Neuroplasticity associated with tactile language communication in a deaf-blind subject.
A long-standing debate in cognitive neuroscience pertains to the innate nature of language development and the underlying factors that determine this faculty. We explored the neural correlates associated with language processing in a unique individual who is early blind, congenitally deaf, and possesses a high level of language function. Using functional magnetic resonance imaging (fMRI), we compared the neural networks associated with the tactile reading of words presented in Braille, Print on Palm (POP), and a haptic form of American Sign Language (haptic ASL or hASL). With all three modes of tactile communication, indentifying words was associated with robust activation within occipital cortical regions as well as posterior superior temporal and inferior frontal language areas (lateralized within the left hemisphere). In a normally sighted and hearing interpreter, identifying words through hASL was associated with left-lateralized activation of inferior frontal language areas however robust occipital cortex activation was not observed. Diffusion tensor imaging -based tractography revealed differences consistent with enhanced occipital-temporal connectivity in the deaf-blind subject. Our results demonstrate that in the case of early onset of both visual and auditory deprivation, tactile-based communication is associated with an extensive cortical network implicating occipital as well as posterior superior temporal and frontal associated language areas. The cortical areas activated in this deaf-blind subject are consistent with characteristic cortical regions previously implicated with language. Finally, the resilience of language function within the context of early and combined visual and auditory deprivation may be related to enhanced connectivity between relevant cortical areas.


An Overview on the Rheology, Mechanical Properties, Durability, 3D Printing, and Microstructural Performance of Nanomaterials in Cementitious Composites.
The most active research area is nanotechnology in cementitious composites, which has a wide range of applications and has achieved popularity over the last three decades. Nanoparticles (NPs) have emerged as possible materials to be used in the field of civil engineering. Previous research has concentrated on evaluating the effect of different NPs in cementitious materials to alter material characteristics. In order to provide a broad understanding of how nanomaterials (NMs) can be used, this paper critically evaluates previous research on the influence of rheology, mechanical properties, durability, 3D printing, and microstructural performance on cementitious materials. The flow properties of fresh cementitious composites can be measured using rheology and slump. Mechanical properties such as compressive, flexural, and split tensile strength reveal hardened properties. The necessary tests for determining a NM's durability in concrete are shrinkage, pore structure and porosity, and permeability. The advent of modern 3D printing technologies is suitable for structural printing, such as contour crafting and binder jetting. Three-dimensional (3D) printing has opened up new avenues for the building and construction industry to become more digital. Regardless of the material science, a range of problems must be tackled, including developing smart cementitious composites suitable for 3D structural printing. According to the scanning electron microscopy results, the addition of NMs to cementitious materials results in a denser and improved microstructure with more hydration products. This paper provides valuable information and details about the rheology, mechanical properties, durability, 3D printing, and microstructural performance of cementitious materials with NMs and encourages further research.


A rare cause for acute cor pulmonale.
A number of diseases may cause right atrial mass. Primary cardiac tumors range from 0.002 to 0.25%. Intracardiac manifestation and pulmonary embolism of hepatocellular carcinoma (HCC) is a very rare finding and uncommon even at autopsy. Here we describe the case of a 32-year-old Asian man who was referred for shortness of breath lasting for a month, along with unproductive cough. He was a manual laborer with a history of diabetes, alcoholism, and smoking. Clinically he was diagnosed as having pulmonary embolism. Echocardiogram showed a mass in the right atrium. Magnetic resonance imaging showed that he had a large mass in the right atrium extending down into the inferior vena cava. Further evaluation showed that he had chronic liver disease with portal hypertension and was hepatitis B surface antigen-positive, indicating hepatitis B infection. He underwent excision of the mass, and the pathological report showed metastasis of HCC with multiple vascular emboli in the lungs. As this is the second reported case of this kind in the literature, we highlight the need of screening at least 6-monthly all patients with chronic liver disease, hepatitis B and C virus infection for the early detection of HCC.


Neuroprotective effect of ischemic preconditioning in focal cerebral infarction: relationship with upregulation of vascular endothelial growth factor.
Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic preconditioning in rats by simulating a transient ischemic attack twice (each a 20-minute occlusion of the middle cerebral artery) before inducing focal cerebral infarction (2 hour occlusion-reperfusion in the same artery). We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after occlusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascular endothelial growth factor.


Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells.
Crocus sativus L. is used in Chinese traditional medicine to treat some disorders of the central nervous system. Crocin is an ethanol-extractable component of Crocus sativus L.; it is reported to prevent ethanol-induced impairment of learning and memory in mice. In this study, we demonstrate that crocin suppresses the effect of tumor necrosis factor (TNF)-alpha on neuronally differentiated PC-12 cells. PC-12 cells dead from exposure to TNF-alpha show apoptotic morphological changes and DNA fragmentation. These hallmark features of cell death did not appear in cells treated in the co-presence of 10 microM crocin. Moreover, crocin suppressed the TNF-alpha-induced expression of Bcl-Xs and LICE mRNAs and simultaneously restored the cytokine-induced reduction of Bcl-X(L) mRNA expression. The modulating effects of crocin on the expression of Bcl-2 family proteins led to a marked reduction of a TNF-alpha-induced release of cytochrome c from the mitochondria. Crocin also blocked the cytochrome c-induced activation of caspase-3. To learn how crocin exhibits these anti-apoptotic actions in PC-12 cells, we tested the effect of crocin on PC-12 cell death induced by daunorubicin. We found that crocin inhibited the effect of daunorubicin as well. Our findings suggest that crocin inhibits neuronal cell death induced by both internal and external apoptotic stimuli.


Screening of Fish Cell Lines for Piscine Orthoreovirus-1 (PRV-1) Amplification: Identification of the Non-Supportive PRV-1 Invitrome.
Piscine reovirus (PRV) is the causative agent of heart and skeletal muscle inflammation (HSMI), which is detrimental to Atlantic Salmon (AS) aquaculture, but so far has not been cultivatable, which impedes studying the disease and developing a vaccine. Homogenates of head kidney and red blood cells (RBC) from AS in which PRV-1 had been detected were applied to fish cell lines. The cell lines were from embryos, and from brain, blood, fin, gill, gonads, gut, heart, kidney, liver, skin, and spleen, and had the shapes of endothelial, epithelial, fibroblast, and macrophage cells. Most cell lines were derived from the Neopterygii subclass of fish, but one was from subclass Chondrostei. Cultures were examined by phase contrast microscopy for appearance, and by quantitative polymerase chain reaction (qPCR) for PRV-1 RNA amplification and for the capacity to transfer any changes to new cultures. No changes in appearance and Ct values were observed consistently or transferable to new cultures. Therefore, 31 cell lines examined were unable to support PRV-1 amplification and are described as belonging to the non-supportive PRV-1 invitrome. However, these investigations and cell lines can contribute to understanding PRV-1 cellular and host tropism, and the interactions between virus-infected and bystander cells.


3120+1 G-->A: a rare variant in Emirati CF patients.
Cystic fibrosis is a multi-system genetic disorder caused by mutation in the cystic fibrosis conductance transmembrane regulator (CFTR) gene located on chromosome 7. In United Arab Emirates (UAE), pattern of CF causing gene mutations is different than rest of the Arabs in the region and 95% of CF in Emirati families has been found due to two mutations only - -p.S549R(T>G) and p.F508del. We report the case of a homozygote for a mutation 3120 +1G-->A in the Emirati population detected in a young boy referred to CF and Respiratory Clinic at Tawam Hospital (Al Ain, UAE) for screening CFTR gene.


Regulation of preglomerular microvascular 20-hydroxyeicosatetraenoic acid levels by salt depletion.
20-hydroxyeicosatetraenoic acid (20-HETE) is the preeminent renal eicosanoid. The protean properties of 20-HETE - vasoactivity, mitogenicity and modulation of transport in key nephron segments - serve as the basis for the essential roles of 20-HETE in the regulation of the renal circulation and electrolyte excretion and as a second messenger for endothelin-1 (ET-1) and a mediator of selective renal effects of angiotensin II (AII). Renal autoregulation and tubular glomerular feedback are mediated by 20-HETE through constriction of preglomerular microvessels, particularly afferent arterioles. We had reported that rat preglomerular microvessels (PGMV; afferent-interlobular-arcuate/interlobular) in response to angiotensin II (AII) generate primarily 20-HETE and lesser quantities of 19-HETE. We have now addressed a possible link between the renin-angiotensin-system (RAS) and induction of cyclooxygenase (COX-2). As Na+ deprivation induces COX-2 expression/activity in the renal cortex and AII stimulates release of 20-HETE from PGMV, we used a stimulus, low dietary salt, to activate the RAS and COX-2 and thereby explore potential interactions involving 20-HETE and COX-2. The capacity of COX to metabolize 20-HETE to prostaglandin analogs e.g., 20-OH PGF2a and 20-OH PGE2, may be critical to modifying the renal vascular and tubular actions of the eicosanoids.


Retinal vasculitis associated with the anti-synthetase syndrome.
A 50-year-old woman with a history of anti-Jo1-positive inflammatory myositis and interstitial lung disease presented with decreased vision in her right eye. Examination revealed white-centered hemorrhages scattered across the posterior pole in addition to several areas of vascular sheathing. Treatment was initiated with intravenous pulse solumedrol, with improvement in vision and resolution of the patient's white-centered hemorrhages. A thorough workup for other causes of vasculitis was unrevealing. Anti-synthetase syndrome is a serologically defined disorder clinically characterized by inflammatory myositis, interstitial lung disease, and other systemic findings. To our knowledge, retinal vasculitis has not been previously reported in patients with anti-synthetase syndrome.


Prolonged morbidity due to delays in the diagnosis and treatment of obstructive sleep apnea in children.
The inclusion of a query concerning the presence of snoring in a questionnaires used by the Allergy Service of Childrens Hospital Los Angeles (CHLA) uncovered a significant number of patients who were experiencing prolonged and discomforting symptoms owing to previously undiagnosed obstructive sleep apnea (OSA) caused by adenotonsillar hypertrophy. Of 352 patients who were discharged with a diagnosis of OSA and tonsillectomy and/or adenoidectomy at CHLA in 1996-1997, a retrospective study of the first 45 randomly selected patients who agreed to participate in a telephone interview was performed. Analysis revealed that all patients experienced severe and discomforting symptoms with all describing severe or moderate snoring. Other symptoms included chronic mouth breathing (84%), frequent otitis media (64%), sinusitis (56%), sore throat (51%), choking (47%), and daytime drowsiness (42%). Other symptoms included poor school performance, enuresis, poor appetite and/or weight gain, dysphagia, and vomiting. Symptoms began at a mean age of approximately 2 years ("birth"-9 years), and the mean period of time between the development of significant symptoms and OSA was 3.3 years (6 months-13 years). Delay between onset of significant symptoms and surgery was > 1 year in 82% of the patients, > 2 years in 51% of the patients, > 4 years in 31% of the patients, and > 6 years in 13% of the patients. Forty percent of patients were self-referred to an otolaryngologist for treatment despite their primary care physician being aware of the symptoms. These results indicate that patient with OSA experienced prolonged morbidity and delays in treatment, which is probably widespread. Physician, parent, and third-party factors were found to have contributed to the delays in treatment.


Confluent and reticulated papillomatosis: clinical and histopathological study of 10 cases from Lebanon.
Confluent and reticulate papillomatosis (CRP) is a rare disorder that has mostly been described in case reports and limited case series. Studies on this condition from our region are lacking. To describe the clinical and histopathological findings, as well as response to treatment of all patients diagnosed with CRP at the American University of Beirut Medical Center (AUB-MC) between 1999 and 2009, and to compare our findings with those published in the literature. Confluent and reticulate papillomatosis was diagnosed in 10 patients (five men, five women). Mean age at diagnosis was 19 years. Duration of lesions ranged from few months to several years. Skin lesions mainly consisted of reticulated, pigmented macules, patches and plaques. The most common area of involvement was the chest in five cases. The rash was asymptomatic in eight patients. Skin biopsy specimens from all patients revealed hyperkeratosis, papillomatosis and variable acanthosis. Whereas follicular plugging was observed in nine cases, anastomosis of the rete ridges was noted in three. Periodic acid Schiff stains highlighted yeast forms in six cases. The clinical and histopathological features of the CRP patients in our study are generally comparable to those published in the literature, with minor differences. Clinically, one case had an atypical clinical presentation, and microscopically follicular plugging was seen in the majority of cases. Yeast-like spores were seen in six cases further supporting a role of Malassezia furfur in the pathogenesis of CRP.


A non-invasive measure of changes in blood flow in the human anterior tibial muscle.
We used photoplethysmography (PPG) to monitor blood flow changes in the human anterior tibial muscle during arterial occlusion and during isometric and concentric contractions. Single-fibre laser-Doppler flowmetry (LDF) was used as a reference in 12 healthy subjects (5 men, 7 women; mean age 24 years). Post-exercise hyperaemic muscle blood flow (MBF) was measured immediately after isometric dorsiflexion of the ankle joint at maximal contraction for 1 min and full range-of-motion dorsiflexion and plantar flexion of the ankle joint for 1 min. A thigh tourniquet was applied for the evaluation of post-occlusive reactive hyperaemia. The MBF (baseline = 100%) was [mean (SD)] 150 (31)% (P = 0.003) by PPG (880 nm) and 182 (66)% (P = 0.012) by LDF. After 1 min of maximal isometric contraction, MBF increased to 150 (51)% (P = 0.003) by PPG (880 nm) and to 169 (43)% (P = 0.005) by LDF. After 1 min of maximal concentric contractions, MBF increased to 158 (59)% (P = 0.003) by PPG (880 nm) and to 170 (99)% (P = 0.008) by LDF. Skin blood flow, PPG (560 nm), did not change significantly after isometric or concentric contractions. The results indicate that reactive hyperaemia after exercise and arterial occlusion can be assessed in the human anterior tibial muscle using PPG.


Oxygen adsorption on β-quartz model surfaces: some insights from density functional theory calculations and semiclassical time-dependent dynamics.
The O/β-quartz interaction is described by combining our time-dependent semiclassical approach to atom-molecule/surface scattering with first-principles electronic structure calculations at the DFT (PBE0) level of accuracy. In particular, the O, O(2) interaction potentials with an on-top Si atom and its nearest O atom both localized over three different silica clusters have been calculated as a function of the oxygen-silica approaching distance. The calculated DFT potential energy surface has been used in semiclassical trajectory calculations to investigate the sticking and inelastic reflection of oxygen atoms from a model β-quartz surface. The collisional mechanism, including the role played by the phonon dynamics, is brought to light and accurate sticking probabilities are calculated at five impact energies in the range [0.05-0.8] eV and T(S) = 1000 K. The different catalytic response of β-quartz and β-cristobobalite to the atomic oxygen flux is also discussed and highlighted.


Palladium-catalyzed cross-coupling of benzyl thioacetates and aryl halides.
A method for preparing benzyl aryl thioethers utilizing an in situ deprotection of benzyl thioacetates as an alternative to free thiols as starting materials has been developed and optimized. Good to excellent yields of diverse benzyl aryl thioethers are obtained with air-stable, odor-free, and easy to prepare thioesters. A one-pot protocol for forming benzyl aryl thioethers from a benzyl halide, potassium thioacetate, and an aryl bromide has also been demonstrated.


Effects of retraction of anterior teeth and initial soft tissue variables on lip changes in Japanese adults.
The aim of this study was to examine the effects of retraction of anterior teeth and the initial soft tissue profile variables on upper and lower lip changes in Japanese adults. Pre- and post-treatment cephalometric radiographs of 33 Japanese female adults (aged 23.0±5.0 years), with a Class II division 1 malocclusion, who had two or four first premolars extracted, were evaluated. Lateral cephalograms taken with the lips in a voluntary relaxed position were traced and compared. Nine linear and eight angular measurements were constructed for the hard tissue measurements and 16 linear and 2 angular for the soft tissue measurements. Stepwise multiple regression analysis revealed that the horizontal upper lip position could be explained by the position of the maxillary incisor cervical point and the occlusal plane to SN with a 54 percent contribution ratio, and horizontal lower lip position, maxillary incisor tip position, initial interlabial gap, and aesthetic line to the tip of lower lip with a 51 percent contribution ratio. All parameters employed explained the horizontal position of the upper and lower lip with higher than 96 percent confidence. While the horizontal positions could not be predicted by a limited number of parameters, the vertical positions of lips could be explained by three parameters with higher than 62 percent confidence. The predictability found in this study could be beneficial for orthodontists in treatment planning.


FdC1 and Leaf-Type Ferredoxins Channel Electrons From Photosystem I to Different Downstream Electron Acceptors.
Plant-type ferredoxins in Arabidopsis transfer electrons from the photosystem I to multiple redox-driven enzymes involved in the assimilation of carbon, nitrogen, and sulfur. Leaf-type ferredoxins also modulate the switch between the linear and cyclic electron routes of the photosystems. Recently, two novel ferredoxin homologs with extra C-termini were identified in the Arabidopsis genome (AtFdC1, AT4G14890; AtFdC2, AT1G32550). FdC1 was considered as an alternative electron acceptor of PSI under extreme ferredoxin-deficient conditions. Here, we showed that FdC1 could interact with some, but not all, electron acceptors of leaf-type Fds, including the ferredoxin-thioredoxin reductase (FTR), sulfite reductase (SiR), and nitrite reductase (NiR). Photoreduction assay on cytochrome c and enzyme assays confirmed its capability to receive electrons from PSI and donate electrons to the Fd-dependent SiR and NiR but not to the ferredoxin-NADP+ oxidoreductase (FNR). Hence, FdC1 and leaf-type Fds may play differential roles by channeling electrons from photosystem I to different downstream electron acceptors in photosynthetic tissues. In addition, the median redox potential of FdC1 may allow it to receive electrons from FNR in non-photosynthetic plastids.


Emphysematous Osteomyelitis of the Pubis Associated With Necrotizing Soft Tissue Infection of the Thigh.
Emphysematous osteomyelitis (EO) is a rare condition identified through the presence of intraosseous gas. It is frequently fatal even with prompt recognition and management. We report a case of EO presenting with a necrotizing soft tissue infection of the thigh in the setting of prior pelvic radiation. The purpose of this study was to highlight the unusual association between EO and necrotizing soft tissue infection.


Alcohol, patient compliance and blood pressure control in hypertensive patients.
The association of self-reported use of alcohol with blood pressure and compliance with antihypertensive medication was studied in a randomly selected population sample in eastern Finland. We found a positive correlation between reported use of alcohol and diastolic blood pressure level and a negative correlation with the reduction of diastolic blood pressure during a five-year treatment. These correlations were independent of age, gender, and blood pressure level 5 years earlier. The use of alcohol was associated, especially in men, with poor compliance with antihypertensive medication. In addition to a possible direct contribution to high blood pressure, alcohol intake resulted in an inadequate control of blood pressure in male hypertensive patients by lowering patient compliance.


Area-Specific Synapse Structure in Branched Posterior Nucleus Axons Reveals a New Level of Complexity in Thalamocortical Networks.
Thalamocortical posterior nucleus (Po) axons innervating the vibrissal somatosensory (S1) and motor (MC) cortices are key links in the brain neuronal network that allows rodents to explore the environment whisking with their motile snout vibrissae. Here, using fine-scale high-end 3D electron microscopy, we demonstrate in adult male C57BL/6 wild-type mice marked differences between MC versus S1 Po synapses in (1) bouton and active zone size, (2) neurotransmitter vesicle pool size, (3) distribution of mitochondria around synapses, and (4) proportion of synapses established on dendritic spines and dendritic shafts. These differences are as large, or even more pronounced, than those between Po and ventro-posterior thalamic nucleus synapses in S1. Moreover, using single-axon transfection labeling, we demonstrate that the above differences actually occur on the MC versus the S1 branches of individual Po cell axons that innervate both areas. Along with recently-discovered divergences in efficacy and plasticity, the synaptic structure differences reported here thus reveal a new subcellular level of complexity. This is a finding that upends current models of thalamocortical circuitry, and that might as well illuminate the functional logic of other branched projection axon systems.SIGNIFICANCE STATEMENT Many long-distance brain connections depend on neurons whose branched axons target separate regions. Using 3D electron microscopy and single-cell transfection, we investigated the mouse Posterior thalamic nucleus (Po) cell axons that simultaneously innervate motor and sensory areas of the cerebral cortex involved in whisker movement control. We demonstrate significant differences in the size of the boutons made in each area by individual Po axons, as well as in functionally-relevant parameters in the composition of their synapses. In addition, we found similarly large differences between the synapses of Po versus ventral posteromedial thalamic nucleus axons in the whisker sensory cortex. Area-specific synapse structure in individual axons implies a new, unsuspected level of complexity in long-distance brain connections.


A phosphodiesterase 2A isoform localized to mitochondria regulates respiration.
Mitochondria are central organelles in cellular energy metabolism, apoptosis, and aging processes. A signaling network regulating these functions was recently shown to include soluble adenylyl cyclase as a local source of the second messenger cAMP in the mitochondrial matrix. However, a mitochondrial cAMP-degrading phosphodiesterase (PDE) necessary for switching off this cAMP signal has not yet been identified. Here, we describe the identification and characterization of a PDE2A isoform in mitochondria from rodent liver and brain. We find that mitochondrial PDE2A is located in the matrix and that the unique N terminus of PDE2A isoform 2 specifically leads to mitochondrial localization of this isoform. Functional assays show that mitochondrial PDE2A forms a local signaling system with soluble adenylyl cyclase in the matrix, which regulates the activity of the respiratory chain. Our findings complete a cAMP signaling cascade in mitochondria and have implications for understanding the regulation of mitochondrial processes and for their pharmacological modulation.


Location is everything: lipid rafts and immune cell signaling.
The cells of both the adaptive and innate immune systems express a dizzying array of receptors that transduce and integrate an enormous amount of information about the environment that allows the cells to mount effective immune responses. Over the past several years, significant advances have been made in elucidating the molecular details of signal cascades initiated by the engagement of immune cell receptors by their ligands. Recent evidence indicates that immune receptors and components of their signaling cascades are spatially organized and that this spatial organization plays a central role in the initiation and regulation of signaling. A key organizing element for signaling receptors appears to be cholesterol- and sphingolipid-rich plasma membrane microdomains termed lipid rafts. Research into the molecular basis of the spatial segregation and organization of signaling receptors provided by rafts is adding fundamentally to our understanding of the initiation and prolongation of signals in the immune system.


Limited-stage small cell lung cancer: current chemoradiotherapy treatment paradigms.
In the U.S., the prevalence of small cell lung cancer (SCLC) is declining, probably reflecting the decreasing prevalence of tobacco use. However, a significant number of patients will receive a diagnosis of SCLC, and approximately 40% of patients with SCLC will have limited-stage (LS) disease, which is potentially curable with the combination of chemotherapy and radiation therapy. The standard therapy for LS-SCLC is concurrent chemoradiotherapy, and the 5-year survival rate observed in clinical trials is approximately 25%. The standard chemotherapy remains cisplatin and etoposide, but carboplatin is frequently used in patients who cannot tolerate or have a contraindication to cisplatin. Substantial improvements in survival have been made through improvements in radiation therapy. Concurrent chemoradiotherapy is the preferred therapy for patients who are appropriate candidates. The optimal timing of concurrent chemoradiotherapy is during the first or second cycle, based on data from meta-analyses. The optimal radiation schedule and dose remain topics of debate, but 1.5 Gy twice daily to a total of 45 Gy and 1.8-2.0 Gy daily to a total dose of 60-70 Gy are commonly used treatments. For patients who obtain a near complete or complete response, prophylactic cranial radiation reduces the incidence of brain metastases and improves overall survival. The ongoing Radiation Therapy Oncology Group and Cancer and Leukemia Group B and the European and Canadian phase III trials will investigate different radiation treatment paradigms for patients with LS-SCLC, and completion of these trials is critical.


Buprenorphine Exposures Among Children and Adolescents Reported to US Poison Control Centers.
To investigate buprenorphine exposures among children and adolescents ≤19 years old in the United States. Data were analyzed from calls to US poison control centers for 2007-2016 from the National Poison Data System. From 2007 to 2016, there were 11 275 children and adolescents ≤19 years old exposed to buprenorphine reported to US poison control centers. Most exposures were among children <6 years old (86.1%), unintentional (89.2%), and to a single substance (97.3%). For single-substance exposures, children <6 years old had greater odds of hospital admission and of serious medical outcome than adolescents 13 to 19 years old. Adolescents accounted for 11.1% of exposures; 77.1% were intentional (including 12.0% suspected suicide), and 27.7% involved multiple substances. Among adolescents, the odds of hospital admission and a serious medical outcome were higher for multiple-substance exposures than single-substance exposures. Buprenorphine is important for the treatment of opioid use disorder, but pediatric exposure can result in serious adverse outcomes. Manufacturers should use unit-dose packaging for all buprenorphine products to help prevent unintentional exposure among young children. Health providers should inform caregivers of young children about the dangers of buprenorphine exposure and provide instructions on proper medication storage and disposal. Adolescents should receive information regarding the risks of substance abuse and misuse. Suspected suicide accounted for 12% of adolescent exposures, highlighting the need for access to mental health services for this age group.


Effects of conjugation length, electron donor and acceptor strengths on two-photon absorption cross sections of asymmetric zinc-porphyrin derivatives.
Exceptionally large two-photon absorption cross sections at the infrared region have been revealed by time-dependent density functional theory calculations for asymmetric charge-transfer conjugated zinc-porphyrin derivatives. The largest two-photon cross section is found to be more than one order of magnitude larger than for the conventional two-photon active organic molecules. The calculations show that the formation of strong charge-transfer states depends on the length of the conjugation bridge between the zinc-porphyrin core and the electron donor/acceptor. The two-photon absorption cross section can be greatly enhanced by increasing the strengths of the electron donor/acceptor.


Conventional wastewater treatment and reuse site practices modify bacterial community structure but do not eliminate some opportunistic pathogens in reclaimed water.
Water recycling continues to expand across the United States, from areas that have access to advanced, potable-level treated reclaimed water, to those having access only to reclaimed water treated at conventional municipal wastewater treatment plants. This expansion makes it important to further characterize the microbial quality of these conventionally-treated water sources. Therefore, we used 16S rRNA gene sequencing to characterize total bacterial communities present in differentially-treated wastewater and reclaimed water (n = 67 samples) from four U.S. wastewater treatment plants and one associated spray irrigation site conducting on-site ultraviolet treatment and open-air storage. The number of observed operational taxonomic units was significantly lower (p < 0.01) in effluent, compared to influent, after conventional treatment. Effluent community structure was influenced more by treatment method than by influent community structure. The abundance of Legionella spp. increased as treatment progressed in one treatment plant that performed chlorination and in another that seasonally chlorinated. Overall, the alpha-diversity of bacterial communities in reclaimed water decreased (p < 0.01) during wastewater treatment and spray irrigation site ultraviolet treatment (p < 0.01), but increased (p < 0.01) after open-air storage at the spray irrigation site. The abundance of Legionella spp. was higher at the sprinkler system pumphouse at the spray irrigation site than in the influent from the treatment plant supplying the site. Legionella pneumophila was detected in conventionally treated effluent samples and in samples collected after ultraviolet treatment at the spray irrigation site, while Legionella feeleii persisted throughout on-site treatment at the spray irrigation site, and, along with Mycobacterium gordonae, was also detected at the sprinkler system pumphouse at the spray irrigation site. These data could inform the development of future treatment technologies and reuse guidelines that address a broader assemblage of the bacterial community of reclaimed water, resulting in reuse practices that may be more protective of public health.


Immunologic aspects of atopic dermatitis.
Atopic dermatitis/eczema is a chronically relapsing, pruritic, and inflammatory skin disease. The term "atopic eczema/dermatitis syndrome" covers the "extrinsic" and "intrinsic" atopic dermatitis. The pathogenesis of atopic dermatitis includes complex interaction between the genetic background, skin barrier defects, abnormalities in innate and adaptive immunity, abnormalities of humoral and cellular immunity, and environmental influences. Understanding the immunopathogenesis of atopic dermatitis leads to new diagnostic and therapeutic approaches. The targets in atopic dermatitis are innate immunity including improvement of skin barrier defects by supplementing lipids or inhibiting proteases, and regulating antimicrobial peptides, adaptive immunity, and induction of regulatory T cells.


Cardiac cGMP Signaling in Health and Disease: Location, Location, Location.
3',5'-Cyclic guanosine monophosphate (cGMP) is a ubiquitous second messenger, which critically regulates cardiac pump function and protects from the development of cardiac hypertrophy by acting in various subcellular microdomains. Although clinical studies testing the potential of cGMP elevating drugs in patients suffering from cardiac disease showed promising results, deeper insight into the local actions of these drugs at the subcellular level are indispensable to inspire novel therapeutic strategies. Detailed information on the spatio-temporal dynamics of cGMP production and degradation can be provided by the use of fluorescent biosensors that are capable of monitoring this second messenger at different locations inside the cell with high temporal and spatial resolution. In this review, we will summarize how these emerging new tools have improved our understanding of cardiac cGMP signaling in health and disease, and attempt to anticipate future challenges in the field.


Removal of copper ions from aqueous solution using low temperature biochar derived from the pyrolysis of municipal solid waste.
Sustainable methods to produce filter materials are needed to remove a variety of pollutants found in water including organic compounds, heavy metals, and other harmful inorganic and biological contaminants. This study focuses on the removal of Cu(II) from copper aqueous solutions using non-activated char derived from the pyrolysis of mixed municipal discarded materials (MMDM) using a new heat pipe-based pyrolysis reactor. Adsorption experiments were conducted by adding the char to copper solutions of varying concentration (50-250 mg/L) at a constant temperature of 30 °C. The effect of pH on copper adsorption onto the char was also investigated in the range of pH 3 to 6. Copper removal using the char was found to be heavily dependent on pH, adsorption was observed to decrease below a pH of 4.5. However, the initial copper concentration had a little effect on the sorption of copper at high concentration solutions (above 100 mg/L). Overall, the biochar showed an effective copper adsorption capacity (4-5 mg/g) when using copper solutions with a concentration below100 mg/L and pH >4.5. Copper removal using the char tended to follow the pseudo second order kinetic model. Langmuir isothermal model was shown to be the closest fitting isotherm using the linearized Langmuir equation. However, the variety of feedstock used to produce the char led to a variation in results compared to other studies of more specific feedstocks.


Vapour phase: a potential future use for essential oils as antimicrobials?
Essential oil (EO) vapours have been known for their antimicrobial properties since the 4th century B.C.; however, it was not until the early 1960s that research into the potential of these volatile oils was explored. More recently, the use of EOs such as tea tree, bergamot, lavender and eucalyptus in vapour form has been shown to have antimicrobial effects against both bacteria and fungi, with range of methods being developed for dispersal and efficacy testing. To date, many applications for EO vapours as antimicrobials have been identified including in the food and clinical arenas.


Complement C5a receptors C5L2 and C5aR in renal fibrosis.
Complement factor C5a has two known receptors, C5aR, which mediates proinflammatory effects, and C5L2, a potential C5a decoy receptor. We previously identified C5a/C5aR signaling as a potent profibrotic pathway in the kidney. Here we tested for the first time the role of C5L2 in renal fibrosis. In unilateral ureteral obstruction (UUO)-induced kidney fibrosis, the expression of C5aR and C5L2 increased similarly and gradually as fibrosis progressed and was particularly prominent in injured dilated tubules. Genetic deficiency of either C5aR or C5L2 significantly reduced UUO-induced tubular injury. Expression of key proinflammatory mediators, however, significantly increased in C5L2- compared with C5aR-deficient mice, but this had no effect on the number of renal infiltrating macrophages or T cells. Moreover, in C5L2-/- mice, the cytokine and matrix metalloproteinase-inhibitor tissue inhibitor of matrix metalloproteinase-1 was specifically enhanced. Consequently, in C5L2-/- mice the degree of renal fibrosis was similar to wild type (WT), albeit with reduced mRNA expression of some fibrosis-related genes. In contrast, C5aR-/- mice had significantly reduced renal fibrosis compared with WT and C5L2-/- mice in UUO. In vitro experiments with primary tubular cells demonstrated that deficiency for either C5aR or C5L2 led to a significantly reduced expression of tubular injury and fibrosis markers. Vice versa, stimulation of WT tubular cells with C5a significantly induced the expression of these markers, whereas the absence of either receptor abolished this induction. In conclusion, in experimental renal fibrosis C5L2 and C5aR both contribute to tubular injury, and, while C5aR acts profibrotic, C5L2 does not play a role in extracellular matrix accumulation, arguing against C5L2 functioning simply as a decoy receptor.


Relapse of HCV Genotype 1b Infection After Sofosbuvir/Ledipasvir Treatment Presenting as De Novo Cryoglobulinemic Vasculitis.
Relapse of hepatitis C virus (HCV) genotype 1 infection after combination therapy with sofosbuvir and ledipasvir is unusual. We report a treatment-naïve, non-cirrhotic patient in whom the relapse of genotype 1b HCV infection was accompanied by de novo cryoglobulinemic vasculitis and glomerulonephritis, requiring hemodialysis for acute renal failure. Sequence analysis revealed several resistance-associated variants in the HCV NS5a gene but not in NS3/4A. The patient's vasculitis was successfully treated with immunosuppression and plasmapheresis, followed by retreatment of HCV with a combination of sofosbuvir, simeprevir, and ribavirin. The patient achieved sustained virological response, recovered his renal function, and remains in remission from cryoglobulinemia.


Nucleosomal dsDNA Stimulates APOL1 Expression in Human Cultured Podocytes by Activating the cGAS/IFI16-STING Signaling Pathway.
APOL1 alleles G1 and G2 are associated with faster progression to lupus nephritis (LN)-associated end-stage renal disease (LN-ESRD) in African Americans. Increased levels of type I interferons (IFNs) and nucleosome-associated double-stranded DNA (dsDNA) fragments (nsDNA) are the hallmark of this disease. Here, we identify cyclic GMP-AMP synthase (cGAS) and interferon-inducible protein 16 (IFI16) as the major DNA sensors in human immortalized podocytes. We also show that nsDNA triggers the expression of APOL1 and IFNβ via IRF3 activation through the cGAS/IFI16-STING pathway. We demonstrate that maximal APOL1 expression also requires the activation of type I IFN receptor (IFNAR) and STAT1 signaling triggered by IFNβ produced in response to nsDNA, or by exogenous IFNβ. Finally, we show that STAT1 activation is sufficient to upregulate IFI16, subsequently boosting APOL1 expression through a positive feedback mechanism. Collectively, we find that nsDNA-induced APOL1 expression is mediated by both IFNβ-independent and dependent signaling pathways triggered by activation of the cGAS/IFI16-STING pathway. We propose that simultaneous inhibition of STING and the IFNAR-STAT1 pathway may attenuate IFI16 expression, reduce IFI16-cGAS cross-talk, and prevent excessive APOL1 expression in human podocytes in response to nsDNA.


Risk Factors for Acute Ischemic Stroke Caused by Anterior Large Vessel Occlusion.
Background and Purpose- Accurate prediction of acute ischemic stroke (AIS) caused by anterior large vessel occlusion (LVO) that is amendable to mechanical thrombectomy remains a challenge. We developed and validated a prediction model for anterior circulation LVO stroke using past medical history elements present on admission and neurological examination. Methods- We retrospectively reviewed AIS patients admitted between 2009 and 2017 to 3 hospitals within a large healthcare system in the United States. Patients with occlusions of the internal carotid artery or M1 or M2 segments of the middle cerebral artery were randomly split into 2/3 derivation and 1/3 validation cohorts for development of an anterior circulation LVO prediction model and score that was further curtailed for potential use in the prehospital setting. Results- A total of 1654 AIS were reviewed, including 248 (15%) with proximal anterior circulation LVO AIS. In the derivation cohort, National Institutes of Health Stroke Scale score at the time of cerebrovascular imaging, current smoking status, type 2 diabetes mellitus, extracranial carotid, and intracranial atherosclerotic stenosis was significantly associated with anterior circulation LVO stroke. The prehospital score was curtailed to National Institutes of Health Stroke Scale score, current smoking status, and type 2 diabetes mellitus. The areas under the curve for the prediction model, prehospital score, and National Institutes of Health Stroke Scale score alone were 0.796, 0.757, and 0.725 for the derivation cohort and 0.770, 0.689, and 0.665 for the validation cohort, respectively. The Youden index J was 0.46 for a score of >6 with 84.7% sensitivity and 62.0% specificity for the prediction model. Conclusions- Previously reported LVO stroke prediction scores focus solely on elements of the neurological examination. In addition to stroke severity, smoking, diabetes mellitus, extracranial carotid, and intracranial atherosclerotic stenosis were associated with anterior circulation LVO AIS. Although atherosclerotic stenosis may not be known until imaging is obtained, smoking and diabetes mellitus history can be readily obtained in the field and represent important elements of the prehospital score supplementing National Institutes of Health Stroke Scale score.


[Reduction of adverse outcome due to COVID-19 infection in a high-risk population: evaluation of an informative intervention through active call by General Practitioners].
currently, individuals at risk of adverse outcomes for COVID-19 can access to vaccination and pharmacological interventions. But, during the first epidemic wave, there were no treatments or therapeutic strategies available to reduce adverse outcomes in patients at risk. to assess the impact of an intervention at 15-month follow-up developed by the Agency for Health Protection of the Metropolitan Area of Milan (ATS Milan) based on telephone triage and consultation by the General Practitioners (GPs) for patient with high-risk for adverse outcomes. intervention on population. a total of 127,292 patients in the ATS aged ≥70 years and with comorbidities associated with an increased risk of dying from COVID-19 infection were identified. Using a specific information system, patients were assigned to their GPs for telephone triage and consultation. GPs inform them about the risks of the disease, non-pharmacological prevention measures, and precautions in contacts with family members and other persons. No specific clinical intervention was carried out, only an information/training intervention was performed. by the end of May 2020, 48.613 patients had been contacted and 78.679 had not been contacted. Hazard Ratios (HRs) of infection hospitalisation and death at 3 and 15 months were estimated using Cox regression models adjusted by confounder. no differences in gender, age class distribution, prevalence of specific diseases, and Charlson Index were found between the two groups (treated such as called patients and not called). Called patients had a higher propensity for influenza and antipneumococcal vaccination and have more comorbidities and greater access to pharmacological therapies. Non-called patients have a greater risk for COVID-19 infection: HR was 3.88 (95%CI 3.48-4.33) at 3 months and 1.28 (95%CI 1.23-1.33) at 15 months; for COVID-19 hospitalization HR was 2.66 (95%CI 2.39-2,95) at 3 months and 1.31 (95%CI 1.25-1.37) at 15 months; for overall mortality HR was 2,52 (95%CI 2.35-2:72) at 3 months and 1.23 (95%CI 1.19-1.27) at 15 months. the results of this study show a reduction in hospitalization and deaths and support, in case of pandemic events, the implementation of new care strategies based on adapted stratification systems in order to protect the population's health. This study presents some limits: it is not randomized; a selection bias is present (called patients were those most in contact with the GPs); the intervention is indication-based (on march 2020, the actual benefit of protection and distancing for high-risk groups was unclear), and the adjustment is not able to fully control for confounding. However, this study points out the importance to develop information systems and improve methods to best protect the health of the population in setting of territorial epidemiology.


UC Pd: a new form of Pd/C for Sonogashira couplings.
Screening of different sources of Pd/C shows reagents of highly variable nanoparticle sizes and oxidation states of the metal. Typically, catalysts with higher surface area are viewed as likely to be the more reactive. In this paper a new form of Pd/C, "UC Pd" is described that is shown to contain larger nanoparticles yet it is the most reactive catalyst of those sold commercially for Sonogashira coupling reactions. UC Pd functions efficiently in the absence of a copper co-catalyst, under very mild and "green" conditions using inexpensive 95% EtOH at 50 degrees C. It is also the only form of Pd/C that can be recycled. In side-by-side reactions with several commercially available forms of Pd/C, none compete successfully with UC Pd under standardized conditions. Physical data obtained from extensive surface analysis using TEM, XRD, XPS, and CO-TPD measurements lead to an explanation behind the unique reactivity of this new recyclable form of Pd/C.


Calcium-ion incorporation into titanium surfaces accompanied by electrochemical apatite-deposition.
The depths of calcium-ion incorporation into a commercially pure titanium and an experimental beta-type titanium alloy were determined using Auger electron spectroscopy. After the electrochemical deposition of apatite, new compositional gradients appeared in the profiles in which the Ca and P concentrations gradually decreased as a function of the depth up to 6-8 nm. The relative concentration of Ca in the outermost layer was higher than that of P. On the other hand, after the soaking in a simulated body fluid, the relative concentration of P was higher than that of Ca in the outermost layer. These results suggested that Ca ions were well incorporated into the outermost oxide layer of titanium accompanied by the electrochemical apatite-deposition on its surface.


Ultrastructural peculiarities of the inner portion of the circular layer of colon. I. Research in the human.
The inner part of the circular layer of the human colon is made up of a special muscle layer, three to eight row thick. Wide areas of connective tissue are found inside this inner circular layer and between it and the outer part of the circular layer. The muscle cells of this innermost layer have several special features: numerous glycogen particles and caveolae, well-developed sarcoplasmic reticulum, and wide contact areas with each other. At the border zone with the tela submucosa, there is a fibrous lamella rich in collagen and elastic fibers, lined by an incomplete layer of circularly orientated fibroblast-like cells. A nerve plexus, rich in varicosities, is located between the two circular layers, and nerve fibers are sparsely located inside the fibrous lamella. Interstitial cells of Cajal were not recognized.


Effect of orally administered beta-glucan on macrophage function in mice.
The effect of orally administered SSG, a beta-1,3-glucan obtained from the culture filtrate of the fungus Sclerotinia sclerotiorum IFO 9395, on the function of peritoneal macrophages in CDF1 mice was examined. Oral administration of SSG (20, 40, 80 or 160 mg/kg, daily for 10 consecutive days) enhanced the acid phosphatase activity of peritoneal macrophages. The greatest enhancing effect was observed at 80 mg/kg of SSG. Relatively long periods of administration (more than 10 consecutive days) were needed to induce significant enhancing effects. Phagocytic activity, candidacidal activity, hydrogen peroxide (H2O2) production and interleukin-1 (IL-1) production of peritoneal macrophages were also enhanced after the administration of SSG by the oral route (80 or 160 mg/kg). However, the durations of the activated state after completion of administration differed depending on the activity. Enhanced activity of lysosomal enzyme (acid phosphatase) was also shown in peritoneal macrophages taken from C3H/HeJ mice, which is a nonresponder strain to bacterial lipopolysaccharide (LPS). These results demonstrate that SSG given by the oral route can activate peritoneal macrophages in mice.


Drug-coated balloon angioplasty, intraoperatively through left anterior descending arteriotomy access, a novel hybrid revascularization strategy: a case report.
Patients undergoing coronary artery bypass graft (CABG) sometimes have critical proximal lesion in left anterior descending (LAD) artery or chronic total occlusion followed by either skip lesions or diffuse disease of late mid-to-distal LAD artery. Such lesions require endarterectomy or atheroma bridging via long venous or arterial patch (patch-plasty), for which clinical outcomes are conflicting in studies due to a more thrombogenic milieu created by patch-plasty as well as incomplete endarterectomy. We present a hybrid approach with drug-coated balloon (DCB) angioplasty of mid-to-distal LAD through LAD arteriotomy followed by left internal mammary artery (LIMA) insertion to LAD. A 35-year-old man who was thrombolyzed for anterior wall myocardial infarction in another city, reported to our hospital four weeks later with persistent angina. Coronary angiography showed severe multivessel coronary artery disease. There was diffuse disease in LAD distal to potential site of LIMA insertion and needed patch-plasty. We carried out a hybrid procedure by performing DCB angioplasty of mid-to-distal LAD through the LAD arteriotomy site during CABG followed by LIMA insertion to the LAD. The patient remained asymptomatic post procedure with a 6-month follow-up computerized tomography scan showing patent LIMA and mid-to-distal LAD. This case shows a novel technique, first in the world, of performing angioplasty during CABG through arteriotomy followed by graft insertion.


Tubal hydatidiform mole treated with salpingotomy: A case report.
Tubal hydatidiform mole is rare and mostly treated with salpingectomy. This manuscript presented a case treated with salpingotomy plus methotrexate that possessed a satisfactory outcome. Our report adds to the experience of using salpingotomy in tubal molar patients.


Improving control over euthanasia of persons with psychiatric illness: Lessons from the first Belgian criminal court case concerning euthanasia.
Belgium is one of very few countries that legally allow euthanasia for suffering caused by psychiatric illness. In the first criminal trial in Belgium of physicians involved in euthanasia, three physicians recently faced the accusation of "murder by poisoning," for allegedly having failed to comply with several requirements of the Belgian Euthanasia Law in granting the euthanasia request a woman suffering from psychiatric illness. Although all three physicians were acquitted, the case generated much debate among policy makers, medical professionals, and the general public. We use this trial as the starting point for a critical analysis of the adequacy of the three-level control system established in the Euthanasia Law, as it is applied in the evaluation of euthanasia requests from persons who suffer unbearably from a psychiatric illness. This analysis is based on information presented during the criminal trial as well as information on the euthanasia that was published in the press. Our analysis highlights substantial problems in the assessment and granting of the euthanasia request. The patient was euthanized without it having been substantiated that her psychiatric illness had no prospect of improvement and that her suffering could not be alleviated. The three-step control system enshrined in the Law and promoted by the Federal Control and Evaluation Commission for Euthanasia appears to have failed at each level. To evaluate requests for euthanasia for mental suffering caused by psychiatric illness, the requirements of the Belgian Euthanasia Law should be complemented by mandating the advice of two psychiatrists, and face-to-face discussions between all physicians involved. In parallel with the process of evaluating the euthanasia request, a treatment track should be guaranteed where reasonable evidence-based treatments and recovery-oriented options are tried.


Unusual localization of a malignant fibrous histiocytoma on the mitral valve.
The present report describes the case of a 55-year-old woman who suffered from cardio-embolic stroke originating from malignant fibrous histiocytoma (MFH) localized on the mitral valve. The patient underwent transthoracic two-/three-dimensional and transoesophageal echocardiography which demonstrated the mass protruding in the outflow tract of the left ventricle. Differential diagnosis had to be made with other masses in the left ventricle, such as thrombi, vegetations, and cardiac tumours. Surgery was performed to remove the tumour and the surgery findings confirmed echocardiographic images. Primary cardiac tumours are a rare entity, and their incidence is approximately 0.0017-0.019%. The majority of them are benign, but in a quarter of cases they are malignant. This case is an example of an MFH which caused embolism to the central nervous system.


H2O2-Activated NIR-II Fluorescent Probe with a Large Stokes Shift for High-Contrast Imaging in Drug-Induced Liver Injury Mice.
Drug-induced liver injury (DILI) is the most common clinical adverse drug reaction, which is closely associated with the oxidative stress caused by overproduced reactive oxygen species. Hepatic H2O2, as an important biomarker of DILI, plays a crucial role in the progression of DILI. However, there remains a challenge to develop H2O2-activatable second near-infrared (NIR-II, 1000-1700 nm) small molecular probes with both a large Stokes shift and a long emission wavelength beyond 950 nm. Herein, we developed an activatable NIR-II fluorescent probe (IR-990) with an acceptor-π-acceptor (A-π-A) skeleton for real-time detection of H2O2 in vivo. In the presence of H2O2, nonfluorescent probe IR-990 was successfully unlocked by generating a donor-π-acceptor (D-π-A) structure and switched on intense NIR-II fluorescence, exhibiting a peak emission wavelength at 990 nm and a large Stokes shift of 200 nm. Moreover, it was able to detect H2O2 with high sensitivity and selectivity in vitro (LOD = 0.59 μM) and monitor the behavior of endogenous H2O2 in the HepG2 cell model of DILI for the first time. Notably, probe IR-990 was successfully applied in real-time imaging of endogenous H2O2 generation in the DILI mouse model, showing a high signal-to-background ratio of 11.3/1. We envision that IR-990 holds great potential as a powerful diagnosis tool for real-time visualization of H2O2 in vivo and revealing the mechanism of DILI in the future.


Unintentional falls mortality in China, 2006-2016.
To examine trends in unintentional falls mortality from 2006 to 2016 in China by location (urban/rural), sex, age group and mechanism. Mortality data were retrieved from the National Disease Surveillance Points system (DSPs) of China, a nationally representative data source. Percent change in mortality between 2006 and 2016 was calculated as "mortality rate ratio - 1" based on a negative binomial regression model. The crude unintentional falls mortality was 9.55 per 100 000 population in 2016. From 2006 to 2016, the age-adjusted unintentional falls mortality increased by 5% (95% confidence interval (CI) = 1%-9%), rising from 7.65 to 8.03 per 100 000 population. Males, rural residents and older age groups consistently had higher falls mortality rates than females, urban residents and younger age groups. Falls on the same level from slipping, tripping and stumbling (W01) was the most common mechanisms of falls mortality, accounting for 29% of total mortality. Unintentional falls continued to be a major cause of death in China from 2006 to 2016. Empirically-supported interventions should be implemented to reduce unintentional falls mortality.


Acceptance and Utilisation of Sulphadoxine-Pyrimethamine and Insecticide-Treated Nets among Pregnant Women in Oyo State, Nigeria.
The study is an investigation of the acceptance and utilisation of Sulphadoxine-Pyrimethamine (Fansidar), the drug of choice for Intermittent Preventive Treatment in pregnancy, and Insecticide-Treated Nets among pregnant women who access different health facilities in Oyo State, Nigeria. Pregnant women (582) attending government primary healthcare antenatal clinics and 50 attending faith clinics purposively selected responded to structured instruments that were analysed using percentages, t-test correlation, and multiple regression. Acceptance and utilisation of RBM tools were higher in government clinics than faith clinics and in rural areas. Pregnant women in government clinics, 60.8% and 66.8%, and faith clinics, 18% and 38.0%, utilised Roll Back Malaria tools, significant at t (630) = 5.81, p ≤ 0.05, and t (630) = 3.99, p ≤ 0.05, respectively. Pregnant women in rural locations who accessed government clinics utilised Roll Back Malaria tools more than those in urban areas, t (580) = -641, p ≤ 0.05. Number of pregnancies, educational qualification of the pregnant women, and marital status significantly and consistently influenced acceptance and utilisation of these tools. To ensure that set targets are met, the utilization of RBM tools among the two categories of pregnant women can be improved by increasing the supply of the tools and ensuring that treatment is free.


Mechanistic Insights into Selective Autophagy Subtypes in Alzheimer's Disease.
Eukaryotic cells possess a plethora of regulatory mechanisms to maintain homeostasis and ensure proper biochemical functionality. Autophagy, a central, conserved self-consuming process of the cell, ensures the timely degradation of damaged cellular components. Several studies have demonstrated the important roles of autophagy activation in mitigating neurodegenerative diseases, especially Alzheimer's disease (AD). However, surprisingly, activation of macroautophagy has not shown clinical efficacy. Hence, alternative strategies are urgently needed for AD therapy. In recent years, selective autophagy has been reported to be involved in AD pathology, and different subtypes have been identified, such as aggrephagy, mitophagy, reticulophagy, lipophagy, pexophagy, nucleophagy, lysophagy and ribophagy. By clarifying the underlying mechanisms governing these various subtypes, we may come to understand how to control autophagy to treat AD. In this review, we summarize the latest findings concerning the role of selective autophagy in the pathogenesis of AD. The evidence overwhelmingly suggests that selective autophagy is an active mechanism in AD pathology, and that regulating selective autophagy would be an effective strategy for controlling this pathogenesis.


Control and evaluation of high-frequency jet ventilation: mechanical lung model.
Ventilation systems that operate at high-frequency and deliver small volumes have the potential to provide adequate alveolar ventilation without excessive pulmonary pressures. One way of producing high-frequency ventilation is by use of jet bursts of an input gas through a cannula controlled by a solenoid valve. This high-frequency jet ventilation has yet to be quantitatively analysed for optimal clinical use. From an analysis of the jet-producing device, we obtained a quantitative relationship which allowed us to predict the gas volume of a jet burst (Vjet) from the driving pressure (Pd), and the jet duration (tI). The device was applied to a mechanical lung model (a tube attached to an elastic bag corresponding to the lung airway and alveolar space). We examined how the control variables of the jet ventilation system changed the bag (alveolar) volume with respect to Vjet, the volume of entrained gas, and the volume of shunted gas. Using a nitrogen washout analysis, we evaluated the operating lung volume, effective dead-space volume (Veds), and effective ventilation rate (Veff). We found that Veds is independent of the individual effects of jet cycle frequency, duty cycle, cannula diameter, and entrainment fraction. While Veds was not affected significantly by the shape of the airway, it did depend on the distance of the jet cannula tip to the ventilated bag (or alveolar region) and on the tidal volume.


Half-life and hypoglycemic effect of intravenous insulin in patients with diabetic ketoacidosis.
Intravenous insulin (0.3 U/kg body weight) was administered at 2-hour intervals to 34 patients with diabetic ketoacidosis (21 women and 13 men; average age 34.4 years). Determination of blood glucose and plasma insulin values after the first two hours of treatment showed a decrease of both glycemia and plasma insulin values after the first two hours of treatment showed a decrease of both glycemia and insulinemia. Insulin half-life was longer (15 min) than it is generally assumed (4--5 min). Discontinuous i.v. administration insulin in doses adapted to the "resistance to insulin" is deprived of risks, easy to apply and as effective as continuous i.v. infusion.


Inverted repeat of a heterologous 3'-untranslated region for high-efficiency, high-throughput gene silencing.
This report describes a method for the easy generation of inverted repeat constructs for the silencing of genes of unknown sequence which is applicable to high-throughput studies. This improved procedure for high-efficiency gene silencing is specific for a target gene, but does not require inverted repeat DNA of the target gene in the construct. The method employs an inverted repeat of the 3'-untranslated region (3'-UTR) of a heterologous gene, and has been demonstrated using the 3'-UTR region of the nopaline synthase (nos) gene from Agrobacterium tumefaciens, which is often used as the 3'-UTR for transgene constructs. In a population of independent tomato primary transformants harboring a stably integrated polygalacturonase (PG) transgene driven by a constitutive promoter and linked to an inverted repeat of the nos 3'-UTR, 51 of 56 primary transformants (91% of the population) showed highly effective post-transcriptional silencing of the PG gene, with PG mRNA abundance in ripe fruit reduced by 98% or more. The method was also effective in Arabidopsis, where two different, relatively uncharacterized plant transcription factors were also targeted effectively. This method has the advantage of ease and rapidity in preparation of the constructs, since a gene of interest can be inserted into a binary vector already containing the promoter and the inverted nos domain in a single-cloning step, and does not require any knowledge of the DNA sequence. The approach is suitable for high-throughput gene silencing studies, where it is necessary to investigate the function of hundreds to thousands of uncharacterized genes.


Metabolomic analysis of human disease and its application to the eye.
Metabolomics, the analysis of the metabolite profile in body fluids or tissues, is being applied to the analysis of a number of different diseases as well as being used in following responses to therapy. While genomics involves the study of gene expression and proteomics the expression of proteins, metabolomics investigates the consequences of the activity of these genes and proteins. There is good reason to think that metabolomics will find particular utility in the investigation of inflammation, given the multi-layered responses to infection and damage that are seen. This may be particularly relevant to eye disease, which may have tissue specific and systemic components. Metabolomic analysis can inform us about ocular or other body fluids and can therefore provide new information on pathways and processes involved in these responses. In this review, we explore the metabolic consequences of disease, in particular ocular conditions, and why the data may be usefully and uniquely assessed using the multiplexed analysis inherent in the metabolomic approach.


Report of a Brazilian multicenter study on nephropathic cystinosis.
The Brazilian Multicenter Nephropathic Study Group, founded in 1999, is currently composed of 16 pediatric nephrology units, which are coordinated by the Pediatric Nephrology Unit of Instituto da Criança--HCFMUSP. This Study Group intends to better know our patients, their special characteristics and facilitates the treatment. To present an update on the demographics of the ongoing study participants with interest on renal function status, response to therapy, and extra-renal complications. Patient recruitment to the study is based on informed consent and has been supported by the Brazilian Society of Nephrology, by the creation of an electronic homepage and by the participation in medical meetings and publications in medical periodicals. Our study protocol involves the initial and follow-up questionnaire, the measurement of intraleukocyte cystine content, initiation and follow-up therapy with cysteamine, and clinical patient follow-up based on a protocol of subsidiary exams. We identified 102 patients (42 females) with nephropathic cystinosis in Brazil since 1999. Forty-six children are followed at the Instituto da Criança/SP, 15 at the Hospital Pequeno Príncipe/PR, 12 at the UNICAMP/SP, 10 at the Unidade de Transplante Renal - HCFMUSP/SP and 3 at the Santa Casa/SP; the remaining patients are followed at the Instituto da Criança and at their respective doctors' offices in different nephrology services in Brazil. Of these patients, 23/102 (22.5%) have normal renal function, 19/102 (18.6%) are in chronic renal failure with conservative treatment, 26/102 are on dialysis (18 on peritoneal dialysis and 8 on hemodialysis), and 34/102 received a renal transplant. The extra-renal involvement diagnosed was: hypothyroidism in 63 patients, diabetes mellitus in 8 patients, muscular involvement in 7 patients, a compromised central nervous system in 5 patients, hepatic complications in 5 patients, and deglutition dysfunction in 2 patients. During this period, 10/102 patients died. Cysteamine has been used by 81/102 patients (20 children started the therapy under 2 years of age). Growth parameters were improved by cysteamine, mainly in the youngest patients. We used recombinant growth hormone in 15 patients with persistent low growth velocity and stature z score under 2.5%. We could also observe a delay in appearance of extra-renal complications in patients receiving cysteamine. Our study demonstrates the importance of a multi-center study for recruitment, diagnosis and management of rare diseases. This study promotes access to the adequate treatment with profound impact on the quality of life.


Evolution of the international workshops on quantitative structure-activity relationships (QSARs) in environmental toxicology.
This presentation will review the evolution of the workshops from a scientific and personal perspective. From their modest beginning in 1983, the workshops have developed into larger international meetings, regularly held every two years. Their initial focus on the aquatic sphere soon expanded to include properties and effects on atmospheric and terrestrial species, including man. Concurrent with this broadening of their scientific scope, the workshops have become an important forum for the early dissemination of all aspects of qualitative and quantitative structure-activity research in ecotoxicology and human health effects. Over the last few decades, the field of quantitative structure/activity relationships (QSARs) has quickly emerged as a major scientific method in understanding the properties and effects of chemicals on the environment and human health. From substances that only affect cell membranes to those that bind strongly to a specific enzyme, QSARs provides insight into the biological effects and chemical and physical properties of substances. QSARs are useful for delineating the quantitative changes in biological effects resulting from minor but systematic variations of the structure of a compound with a specific mode of action. In addition, more holistic approaches are being devised that result in our ability to predict the effects of structurally unrelated compounds with (potentially) different modes of action. Research in QSAR environmental toxicology has led to many improvements in the manufacturing, use, and disposal of chemicals. Furthermore, it has led to national policies and international agreements, from use restrictions or outright bans of compounds, such as polychlorinated biphenyls (PCBs), mirex, and highly chlorinated pesticides (e.g. DDT, dieldrin) for the protection of avian predators, to alternatives for ozone-depleting compounds, to better waste treatment systems, to more powerful and specific acting drugs. Most of the recent advances in drug development could not have been achieved without the use of QSARs in one form or another. The pace of such developments is rapid and QSARs are the keystone to that progress. These workshops have contributed to this progress and will continue to do so in the future.


Fiber Fundamentals: Up-to-Date Answers to Common Questions.
Some of the most common nutrition questions are about fiber: "Am I eating enough?" "How do I get more?" "Don't only older people have to worry about fiber?" "I don't have bowel problems-why do I need more fiber?" "Won't a high-fiber diet make me too full to exercise?" Because research continues to confirm fiber's benefits, here are up-to-date answers and practical ways you can increase the fiber in your diet.


Molecular and biochemical characterization of three WD-repeat-domain-containing inositol polyphosphate 5-phosphatases in Arabidopsis thaliana.
Type II inositol polyphosphate 5-phosphatases (5PTases) in animals and yeast have been known to be important for regulating inositol and phospholipid signaling by hydrolyzing phosphate from both inositol polyphosphates and phosphoinositides. However, the molecular and biochemical properties of type II 5PTases in plants have not yet been studied. In this report, we show that three Arabidopsis genes, At5PTase12, At5PTase13 and At5PTase14, encode proteins with a 5PTase domain and a WD-repeat domain, a novel combination present only in plant 5PTases. We demonstrate that these genes are differentially expressed in Arabidopsis organs and At5PTase13 is induced in response to ABA and wounding treatments. Our biochemical studies reveal that although both At5PTase12 and At5PTase13 exhibit phosphatase activity toward only Ins(1,4,5)P3, At5PTase14 hydrolyzes phosphate from PI(4,5)P2, PI(3,4,5)P3 and Ins(1,4,5)P3 with the highest substrate affinity toward PI(4,5)P2. All three At5PTases require Mg2+ for their phosphatase activities. Our molecular and biochemical characterization of three WD-repeat-domain-containing At5PTases provides a foundation for further elucidation of their cellular functions in Arabidopsis.


Anomalous thermal conduction in one dimension: a quantum calculation.
In this paper, we study the thermal conductivity of an anharmonically coupled chain of atoms. Numerical studies using classical dynamics have shown that the conductivity of a chain with nearest neighbor couplings diverges with chain length L as L(alpha); earlier studies found alpha approximately = 0.4 under a range of conditions, but a recent study on longer chains claims alpha = 1/3. Analytically, this problem has been studied by calculating the relaxation rate gamma(q) of the normal modes of vibration as a function of its wave vector q. Two theoretical studies of classical chains, one using the mode-coupling formulation and the other the Boltzmann equation method, led to gamma(q) proportional to q(5/3), which is consistent with alpha = 0.4. Here we study the problem for a quantum anharmonic chain with quartic anisotropy. We develop a low-temperature expansion for gamma(q) and find that, in the regime Dirac's constant omega(q) << k(B)T, gamma(q) is proportional to q(5/3)T2, where omega(q) is the frequency of the mode. In our analysis, the relaxation arises due to umklapp scattering processes. We further evaluate the thermal conductivity of the chain using the Kubo formula, which enables us to take into account the transport relaxation time through vertex corrections for the current-current correlator. This calculation also yields alpha = 0.4.


The Rap1-Rgl-Ral signaling network regulates neuroblast cortical polarity and spindle orientation.
A crucial first step in asymmetric cell division is to establish an axis of cell polarity along which the mitotic spindle aligns. Drosophila melanogaster neural stem cells, called neuroblasts (NBs), divide asymmetrically through intrinsic polarity cues, which regulate spindle orientation and cortical polarity. In this paper, we show that the Ras-like small guanosine triphosphatase Rap1 signals through the Ral guanine nucleotide exchange factor Rgl and the PDZ protein Canoe (Cno; AF-6/Afadin in vertebrates) to modulate the NB division axis and its apicobasal cortical polarity. Rap1 is slightly enriched at the apical pole of metaphase/anaphase NBs and was found in a complex with atypical protein kinase C and Par6 in vivo. Loss of function and gain of function of Rap1, Rgl, and Ral proteins disrupt the mitotic axis orientation, the localization of Cno and Mushroom body defect, and the localization of cell fate determinants. We propose that the Rap1-Rgl-Ral signaling network is a novel mechanism that cooperates with other intrinsic polarity cues to modulate asymmetric NB division.


Synthesis, Crystal Structures, and Photochemical Properties of a Family of Heterometallic Titanium Oxo Clusters.
The incorporation of heterometallic atoms into the structure of titanium-oxygen nanomaterials is one of the known and effective strategies to develop new high-performance photovoltaic active materials. In this study, we have synthesized three benzoic acid-stabilized heterometallic titanium oxo clusters with the different transition metals Co, Cu, and Cd, formulated as [Ti4Co2(μ2-O)2(μ3-O)2(C6H5COO)12(CH3CN)2]·2CH3CN (1), [Ti5Cu4(μ3-O)6(C6H5COO)16] (2), and [Ti12Cd5(μ2-O)(μ3-O)15(μ4-O)2(C6H5COO)22(C6H5COOH)(CH3CN)]·CH3CN·C6H5COOH (3), and then we characterized their structures. UV-vis spectroscopy analysis revealed an enhanced UV-vis-light absorption of those heterometallic clusters. The density functional theory calculations indicated that charge transfer occurs from the p orbital of O atoms to the d orbital of Ti atoms in the TiO core (O → Ti) as well as from the metal to the core in 1 and 2. We also measured the photocurrent response and photocatalytic H2 evolution, which shows enhancement in the photocurrent intensity and good H2 evolution ability because of the cooperative effect of heterometal doping in titanium oxo clusters.


A rabbit model of tracheal collapse for optimal self-expanding metal stents.
Investigating the characteristics of tracheas can help the understanding of diseases related to the trachea, particularly tracheal collapse (TC) in dogs. This study aimed to compare the mechanical properties of tracheas from New Zealand White (NZW) rabbits and dogs and to introduce a method for inducing a model of TC in the normal trachea. Tracheal samples were obtained from NZW rabbit cadavers (n=5) weighing 3.62-3.92 kg and from dog cadavers (n=5) weighing 2.97-3.28 kg. Three live NZW rabbits weighing 3.5-4.0 kg were used to establish the model. The radial forces of both sample sets were measured using a digital force gauge and statistically compared. Subsequently, TC was surgically induced in three female NZW rabbits by physically weakening their tracheal cartilage under general anesthesia. Their clinical signs were monitored for 3 months, and radiographic examinations were performed monthly for 3 months. The mean radial forces of the two sample sets were comparable (P>0.05). The clinical signs, radiographic examinations, and macroscopic examinations were all comparable to those of dogs with TC. The cadaveric study between the rabbits and dogs demonstrated that the surgically induced rabbit model of TC is an excellent candidate for the experimental study of dogs with TC. This study also provides a reference of tracheal radial force values to enable selection of appropriate mesh types and wire diameters of self-expanding metal stents.


[HRV analysis system based on Windows 95 and its preliminary application].
Objective. To provide a real useful application system for the HRV research. Method. The acquisition, detection and analysis system of HRV signal was set up based on Windows 95. The system analyzes the HRV signal with statistic method in time domain and power spectrum in frequency domain. And the power spectrum array was also introduced into the analysis. HRV signals of some healthy persons and some patients were detected and analyzed. Result. The HRV characteristic is much more obvious in the diabetics patients. Conclusion. The system is useful in HRV signal analysis and cardiovascular research.


Phytotoxic effects of Acacia saligna dry leachates on germination, seedling growth, photosynthetic performance, and gene expression of economically important crops.
The influence of dry leachates of Acasia saligna was tested on the seedling growth, photosynthesis, biochemical attributes, and gene expression of the economically important crops, including wheat (Triticum aestivum L.), radish (Raphanus sativus L.), barley (Hordeum vulgare L.) and arugula (Eruca sativa L.). Different concentrations (5%, 10%, 15%, 20%, and 25%) of stem extract (SE) and leaf extract (LE) of A. saligna were prepared, and seedlings were allowed to grow in Petri plates for 8 days. The results showed that all plant species exhibited reduced germination rate, plant height, and fresh and dry weight due to leachates extracts of A. saligna. Moreover, the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX), exhibited differential regulation due to the extract treatment. The SOD was increased with increasing the concentration of extracts, while CAT and APX activities were decreased with increasing the extract concentrations. In addition, leachate extract treatment decrease chlorophyll content, photosynthesis, PSII activity, and water use efficiency, with evident effects at their higher concentrations. Furthermore, the content of proline, sugars, protein, total phenols, and flavonoids were reduced considerably due to leachates extract treatments. Furthermore, seedlings treated with high concentrations of LE increased the expression of genes. The present results lead to the conclusion that A. saligna contains significant allelochemicals that interfere with the growth and development of the tested crop species and reduced the crops biomass and negatively affected other related parameters. However, further studies are suggested to determine the isolation and purification of the active compounds present in A. saligna extracts.


[Histoculture drug response assay (HDRA) guided induction concurrent chemoradiotherapy for mediastinal node-positive non-small cell lung cancer].
To improve the response to chemotherapy for non-small cell lung cancer (NSCLC), effective drugs should be selected for each patient. In 1994 we introduced histoculture drug response assay (HDRA) for NSCLC patients. For clinical N2 patients, biopsy of mediastinal lymph node is performed both for histological diagnosis and for HDRA. Induction concurrent chemoradiotherapy is then performed using HDRA positive chemotherapy agents. We have treated three patients with this strategy. HDRA could be performed using mediastinal lymph node biopsy specimens. Tumor reduction rates of these patients were 80.4%, 85.3%, and 57.1%. Their histological responses were Ef.3, Ef.2, and Ef.1b, respectively. Complete resection was done in all patients. This strategy appeared to be useful in NSCLC patients with mediastinal lymph node metastasis.


Therapeutic Silencing of miR-214 Inhibits Tumor Progression in Multiple Mouse Models.
We previously demonstrated that miR-214 is upregulated in malignant melanomas and triple-negative breast tumors and promotes metastatic dissemination by affecting a complex pathway including the anti-metastatic miR-148b. Importantly, tumor dissemination could be reduced by blocking miR-214 function or increasing miR-148b expression or by simultaneous interventions. Based on this evidence, with the intent to explore the role of miR-214 as a target for therapy, we evaluated the capability of new chemically modified anti-miR-214, R97/R98, to inhibit miR-214 coordinated metastatic traits. Relevantly, when melanoma or breast cancer cells were transfected with R97/R98, anti-miR-214 reduced miR-214 expression and impaired transendothelial migration were observed. Noteworthy, when the same cells were injected in the tail vein of mice, cell extravasation and metastatic nodule formation in lungs were strongly reduced. Thus, suggesting that R97/R98 anti-miR-214 oligonucleotides were able to inhibit tumor cell escaping through the endothelium. More importantly, when R97/R98 anti-miR-214 compounds were systemically delivered to mice carrying melanomas or breast or neuroendocrine pancreatic cancers, a reduced number of circulating tumor cells and lung or lymph node metastasis formation were detected. Similar results were also obtained when AAV8-miR-214 sponges were used in neuroendocrine pancreatic tumors. Based on this evidence, we propose miR-214 as a promising target for anti-metastatic therapies.


Sperm aneuploidy and DNA fragmentation in unexplained recurrent pregnancy loss: a multicenter case-control study.
Recurrent pregnancy loss (RPL) is defined as the loss of at least three pregnancies in the first trimester. Although the most common cause is embryo aneuploidy, and despite female checkup and couple karyotyping, in about 50% of cases RPL remain unexplained. Male implication has little been investigated and results are discordant. In this context, we conducted a multi-center prospective case-control study to investigate male gamete implication in unexplained RPL. A total of 33 cases and 27 controls were included from three university hospitals. We investigated environmental and family factors with a detailed questionnaire and andrological examination, sperm characteristics, sperm DNA/chromatin status using the sperm chromatin structure assay (SCSA) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and sperm aneuploidy using fluorescence in situ hybridization (FISH). The Mann-Whitney test and the Wilcoxon or Fisher exact tests were used. A non-parametric Spearman correlation was performed in order to analyze the relationship between various sperm parameters and FISH and sperm DNA fragmentation results. We found significant differences between cases and controls in time to conceive, body mass index (BMI), family history of infertility and living environment. In cases, total sperm motility and the percentage of morphologically normal spermatozoa were significantly decreased. No difference was found between cases and controls in sperm DNA fragmentation or chromatin integrity. In cases, spermatozoa with aneuploidy, hyperhaploidy and chromosome 18 disomy were significantly increased. This prospective case-control study is one of the largest to examine environmental factors, sperm characteristics, sperm DNA fragmentation and chromatin, and chromosome anomalies in spermatozoa in relation to unexplained recurrent pregnancy loss. The originality of our study lies in the comprehensive andrological examination and search for risk factors and fertility history. Further studies are needed to confirm the links between unexplained RPL and a male family history of infertility or miscarriages. The increased sperm aneuploidy observed in unexplained RPL supports a male etiology. These data pave the way for further studies to demonstrate the value of preimplantation genetic screening in men with increased sperm aneuploidy whose partners experience unexplained RPL.


Perineal lacerations during spontaneous vaginal delivery.
The aim of the study was to assess the frequency of perineal lacerations during normal spontaneous vaginal delivery and to evaluate potential risk factors. The study is based on an analysis of data from the obstetric database of the University Hospital of Vienna and the Semmelweis Women's Hospital Vienna, from February 1999 through to July 1999. Women with vaginal deliveries, uncomplicated pregnancies, uncomplicated first and second stage of labor, gestational age > 37 weeks and pregnancies with cephalic presentation were included. Of 1009 women, 36.2% had perineal lacerations (18.1% had first-degree, 15.2% second-degree, and 2.9% third-degree perineal tears). Univariate logistic regression models showed that only low parity (p = 0.004), the absence of episiotomy (p = 0.0001), and a large head diameter of the infant (p = 0.005) increased the risk for perineal laceration. After adjustment in multivariate analysis, low parity (p = 0.0001), the absence of episiotomy (p = 0.0001) and a large head diameter (p = 0.0004) remained independent risk factors for perineal laceration. Additionally, advanced age of the mother was associated with an increased risk of perineal laceration (p = 0.03). When analyzing the probability for third-degree perineal tears, a strong association with primiparity (p = 0.01), the use of episiotomy (p = 0.0001), a prolonged second stage of labor (p = 0.0001), a large head diameter of the infant (p = 0.01) and the use of oxytocin (p = 0.008) was found. Primiparous women who are being delivered of a large child are at a greater risk for severe perineal lacerations. In the study population episiotomy did not appear to protect against severe perineal lacerations.


Transient transfection of Cryptosporidium baileyi.
Here we demonstrate the transient transfection of C. baileyi. We describe the transfection of this apicomplexan parasite and the cultivation in ovo. The functionality of heterologous sequences in C. baileyi was demonstrated by the expression and detection of the mCherry protein in ovo. The mCherry protein was expressed in parasitic stages up to the oocyst stage under the control of the heterologous promoter region of the C. parvum actin gene.


HandiStroke: a handheld tool for the emergent evaluation of acute stroke patients.
The management of acute stroke is time-sensitive. Clinical decision making requires data not only from laboratory testing and neuroimaging, but also from a detailed history and neurologic examination. The neurologic examination provides baseline information and assists in differentiating acute stroke from its mimickers. There is a need for tools to facilitate the evaluation and decision making in the acute stroke patient to make the correct diagnosis and, when indicated, to properly administer intravenous thrombolytic therapy. The goals of this project were to create a standardized, handheld software program to aid physicians in their evaluation of patients presenting to the emergency department (ED) with acute ischemic stroke, and to create an educational tool with which residents and other health care professionals can gain a level of proficiency in treating these patients. A comprehensive handheld tool was created that incorporates a National Institutes of Health Stroke Scale (NIHSS) calculator, inclusion criteria, absolute contraindications, and relative warnings for thrombolytic use (i.e., recombinant tissue plasminogen activator), and a weight-based dosing calculator that flows in a logical and clinically relevant format. Additionally, the program includes reference materials and guidelines for clinical management to further assist the clinician. Applications of this program include reformatting for use as a data-gathering tool in future clinical studies investigating the treatment of stroke patients, increasing the use and documentation of the NIHSS within the ED in acute ischemic stroke patients, and improving protocol adherence for rt-PA use.


Risk of second primary cancer among breast cancer patients: A systematic review and meta-analysis.
The aim of this study was to estimate the extra risk of second primary cancer among breast cancer patients. This is a systematic review. A comprehensive search of literature was performed in PubMed, Web of Science, Cochrane library, and Scopus. The search included all published studies up to October 2022. This systematic review included studies published in the English language that reported the risk of second primary non-breast cancer [i.e., standardized incidence ratio (SIR)] among breast cancer patients older than 15 years. After evaluating the methodological quality of the selected studies, SIRs were pooled with consideration of heterogeneity among studies. The estimates were pooled by age and time since the diagnosis of primary breast cancer for both sexes (male and female). Age was categorized based on before 50 years and after 50 years, and time was categorized as duration of less than and more than 10 years, respectively. From 2,484 articles, 30 articles were eligible for inclusion in the systematic review and meta-analysis. The studies varied in terms of population, number of cases, study design, setting, and year of implementation of the research. The estimated SIR for men and women was 1.28 (95% CI: 1.18, 1.38) and 1.27 (95% CI: 1.15, 1.39), respectively. Women diagnosed with breast cancer before menopause [SIR: 1.52 (95% CI: 1.34, 1.71) vs. 1.21 (95% CI: 1.08, 1.34)] as well as women after 10 years since their breast cancer diagnosis [1.33 (95% CI: 1.22, 1.431) vs. 1.24 (95% CI: 1.10, 1.37)] were at a higher risk of developing second primary cancer. Among men, while there were no differences in risk based on age, with the increase of time, the risk of second primary cancer was reduced [SIR: 1.22 (95% CI: 1.12, 1.33) vs. 1.00 (95% CI: 0.79, 1.22)]. There is an extra risk of second primary cancer among breast cancer patients. The extra risk should be considered for further screening and preventive measures among this population. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=336062, identifier (CRD42022336062).


Identification of Rv3230c as the NADPH oxidoreductase of a two-protein DesA3 acyl-CoA desaturase in Mycobacterium tuberculosis H37Rv.
DesA3 is a membrane-bound stearoyl-CoA Delta(9)-desaturase that produces oleic acid, a precursor of mycobacterial membrane phospholipids and triglycerides. The sequence of DesA3 is homologous with those of other membrane desaturases, including the presence of the eight-His motif proposed to bind the diiron center active site. This family of desaturases function as multicomponent complexes and thus require electron transfer proteins for efficient catalytic turnover. Here we present evidence that Rv3230c from Mycobacterium tuberculosis H37Rv is a biologically relevant electron transfer partner for DesA3 from the same pathogen. For these studies, Rv3230c was expressed as a partially soluble protein in Escherichia coli; recombinant DesA3 was expressed in Mycobacterium smegmatis as a catalytically active membrane protein. The addition of E. coli lysates containing Rv3230c to lysates of M. smegmatis expressing DesA3 gave strong conversion of [1-(14)C]-18:0-CoA to [1-(14)C]-cis-Delta(9)-18:1-CoA and of [1-(14)C]-16:0-CoA to [1-(14)C]-cis-Delta(9)-16:1-CoA. Both M. tuberculosis proteins were required for reconstitution of activity, as various combinations of control lysates lacking either Rv3230c or DesA3 gave minimal or no activity. Furthermore, the specificity of interaction between Rv3230c and DesA3 was implied by the inability of other related redox systems to substitute for Rv3230c. The reconstituted activity was dependent upon the presence of NADPH, could be saturated by increasing the amount of Rv3230c added, and was also sensitive to the salt concentration in the buffer. The results are consistent with the formation of a protein-protein complex, possibly with electrostatic character. This work defines a multiprotein, acyl-CoA desaturase complex from M. tuberculosis H37Rv to minimally consist of a soluble Rv3230c reductase and integral membrane DesA3 desaturase. Further implications of this finding relative to the properties of other multiprotein iron-enzyme complexes are discussed.


Comprehensive cross-genome survey and phylogeny of glycoside hydrolase family 16 members reveals the evolutionary origin of EG16 and XTH proteins in plant lineages.
Carbohydrate-active enzymes (CAZymes) are central to the biosynthesis and modification of the plant cell wall. An ancient clade of bifunctional plant endo-glucanases (EG16 members) was recently revealed and proposed to represent a transitional group uniting plant xyloglucan endo-transglycosylase/hydrolase (XTH) gene products and bacterial mixed-linkage endo-glucanases in the phylogeny of glycoside hydrolase family 16 (GH16). To gain broader insights into the distribution and frequency of EG16 and other GH16 members in plants, the PHYTOZOME, PLAZA, NCBI and 1000 PLANTS databases were mined to build a comprehensive census among 1289 species, spanning the broad phylogenetic diversity of multiple algae through recent plant lineages. EG16, newly identified EG16-2 and XTH members appeared first in the green algae. Extant EG16 members represent the early adoption of the β-jellyroll protein scaffold from a bacterial or early-lineage eukaryotic GH16 gene, which is characterized by loop deletion and extension of the N terminus (in EG16-2 members) or C terminus (in XTH members). Maximum-likelihood phylogenetic analysis of EG16 and EG16-2 sequences are directly concordant with contemporary estimates of plant evolution. The lack of expansion of EG16 members into multi-gene families across green plants may point to a core metabolic role under tight control, in contrast to XTH genes that have undergone the extensive duplications typical of cell-wall CAZymes. The present census will underpin future studies to elucidate the physiological role of EG16 members across plant species, and serve as roadmap for delineating the closely related EG16 and XTH gene products in bioinformatic analyses of emerging genomes and transcriptomes.


Theoretical study of the 13C NMR spectroscopy of single-walled carbon nanotubes.
The 13C NMR spectroscopy of armchair and zigzag single-walled carbon nanotubes has been investigated theoretically. Spectra for (4,4), (5,5), (6,6), (6,0), (9,0), and (10,0) nanotubes have been simulated based on ab initio calculations of model systems. The calculations predict a dominant band arising from the carbon atoms in the "tube" with smaller peaks at higher chemical shifts arising from the carbon atoms of the caps. The dominant band lies in the range of 128 and 138 ppm. Its position depends weakly on the length, width, and chirality of the tubes. The calculations demonstrate how structural information may be gleaned from relatively low-resolution nanotube 13C NMR spectra.