirable but remains challenging. Herein, a novel type of coupled heterostructure was designed by simple electrodeposition followed by a sulfurization treatment. This hierarchical structure was composed of nickel sulfides (NiS, NiS2 , denoted as NiSx ) and oxygen-deficient tungsten oxide (WO2.9 ), which was directly grown on nickel foam (NF) as self-supporting electrodes (NiSx -WO2.9 /NF) for HER over a wide pH range. The systematic experimental characterizations confirmed that the material had abundant catalytic active sites, fast interfacial electron transfer ability, and strong electronic interaction, resulting in the optimized reaction kinetics for HER. Consequently, the NiSx -WO2.9 /NF catalyst required low overpotentials of 96 and 117 mV to reach current densities of 50 and 100 mA cm-2 in an alkaline medium, outperforming most of the reported non-noble metal-based materials. Moreover, this self-supported electrode exhibited impressive performance over a wide pH range, only requiring 220 and 304 mV overpotential at 100 mA cm-2 in 0.5 m H2 SO4 and 1 m phosphate-buffered saline electrolytes. This work may offer a new approach to the development of advanced pH-universal electrodes for hydrogen production.


Evaluation of the integrity of the deltoid ligament in supination external rotation ankle fractures: a systematic review of the literature.
Review the literature concerning modalities to evaluate the integrity of the deltoid ligament in patients with supination external rotation ankle fractures. The electronic databases Pubmed/Medline, CINAHL and Embase were searched from 1987 to November 2007 to identify all published original studies concerning diagnostic modalities to evaluate the integrity of the deltoid ligament in adult ankle fractures. This review included nine studies involving 423 ankle fractures. Three trails investigated medial tenderness; two studies, ecchymosis; two studies, swelling; one study, an injury radiograph; six studies, a type of radiographic stress view; one study, the Lauge-Hansen classification; one study, MRI; and one article studied arthroscopy in the evaluation of the deltoid ligament integrity. Swelling, ecchymosis, medial tenderness, initial injury radiographs and the Lauge-Hansen classification are less adequate predictors of the integrity of the deltoid ligament. Manual or the less painful variant, the gravity external rotation stress radiographs are considered the gold standard. The amount of medial clear space widening indicative of a positive external rotation stress test has been somewhat variable in the literature but > or =5 mm is generally regarded as most reliable. Achieving adequate external rotation of the foot when obtaining stress radiographs is more important than positioning the ankle in the appropriate degree of ankle flexion. The amount of applied force necessary when performing an external rotation stress radiograph is not well defined and mainly determined by the patient's pain level. The indication for surgery should not be based on the absolute value of one parameter but on the combination of several parameters. If nonoperative treatment is chosen despite a positive stress radiograph, close follow-up is critical because subluxation of the ankle joint is still possible. MRI could be useful in individual cases.


Genetic surface-display of methyl parathion hydrolase on Yarrowia lipolytica for removal of methyl parathion in water.
In this study, the mph gene encoding methyl parathion hydrolase from Pseudomonas sp. WBC-3 was expressed in Yarrowia lipolytica and the expressed methyl parathion hydrolase was displayed on cell surface of Y. lipolytica. The activity of methyl parathion hydrolase displayed on the yeast cells of the transformant Z51 was 59.5 U mg⁻¹ of cell dry cells (450.6 U per mL of the culture) in the presence of 5.0 mM of Co²⁺. The displayed methyl parathion hydrolase had the optimal pH of 9.5 and the optimal temperature of 40 °C, respectively and was stable in the pH range of 4.5-11 and up to 40 °C. The displayed methyl parathion hydrolase was also stimulated by Co²⁺, Cu²⁺, Ni²⁺ and Mn²⁺, and was not affected by Fe²⁺, Fe³⁺, Na⁺, K⁺, Ca²⁺ and Zn²⁺, but was inhibited by other cations tested. Under the optimal conditions (OD(600 nm) = 2.6, the substrate concentration = 100 mg L⁻¹ and 40 °C), 90.8 % of methyl parathion was hydrolyzed within 30 min. Under the similar conditions, 98.7, 97.0, 96.5 and 94.4 % of methyl parathion in tap water (pH 9.5), tap water (pH 6.8), seawater (pH 9.5) and natural seawater (pH 8.2) were hydrolyzed, respectively, suggesting that the methyl parathion hydrolase displayed on the yeast cells can effectively remove methyl parathion in water.


The key role of glutamine for protein expression and isotopic labeling in insect cells.
Nuclear magnetic resonance studies of many physiologically important proteins have long been impeded by the necessity to express such proteins in isotope-labeled form in higher eukaryotic cells and the concomitant high costs of providing isotope-labeled amino acids in the growth medium. Economical routes use isotope-labeled yeast or algae extracts but still require expensive isotope-labeled glutamine. Here, we have systematically quantified the effect of 15N2-glutamine on the expression and isotope labeling of different proteins in insect cells. Sufficient levels of glutamine in the medium increase the protein expression by four to five times relative to deprived conditions. 1H-15N nuclear magnetic resonance spectroscopy shows that the 15N atoms from 15N2-glutamine are scrambled with surprisingly high (60-70%) efficiency into the three amino acids alanine, aspartate, and glutamate. This phenomenon gives direct evidence that the high energy demand of insect cells during baculovirus infection and concomitant heterologous protein expression is predominantly satisfied by glutamine feeding the tricarboxylic acid cycle. To overcome the high costs of supplementing isotope-labeled glutamine, we have developed a robust method for the large-scale synthesis of 15N2-glutamine and partially deuterated 15N2-glutamine-α,β,β-d3 from inexpensive precursors. An application is shown for the effective large-scale expression of the isotope-labeled β1-adrenergic receptor using the synthesized 15N2-glutamine-α,β,β-d3.


NRG1/ErbB2 axis regulated mitochondrial function and antioxidant enzymes of neural stem cells in the cochlear nucleus partially through PGC-1α.
Neuregulin-1 (NRG1)/erythroblastic leukaemia viral oncogene homologues 2 (ErbB2) pathway had been implicated in promoting differentiation and suppressing apoptosis of neuronal stem cells (NSCs) isolated from cochlear nucleus. In the current study, we aimed at determining the effects of NRG1/ErbB2 on mitochondrial (mt) function of NSCs. As expected, NRG1 increased the expression of mitofusin (Mfn) 1 and Mfn2 and decreased the expression of mitochondrial fission protein 1 (Fis1) and dynamin-related protein 1 (Drp1). However, after ErbB2 knockout, Mfn1 and Mfn2 expression decreased while Fis1 and Drp1 increased. Moreover, the increased mtDNA copy number and intracellular ATP level, elevated ATPase activities as well as decreased lactate production induced by NRG1 were partially reversed by ErbB2 knockout. Additionally, NRG1 treatment increased the activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and upregulated the protein expression of catalase, manganese superoxide dismutase (MnSOD), peroxisome proliferator-activated receptor-γ coactlvator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and transcription factor A, mitochondrial (TFAM), which were also reversed by ErbB2 knockout. Furthermore, PGC-1α overexpression partially reversed the above effects of ErbB2 knockout. In conclusion, these findings suggest that the promotion of mitochondrial function of NRG1/ErbB2 axis is at least in part mediated by PGC-1α in NSCs from cochlear nucleus.