Record-breaking marine heatwave in northern Yellow Sea during summer 2018: Characteristics, drivers and ecological impact.
Globally, marine heatwaves (MHWs) are becoming more common, more intense, and longer-lasting. They could have a large ecological and societal impact when compounded by low oxygen concentrations or high acidity. Here, using a high-resolution satellite product and reanalysis datasets, we investigated the characteristics of the MHW at northern Yellow Sea (NYS) during mid-summer 2018 and the driving mechanisms of large-scale atmospheric circulations. Results showed that the MHW in mid-summer 2018 (lasting from 26 July to 18 August 2018) had been the most intense since 1982, reaching an anomaly peak of 5.15 °C. For the 2018 MHW, the onset rate was 0.49 °C/day, indicating that the reaction window was relatively short and hard to take mitigation measures, while the decline rate was 0.19 °C/day, meaning the coping window was long and easy to push an already stressed system. The synergy of the two large-scale dynamic systems, i.e., the northward-shifted western north Pacific subtropical high (WNPSH) and the northeastward-expanded South Asia high (SAH), was likely responsible for establishment and maintenance of the hot-weather conditions. These high-pressure systems could result in stronger descending motion, less cloud cover, more solar radiation, and smaller wind speeds which in combination aggravated the MHW. We further found that the unprecedented MHW was actually also impacted by terrestrial heatwave. From 14 July to 15 August 2018, Northeast China was affected by an exceptionally long and intense atmospheric heat wave (AHW). The AHW had impacted on the MHW through warm advection transportation and may significantly contribute to the record-breaking intensity of the MHW, in addition to the impact of abnormal atmospheric circulations. Finally, we showed that a mass mortality of sea cucumbers in the study region during mid-summer 2018 was highly likely caused by the MHW through severe heat stress.


Cell junctions and membrane specializations in the ventricular zone (germinal matrix) of the developing sheep brain: a CSF-brain barrier.
Cell junctions in the ventricular zone (germinal matrix) of the embryonic and foetal sheep brain were examined with thin-section and freeze-fracture electron microscopy. Neuroependymal cells in the early ventricular zone (days 19-40 of embryonic development, gestation period 147 days) exhibit a novel arrangement of cell junctions that connect adjacent neuroependymal cells at their lateral cell membranes next to the ventricular system. Small but typical gap junctions were also identified from the earliest stages examined. In serial thin sections and using a goniometer with a tilting device, the cell contacts showed a tight junction-like appearance of close and continuous fusion between neighbouring cell membranes. However, they were not arranged in a belt-like fashion close to the ventricular surface, but spiralled from the ventricular pole of the cells along the lateral cell membrane towards the deeper parts of the ventricular zone. Their freeze fracture appearance was different from that of single-stranded tight junctions in that the dimensions of their ridges and grooves were generally greater and the E-face grooves contained many particles. The junctions were especially prominent where more than two cells made contact. At mid-gestation they were less prominent than earlier and at 125 days gestation the neuroependymal layer was replaced by a mature-looking normal ependymal layer in which individual ependymal cells were connected by zonulae adherentes and large gap junctions; orthogonal arrays were also prominent. The close contact between gap junctions and single-stranded junctions found early in gestation suggests that there may be some developmental relation between these two membrane specializations. The transient single-strand junctions presumably form the morphological basis for a recently described CSF-brain barrier in the early foetal sheep brain. They may also have some mechanical function in anchoring neighbouring cells together in the region of the developing brain where cells are continuously dividing and migrating.


Evaluation and control of Durasoft lens rotation.
Fifteen subjects forming three groups of refractive astigmats (astigmation less than 1.00 D., astigmatism greater than or equal to 1.00 D and less than 2.00 D, and astigmatism greater than or equal to 2.00 D) were fitted with spherical DuraSoft lenses. Rotation was assessed from slit-lamp photographs taken after 30 min and after 4 hr of lens wear. The results show that incorporating either a prism or a single truncation alone into a spherical DuraSoft lens suffices as a method of stabilization, stabilization being effectively achieved with this lens in subjects with refractive astigmatism less than 2.00 D.


The perspectives of injection drug users regarding safer injecting education delivered through a supervised injecting facility.
Unsafe injection practices are prevalent among injection drug users (IDU) and have resulted in numerous forms of drug-related harm including HIV/HCV transmission and other bacterial and viral infections. North America's first supervised injection facility (SIF) was established in Vancouver in order to address injection-related harms among IDU. This study sought to examine injection drug users' experiences receiving safer injecting education in the context of a SIF. Semi-structured qualitative interviews were conducted with 50 individuals recruited from a cohort of SIF users known as the Scientific Evaluation of Supervised Injection (SEOSI) cohort. Audio recorded interviews elicited IDU perspectives regarding the provision of safer injecting education within the context of a SIF. Interviews were transcribed verbatim and a thematic analysis was conducted. Participant narratives indicate that significant gaps in knowledge regarding safer injecting practices exist among local IDU, and that these knowledge deficits result in unsafe injecting practices and negative health outcomes. However, IDU perspectives reveal that the SIF allows clients to identify and address these gaps in knowledge through a number of mechanisms that are unique to this facility, including targeted educational messaging that occurs as a part of the drug use cycle and not outside of it, in situ demonstration of safer injecting techniques that takes place the moment a client is experiencing difficulties, and enhanced opportunities to seek help from 'expert' healthcare professionals. Importantly, study participants indicated that the overall environment of the SIF promotes the adoption of safer injecting practices over time, both within and outside of the facility. We conclude that the SIF has been particularly effective in transmitting educational messages targeting unsafe and unhygienic injection practices to a population of active IDU. Consistent with previous work, results of this study indicate that SIFs represent a unique 'micro-environment' that can facilitate the reduction of numerous drug related harms.


Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2 diabetes.
In a short-term study including 31 patients with type 2 diabetes, glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment was associated with a significant reversible decline in GFR. Twenty-three patients re-initiated GLP-1 RA treatment after the primary study, and the aim was to investigate the long-term effect on kidney function. We included 30 patients in a one-year extension study, all initially treated with liraglutide for seven weeks. During follow-up 23 were treated with liraglutide and seven untreated. Primary outcome was change in GFR ((51)Cr-EDTA plasma clearance). Patients were 61.5 (10.0) years and HbA(1c) 60.1 (13.8) mmol/mol. Baseline GFR was 100.6 (24.9) mL/min/1.73 m(2) and was reduced by 11 (95% CI: 6.6-15.7, p < 0.001) mL/min/1.73 m(2), independent of change in 24-h systolic blood pressure (SBP), weight, UAER or HbA(1c) (p≥0.33). Geometric mean (IQR) of UAER was 25.5 (9.9-50.9) mg/d and was reduced by 27 (95% CI: 5-44; p = 0.020)%, and 24-h SBP was reduced by 8.2 (p = 0.048) mmHg. No changes occurred in untreated patients. Long-term treatment with liraglutide was associated with a reduction in measured GFR similar to the effect during short-term treatment, suggesting a metabolic or haemodynamic reversible effect and not structural changes. Moreover, UAER and 24-h SBP were reduced. ClinicalTrials.gov identifier: NCT01499108.


A combined system for asbestos-cement waste degradation by dark fermentation and resulting supernatant valorization in anaerobic digestion.
The use of biological processes for the treatment of asbestos cement waste (ACW) has gained interest in recent years. Nevertheless, this methodology is not yet consolidated because of the incomplete ACW conversion during the biological treatment and the consequent need for further treatments that generally require a high amount of energy and chemicals. In this study, the efficiency of both mesophilic and thermophilic dark fermentation (DF) fed with glucose in fed-batch conditions was assessed for ACW biological treatment. Both thermophilic and mesophilic DF of glucose resulted in a partial conversion of glucose into organic acids that successfully degraded all the asbestos fibers contained in an ACW sample. A hydrogen-rich biogas was produced as well: at the end of the mesophilic DF treatment 0.14 LH2 gglucose-1 were obtained. In addition, the anaerobic digestion (AD) of the DF supernatants led to the production of 0.38 LCH4 gCOD-1.


Identification of Scedosporium boydii catalase A1 gene, a reactive oxygen species detoxification factor highly expressed in response to oxidative stress and phagocytic cells.
Scedosporium boydii is an opportunistic filamentous fungus which may be responsible for a large variety of infections in both immunocompetent and immunocompromised individuals. This fungus belongs to the Scedosporium apiospermum species complex which usually ranks second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). Species of the S. apiospermum complex are able to chronically colonize the CF airways suggesting pathogenic mechanisms allowing persistence and growth of these fungi in the respiratory tract. Few putative virulence factors have been purified and characterized so far in the S. apiospermum complex including a cytosolic Cu,Zn-superoxide dismutase (SOD) and a monofunctional catalase (catalase A1). Upon microbial infection, host phagocytes release reactive oxygen species (ROS), such as hydrogen peroxide, as part of the antimicrobial response. Catalases are known to protect pathogens against ROS by degradation of the hydrogen peroxide. Here, we identified the S. boydii catalase A1 gene (CATA1) and investigated its expression in response to the environmental conditions encountered in the CF airways and to the oxidative stress. Results showed that S. boydii CATA1 gene expression is not affected by hypoxia, hypercapnia or pH changes. In contrast, CATA1 gene was overexpressed in response to a chemically induced oxidative stress with a relative gene expression 37-fold higher in the presence of 250 μM H(2)O(2), 20-fold higher with 250 μM menadione and 5-fold higher with 2 mM paraquat. Moreover, S. boydii CATA1 gene expression progressively increased upon exposure to activated THP-1-derived macrophages, reaching a maximum after 12 h (26 fold). Activated HL60-derived neutrophils and activated human peripheral blood neutrophils more rapidly induced S. boydii CATA1 gene overexpression, a maximum gene expression level being reached at 75 min (17 fold) and 60 min (15 fold), respectively. In contrast expression of the gene encoding the Cu,Zn-SOD (SODC gene) was not affected by H(2)O(2), menadione, paraquat or in co-culture with phagocytic cells. These results suggest that S. boydii CATA1 gene is highly stimulated by the oxidative burst response whereas SODC gene is constitutively expressed.


Gender Differences in Concussion and Postinjury Cognitive Findings in an Older and Younger Pediatric Population.
Studies have documented gender differences associated with concussion. The purpose of this study was to determine if these gender differences are also noted within a pediatric population. This prospective study analyzed 1971 patients who had completed preconcussion and postconcussion neuropsychological testing within the Washington, DC, area. Our results showed that children and adolescents with concussion exhibit gender differences with respect to risk factors, recovery, and symptomatology. Females are more likely to present with a concussion (P < 0.001), experience more discomfort from a concussion (P < 0.001), and seek treatment for postconcussive headaches (P < 0.001). On the other hand, males are more likely to sustain a concussion from a contact sport (P < 0.001) and experience loss of consciousness, confusion, and amnesia with a concussion more frequently than females (P < 0.001). Postconcussive cognitive function also differs by gender. Both males and females exhibit a decline in cognitive testing compared with baseline (P < 0.001); however, visual memory (P = 0.02) is more affected in females than in males. These findings remain unchanged among pediatric patients aged ≥14 years; however, no gender differences were noted in individuals aged ≤13 years. It is important for health care providers, schools, athletic trainers, and coaches to be aware of these gender differences associated with concussion in order to provide adequate surveillance and appropriate monitoring and support during the recovery period.


Surgical survival in the Coronary Artery Surgery Study (CASS) registry.
The overall surgical survival data in the Coronary Artery Surgery Study (CASS) registry have not been published to date, pending the report of the randomized medical-surgical comparison (CASS randomized trial). Non-randomized surgical survival data from the CASS registry are given in this article. The overall medical survival data from the registry were reported previously as a natural history study. There were 8,991 patients in the registry portion of CASS who had primary isolated coronary artery bypass grafting and 8,971 with follow-up of more than 30 days. The 5-year survival for all 8,971 patients was 90%, and the operative mortality was 2.37%. Patients with left main coronary artery disease had an operative mortality of 3.84% and a 5-year survival of 85%, while patients with lesions in other vessels had an operative mortality of 2.12% and a 5-year survival of 91%. Among patients without left main coronary disease, the 5-year survival was 93% in those with single-vessel and 92% in those with double-vessel disease (operative mortality was 1.50% and 1.92%, respectively) and 88% in patients with triple-vessel disease (operative mortality was 2.62%; p = 0.009). When results for patients with left main coronary artery obstruction were compared with those for triple-vessel disease, the 5-year survival figures were 85% and 88%, respectively (p = 0.02) and the operative mortality, 3.84% and 2.62%, respectively (p = 0.03). Patients with normal or nearly normal left ventricular (LV) function (i.e., LV segmental wall motion scores ranging from 5 through 11) had a 5-year survival of 92% and an operative mortality of 1.97%. Patients with moderate impairment (LV score range, 12 through 16) had a 5-year survival of 80% and an operative mortality of 4.21%. In those with poor ventricular function (LV score of 17 or greater), the 5-year survival was 65% and the operative mortality was 6.21%. The difference in survival among the three groups was significant (p less than 0.0001). Of 29 variables used in a stepwise Cox regression analysis, LV wall motion score, congestive heart failure score, age, number of operable vessels, smoking history, LV end-diastolic pressure, and percent of left main coronary artery stenosis were found to have a significant effect on long-term survival (excluding 30-day mortality), and these variables plus surgical priority and height influenced surgical mortality. When height was used in the Cox proportional hazards model, female sex was no longer a significant variable.


Hepatic binding protein: the protective role of its sialic acid residues.
Removal of sialic acid from a specific hepatic binding protein virtually abolishes its capacity to bind certain asialoglycoproteins. The loss of this capacity is the result of competition for the binding sites by galactosyl residues, of hepatic binding protein, that become terminal after desialylation.


Transport of acyclic polyols in Saccharomyces cerevisiae.
Acyclic polyols (erythritol, xylitol, ribitol, D-arabinitol, mannitol, sorbitol and galactitol) are not metabolized by Saccharomyces cerevisiae. They are taken up by a fast non-active process, reaching 40-70% distribution referred to total cell water. The uptake is insensitive to temperature, pH (between 4 and 8), 2,4-dinitrophenol and uranyl ions. Its initial rate rises linearly with concentration from 10(-5)M to 1M. The process resembles simple diffusion through large pores or the trapping of the whole solution on the surface. Protoplasts behave like whole cells in this respect. Only erythritol shows a second type of uptake which is inhibitor-insensitive but temperature-dependent.


New developments in spinal anesthesia.
Spinal anesthesia can be used effectively and efficiently for a variety of cases in both the inpatient and the ambulatory surgery setting. Choice of agent, dose, distribution, use of adjuncts, and occasionally the use of continuous spinal anesthesia can tailor the spinal anesthetic to a specific type and duration of surgery. Although spinal anesthesia is extremely safe, adherence of new guidelines for patients receiving anticoagulant drugs, LMWH in particular, may minimize the risk of neurologic injury from spinal bleeding. At present, intrathecal adjuncts, such as neostigmine and clonidine used with local anesthetics, have shown limited usefulness, whereas lipophilic opioids, such as fentanyl, appear to increase duration and quality of spinal block without increasing the time to recovery. In the future, shorter-acting local anesthetics, possibly in conjunction with continuous catheter technologies, may reduce recovery times after spinal anesthesia without increasing risk. Spinal agents with long-acting analgesic properties that do not produce sensorimotor deficits may go beyond the immediate perioperative period and relieve postoperative pain. Currently there is controversy surrounding the use of spinal lidocaine and the occurrence of TNS, especially in the outpatient setting. The prudent use of small-dose bupivacaine and possibly procaine may reduce this risk, further supporting the use of spinal anesthesia for ambulatory as well as inpatient surgical procedures.


Head and neck endocrine surgery in children: 1997 and 2000.
To characterize children undergoing parathyroid, thyroid, and thyroglossal duct cyst surgery in 1997 and 2000 using a nationally representative discharge database to determine whether rates and outcomes of these surgical treatments vary by age, sex, and health care system attributes. The 1997 and 2000 Kids' Inpatient Database, available through the Agency for Healthcare Research and Quality. All patients 18 years and younger undergoing head and neck endocrine (HNE) procedures were included. The sampling scheme of this database allowed for calculation of national and regional estimates using Stata 7.0. An estimated 2077 and 1871 inpatient pediatric HNE procedures were performed nationally in 1997 and 2000, respectively. Most were performed at general (nonpediatric) teaching hospitals. There were an estimated 1102 thyroglossal duct cyst excisions, making this the most common HNE procedure and diagnosis. Thyroid lobectomy was the second most common HNE surgical treatment. Thyroid malignant neoplasm (usually treated by total thyroidectomy) was the second most common diagnosis. Neck dissections were performed in 32% of patients with thyroid malignant neoplasm. These HNE procedures accounted for more than 28 million dollars in hospital charges in 1997 and nearly 38 million dollars in 2000. Surgical treatment trends for pediatric HNE procedures remained stable between 1997 and 2000. Thyroglossal duct cyst excision and thyroid lobectomy are the most common procedures. There were regional differences in the rates of most HNE surgical treatments. In addition, hospital charges increased between 1997 and 2000.


Cholinergic and electrical synapses between synergistic spinal motoneurones in the Xenopus laevis embryo.
1. To investigate central motoneurone synapses within the spinal cord of a simple vertebrate, the Xenopus embryo, simultaneous intracellular recordings were made from fifty-five pairs of spinal motoneurones. 2. Chemical synapses were found between seventeen out of thirty-five pairs on the same side of the spinal cord. Current-evoked spikes in the presynaptic neurone led to fast depolarizing postsynaptic potentials (PSPs) in the postsynaptic neurone at latencies of 0.5-1.5 ms. The PSPs had an average amplitude of 7 mV, a rise time of 8 ms and a half-fall time of 18 ms. 3. The presynaptic motoneurone was always the more rostral of the pair. No excitatory connections were found which crossed the cord. The fast PSPs were blocked by 10 microM mecamylamine but not by 1 mM kynurenic acid, so were mediated by nicotinic acetylcholine receptors (nAChRs). These are the first unitary excitatory postsynaptic potentials (EPSPs) mediated by nAChRs recorded intracellularly within the vertebrate central nervous system. 4. Bidirectional electrical synapses were found between five pairs of motoneurones. All these pairs were on the same side of the spinal cord and less than 70 microns apart. Each neurone responded in a graded manner to either hyperpolarizing or depolarizing current injected into the other. 5. Since motoneurones are rhythmically active during swimming, both chemical and electrical synapses will add to the fast on-cycle excitation underlying spiking activity in other motoneurones. This may increase the reliability and local synchrony of synergistic motoneurone firing during locomotion.


A treatment planning and acute toxicity comparison of two pelvic nodal volume delineation techniques and delivery comparison of intensity-modulated radiotherapy versus volumetric modulated arc therapy for hypofractionated high-risk prostate cancer radiotherapy.
To perform a comparison of two pelvic lymph node volume delineation strategies used in intensity-modulated radiotherapy (IMRT) for high risk prostate cancer and to determine the role of volumetric modulated arc therapy (VMAT). Eighteen consecutive patients accrued to an ongoing clinical trial were identified according to either the nodal contouring strategy as described based on lymphotropic nanoparticle-enhanced magnetic resonance imaging technology (9 patients) or the current Radiation Therapy Oncology Group (RTOG) consensus guidelines (9 patients). Radiation consisted of 45 Gy to prostate, seminal vesicles, and lymph nodes, with a simultaneous integrated boost to the prostate alone, to a total dose of 67.5 Gy delivered in 25 fractions. Prospective acute genitourinary and gastrointestinal toxicities were compared at baseline, during radiotherapy, and 3 months after radiotherapy. Each patient was retrospectively replanned using the opposite method of nodal contouring, and plans were normalized for dosimetric comparison. VMAT plans were also generated according to the RTOG method for comparison. RTOG plans resulted in a significantly lower rate of genitourinary frequency 3 months after treatment. The dosimetric comparison showed that the RTOG plans resulted in both favorable planning target volume (PTV) coverage and lower organs at risk (OARs) and integral (ID) doses. VMAT required two to three arcs to achieve adequate treatment plans, we did not observe consistent dosimetric benefits to either the PTV or the OARs, and a higher ID was observed. However, treatment times were significantly shorter with VMAT. The RTOG guidelines for pelvic nodal volume delineation results in favorable dosimetry and acceptable acute toxicities for both the target and OARs. We are unable to conclude that VMAT provides a benefit compared with IMRT.


Abnormal Neuronal Response to Rectal and Anal Stimuli in Patients Treated for Distal Rectal Cancer With High-Dose Chemoradiotherapy Followed By Watchful Waiting.
Watchful waiting in patients with rectal cancer with complete clinical response after chemoradiation therapy has gained increased popularity to avoid morbidity and mortality associated with surgery. Irradiation of the pelvis causes bowel dysfunction, but the effect on anorectal sensory function remains obscure in this patient category. The aim of this study was to characterize the sensory pathways of the gut-brain axis in patients with rectal cancer treated solely with chemoradiation therapy (nonconventional regime/dose) compared with healthy volunteers. This is an explorative study. Sensory evaluation by rectal distension was performed and cortical evoked potentials were recorded during rapid balloon distensions of the rectum and anal canal. Latencies and amplitudes of cortical evoked potentials were compared, and the relative amplitude of 5 spectral bands from recorded cortical evoked potentials was used as an additional proxy of neuronal processing. Patients with rectal cancer solely with chemoradiation therapy (n = 13) a median of 3.2 years ago (range, 2.3-5.6 y) and healthy volunteers (n = 13) were included. Cortical evoked potentials were measured. Patients had 35% lower rectal capacity at a maximum tolerable volume (p = 0.007). We found no differences in rectal cortical evoked potential latencies (p = 0.09) and amplitudes (p = 0.38) between groups. However, spectral analysis of rectal cortical evoked potentials showed a decrease in θ (4-8 Hz) and an increase in β (12-32 Hz) band activity in patients (all p < 0.001). Anal cortical potentials showed an increase in α (8-12 Hz) and β and a decrease in γ (32-70 Hz) band activity (all p < 0.001) in patients compared with healthy volunteers. This is an explorative study of limited size. Chemoradiation therapy for distal rectal cancer causes abnormal cortical processing of both anal and rectal sensory input. Such central changes may play a role in symptomatic patients, especially when refractory to local treatments. See Video Abstract at http://links.lww.com/DCR/B270. RESPUESTA NEURONAL ANORMAL A ESTÍMULOS RECTALES Y ANALES, EN PACIENTES TRATADOS POR CÁNCER RECTAL DISTAL, CON QUIMIORRADIOTERAPIA DE DOSIS ALTA, SEGUIDA DE ESPERA VIGILANTE: La espera vigilante en pacientes de cáncer rectal, con respuesta clínica completa después de la quimiorradiación, ha ganado una mayor popularidad en evitar la morbilidad y mortalidad asociadas con la cirugía. La irradiación de la pelvis causa disfunción intestinal, pero el efecto sobre la función sensorial ano-rectal sigue siendo no claro, en esta categoría de pacientes.El objetivo de este estudio, fue caracterizar las vías sensoriales del eje intestino-cerebro en pacientes con cáncer rectal, tratados únicamente con quimiorradiación (régimen / dosis no convencional), en comparación con voluntarios sanos.Es un estudio exploratorio.Se realizó una evaluación sensorial por distensión rectal y se registraron los potenciales evocados corticales, durante las distensiones rápidas con balón en recto y canal anal. Se compararon las latencias y amplitudes de los potenciales evocados corticales, y la amplitud relativa de cinco bandas espectrales registradas, de potenciales evocados corticales, se usaron como proxy adicional del procesamiento neuronal.Pacientes de cáncer rectal, únicamente con terapia de quimiorradiación (n = 13) mediana de 3.2 años (rango 2.3-5.6) y voluntarios sanos (n = 13).Potenciales evocados corticales.Pacientes tuvieron una capacidad rectal menor del 35%, al volumen máximo tolerable (p = 0.007). No encontramos diferencias en las latencias potenciales evocadas corticales rectales (p = 0.09) y amplitudes (p = 0.38) entre los grupos. Sin embargo, el análisis espectral de los potenciales evocados corticales rectales, mostró una disminución en theta (4-8 Hz) aumento en beta (12-32 Hz), y actividad en banda en pacientes (todos p <0.001). Los potenciales evocados corticales anales mostraron un aumento en alfa (8-12 Hz) y beta, disminución en gamma (32-70 Hz), y actividad en banda (todos p <0.001), en pacientes comparados a voluntarios sanos.Este es un estudio exploratorio de tamaño limitado.La quimiorradiación para el cáncer rectal distal, ocasiona procesos corticales sensoriales anormales anales y rectales. Tales cambios centrales pueden desempeñar un papel en pacientes sintomáticos, especialmente cuando son refractarios a tratamientos locales. Consulte Video Resumen en http://links.lww.com/DCR/B270.


Difference in the expression of alpha 7 nicotinic receptors in the placenta in normal versus severe preeclampsia pregnancies.
The prevalence of preeclampsia is low in smokers, suggesting a possible role of nicotinic receptor in the pathophysiology of the disease. Alpha 7 nicotinic acetylcholine receptor (alpha7 nAChR) was recently found in non-neuronal tissue with various mediating functions. Therefore, we investigated the difference in the placental expression of the alpha7 nAChR in normal versus severe preeclampsia placentas. Central portions of placenta were obtained from 9 severe preeclampsia women and 11 gestational-age-matched normal pregnant women delivered between the gestational ages of 33 and 40 weeks following elective or emergency cesarean section. RT-PCR, western blotting, and immunohistochemical staining were performed to evaluate the alpha7 nAChR expression difference. In all the placentas, the alpha7 nAChR was expressed in endothelial cells, vascular smooth muscle cells, and stromal cells, but not in trophoblasts. The vascular staining was more intense in the severe preeclampsia placenta (p=0.02). Although the gene expression did not differ between the two groups, protein expression was greater in 7 of 9 placenta samples from the severe preeclampsia group. Placental expression of alpha7 nAChR differs between normal and severe preeclampsia placentas, suggesting that it may be involved in the pathogenesis of preeclampsia.


Fake gunshot wounds in the skull-post-mortem artifact caused by steel probe during police search for a missing body.
The paper presents a case of a forensic autopsy of a young woman who was murdered and her dismembered body was hidden in soil and water. In the skull of the deceased, in the temporal and occipital regions, the autopsy revealed 3 round, almost identical holes, which looked like small caliber gunshot wounds. Doubts about the cause of these injuries were raised by the fact that despite the decomposition of the body, the continuity of the dura at the site of these holes remained undamaged and the absence of any trace of a bullet's wound track in the brain, the absence of a foreign body in the cranial cavity, as well as the absence of wounds on the opposite side of the skull that could be exit wounds. A thorough analysis of the investigation and the activities carried out during the search for the missing body allowed to adopt and finally confirm the hypothesis that the above mentioned skull damage occurred during the search for the cut-off head of the deceased in shallow water by means of special tapered conical steel probes used by the rescue/search teams. Due to the structure of such a spike, i.e., a sharp end and then a wide cone, only a superficial puncture of the steel probe tip three times into the skull had taken place, which caused regular, rounded bone damage without damaging the dura and brain. The presented case indicates that sometimes post-mortem artifacts may suggest a completely different origin of wounds, which emphasizes the need for a comprehensive analysis of all possible causes of their occurrence, particularly data concerning the handling of the corpse before it is delivered to the morgue, so as not to make a diagnostic error during autopsy.


Removal of fluoride from aqueous solution using protonated chitosan beads.
In the present study, chitosan in its more usable bead form has been chemically modified by simple protonation and employed as a most promising defluoridating medium. Protonated chitosan beads (PCB) showed a maximum defluoridation capacity (DC) of 1664mgF-/kg whereas raw chitosan beads (CB) possess only 52mgF-/kg. Sorption process was found to be independent of pH and altered in the presence of other co-existing anions. The sorbents were characterized using FTIR and SEM with EDAX analysis. The fluoride sorption on PCB follows both Freundlich and Langmuir isotherms. Thermodynamic parameters, viz., DeltaG degrees , DeltaH degrees DeltaS degrees and Ea indicate that the nature of fluoride sorption is spontaneous and endothermic. The sorption process follows pseudo-second-order and intraparticle diffusion kinetic models. 0.1M HCl was identified as the best eluent. The suitability of PCB has been tested with field samples collected from a nearby fluoride-endemic area.


Microsaccadic responses in a bimodal oddball task.
In a visual oddball task the presentation of rare targets induces a prolonged microsaccadic inhibition as compared to standards. Here, we replicated this effect also in the auditory modality. In addition, although auditory standards induced a more limited modulation of microsaccadic frequency as compared to visual standards, auditory oddballs induced a prolonged microsaccadic inhibition. With bimodal standard stimuli the microsaccadic response was determined by the attended modality, resembling that produced by attended unimodal stimuli. The present findings support the idea that the microsaccadic response to oddball and standard stimuli is partly driven by cognitive mechanisms common to both the visual and the auditory modality, and that microsaccades can be used as an implicit behavioral measure of ongoing cognitive processes.


Fgf21 knockout mice generated using CRISPR/Cas9 reveal genetic alterations that may affect hair growth.
To investigate fibroblast growth factor 21 (Fgf21) alterations that may affect hair growth and the underlying molecular mechanisms by constructing Fgf21 global knockout (KO) mice using microinjection-mediated CRISPR/Cas9. Following genomic DNA sequencing, we identified 18 mice carrying Ffg21 mutations among the total 63 offspring mice obtained by injecting 340 embryos, which yielded a mutation rate of 28.6 percent. Of these 18 mice, three had both alleles knocked out and 15 were monoallelic KO mice. Compared with the wild-type (WT) mice, the phenotypic analysis showed that the litter size of Fgf21 KO mice significantly reduced (p < 0.05), but physiological indexes of the birth weight, gender rate, body weight (0-8 week) and body weight of adult male and female were no significant difference (p > 0.05). Compared to WT mice, physiological anatomy indicated that the morphological characters of vital organs in Fgf21 KO mice were normal. Depilation experiments demonstrated that compared to the WT mice, the hair regrowth speed was reduced in the Fgf21 KO mice. The number of hair shafts in these mice considerably decreased, as indicated by the tissue sample analyses. Real-time quantitative PCR showed that Erk and Akt expression in the KO mice was significantly decreased (P < 0.05), whereas western blotting demonstrated that the expression of Erk and Akt proteins and their phosphorylation levels in KO mice decreased at different rates (P < 0.05). Fgf21 was shown to affect hair follicle development and growth cycle, which may be associated with Pi3k/Akt and Mapk/Erk signaling pathways.


Polyacetylenes with xanthine oxidase inhibitory activity from the medicinal and edible fruits of Cyclocodon lancifolius (Roxburgh) Kurz.
Five new polyacetylene derivatives (1-5), cyclocodonlandiynosides A-E, and eight known analogues (6-13) were isolated and identified from the fruits of Cyclocodon lancifolius. Their structures were established via spectroscopic and chemical methods, including NMR, HRESIMS, enzymatic hydrolysis, Mo2(OAc)4-induced circular dichroism and sugar derivatization. Compound 1 contains a nitrogenous fragment, which was rarely found in C14 polyacetylenes. Compounds 3 and 4 are polyacetylene glucosides possessing novel aglycones. All the isolated polyacetylenes (except 12) were screened for their xanthine oxidase (XO) inhibitory activity. All the tested compounds, at the concentration of 62.5 μg/mL, showed XO inhibiting effects. Among them, 13 and 3 showed the most potent XO inhibitory activity with IC50 values of 87.65 and 96.32 μM, compared to the positive control allopurinol with an IC50 value of 19.25 μM.


Assessment of magnetic resonance images of displacement of the disc of the temporomandibular joint in different types of condylar fracture.
To evaluate the displacement of the disc of the temporomandibular joint (TMJ) in different types of condylar fracture we studied 160 patients (222 joints) from May 2009-June 2014. All patients had computed tomographic scans (CT) and magnetic resonance images (MRI) taken preoperatively, and 24 patients (32 joints) had MRI postoperatively. CT scans were reviewed to categorise the types of condylar fracture (intracapsular, condylar neck, and subcondylar), and intracapsular condylar fractures were further classified into subtypes A, B, C, and M. MRI were then reviewed to record the position of the disc in each type of condylar fracture. The results were compared using the chi square test. There were 160 intracapsular condylar fractures, 40 fractures of the condylar neck, and 22 subcondylar fractures. Of the intracapsular condylar fractures, 75 were type A, 49 type B, 11 type C, and 25 type M. Discs were displaced in 153 intracapsular condylar fractures, 17 fractures of the condylar neck, and eight subcondylar fractures. Among the type A intracapsular condylar fractures, discs were displaced in 71/75, type B in 47/49, type C in 10/11, and in all 25 type M. The incidence of displaced discs between intracapsular condylar fractures on the one hand, and those of the condylar neck or subcondylar region on the other, was significant (p<0.001), but there were no differences among the various subtypes of intracapsular condylar fractures. Postoperative MRI showed successful results in 28/32 joints. Intracapsular condylar fractures were more likely to have displaced discs than the other types. But there were no differences among different subtypes of intracapsular condylar fractures.


Synergic effect of eugenol oleate with amphotericin B augments anti-leishmanial immune response in experimental visceral leishmaniasis in vitro and in vivo.
Present treatment regimen on visceral leishmaniasis has multiple limitations including severe side effects, toxicity, and resistance of Leishmania strains. Amphotericin B is a well-established pharmacologically approved drug; however, mainly toxicity is a foremost issue with that drug. Recently, our group identified eugenol oleate as an anti-leishmanial immunomodulatory compound. The important objectives of this present study was to evaluate the possible synergistic effect of eugenol oleate with amphotericin B to reduce the toxicity of this approved drug. Results obtained from this study signified that combination of eugenol oleate and amphotericin B showed indifferent combinatorial effect against promastigotes with xΣFIC 1.015, while, moderate synergistic activity with xΣFIC 0.456 against amastigotes. It was also notable that eugenol oleate (2.5 μM) with low concentrations of amphotericin B (0.3125 μM) showed 96.45% parasite reduction within L. donovani-infected murine macrophages. Furthermore, eugenol oleate and amphotericin B significantly (p < 0.01) enhanced the nitrite generation, and pro-inflammatory cytokines (IL-12, IFN-γ and TNF-α) in infected macrophages in vitro and in BALB/c mice in vivo. Eugenol oleate (10 mg/Kg b. wt.) with amphotericin B (1 mg/Kg b.wt.) significantly (p < 0.01) controlled the parasite burden in liver by 96.2% and in spleen by 93.12%. Hence, this study strongly suggested the synergic potential of eugenol oleate with low concentration of amphotericin B in experimental visceral leishmaniasis through anti-leishmanial immune response.


Maternal deaths attributable to hypertensive disorders in a tertiary hospital in Ghana.
To determine the contribution of hypertensive disorders of pregnancy to maternal deaths at Korle Bu Teaching Hospital (KBTH) in Accra, Ghana. The retrospective descriptive study conducted at KBTH during 2010-2011 involved a comprehensive review of all maternal deaths attributable to hypertensive disorders. There were 21 385 deliveries, 21742 live births, and 199 maternal deaths, resulting in a maternal mortality ratio of 915.3 per 100000 live births. In total, 63 (31.7%) maternal deaths were attributable to hypertensive disorders with a case fatality rate of 3.9%. The incidence of hypertensive disorders of pregnancy was 7.6%. Hypertensive disorders were the most common direct cause of maternal death followed by obstetric hemorrhage (26.6%), unsafe abortion (11.1%), and puerperal sepsis (3.5%). Most (38.1%) hypertension-related maternal deaths occurred within 24hours of admission and the majority (79.4%) had been referred. Eclampsia was the leading immediate cause of hypertension-related death (23.8%), followed by acute renal failure (20.6%), intracerebral hemorrhage (15.9%), and pulmonary edema (12.7%). Hypertensive diseases are the leading cause of maternal death at KBTH, having overtaken obstetric hemorrhage, with eclampsia, acute renal failure, intracerebral hemorrhage, and pulmonary edema representing the major immediate causes of hypertension-related maternal death.


[Modulation of the chronotropic effect of the vagus nerve during stimulation of various sympathetic nerves in the cat].
Sympathetic nerves were shown to perform potentiation or inhibition of synchronizing or tonic components of vagal chronotropic effect. The potentiation of the synchronizing component seems to be exerted through the ansa subclavia whereas the other effects--through the caudal cardiac nerve.


Cost-effectiveness of school-based caries screening using transillumination.
School-based screening for caries lesions usually only employs visual-tactile detection means (standard of care). Near-infrared-light-transillumination (NILT) could be used to support school-based screening and to identify early proximal caries, facilitating referral and appropriate non- or micro-invasive management in dental practice. We assessed the cost-effectiveness of NILT for school-based caries screening. A German mixed-payers' perspective was adopted. A Markov model was used to simulate the consequences of true and false positive and negative detections and the subsequent decisions over the lifetime of initially 12 years old patients. Our health outcome was tooth retention in years. Costs were measured in Euro 2020. Monte-Carlo-microsimulations, univariate and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratio (ICER) and the cost-effectiveness-acceptability at different willingness-to-pay-thresholds were quantified. NILT was minimally more effective (tooth retention for a mean (2.5-97.5%) 56 (53-59) years) and minimally less costly (515 (416-616) Euro) than standard of care (56 (50-59) years; 526 (427-628 Euro)). The ICER was -503 Euro/year, i.e. school-based caries screening using NILT saved money at higher effectiveness in the modelled population. The cost-effectiveness of NILT increased for payers with a willingness-to-pay for additional tooth retention time. The biggest driver of costs were (avoided) tooth replacements later in life. NILT-based screening is likely to yield limited effectiveness gains and cost savings in the modelled populations. In countries where regular practice-based screening of children is less common than in Germany, the cost-effectiveness of NILT for school-based caries screening is likely higher. NILT-based caries screening in German schools is unlikely to be cost-effective. In countries with different utilization patterns or generally higher caries prevalence and risk, this may differ.


Stress in children exposed to violence. Reenactment and rage.
Violence is a major public health problem that increasingly involves children and adolescents as both victims and witnesses. Exposure to violence is now implicated in the development of stress conditions. This article uses Terr's typology to describe responses to various kinds of violence and suggests that the posttraumatic stress model adds a unique dimension to our understanding of the effects of violence on children and adolescents.


Hepatitis B virus-related cryoglobulinemia: Clinical characteristics, virological features, and treatment.
Hepatitis B virus (HBV) infection is a rare etiology of cryoglobulinemia, and its clinical characteristics, virological features and treatment are poorly understood. This retrospective study enrolled 23 patients with HBV-related cryoglobulinemia from 497 cryoglobulinemia patients at Peking Union Medical College Hospital between January 2015 and February 2023. We analyzed the clinical characteristics, virological features and management of patients with HBV-related cryoglobulinemia. The 23 patients (13 males; median age 48 years) were all mixed cryoglobulinemia and serological HBsAg positive, while 15 patients exhibited HBV-DNA replication. The presence of HBsAg in cryoglobulins was evaluated in 7 patients, all of whom were positive. The most commonly involved organs were kidneys (69.6%), skin (65.2%), peripheral nerves (21.7%), joints (8.7%), gastrointestinal tract (4.3%), and cardiac (4.3%). Eight patients received antiviral therapy with nucleot (s)ide analogues (NAs) alone, 12 patients received NA- and corticosteroid-based regimens, and 3 patients received NA- and rituximab-based regimens based on the severity of clinical symptoms. After a median follow-up of 44 months, four patients died, and one patient was lost to follow-up. All remaining patients (n = 18) achieved clinical remission, and HBV-DNA replication was not detected in 16 out of 18 patients. There was no HBV reactivation in patients treated with rituximab. The three-year overall survival and progression-free survival were 87.0% and 80.3%, respectively. HBV-related cryoglobulinemia patients should be treated with antiviral therapy. Corticosteroids and rituximab are effective for severe cases, but patients need to be closely monitored for therapy-related infection.


[Liver surgery: what is feasible?].
Bilobar hepatic metastases, a small residual liver volume, de-novo and recurrent lesions, simultaneous pulmonary metastases and infiltration of vascular structures are often limiting factors in the surgical treatment of primary and secondary liver tumors. Nevertheless surgery is the "gold standard" with the chance of long-term survival, not possible to achieve with locally ablation and chemotherapy. The combination with neoadjuvant chemotherapy and radiofrequency ablation, extended liver resection after selective portal vein embolization, two-stage hepatectomy, resection and reconstruction of vascular structures in deep hypothermia and simultaneous resection of pulmonary metastases, increase the resectability even in patients with poor prognosis achieving 5-year-survival rates between 26-46 % in colorectal liver metastases, 40 % in primary liver tumors and a median survival of 42 months after resection of liver and lung metastases. Interdisciplinary treatment and aggressive surgical resection seem to be justified, when performed safely as a curative option.


Staged Excision Technique to Reduce Scar Length.
Patients and surgeons are often disappointed with the scar length after conventional staged excision of large disfiguring skin lesions. We have developed an alternative approach to facilitate scar length reduction. We aimed to report the efficacy of our staged excision method, which includes a hexagonal-pattern excision, wide undermining, and purse-string suture. Sixty-five patients, each with one lesion, were included in the current study. The lesion length and width were recorded, and the scar area was calculated at each stage. The final scar length after performing the altered staged excision method was compared with that obtained after the conventional staged excision method, which was calculated using a theoretical scar model. Patient satisfaction was also evaluated. The mean longest axis length was 9.41 ± 3.83 cm preoperatively, 9.50 ± 3.92 cm after the first stage postoperatively, and 10.19 ± 3.98 cm after the final stage. The mean lesion width was 6.50 ± 3.48 cm preoperatively, 3.60 ± 1.77 cm after the first stage postoperatively, and 0.42 ± 0.31 cm after the final stage. The final scar length obtained using the altered procedure was much shorter than what would be obtained using conventional staged excision. The patient satisfaction score was 8.8 ± 1.1 out of a possible 10.0 rating. Staged excision with a hexagonal-pattern excision, wide undermining, and purse-string closure may improve aesthetic results.


Growth promoting potential of fresh and stored Moringa oleifera leaf extracts in improving seedling vigor, growth and productivity of wheat crop.
Wheat is staple food of region, as it contributes 60% of daily caloric intake, but its delayed sowing reduces yield due to short life span. Moringa leaf extract (MLE) is considered to improve growth and development of field crops. Study comprised of two experiments. First experiment, freshly extracted MLE and in combination with growth-promoting substances were stored at two temperature regimes. Chemical analysis, after 1, 2, and 3 months' storage period, showed that phenolics and ascorbic acid concentrations decreased with increasing storage period. Fresh extracts improved speed and spread of emergence and seedling vigor. Effectiveness of MLE in terms of phenolics and ascorbate concentrations was highest up to 1 month which decreased with prolonged storage. Growth enhancing potential of MLE also reduced with increasing storage duration. Under field conditions, the bio-efficacy of these fresh and stored MLE was compared when applied as foliar spray at tillering and booting stages of wheat. Foliar applied fresh MLE was the most effective in improving growth parameters. Fresh MLE enhanced biochemical and yield attributes in late sown wheat. This growth-promoting potential of MLE decreased with storage time. Application of fresh MLE helped to achieve higher economic yield.


An in vivo assessment of in vitro sensitized human lymphocytes using athymic, "nude" mice.
Cytotoxic lymphocytes were generated in vitro by co-cultivation of human peripheral blood lymphocytes with cultured human tumor cells. Their cytotoxic action was demonstrated in vivo in immunologically deficient "nude" mice.


Expression profiling of chicken DT40 lymphoma cells indicates clonal selection of knockout and gene reconstituted cells.
The DT40 cell-line has been extensively used to create deletion mutants, one of which lacks Bruton's tyrosine kinase (Btk). Btk is a cytoplasmic tyrosine kinase important for B-lymphocyte maturation. It was previously shown that there are differences in gene expression between wild-type and Btk-deficient animals. Global gene expression profiling of the avian B-lymphoma DT40 cell-line was used as a model to differentiate among Btk knockout (KO) and Btk KO cells reconstituted with human Btk. Differences in the gene expression pattern showed statistically significant changes between parental DT40 and all the Btk KO cell populations irrespective of whether they are reconstituted or not. These results imply that in the process of generating a knockout cell-line, sub-clones are selected, which have multiple changes in their gene expression pattern (p<0.01). Although other parameters could also influence the expression profile, this potentially has important implications when interpreting microarray data from gene-deleted cell-lines.


Current approaches in identification and isolation of human renal cell carcinoma cancer stem cells.
In recent years, cancer stem cells (CSCs)/tumor initiating cells (TICs) have been identified inside different tumors. However, currently used anti-cancer therapies are mostly directed against somatic tumor cells without targeting CSCs/TICs. CSCs/TICs also gain resistance to chemotherapies/radiotherapies. For the development of efficient treatment strategies, choosing the best method for isolation and characterization of CSCs/TICs is still debated among the scientific community. In this review, we summarize recent data concerning isolation techniques for CSCs using magnetic cell sorting and flow cytometry. The review focuses on the strategies for sample preparation during flow cytometric analysis, elaborating biomarkers such as CXCR4, CD105, and CD133. In addition, functional properties characteristic of CSCs/TICs using side population selection through Hoechst 33342 dye, aldehyde dehydrogenase 1, dye-cycle violet, and rhodamine 123 are also discussed. We also include a special focus on enriching CSCs/TICs using three-dimensional cell culture models such as agarose-agarose microbeads and sphere formation.


Multivariate neural network operators with sigmoidal activation functions.
In this paper, we study pointwise and uniform convergence, as well as order of approximation, of a family of linear positive multivariate neural network (NN) operators with sigmoidal activation functions. The order of approximation is studied for functions belonging to suitable Lipschitz classes and using a moment-type approach. The special cases of NN operators, activated by logistic, hyperbolic tangent, and ramp sigmoidal functions are considered. Multivariate NNs approximation finds applications, typically, in neurocomputing processes. Our approach to NN operators allows us to extend previous convergence results and, in some cases, to improve the order of approximation. The case of multivariate quasi-interpolation operators constructed with sigmoidal functions is also considered.


The Acceptable Text Similarity Level in Manuscripts Submitted to Scientific Journals.
Plagiarism is among commonly identified scientific misconducts in submitted manuscripts. Some journals routinely check the level of text similarity in the submitted manuscripts at the time of submission and reject the submission on the fly if the text similarity score exceeds a set cut-off value (e.g., 20%). Herein, I present a manuscript with 32% text similarity, yet without any instances of text plagiarism. This underlines the fact that text similarity is not necessarily tantamount to text plagiarism. Every instance of text similarity should be examined with scrutiny by a trained person in the editorial office. A high text similarity score does not always imply plagiarism; a low score, on the other hand, does not guarantee absence of plagiarism. There is no cut-off for text similarity to imply text plagiarism.


Increasing DNA repair capacity in bone marrow by gene transfer as a prospective tool in cancer therapy.
Resistance of tumor cells to alkylating anticancer agents that produce adducts at the O6 position of guanine in DNA, the O6-alkylating agents, correlates with the expression of O6-alkylguanine-DNA alkyltransferase (ATase). O6-benzylguanine and related pseudosubstrates are able to inactivate human ATase in vitro and in vivo and they are being tested as chemotherapeutic adjuvants for enhancing the effectiveness of O6-alkylating drugs. On the other hand, the clinical consequences of ATase depletion may be fatal for some sensitive systems e.g. hematopoiesis. To overcome this problem, strategies for the protection of primary bone marrow cells by targeted transfer of pseudosubstrate-resistant ATase genes have been considered and recently achieved at the laboratory level. This approach could therefore be now extended to a clinical cancer gene therapy program.


Indirect effects of granivory by harvester ants: plant species composition and reproductive increase near ant nests.
Of 36 plant species surveyed, 6 were significantly associated with nests of the desert seed-harvester ant Veromessor pergandei or Pogonomyrmex rugosus; two other plant species were significantly absent from ant nests. Seeds of two common desert annuals, Schismus arabicus and Plantago insularis, realize a 15.6 and 6.5 fold increase (respectively) in number of fruits or seeds produced per plant growing in ant nest refuse piles compared to nearby controls. Mass of individual S. arabicus seed produced by plants growing in refuse piles also increased significantly. Schismus arabicus, P. insularis and other plants associated with ant nests do not have seeds with obvious appendages attractive to ants. Dispersal and reproductive increase of such seeds may represent a relatively primitive form of ant-plant dispersal devoid of seed morphological specializations. Alternatively, evolution of specialized seed structures for dispersal may be precluded by the assemblage of North American seed-harvester ants whose workers are significantly larger than those ants normally associated with elaiosome-attached seed dispersal. Large worker size may permit consumption of elaiosome and seed.


Epiphytic colonization of pear stigmas and hypanthia by bacteria during primary bloom.
ABSTRACT Pear blossoms were sampled during various stages of bloom in 1991 and 1992 from orchards at Cashmere, WA, and Corvallis and Medford, OR, for epiphytic populations of culturable bacteria. On stigmatic surfaces, bacteria were isolated from 2 to 32% of blossoms prior to petal expansion and from 47 to 94% of blossoms by petal fall. In general, a lower percentage of hypanthia than stigmas supported bacterial populations. Randomly selected bacteria isolated at population levels of >/=10(4) CFU/tissue were identified by fatty acid methyl ester analysis. Diverse genera of gram-negative and -positive bacteria were identified from the Medford and Cashmere field sites. Pseudomonas syringae and Pseudomonas viri-diflava were isolated from all sites and were the predominant species detected at Corvallis, where they were isolated from 28% of the blossoms sampled on a given date. Because most pear blossoms do not support detectable populations (>/=10(2) CFU/tissue) of culturable bacteria prior to petal expansion, we speculate that introduced biocontrol agents may become established with minimal competition from indigenous epiphytes at early bloom stages.


Relationship of binding-site occupancy, transthyretin stabilisation and disease modification in patients with tafamidis-treated transthyretin amyloid cardiomyopathy.
Tafamidis inhibits progression of transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) by binding TTR tetramer and inhibiting dissociation to monomers capable of denaturation and deposition in cardiac tissue. While the phase 3 ATTR-ACT trial demonstrated the efficacy of tafamidis, the degree to which the approved dose captures the full potential of the mechanism has yet to be assessed. We developed a model of dynamic TTR concentrations in plasma to relate TTR occupancy by tafamidis to TTR stabilisation. We then developed population pharmacokinetic-pharmacodynamic models to characterise the relationship between stabilisation and measures of disease progression. Modelling individual patient data of tafamidis exposure and increased plasma TTR confirmed that single-site binding provides complete tetramer stabilisation in vivo. The approved dose was estimated to reduce unbound TTR tetramer by 92%, and was associated with 53%, 56% and 49% decreases in the rate of change in NT-proBNP, KCCQ-OS, and six-minute walk test disease progression measures, respectively. Simulating complete TTR stabilisation predicted slightly greater reductions of 58%, 61% and 54%, respectively. These findings support the value of TTR stabilisation as a clinically beneficial treatment option in ATTR-CM and the ability of tafamidis to realise nearly the full therapeutic benefit of this mechanism. NCT01994889.


Knowledge gain and usage of knowledge learned during internet-based CBT treatment for adolescent depression - a qualitative study.
The role of explicit learning of treatment content in internet-based cognitive-behavioural treatment (ICBT) is an emerging field of research. The objective of this study was to explore clients experiences of their ICBT treatment for depression with a focus on knowledge gain and usage of knowledge learned during treatment. A strategic sample of ten adolescents, aged between 15 and 19 years, who had received ICBT for major depression within a clinical controlled trial were recruited for the study. Semi-structured interviews were conducted 6 months following trial completion. Data were transcribed and analysed using thematic analysis. The participants had a general adherence rate of 6-8 opened modules out of 8 possible. Two main themes were identified; "Active agents of CBT" and "Passive agents of CBT", with each theme consisting of three and two sub-themes. Active agents of CBT reflect a tendency to specifically remember and actively apply specific CBT principles in present life situations. Passive agents of CBT reflect a tendency to remember CBT treatment principles vaguely and express a passive or reactive usage of learned therapy content. The findings suggest that young clients can remember and apply CBT principles 6 months after their treatment. However, while experiencing benefits of treatment, clients recall and application of treatment strategies vary. The study emphasizes the importance of exploring client recall of CBT components and how valuable it is to explicitly remember contents of a treatment in order to improve and maintain improvement. Further studies on the role of knowledge and memory of ICBT for adolescent populations are warranted.


Changes in children's dental fear: a longitudinal study.
The study aimed to evaluate the development of dental fear in a low fear group and a fearful group of children aged between 8 and 13 years of age and to assess the differences between these groups over time taking into account general variables, such as gender, and treatment variables, such as restorations. Furthermore it was evaluated to what extent general variables and treatment variables predict the change in dental fear or dental fear at later age. A three-year longitudinal study. 401 parents completed the Children's Fear Survey Schedule-Dental Subscale (CFSS-DS), 218 of them repeating this after a 3-year interval. Dental records were used to collect the clinical data, starting from the children's first dental appointment and the CFSS-DS was used to assess the child's dental fear. Analysis of variance for repeated measures showed an interaction effect between fear level and mean total CFSS-DS score. Regression analyses applied to the mean total CFSS-DS score at the second measurement moment and the change in total CFSS-DS score between both measurement moments revealed that little variance could be explained by the treatment variables over the various periods, such as extractions in the first period, and that child-characteristic variables could not predict much variance. Independent-samples t-tests showed a significant difference in means for extractions over the whole period between the fearful group (mean=1.73, SD+/-1.18) and low fear group (mean= 0.68, SD+/-2.01) (t=-4.05, p<0.001, n=218). Also the frequency of Behavioural Management Problems (BMP) over the whole period differed between these groups (fearful group: mean=1.40, SD+/-1.90 and low fearful group: mean= 0.40, SD+/-0.93) (t= -4.58, p<0.001, n=218). The effect of treatment variables and subjective experiences on child dental fear seems to diminish over time. Findings support the theoretical framework of conditioning and gradual exposure in children to prevent dental fear.


Clinical significance of SUVmax in (18)F-FDG PET/CT scan for detecting nodal metastases in patients with oral squamous cell carcinoma.
To retrospectively investigate the diagnostic accuracy of FDG-PET/CT relative to CT for detection of cervical node metastases in patients with oral squamous cell carcinoma (OSCC), using histologic evaluation of dissected cervical nodes as the reference standard. Thirty-six patients with OSCC who underwent neck dissection (4 bilateral, 32 unilateral; 250 nodal levels) after FDG-PET/CT. Two observers consensually determined the lesion size and SUVmax of visible cervical nodes and compared the results with pathologic findings at the nodal level. Histopathology revealed nodal metastases in 13 (36.1 %) of 36 patients and 28 (11.2 %) of 250 nodal levels. Using a best discriminative SUVmax cut-off of 3.5 for the node, the sensitivity, specificity and accuracy of FDG-PET/CT for identification of nodal metastases on a level-by-level basis were 67.9, 94.6, and 91.6 %, respectively. The corresponding figures for CT were 42.9, 96.8, and 90.8 %, respectively. The sensitivity of FDG-PET/CT was significantly better than CT (p = 0.023). Moreover, using the level-based modified SUVmax cut-off, the respective figures for FDG-PET/CT were 71.4, 95.9, and 93.2 %, with significantly higher sensitivity (p = 0.013) and accuracy (p = 0.041) than CT. FDG PET/CT with SUVmax is a useful modality for preoperative evaluation of cervical neck lymph node metastases in patients with OSCC.


Facile ion-exchange synthesis of mesoporous Bi2S3/ZnS nanoplate with high adsorption capability and photocatalytic activity.
Novel Bi2S3/ZnS nanoplates have been successfully prepared by simple reflux and cation exchange reaction between the preformed ZnS spheres and Bi(NO3)3·5H2O. The synthesized Bi2S3/ZnS nanoplates are mesoporous structures, possess a high specific surface area of 101.30m(2)/g and exhibit high adsorption capability and photocatalytic activity for methylene blue (MB) degradation under UV light irradiation. The high adsorption capability and photocatalytic activity can be ascribed to the fact that the formation of Bi2S3/ZnS nanoplates with large specific surface area provides more reactive sites and facilitates the separation of photogenerated electron-hole pairs. The possible formation mechanism of Bi2S3/ZnS nanoplates is proposed based on the time-dependent observation. Moreover, a tentative mechanism for degradation of MB over Bi2S3/ZnS has been proposed involving OH radical and photoinduced holes as the active species, which is confirmed by using methanol or ammonium oxalate as scavengers. This work provides a cost-effective method for large-scale synthesis of composite with controlled architectural morphology and highly promising applications in photocatalysis.


Cancer-testis antigen expression and its epigenetic modulation in acute myeloid leukemia.
Cancer-testis antigens (CTA) represent attractive targets for tumor immunotherapy. However, a broad picture of CTA expression in acute myeloid leukemia (AML) is missing. CTA expression was analyzed in normal bone marrow (BM) as well as in AML cell lines before and after treatment with demethylating agents and/or histone acetylase inhibitors. Presence of selected CTA with a strictly tumor-restricted expression was then determined in samples of patients with AML before and after demethylating therapy. Screening AML cell lines for the expression of 20 CTA, we identified six genes (MAGE-A3, PRAME, ROPN1, SCP-1, SLLP1, and SPO11) with an AML-restricted expression. Analyzing the expression of these CTA in blast-containing samples from AML patients (N = 64), we found all samples to be negative for MAGE-A3 and SPO11 while a minority of patients expressed ROPN1 (1.6%), SCP-1 (3.1%), or SLLP1 (9.4%). The only CTA expressed in substantial proportion of patients (53.1%) was PRAME. Following demethylating treatment with 5'-aza-2'-deoxycytidine, we observed an increased or de novo expression of CTA, in particular of SSX-2, in AML cell lines. In AML patients, we detected increased expression of PRAME and induction of SSX-2 after demethylating therapy with 5-azacytidine. With the exception of PRAME, CTA are mostly absent from AML blasts. However, demethylating treatment induces strong expression of CTA, particularly of SSX-2, in vitro and in vivo. Therefore, we propose that CTA-specific immunotherapy for AML should preferentially target PRAME and/or should be combined with the application of demethylating agents opening the perspective for alternative targets like CTA SSX-2.


A novel specimen-preparing method using epoxy resin as binding material for LIBS analysis of powder samples.
In view of the inevitable preprocessing of powder samples for LIBS detection, epoxy resin glue was investigated for the first time as a binder of powder samples due to its superior property of improved performance in laser induced breakdown spectroscopy (LIBS) technique as a quantitative analytical tool. For comparative studies of the epoxy resin and traditional polyethylene (PE) pellets in soil, sample detection, the signal intensities of Fe (I) at 404.58 nm, Ca (I) at 443.57 nm, and Cr (I) at 453.52 nm, were studied and subsequently, the calibration curves for these elements were constructed using the standard samples with variable concentrations. The signal intensities of epoxy resin samples were, on average, about 2 times greater than those obtained with the traditional PE pellet samples. Meanwhile, the resin samples showed better R square values of 0.981, 0.985 and 0.979 for curves of Fe (I) 404.58 nm, Ca (I) 443.57 nm, and Cr (I) 453.52 nm, compared to the 0.974, 0.950 and 0.934, of the PE pellet samples. Furthermore, the former represented lower limits of detection (LOD) for Fe, Ca and Cr. These experimental results indicated that this proposed novel method based on epoxy resin can attach samples of properties of high homogeneity, cohesiveness, smoothness and hardness, which are conducive to system stability, testing accuracy and signal enhancement. This method can make LIBS more practical in powder sample analysis.


Vibration and noise in pediatric emergency transport vehicles: a potential cause of morbidity?
Noise and vibration are stressors that may adversely affect the well-being of infants and children being transported between facilities. Although the problem has been recognized, little has been done to rectify the situation. That noise levels in transport incubators during use in transport vehicles exceed the recommended standards, and that vibration levels exceed those that are "very uncomfortable" for healthy adults. We measured noise and vibration (n/v) levels inside and outside a neonatal transport incubator in seven transport vehicles (land, air, and water), and calculated maximum and average, weighted and unweighted levels. The maximum and average unweighted noise levels in all but one vehicle were over 99 dB. The incubator amplified noise at the lower frequencies (The Canadian Standards Association 1992 recommendation is that the noise level in transport incubators not exceed 60 dBA). The maximum vibration levels ranged from 0.86 m.S-2 to 2.35 m.S-2, and the average levels ranged from 0.33 m.S-2 to 1.46 m.S-2. (Vibration in excess of 1.5 is considered "very uncomfortable," and in excess of 2.0 is "extremely uncomfortable" for healthy adults.) Noise and vibration levels inside transport incubators in our most-commonly used transport vehicles often exceed the recommended limits. For neurologically immature and/or physiologically compromised infants and children, current levels of n/v in transport vehicles are too high, and could affect patient morbidity. These n/v levels require further study, and modification of equipment, primarily the incubators, is overdue.


Factors affecting the production of SCEs by maleic hydrazide in root-tip chromosomes of Allium cepa.
We have investigated the influence of pH on the induction of chromatid-type aberrations and sister-chromatid exchanges (SCEs) by maleic hydrazide (MH) in root-tip cells of Allium cepa. For both cytogenetic endpoints, the lower the pH of the treatment solution, the higher were the frequencies of chromosome alterations detected at metaphase. We have further studied the persistence of lesions giving rise to SCEs during successive cell cycles, as well as the influence of BrdU concentration in the post-treatment medium on the yield of MH-induced SCEs. Our results suggest that the cytogenetic action of MH in many respects resembles that of bifunctional alkylating agents.


Quantum oscillations of the quasiparticle lifetime in a metal.
Following nearly a century of research, it remains a puzzle that the low-lying excitations of metals are remarkably well explained by effective single-particle theories of non-interacting bands1-4. The abundance of interactions in real materials raises the question of direct spectroscopic signatures of phenomena beyond effective single-particle, single-band behaviour. Here we report the identification of quantum oscillations (QOs) in the three-dimensional topological semimetal CoSi, which defy the standard description in two fundamental aspects. First, the oscillation frequency corresponds to the difference of semiclassical quasiparticle (QP) orbits of two bands, which are forbidden as half of the trajectory would oppose the Lorentz force. Second, the oscillations exist up to above 50 K, in strong contrast to all other oscillatory components, which vanish below a few kelvin. Our findings are in excellent agreement with generic model calculations of QOs of the QP lifetime (QPL). Because the only precondition for their existence is a nonlinear coupling of at least two electronic orbits, for example, owing to QP scattering on defects or collective excitations, such QOs of the QPL are generic for any metal featuring Landau quantization with several orbits. They are consistent with certain frequencies in topological semimetals5-9, unconventional superconductors10,11, rare-earth compounds12-14 and Rashba systems15, and permit to identify and gauge correlation phenomena, for example, in two-dimensional materials16,17 and multiband metals18.


Pharmacological responses to acute morphine administration in normotensive Wistar-Kyoto and spontaneously hypertensive rats.
The effect of acute administration of morphine on analgesia, hyperthermia, hypothermia and catalepsy was determined in spontaneously hypertensive (SH) rats and normotensive Wistar-Kyoto (WKY) rats. A greater analgesic and hyperthermic response to morphine was observed in SH rats than in WKY rats. A dose of morphine (50 mg/kg ip) which produced hypothermia in WKY rats produced pronounced hyperthermia in SH rats. The cataleptic response to morphine was lower in SH rats. The cataleptic response to morphine was lower in SH rats than in WKY rats. The brain and plasma levels of morphine in SH rats were significantly lower as compared to the WKY rats at any dose of morphine used but the ratio of brain to plasma did not differ. It is concluded that SH rats exhibit altered sensitivity to morphine in comparison with their normotensive counterparts.


[Current contact allergens].
Ever-changing exposure to contact allergens, partly due to statutory directives (e.g. nickel, chromate, methyldibromo glutaronitrile) or recommendations from industrial associations (e.g. hydroxyisohexyl 3-cyclohexene carboxaldehyde), requires on-going epidemiologic surveillance of contact allergy. In this paper, the current state with special focus in fragrances and preservatives is described on the basis of data of the Information Network of Departments of Dermatology (IVDK) of the year 2010. In 2010, 12,574 patients were patch tested in the dermatology departments belonging to the IVDK. Nickel is still the most frequent contact allergen. However the continuously improved EU nickel directive already has some beneficial effect; sensitization frequency in young women is dropping. In Germany, chromate-reduced cement has been in use now for several years, leading to a decline in chromate sensitization in brick-layers. Two fragrance mixes are part of the German baseline series; they are still relevant. The most important fragrances in these mixes still are oak moss absolute and hydroxyisohexyl 3-cyclohexene carboxaldehyde. However, in relation to these leading allergens, sensitization frequency to other fragrances contained in the mixes seems to be increasing. Among the preservatives, MCI/MI has not lost its importance as contact allergen, in contrast to MDBGN. Sources of MCI/MI sensitization obviously are increasingly found in occupational context. Methylisothiazolinone is a significant allergen in occupational settings, and less frequently in body care products.


Low over-expression of TNFalpha in the mouse heart increases contractile performance via TNFR1.
TNFalpha is a cytokine wit pleiotropic functions in many organs. In the heart increased TNFalpha levels are not only associated with heart failure, but also, paradoxically, with protection from ischemic damage. To test whether the protective role of TNFalpha in the heart is concentration-dependent, we studied two mouse heart models with low (two- to threefold) over-expression of endogenous TNFalpha: mice deficient in a translational repressor of TNFalpha mRNA, TIA-1(-/-), and mice over-expressing human TNFalpha. Hearts lacking TIA-1 were characterized for their endogenous TNFalpha over-expression during normal Langendorff perfusion. To define which TNFalpha receptor mediates cardiac protection, we also used mice lacking the TNFR1 receptor. Contractile function was assessed in isolated hearts perfused in the isovolumic Langendorff mode during and following global no-flow ischemic stress and in response to varying extracellular [Ca(2+)] to determine their contractile response and Ca(2+) sensitivity. All hearts with low over-expression of TNFalpha, independent of human or murine origin, have improved contractile performance and increased Ca(2+) sensitivity (by 0.2-0.26 pCa). Hearts lacking TNFR1 have contractile performance equal to wild type hearts. Recovery from ischemia was greater in TIA-1(-/-) and was diminished in TNFR1(-/-). Better contractile function in TNFalpha over-expressing hearts is not due to improved cardiac energetics assessed as [ATP] and glucose uptake or to differences in expression of SERCA2a or calmodulin. We suggest that low levels of TNFalpha increase the Ca(2+) sensitivity of the heart via a TNFR1-mediated mechanism.


Improvement for enhanced xylanase production by Cellulosimicrobium cellulans CKMX1 using central composite design of response surface methodology.
The effects of yeast extract (X1), NH4NO3 (X2), peptone (X3), urea (X4), CMC (X5), Tween 20 (X6), MgSO4 (X7), and CaCO3 (X8) on production of xylanase from Cellulosimicrobium cellulans CKMX1 were optimized by statistical analysis using response surface methodology (RSM). The RSM was used to optimize xylanase production by implementing the Central composite design. Statistical analysis of the results showed that the linear, interaction and quadric terms of these variables had significant effects. However, only the linear effect of X4, X5, interaction effect of X1X7, X1X8, X2X3, X2X8, X3X6, X3X8, X4X6, X4X7, X5X7, X5X8 and quadratic effect of X 32 , X 52 and X 72 found to be insignificant terms in the quadratic model and had no response at significant level. The minimum and maximum xylanase production obtained was 331.50 U/g DBP and 1027.65 U/g DBP, respectively. The highest xylanase activity was obtained from Run No. 30, which consisted of yeast extract (X1), 1.00 g (%); NH4NO3 (X2), 0.20 g (%); peptone (X3), 1.00 g (%); urea (X4), 10 mg (%); CMC (X5), 1.00 g (%); Tween 20 (X6), 0.02 mL (%); CaCO3 (X7), 0.50 g (%) and MgSO4 (X8), 9.0 g (%). The optimization resulted in 3.1-fold increase of xylanase production, compared with the lowest xylanase production of 331.50 U/g DBP after 72 h of incubation in stationary flask experiment. Application of cellulase-free xylanase in pulp biobleaching from C. cellulans CKMX1 under C-EP-D sequence has been shown to bring about a 12.5 % reduction of chlorine, decrease of 0.8 kappa points (40 %), and gain in brightness was 1.42 % ISO points in 0.5 % enzyme treated pulp as compared to control.


Treatment of severe diabetic hypoglycemia with glucagon: an underutilized therapeutic approach.
Tight glycemic control is important in reducing and delaying vascular complications in type 1 and 2 diabetes patients; however, the benefits achieved through strict metabolic control are counterbalanced by an increased risk of hypoglycemia. Glucagon is an effective therapy for treating severe hypoglycemia. Available as an emergency kit, glucagon is an essential tool for rapid response, but remains underappreciated and underused. This article reviews the role of glucagon in treating severe hypoglycemia and discusses the need for better education on glucagon for people with diabetes and their caregivers in order to alleviate fears of hypoglycemia and of administering glucagon in the event of an emergency.


D-dimer testing, with gender-specific cutoff levels, is of value to assess the individual risk of venous thromboembolic recurrence in non-elderly patients of both genders: a post hoc analysis of the DULCIS study.
Male patients, especially the young, are at a higher risk of recurrent venous thromboembolism (RVTE) than females. Recent scientific reports show the use of D-dimer does not help predict RVTE risk in males. In the present report, we reviewed the data obtained in the DULCIS study (main report published in Blood 2014), focusing on D-dimer results recorded in non-elderly patients of both genders included in the study, and their relationship with RVTE events occurring during follow-up. Using specifically designed cutoff values for positive/negative interpretation, serial D-dimer measurements (performed during warfarin treatment and up to 3 months after discontinuation of anticoagulation) in 475 patients (males 57.3%) aged ≤ 65 years were obtained. D-dimer resulted positive in 46.3% and 30.5% of males and females, respectively (p = 0.001). Following management procedure, anticoagulation was stopped in 53.7% of males and 69.5% of females, who had persistently negative D-dimer results. The rate of subsequent recurrent events was 1.7% (95% CI 0.5-4.5%) and 0.4% (95% CI 0-2.5%) patient-years in males and females, respectively, with upper limits of confidence intervals always below the level of risk considered acceptable by international scientific societies for stopping anticoagulation (< 5%). In conclusion, using sensitive quantitative assays with specifically designed cutoff values and serial measurements during and after discontinuation of anticoagulation, D-dimer testing is useful to predict the risk of RVTE and is of help in deciding the duration of anticoagulation in both male and female adult patients aged up to 65 years.


The emergence of Ph-, trisomy -8+ cells in patients with chronic myeloid leukemia treated with imatinib mesylate.
To describe clinical and laboratory features of a cohort of patients with chronic myelogenous leukemia (CML) who developed Ph(-), trisomy 8(+) metaphases while on treatment with imatinib mesylate. Conventional cytogenetics and triple-color interphase fluorescence in situ hybridization were used to identify 5 of 310 studied patients who, on follow-up analysis, had Ph(-), trisomy 8(+) cells while on therapy. None of the 5 patients had cytogenetic evidence of clonal evolution at the start of treatment with imatinib. All patients developed grade 3 or 4 neutropenia and thrombocytopenia during treatment. The emergence of Ph(-), trisomy 8(+) metaphases was seen at 3, 6, 13, 16, and 18 months from the start of treatment and was present at multiple time points. The maximum number of trisomy 8 metaphases ranged from 25 to 50%. Concomitantly, all patients had a profound suppression of Ph(+) cells (ranging from 0 to 65%) as well as the appearance of normal metaphases, ranging from 6 to 55%. None of the patients has shown clinical or hematologic signs of progression to a more advanced phase of CML. While on treatment with imatinib mesylate a small group (less than 5%) of patients with CML developed Ph(-) trisomy 8(+) clone associated with pancytopenia. None of the patients developed clinical or hematological signs of progression to a more advanced phase of CML. These observations suggest that identification of trisomy 8 cells may represent clonal Ph(-) cells that were uncovered by treatment with a selective and potent inhibitor of Ph(+) cells.


Regional heterogeneity of malaria prevalence and associated risk factors among children under five in Togo: evidence from a national malaria indicators survey.
Malaria remains a major cause of morbidity and death among children less than 5 years of age. In Togo, despite intensification of malaria control interventions, malaria remained highly prevalent, with significant heterogeneity from one region to another. The aim of this study is to explore further such regional differences in malaria prevalence and to determine associated risk factors. Data from a 2017 cross-sectional nationally representative malaria indicator survey was used. Children aged 6-59 months in selected households were tested for malaria using a rapid diagnostic test (RDT), confirmed by microscopy. Univariate and multivariate logistic regression analysis were performed using Generalized Linear Models. A total of 2131 children aged 6-59 months (1983 in rural areas, 989 in urban areas) were enrolled. Overall 28% of children tested positive for malaria, ranging from 7.0% in the Lomé Commune region to 4% 7.1 in the Plateaux region. In multivariate analysis, statistically significant differences between regions persisted. Independent risk factors identified were higher children aged (aOR = 1.46, 95% CI [1.13-1.88]) for those above 24 months compared to those below; households wealth quintile (aOR = 0.22, 95% CI [0.11-0.41]) for those richest compared to those poorest quintiles; residence in rural areas (aOR = 2.02, 95% CI [1.32-3.13]). Interventions that target use of combined prevention measures should prioritise on older children living in poorest households in rural areas, particularly in the regions of high malaria prevalence.


Comparative Serum and Brain Pharmacokinetics of Quercetin after Oral and Nasal Administration to Rats as Lyophilized Complexes with β-Cyclodextrin Derivatives and Their Blends with Mannitol/Lecithin Microparticles.
Quercetin (Que) is one of the most studied flavonoids with strong antioxidant properties ascribed to its ability to bind free radicals and inactivate them. However, the low solubility of the compound along with its inadequate absorption after oral administration limit its beneficial effects. Que's complexation with two different cyclodextrin (CD) derivatives (hydroxypropyl-β-CD and methyl-β-CD) via the neutralization/lyophilization method has been found to improve its physicochemical properties. Moreover, blends of the lyophilized powders with mannitol/lecithin microparticles (MLMPs) have been proposed as candidates for intranasal (IN) administration after in vitro and ex vivo evaluations. In this context, a comparative pharmacokinetic (PK) study of the IN vs oral administration of Que lyophilized powders and their blends with MLMPs (75:25 w/w) was performed on Wistar rats. The PK parameters estimated by a non-compartmental analysis using the sparse data methodology in Phoenix® 8.3 (Certara, Princeton, NJ, USA) illustrated the effectiveness of IN administration either in brain targeting or in reaching the bloodstream. Significant levels of the compound were achieved at both sites, compared to those after oral delivery which were negligible. These results favor the potential application of the prepared Que nasal powders for systemic and nose-to-brain delivery for the prevention and/or treatment of neuroinflammatory degenerative conditions, such as Parkinson's and Alzheimer's disease.


Ay, there's the Rab: organelle maturation by Rab conversion.
Is endocytosed cargo transported by vesicular intermediates between early and late endosomes, or does an endosome mature while its cargo remains in place? Current work suggests that the latter takes place within the endosomal system via a process termed Rab conversion.


Rapid reversal of digitalis delirium using digoxin immune Fab therapy.
A fulminant psychiatric disturbance, as the sole noncardiac manifestation of digitalis toxicity, emerged in a 85-year-old woman during treatment for congestive heart failure. Described more than a century ago as "digitalis delirium," the disorder is characterized by severe agitation, delusional thinking, assaultive behavior, and even death. Digoxin immune Fab therapy was begun because of the fulminant psychiatric manifestations of this toxic state and the clear danger of self-inflicted physical harm. Within 3 h of therapy, a complete and spectacular resolution of all mental symptoms was observed.


Characteristics of population structure, antimicrobial resistance, virulence factors, and morphology of methicillin-resistant Macrococcus caseolyticus in global clades.
Macrococcus caseolyticus is an opportunistic pathogen that is frequently isolated from dairy products and veterinary infections. Recent studies have reported the possibility of methicillin resistance that be transferred among staphylococcal species in foods. The present study examined the population structure, antimicrobial resistance, virulence factors, and morphology of methicillin-resistant M. caseolyticus by investigation of 94 genomes derived from both isolates in beef (n = 7) and pork (n = 2) at Shanghai and those deposited in public domain (n = 85). Phylogenetically, M. caseolyticus were divided into four clades, which each consisted of genomes isolated from continent of European countries (82.4%, n = 78), Asian countries (11.3%, n = 10), United States (4.1%, n = 4), Australia (1%, n = 1), and Sudan (1%, n = 1). The M. caseolyticus isolated from present study formed a genetically distinguished clade, which was characterized by novel alleles in the traditional 7-gene MLST scheme. Furthermore, we identified 24 AMR genes that were associated with 10 classes of antimicrobial agents in M. caseolyticus. Most AMR genes were carried by dominant plasmids such as rep7a, rep22 and repUS56. The genomes in the global clades carried significantly less AMR genes (p < 0.05) and more virulence factors (p < 0.001) than present clade. Virulence factors were detected in methicillin resistant M. caseolyticus including genes coding hemolysin, adherence, biofilm formation, exotoxin, and capsule that associated to human health and infection. Finally, as the close relative of the genus Staphylococcus, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were performed for morphological comparison that M. caseolyticus has a larger diameter and thicker cell wall compared with S. aureus ATCC 25,923. Taken together, our study suggested that M. caseolyticus mediating divergent antimicrobial resistance and virulence factors could serve as the vector for methicillin resistance habitats in foodborne microorganisms.


Soil organic matter as sole indicator of soil degradation.
Soil organic matter (SOM) is known to play vital roles in the maintenance and improvement of many soil properties and processes. These roles, which largely influence soil functions, are a pool of specific contributions of different components of SOM. The soil functions, in turn, normally define the level of soil degradation, viewed as quantifiable temporal changes in a soil that impairs its quality. This paper aims at providing a generalized assessment of the current state of knowledge on the usefulness of SOM in monitoring soil degradation, based on its influence on the physical, chemical and biological properties and processes of soils. Emphasis is placed particularly on the effect of SOM on soil structure and availability of plant nutrients. Although these properties are discussed separately, the soil system is of dynamic and interactive nature, and changes in one property will likely affect other soil properties as well. Thus, functions of SOM almost always affect various soil properties and processes and engage in multiple reactions. In view of its role in soil aggregation and erosion control, in availability of plant nutrients and in ameliorating other forms of soil degradation than erosion, SOM has proven to be an important indicator of soil degradation. It has been suggested, however, that rather than the absolute amount, temporal change and potential amount of SOM be considered in its use as indicator of soil degradation, and that SOM may not be an all-purpose indicator. Whilst SOM remains a candidate without substitute as long as a one-parameter indicator of soil degradation is needed, narrowing down to the use of its labile and microbial components could be more appropriate, since early detection is important in the control and management of soil degradation.


Dual Therapy vs. Monotherapy for the Patent Ductus Arteriosus: A Systematic Review.
To evaluate the efficacy of dual patent ductus arteriosus (PDA) pharmacotherapy compared to monotherapy we searched Medline, Embase, Cochrane Library, and references of relevant articles through October 20, 2021 for randomized clinical trials (RCTs) and cohort studies comparing dual PDA treatment vs. monotherapy. Data were analyzed using a fixed effects model. The fixed effects model assumes that all studies included in a meta-analysis are estimating a single true underlying effect, that of ductal closure. Primary outcome was ductal closure; secondary outcome was surgical ligation. Of 170 articles retrieved, three cohort studies and two RCTs were included, totaling 470 patients: 384 babies received monotherapy and 86 dual therapy. Because of the small numbers, RCTs and cohort studies were pooled for analysis. Ductus closed in 67% of those who received combination compared with 58% those with monotherapy. Overall fixed effect shows an OR of 1.97 [1.10; 3.53; p = 0.023] favoring dual therapy. Dual pharmacologic treatment appears more effective than monotherapy. Future well-powered, high-quality, prospective RCTs are needed to further investigate this potential approach.


Clinical and therapeutic studies in mesangial immunoglobulin A glomerulonephritis.
A long-term clinical and therapeutic study was performed in 47 patients with mesangial IgA glomerulonephritis. The male to female ration was 2.9:1. An episode of gross haematuria or the incidental discovery of asymptomatic microscopic haematuria with associated mild proteinuria heralded the apparent onset of renal disease. At the onset of observation 18 patients (38.2%) had high blood pressure. Other 17 patients developed hypertension during observation. Anaemia was uncommon. No essential abnormalities in serum protein and lipid patterns were found. Twenty-nine patients (61.6%) had higher levels of serum immunoglobulins--most frequently of IgA (42.5%). Twenty-two patients had low serum C3 levels (46.8%). The percentage of patients with renal failure increased from 21.2 to 36.1 during observation. Male sex, hypertension, proteinuria higher than 2 g/24 h, elevated ESR, high serum IgA levels, longer duration of the disease and older age of patients suggest an unfavourable outcome. Long-term treatment with a combination of azathioprine/acenocumarol, or indomethacin, or levamisole has no effect on the clinical manifestation and evolution.


Dynamic survival analysis of gastrointestinal stromal tumors (GISTs): a 10-year follow-up based on conditional survival.
The prognosis of patients with gastrointestinal stromal tumors (GISTs) is generally evaluated at the time of diagnosis but does not reflect the survival dynamics of patients in the future. Therefore, the purpose of this article was to evaluate the conditional survival (CS) of Chinese patients with GISTs after radical resection. This retrospective study included 451 patients who underwent radical surgery for GISTs. A Cox proportional hazard model was used to evaluate the prognostic factors of disease-free survival (DFS). The 3-year conditional DFS (CDFS3) of patients who survived for x years was expressed as CDFS3=DFS(x + 3)/DFS(x). The traditional 3-year DFS rate decreased gradually from 94.0% at 3 years to 77.3% at 7 years, while the CDFS3 rate increased from 94.0 to 95.2% over the survival time of the patients. In addition, classic clinicopathological prognostic factors had different effects on CDFS3, with changes observed in survival time, but these effects were only slight or moderate (|d|<0.5). Although multivariate analysis showed that age, sex, mitotic index and tumor rupture were independent risk factors for DFS at baseline, all adverse prognostic factors, except for the mitotic index, lost their predictive significance at 5 years after operation. When the Modified NIH criteria were included, the risk staging was found to be an independent risk factor for recurrence or death. Time-dependent Cox regression analysis showed that the modified NIH criteria independently affected the recurrence or death of GIST patients within 2 years after operation. CS provides detailed dynamic survival information about Chinese patients with primary resected GISTs. The mitotic index is of great clinical significance for the monitoring and follow-up of patient populations with a high risk of tumor recurrence or death until 5 years after surgery.


Specification of anteroposterior cell fates in Caenorhabditis elegans by Drosophila Hox proteins.
Antennapedia class homeobox (Hox) genes specify cell fates in successive anteroposterior body domains in vertebrates, insects and nematodes. The DNA-binding homeodomain sequences are very similar between vertebrate and Drosophila Hox proteins, and this similarity allows vertebrate Hox proteins to function in Drosophila. In contrast, the Caenorhabditis elegans homeodomains are substantially divergent. Further, C. elegans differs from both insects and vertebrates in having a non-segmented body as well as a distinctive mode of development that involves asymmetric early cleavages and invariant cell lineages. Here we report that, despite these differences, Drosophila Hox proteins expressed in C. elegans can substitute for C. elegans Hox proteins in the control of three different cell-fate decisions: the regulation of cell migration, the specification of serotonergic neurons, and the specification of a sensory structure. We also show that the specificity of one C. elegans Hox protein is partly determined by two amino acids that have been implicated in sequence-specific DNA binding. Together these findings suggest that factors important for target recognition by specific Hox proteins have been conserved throughout much of the animal kingdom.