Characterization of major lipid droplet proteins from Dunaliella.
Many green algal species can accumulate large amounts of triacylglycerides (TAG) under nutrient deprivation, making them a potential source for production of biodiesel. TAG are organized in cytoplasmic lipid bodies, which contain a major lipid droplet protein termed MLDP. Green algae MLDP differ in sequence from plant oleosins and from animal perilipins, and their structure and function are not clear. In this study, we describe the isolation of MLDP from three species of the extreme halotolerant green algae Dunaliella. Sequence alignment with other green algae MLDP proteins identified a conserved 4-proline domain that may be considered as a signature domain of Volvocales green algae MLDP. Gold immunolabeling localized MLDP at the surface of lipid droplets in D. salina. The induction of MLDP by nitrogen deprivation is kinetically correlated with TAG accumulation, and inhibition of TAG biosynthesis impairs MLDP accumulation suggesting that MLDP induction is co-regulated with TAG accumulation. These results can lead to a better understanding of the structure and function of Volvocales green algae MLDP proteins.


Use of subcutaneous cardioverter-defibrillator. First cases reported from National Institute of Cardiology Ignacio Chávez-Mexico.
The transvenous implantable cardioverter defibrillator (ICD) is the treatment of choice for the prevention of sudden cardiac death (SCD). Its use could be restricted when device-related infections occurs or in the pediatric population. In the later, an ICD represents a challenge, due to the minimal dimensions of the venous system in children, the length of the electrodes, the size of the generator, as well as the anatomical complexity in cases with associated congenital heart disease. This article presents the first Mexican patients with a subcutaneous ICD (SC-ICD) implant as a therapy for the prevention of SCD. The first four cases were implanted at the Ignacio Chávez National Institute of Cardiology with a SC-ICD (Emblem, Boston Scientific, USA), three of them were pediatric patients, including the first implant of this type of device in a pediatric patient in Latin America. The 3-incision and 2-incision techniques were used under general anesthesia. A successful implantation was obtained with the 3-incision technique in the first 2 cases and the last 2 with the 2-incision technique. Proper functioning of the device was corroborated in the operating room with proof of appropriate therapy (65 J) for ventricular fibrillation induced with 50 Hz stimulation. No immediate complications were observed. One patient had appropriate shocks two months after the implant. During follow-up, one child developed skin erosion at the level of the curve of the electrode on the sternum, with no signs of infection. In the operating room, the damaged skin was resected, the barrel and the fixation silk were removed, surgical lavage was performed, and the skin was closed again, thus avoiding removal of the system. The SC-ICD is an alternative therapy to the transvenous ICD. It can be considered first choice in subjects who do not require ventricular pacing, including pediatric patients. Skin complications can occur but do not pose a threat as venous complications of conventional ICDs.


Sex-, Stress-, and Sympathetic Post-Ganglionic Neuron-Dependent Changes in the Expression of Pro- and Anti-Inflammatory Mediators in Rat Dural Immune Cells.
Migraine attacks are associated with sterile inflammation of the dura. Immune cells are a primary source of inflammatory mediators, and we therefore sought to further explore the link between dural immune cells and migraine. Based on the observations that migraine is more common in women than in men, stress is the most common trigger for a migraine attack, and sympathetic post-ganglionic innervation of the dura enables local control of dural immune cells, we hypothesized that stress shifts the balance of inflammatory mediator expression in dural immune cells toward those that trigger a migraine attack, where these changes are larger in females and dependent, at least in part, on sympathetic post-ganglionic innervation of the dura. Our objective was to test this hypothesis. Dura were obtained from naïve or stressed, intact or surgically sympathectomized, adult male and female rats. Dura were assessed immediately or 24 hours after termination of 4 continuous days of unpredictable, mild stressors. Following enzymatic digestion of each dura, myeloid and lymphoid-derived dural immune cells were isolated by fluorescence-activated cell sorting for semi-quantitative polymerase chain reaction analysis. In myeloid-derived dural immune cells, there was an increase in pro-inflammatory mediator mRNA following stress, particularly in females, which remained elevated with a 24-hour delay after stress. There was a stress-induced decrease in anti-inflammatory mediator mRNA immediately after stress in females, but not males. The stress-induced changes were attenuated in sympathectomized females. In lymphoid-derived dural immune cells, there was a persistent increase in pro-inflammatory mediator mRNA following stress, particularly in females. A stress-induced increase in anti-inflammatory mediator mRNA was also observed in both males and females, and was further attenuated in sympathectomized females. Consistent with our hypothesis, there is a stress-induced shift in the balance of pro- and anti-inflammatory mediator expression in dural immune cells that is more pronounced in females, and is dependent, at least in part, on sympathetic post-ganglionic innervation in females. This shift in the balance of inflammatory mediator expression may not only play an important role in triggering migraine attacks, but also suggests it may be possible, if not necessary, to employ different strategies to most effectively treat migraine in men and women.


Reoperation after arterial switch: a 27-year experience.
The long-term outcome and spectrum of reoperation after the arterial switch operation (ASO) has not been fully defined, and there are limited data in the literature. We reviewed our institutional experience with reoperation(s) after ASO. Between January 1984 and January 2012, 32 patients (23 male) underwent reoperation(s) after ASO. Anatomy included simple transposition of the great arteries in 14, complex transposition of the great arteries in 14, and Taussig-Bing in 4. Mean age was 6.7 ± 1.4 years at first operation and 10.8 ± 13.4 years at the second operation. Isolated pathology was present in 11 (34.3%) and multiple pathologies in 21 (65.6%). Abnormalities at first reoperation were right-sided pathology in 18 (56.3%), left-sided pathology in 10 (31%), coronary artery in 3 (9%), mitral valve in 3 (9%), residual ventricular septal defect in 4 (12.5%), and recoarctation in 2 (6.3%). It was the second reoperation in 12 and the third reoperation in 3 patients. The first reoperation included pulmonary artery patch plasty in 18, aortic valve operation in 8 (4 valve replacement, 3 root replacement, and 1 repair), pulmonary valve replacement in 4, coronary artery bypass grafting in 3, and mitral valve repair in 3. Multiple reoperations occurred in 15 patients, comprising right-sided procedures (11), left-sided (2), and other (2). Pulmonary artery reconstruction occurred earlier than neoaortic intervention (5.4 ± 6.8 vs 13.8 ± 7.7 years, p < 0.001). There were 2 early deaths (6.2%); both patients had complex transposition of the great arteries and both were at early reoperation after ASO. Median follow-up was 14.5 years (maximum, 27 years). There were no late deaths. Freedom from reoperation at 1, 5, and 15 years was 88%, 78%, and 41%, respectively. The most common indication for reoperation after ASO is right-sided pathology, followed by neoaortic root pathology. Late survival after ASO is excellent and risk of late reoperation is low. Life-long medical surveillance is required.


Neurophysiological and clinical findings on Nodding Syndrome in 21 South Sudanese children and a review of the literature.
To describe the neurophysiological and clinical features of Nodding Syndrome (NS) in South Sudan. The study was performed at the Epilepsy Service of "Usratuna" sited in Juba, South Sudan. The clinical history of each subject was collected along with an EEG tracing. Twenty-one children (10 females) were diagnosed with NS. Fifteen (72%) children were classified as Probable NS and six (28%) as Confirmed NS. They ranged in age between 6 and 14 years, and age at seizure onset ranged from 5 to 12 years. All the subjects presented with intellectual disability which was mild in severity in 12 (57%) cases, moderate in seven (33%) cases and severe in two (10%) cases. Interictal EEG was abnormal in 20 subjects. In 18 (85%) subjects, the EEG showed 2-3.5 Hz spike-and-wave discharges often intermingled with sharp waves. Intermittent light stimulation was normal. In 12 (57%) children, interictal abnormalities were activated by hyperventilation. Ictal EEG was obtained in three patients. In all ictal EEGs head nodding episodes came in clusters during hyperventilation. None of the patients achieved good seizure control even if all of them received antiepileptic treatment (carbamazepine alone [43%] or in association with phenobarbitone or phenytoin). This study confirms that NS is an encephalopathy and intellectual disabilities are partially independent of seizure frequency and EEG pathological activity. Based on interictal and ictal EEG patterns and on the experience of other researchers, valproic acid would seem to be the first-choice antiepileptic drug. NS in South Sudan presents with clinical and neurophysiological features which are similar to those described in northern Uganda and more severe than in Tanzania.


Effects of Pharmacological Treatments in Alzheimer's Disease: Permutation Entropy-Based EEG Complexity Study.
Alzheimer's disease (AD) is a neurodegenerative brain disease affecting cognitive and physical functioning. The currently available pharmacological treatments for AD mainly contain cholinesterase inhibitors (AChE-I) and N-methyl-D-aspartic acid (NMDA) receptor antagonists (i.e., memantine). Because brain signals have complex nonlinear dynamics, there has been an increase in interest in researching complexity changes in the time series of brain signals in individuals with AD. In this study, we explore the electroencephalographic (EEG) complexity for making better observation of pharmacological therapy-based treatment effects on AD patients using the permutation entropy (PE) method. We examined EEG sub-band (delta, theta, alpha, beta, and gamma) complexity in de-novo, monotherapy (AChE-I), dual therapy (AChE-I and memantine) receiving AD participants compared with healthy elderly controls. We showed that each frequency band depicts its own complexity profile, which is regionally altered between groups. These alterations were also found to be associated with global cognitive scores. Overall, our findings indicate that entropy measures could be useful to show medication effects in AD.


Characterization of Coffea arabica monofloral honey from Espírito Santo, Brazil.
In this study, samples of coffee honey produced in Espírito Santo State, Brazil, were characterized based on their melissopalynology, physicochemical and nutritional properties, and mineral and caffeine contents. The caffeine content in the nectar from coffee flowers was measured by high performance liquid chromatography (HPLC). Blends of honey were obtained from three Coffea arabica crops, each with 10 colonies of Africanized Apis mellifera. All honey samples contained monofloral (75-78%) pollen belonging to C. arabica. Physicochemical parameters (total acidity, pH, moisture, dry matter, ash, and qualitative hydroxymethylfurfural) were within the approved limits established by EU legislation. Coffee honey contains high levels of ascorbic acid (294.68 mg kg(-1)) and low amounts of total flavonoids (3.51 ± 0.18 mg QE kg(-1)). The most abundant minerals were potassium and calcium (962.59 ± 154.3 and 343.75 ± 25.56 mg kg(-1), respectively). The caffeine content in coffee nectar (1.64 mg kg(-1)) was approximately 8-fold lower than that in honey (12.02 ± 0.81 mg kg(-1)).


The survival of heavy ion-irradiated Bcl-2 overexpressing radioresistant tumor cells and their progeny.
Here, we investigated the cell killing effectiveness of heavy-ion radiation in Bcl-2 overexpressing radioresistant tumor cells. First, irradiated cells underwent primary colony formation. Radioresistance decreased with increasing linear energy transfer (LET), indicating that heavy ions may be a promising therapeutic modality for Bcl-2 overexpressing tumors. Second, cells in primary colonies were reseeded for secondary colony formation. The incidence of delayed reproductive death increased with LET irrespective of Bcl-2 overexpression, suggesting that Bcl-2 overexpression may not facilitate heavy ion-induced genomic instability.


Isolation and crystal and molecular structures of [(C5H2Br3)2Fe], [(C5HBr4)2Fe] and [(C5Br5)(C5Br4HgBr)Fe].
The reaction of [(C5H3Br2)2Fe] with lithium tetramethylpiperidinide (LiTMP) in a 1:10 molar ratio in tetrahydrofuran yields, after quenching with C2H2Br4, a mixture of the polybromoferrocenes [C10H10-nBrnFe] with n = 4-9, from which single crystals of bis(1,2,3-tribromocyclopentadienyl)iron(II), [Fe(C5H2Br3)2], and bis(1,2,3,4-tetrabromocyclopentadienyl)iron(II), [Fe(C5HBr4)2Fe], were obtained by a combination of chromatography and fractional crystallization. Treatment of `[C10(HgOAc)10Fe]' with KBr3 yields a mixture of polybromoferrocenes [C10H10-nBrnFe] with n = 8-10 and bromomercurioferrocenes [C10H9-nBrn(HgBr)Fe] with n = 7-9, from which single crystals of (1-bromomercurio-2,3,4,5-tetrabromocyclopentadienyl)(1,2,3,4,5-pentabromocyclopentadienyl)iron(II), [FeHgBr(C5Br4)(C5Br5)], were obtained by fractional crystallization. The crystal structures of all the compounds show Br...Br, Br...H and sometimes Br...Cp...π (Cp is a ring centroid) interactions, as well as π-π interactions. The findings are supported by Hirshfeld analyses.


The identification of two novel prostaglandins and a thromboxane.
6,15-Dioxo-PGF1alpha, 6,15-dioxo-13,14-dihydro-PGF1alpha and 15-oxo-thromboxane B2 have been identified in incubates of ram seminal vesicle homogenates with added arachidonic acid or in the perfusate from sensitised challenged guinea pig lungs. These compounds are probably related to 6-oxo-PGF1alpha and thromboxane B2. The structures have been determined by gas chromatography mass spectrometry, following suitable chemical derivatisation.


The antithrombotic effect of melagatran in combination with clopidogrel and/or aspirin (carotid artery primary thrombosis study).
Melagatran with aspirin and/or clopidogrel was evaluated for prevention of arterial thrombosis in a model of vessel wall injury. Thirty-five dogs were randomized to receive placebo (n=14), aspirin (7 to 8 mg/kg, p.o. q12 h for three doses with the last dose administered 12 hours before surgery, n=7), clopidogrel (1 mg/kg p.o. QDx3, n=7), or aspirin+clopidogrel (n=7). The right carotid artery (RCA) was the control vessel, whereas the left carotid artery (LCA) was subjected to injury after administration of Melagatran (0.033 mg/kg i.v.+0.1 mg/kg/h). Clopidogrel, but not aspirin pretreatment, increased time (135.6+/-13.5 vs. 116.1+/-27.8 minutes) to RCA thrombosis versus placebo (88.1+/-10.5 minutes). Melagatran prolonged time to occlusion (min) in the LCA (192.4+/-10.9) versus the placebo-treated RCA (88.1+/-10.5). Addition of Melagatran plus aspirin or clopidogrel prevented formation of occlusive thrombosis, in all LCAs. A two-fold increase in tongue bleeding time was observed after aspirin+Melagatran (178.6+/-14.7 to 347.1+/-87.3 seconds) or clopidogrel+Melagatran (279.9+/-97.3 to 437.1+/-142.5 seconds). However, the combination of aspirin and clopidogrel prevented occlusive thrombosis in the RCA and the subsequent addition of Melagatran did not further increase bleeding time. The combination of Melagatran+aspirin or clopidogrel can reduce formation of occlusive arterial thrombosis without eliciting a significant increase in bleeding-time.


The reproductive and occupational health of women street vendors in Johannesburg, South Africa.
While the informal sector is rapidly emerging as the major source of employment in poor countries, little attention has been paid to the health hazards encountered by workers in this sector. Women, the majority of informal sector workers in most parts of the world, are particularly at risk. This paper reports on 422 women street vendors trading in 323 city blocks in Johannesburg, South Africa. The median age was 29 years, 66% were single, 29% had primary education and 58% had secondary schooling. Foreign-born women accounted for 15% of the sample and a further 59% of the women were not born in Johannesburg. More than a third of the women did not work for themselves and 48% earned <115 US dollars per month. Fertility was positively related to age and inversely related to education, while reported infertility was related to gynaecological disease. More than half the women used, mainly injectable, contraceptives and only 5% reportedly had PAP smears taken. Most of the women sold food and clothing, 51% lifted heavy weights and a small proportion of the women worked with fire. Over half of the women (54%), mainly those over 40 years and the self-employed, complained of a work-related illness or injury, mainly burns, cuts, headaches and musculoskeletal problems. The type of health problem was related to age and 32% had received treatment. More than half (52%) of the respondents reported that they were not comfortable with the working environment, for reasons ranging from lack of shelter and dirt (34%), noise (26%) and having to clean the area themselves (24%). While only 2% reported that they felt unsafe, violence and abuse was ever present. Approximately one in four women reported some form of abuse, either verbal or physical, while 7% reported that they had been sexually harassed. A substantial proportion (29%) of the women reported that they had been robbed of money or goods while trading in the streets. The implications of these findings are discussed.


Augmented upper body contribution to oxygen uptake during upper body exercise with concurrent leg functional electrical stimulation in persons with spinal cord injury.
The purpose of this pilot study was to compare the contribution of upper body musculature to VO2 with and without concurrent leg FES (LFES). Eight subjects with spinal cord injury, lesion levels range C6-T12, performed upper body exercise (UBE) during no LFES (NOS), LFES at 40 mA (LOS), and 80 mA (HIS), at rest, 60% and 80% of VO2peak. Resting VO2 values were obtained during NOS, LOS and HIS conditions and were then subtracted from their respective whole body VO2 values to give an estimate of upper body VO2. Small and non significant increases were found in the HIS vs NOS condition at 60% VO2peak. Larger differences of 7.8% were found in the HIS vs NOS condition at 80% VO2peak (11.35+/-3.8 ml kg(-1) min(-1) to 12.24+/-4.0 ml kg(-1) min(-1)), although this too was not significant, perhaps due to the small number of subjects in this study and the consequently low statistical power to detect a significant difference. We discuss the implications for these preliminary results in the context of the existing literature on this topic.


Telmisartan as a metabolic sartan for targeting vascular failure.
An angiotensin II type 1 receptor blocker (ARB), telmisartan, has the unique property of activation of PPAR-gamma. This review aims to discuss clinical perspective of telmisartan for cardiovascular protection. Recent in vitro and in vivo telmisartan data in regard to metabolic regulations were overviewed. Telmisartan has direct cardiovascular end-organ protection that goes beyond blood pressure control. In addition, it ameliorates insulin resistance and hypertriglyceridemia, and thereby improves metabolic syndrome. Moreover, it reduces total cholesterol and low-density lipoprotein (LDL)-cholesterol levels, although the mechanisms have not been elucidated. The authors propose to classify this unique ARB as a 'metabolic sartan'. To reduce cardiovascular mortality or morbidity, intense effort should be focused on aggressively modifying risk factors and the early stage of 'vascular failure'. A metabolic sartan may be a powerful tool for targeting 'vascular failure'.


Potential applications of PET/MRI in non-oncologic conditions within the abdomen and pelvis.
PET/MRI is a relatively new imaging modality with several advantages over PET/CT that promise to improve imaging of the abdomen and pelvis for specific diagnostic tasks by combining the superior soft tissue characterization of MRI with the functional information acquired from PET. PET/MRI has an established role in staging and response assessment of multiple abdominopelvic malignancies, but the modality is not yet established for non-oncologic conditions of the abdomen and pelvis. In this review, potential applications of PET/MRI for non-oncologic conditions of abdomen and pelvis are outlined, and the available literature is reviewed to highlight promising areas for further research and translation into clinical practice.


Transient analysis of vestibular nystagmus.
The significance of a nystagmus-dependent, transient component in the overall slow-phase response of the vestibulo-ocular reflex (VOR) is brought into focus. First, a simulated example is presented that shows how this transient component can bias current algorithms for the estimation of VOR parameters. Second, new algorithms are proposed that are able to estimate VOR parameters regardless of the presence of transients. Third, the new algorithms are applied to experimental data, and the results are compared with those from current algorithms. The results clearly show that the transient component can significantly alter the apparent VOR time constant, particularly when the reflex has been lesioned. The algorithms open new areas of research on the possible role of nystagmus in enhancing the compensatory function of the VOR.


CSF neopterin and beta-2-microglobulin as inflammation biomarkers in newborns with hypoxic-ischemic encephalopathy.
Inflammation plays a crucial role in the pathogenesis of hypoxic-ischemic encephalopathy (HIE). The aim of this study was to measure inflammation in HIE through an analysis of CSF neopterin and β2-microglobulin and to study the association with brain injury as shown by MRI findings and neurodevelopmental outcomes. CSF biomarkers were measured in study patients at 12 and 72 h. Brain injury was evaluated by MRI, and neurodevelopmental outcomes were assessed at 2-3 years of life. An adverse outcome was defined as the presence of motor or cognitive impairment. Sixty-nine HIE infants were included. Median values of neopterin and β2-microglobulin paralleled the severity of HIE. Adverse outcomes were associated with early neopterin and β2-microglobulin values, late neopterin values, and the neopterin percentage change between the two samples. A cutoff value of 75% neopterin change predicted adverse outcomes with a specificity of 0.9 and a sensitivity of 0.75. CSF neopterin and β2-microglobulin are elevated in HIE, indicating the activation of inflammation processes. Infants with adverse neurodevelopmental outcomes show higher levels of CSF neopterin and β2-microglobulin. The evolution of neopterin levels provides a better predictive capacity than a single determination. Brain inflammation in newborns with HIE could be measurable through the analysis of CSF neopterin and β2-microglobulin, both of which are associated with neurodevelopmental outcomes. Our study introduces two inflammatory biomarkers for infants with HIE that seem to show a more stable profile and are easier to interpret than cytokines. CSF neopterin and β2-m may become clinical tools to monitor inflammation in HIE and might eventually be helpful in measuring the response to emerging therapies.


Intermittent Cushing's disease.
Described here is a young woman with intermittent Cushing's disease associated with psychotic disturbance. On five occasions, over a period of four years, she became severely depressed and had acne, amenorrhea, hirsuties and moon facies. On each of the first four occasions the symptoms lasted from two to three months and disappeared spontaneously. Biochemical investigations, including plasma ACTH estimations during the last two episodes, indicated that the adrenocortical overactivity was pituitary-dependent. During the fifth relapse the patient experienced a very severe, depressive psychosis, necessitating bilateral adrenalectomy, which resulted in complete remission.


Transplanted human neurons derived from a teratocarcinoma cell line (NTera-2) mature, integrate, and survive for over 1 year in the nude mouse brain.
Retinoic acid (RA) induces a human teratocarcinoma cell line (NTera-2 or NT2) to give rise exclusively to post-mitotic neuron-like (NT2N) cells, but NT2N cells never acquire a fully mature neuronal phenotype in vitro. To determine whether NT2N cells can mature into adult neuron-like cells in vivo, purified NT2N cells were grafted into different regions of the central nervous system (CNS) of adult and neonatal athymic mice, and the grafts were examined immunohistochemically by light, confocal, and electron microscopy using antibodies to a panel of developmentally regulated neuronal polypeptides. NT2N grafts were distinguished from endogenous mouse neurons with antibodies that recognize human or murine specific epitopes in selected neuronal polypeptides. Viable NT2N cells were identified in > 89% of graft recipients (N = 90), and some grafts survived 14 months. Within 3 weeks of implantation, grafted NT2N cells re-extended their processes, and the location of the grafts (e.g., septum versus neocortex) appeared to determine the extent to which processes were elaborated. Within the early post-transplantation period, grafted NT2N cells expressed the same neuronal polypeptides as their in vitro counterparts. However, between 6 weeks and 4-6 months post-implantation, the grafted NT2N cells progressively acquired the molecular phenotype of fully mature in vivo neurons as evidenced by dramatically increased expression of the most highly phosphorylated isoforms of the heavy neurofilament subunit, and the de novo expression of adult CNS tau. Notably, the time course for the extension of processes and the expression of neuronal polypeptides by NT2N grafts was similar in neonatal and adult mice. Although grafted NT2N cells formed synapse-like structures and elaborated dendrites and axons, these axons remained unmyelinated. Finally, none of the transplanted NT2N cells reverted to a neoplastic state. These studies demonstrate that pure populations of grafted human NT2N cells acquire a fully mature neuronal phenotype in vivo, and that these cells integrate and survive for > 1 year post-implantation in the mouse CNS. These human neuron-like cells are an attractive model system for studies of neuronal development, polarity and transplantation.


Validation of a real-time RT-PCR assay for sensitive and specific detection of classical swine fever.
A fully validated, ready-to-use, real-time reverse transcription-polymerase chain reaction (RT-PCR) assay, multiplexed for simultaneous detection of an internal control, for the simple and rapid diagnosis of classical swine fever (CSF) was developed. Primers and FAM-labeled TaqMan-probes specific for classical swine fever virus (CSFV) were selected from the consensus sequence of the 5' non-translated region (5' NTR) of 78 different CSFV strains. For determining analytical sensitivity, an in vitro transcript (T7-PC3alf) of the 5' NTR was constructed and tested. In addition, the T7-PC3alf transcript was further used as a positive control and a standard for quantitation of CSFV genome copies. A second heterologous in vitro transcript based on a specific primer-probe HEX-system was designed as an internal positive control for the RNA isolation step and RT-PCR. By using limited primer concentrations for the internal control, no adverse effects on the sensitivity of the CSF-system could be observed, and the newly designed duplex real-time RT-PCR proved to have a sensitivity of approximately eight copies. The primer-probe combination selected was strictly CSFV-specific and no amplification was observed in all non-CSFV pestiviruses tested.


Impacts of diclidophorid monogenean infections on fisheries in Japan.
Many monogeneans are pathogenic to economically important fish in Japan. However no other monogenean is comparable with the diclidophorids, Heterobothrium okamotoi and Neoheterobothrium hirame, on the scale of impacts they inflict on Japanese fisheries. The shared importance of the two monogenean infections lies in their pathogenicity, fecundity and tolerance to chemical treatment. Heterobothrium okamotoi infects the gills and wall of the branchial cavity of the tiger puffer, Takifugu rubripes (Tetraodontidae), which is widely cultured in western Japan. The main presenting signs of infected fish are anaemia and extensive necrosis caused by adult worms. This monogenean deposits long strings of eggs, which reach lengths of almost 3 m. Egg entanglement with the mesh of culture nets increases the chance of hatched larvae encountering susceptible fish. The oncomiracidium maintains infectivity for up to 4 days after hatching. Hydrogen peroxide is the only commercially available chemical able to control the infection, but can only kill immature worms on the gills. Neoheterobothrium hirame infects the gills and wall of the buccal cavity of the Japanese flounder, Paralichthys olivaceus (Paralichthyidae). Since the first known occurrence of this monogenean in 1993, the species has been recorded from almost all areas where the host is distributed. Neoheterobothrium hirame has the potential to produce 781 eggs per day at 20 degree C. In the western Sea of Japan, wild young-of-the-year flounder became infected in early summer, followed by a sharp increase in prevalence in late summer. By late summer, juvenile flounder have nearly disappeared from the area, strongly suggesting that N. hirame is responsible for mortality of young fish. This is in good agreement with the recent decline in the local flounder population. Neoheterobothrium hirame has also been considered the causative agent of anaemia among wild Japanese flounder since the late 1990s.


Endoscopic treatment of benign anastomotic esophageal stenosis with electrocautery.
Stricture of the esophagus following surgical resection is uncommon. Several methods have been described for treatment of this entity, but the therapeutic success may be impaired either by poor long-term results or by poor acceptance by patients. Even the high cost of the therapeutic management may represent a problem. We describe the use of electrocautery to treat benign anastomotic esophageal stenosis. Six unselected consecutive patients (four men, two women; mean age 68.3, range 54 - 82) with stenosis following esophagojejunostomy were enrolled in this trial. Postoperative stenoses were shown endoscopically (four patients) or radiographically (two patients). We performed endoscopic dilation of the strictures using electrocautery. In all patients we obtained dilation of the strictures, without any immediate or delayed procedure-related complication. No recurrence of the stenosis was demonstrated during a mean 24-month follow-up (range 8 - 33 months). This study showed that endoscopic electrocautery is a safe and effective treatment for benign anastomotic esophageal stenosis.


Homogeneous gels for capillary electrochromatography.
Homogeneous gels represent a new type of (electro)chromatographic media possessing unique separation properties unmatched with any other chromatographic beds. It is important to emphasize that they principally differ from continuous beds, polymer rods (better known as monoliths), which are particulate separation media with pores permitting hydrodynamic flow through the columns. Monoliths, thus, are more similar to beds conventionally packed with beads, although the particles building up monolithic columns are usually smaller in size (few submicometers) and covalently linked together. Consequently, homogeneous gels deserve better the term "monoliths" having a non-particulate structure formed by crosslinked free polymer chains (according to a dictionary a monolith is a non-modularized column). The goals of this minireview are to clarify the position of homogeneous gels among the separation media (including polymer solutions), to explain and to exemplify their outstanding (electro)chromatographic properties. This review gives hopefully a complete list of references to homogeneous gels developed for capillary electrochromatography.


Spontaneous epileptiform activity of CA1 hippocampal neurons in low extracellular calcium solutions.
Lowering extracellular [Ca2+] in rat hippocampal slices induces spontaneous epileptiform activity in area CA1, which is characterized by rhythmic burst firing of CA1 neurons and by prolonged negative potential shifts at the pyramidal cell body layer. This activity is accompanied by transient decreases of [Na+] and increases of [K+] in the extracellular space. In spite of the complete blockade of synaptic transmission, the wave of epileptiform activity propagates across area CA1. These findings suggest, that non-synaptic mechanisms may play a role in the generation and spread of epileptiform activity in the mammalian CNS.


Newly synthesized extracellular ribonucleic acids in the amphibian gastrula.
The possible synthesis of RNA located in the extracellular compartment of Bufo arenarum gastrula was studied using a biochemical method. [3H]adenosine was microinjected into the blastocoel of late blastulae or early gastrulae, which were then dissociated at advanced gastrula stage. RNA was extracted from both, the cellular supernatant and the disaggregated cells, by the Kirby-phenol procedure. Most of the ethanol-precipitable radioactivity was sensitive to RNase and alkaline treatment. The partial characterization of these molecules indicate that the radioactive pattern of total RNA, found in sucrose gradients, the ratio Poly(A)+RNA/Poly(A)-RNA as well as the radioactive pattern of Poly(A) fraction in acrylamide gels were different in samples from cellular and from extracellular origin. Although not conclusive, these results are proposed as a new argument for the existence of an extracellular RNA in the amphibian embryo.


A Patient-Level Data Meta-analysis of the Abscopal Effect.
The abscopal effect is defined when a form of local therapy causes tumor regression of both the target lesion and any untreated tumors. Herein cases of the abscopal effect were systematically reviewed and a patient-level data analysis was performed for clinical predictors of both duration of response and survival. The Population, Intervention, Control, Outcome, Study (PICOS) design approach, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) literature selection process, and Meta-analysis of Observational Studies in Epidemiology (MOOSE) were used to find articles published before September 2019 in MEDLINE/PubMed and Google Scholar. Inclusion criteria were (1) population: patients with reported abscopal response; (2) intervention: documented treatment(s); (3) control: none; (4) outcomes: overall and progression-free survival; and (5) setting: retrospective case reports. Time from treatment until abscopal response and time from abscopal response until progression/death were calculated. Univariate and multivariate analyses were conducted for survival outcomes. Fifty studies (n = 55 patients) were included. Median age was 65 years (interquartile range [IQR], 58-70) and 62% were male. Fifty-four (98%) patients received radiation therapy, 34 (62%) received radiation therapy alone, 5 (9.1%) underwent surgery, 4 (7.3%) received chemotherapy, and 11 (20%) received immunotherapy. Median total dose was 32 Gy (IQR, 25.5-48 Gy) and median dose per fraction was 3 Gy (IQR, 2-7.2). Median time until abscopal response was 4 months (IQR, 1-5; min 0.5, max 24). At 5 years, overall survival was 63% and distant progression-free survival was 45%. No variables had statistical significance in predicting duration of response or survival. Almost all reported cases of the abscopal response are after radiation therapy; however, there are no known predictors of duration of response or survival in this population.


Spectrum of Cantrell's pentalogy: case series from a single tertiary care center and review of the literature.
The pentalogy of Cantrell (PC) was first described in 1958. It includes five anomalies: a deficiency of the anterior diaphragm, a midline supraumbilical abdominal wall defect, a defect in the diaphragmatic pericardium, various congenital intracardiac abnormalities, and a defect of the lower sternum. Five patients showing the PC spectrum are reported. The report presents the prenatal diagnosis, the postnatal course, and the patients' outcome at a tertiary care center from June 2001 to May 2012. A literature review and the management plan for this group of patients also are discussed. All patient data were obtained via electronic medical records retrospectively after approval by the institutional review board at the home institution. The patients in the study were three males and two females. For all of the patients, a prenatal diagnosis had been determined. The mean gestational age at delivery was 36.6 weeks. One patient had associated cranial and spine malformations. All the patients had associated congenital heart disease but a normal karyotype. Four of the five patients died in the first year of life. The ages at death ranged from 0 to 259 days (mean, 46.2 ± 51.8 days). The patients who did not survive had withdrawal of care due to increased morbidity, associated complications, or parental wishes. The pentalogy of Cantrell is a wide spectrum of associations. Patients with the complete PC together with complex congenital heart disease or extracardiac malformations may have a poor prognosis. Incomplete PC cases may have a better outcome based on associated anomalies. Prenatal counseling plays a very important role in the decision-making process for the families and has a significant impact on the postnatal management. A multidisciplinary team approach is essential for successful postpartum outcomes.


The C2 domains of synaptotagmin--partners in exocytosis.
Rapid signaling between neurons relies on the Ca(2+)-triggered exocytosis of neurotransmitters. Release is mediated by 'kiss-and-run' or complete fusion of secretory organelles with the plasma membrane. Current models indicate that exocytosis is regulated by synaptotagmin I (syt) and mediated by SNARE (soluble NSF-attachment protein receptor) proteins. Syt senses Ca(2+) via two conserved motifs, C2A and C2B. C2B engages a wider array of effector molecules than C2A and appears to play a more crucial role in synaptic transmission. However, it has recently become clear that the tandem C2 domains of syt influence each another in unexpected ways. Here, we focus on recent structure-function studies that are beginning to provide insights into the mechanism through which the C2 domains of syt trigger exocytosis.


Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization.
Immobilization of antibodies and enzyme-labeled antibodies by radiation polymerization at low temperatures was studied. The antibody activity of antibody was not affected by irradiation at an irradiation dose of below 8 MR and low temperatures. Immobilization of peroxidase-labeled anti-rabbit IgG goat IgG, anti-peroxidase, peroxidase, and anti-alpha-fetoprotein was carried out with hydrophilic and hydrophobic monomers. The activity of the immobilized enzyme-labeled antibody membranes varied with the thickness of the membranes and increased with decreasing membrane thickness. The activity of the immobilized antibody particles was varied by particle size. Immobilized anti-alpha-fetoprotein particles and membranes can be used for the assay of alpha-fetoprotein by the antigen-antibody reaction, such as a solid-phase sandwich method with high sensitivity.


CMOS-compatible, label-free silicon-nanowire biosensors to detect cardiac troponin I for acute myocardial infarction diagnosis.
A label-free biosensor for electrical detection of cardiac troponin I (cTnI), a highly sensitive and selective biomarker of acute myocardial infarction (AMI), is demonstrated using silicon nanowire (SiNW) based field-effect transistors (FETs). The FET devices were fabricated by a complementary metal oxide semiconductor (CMOS) compatible top-down approach to define the SiNW followed by tetramethylammonium hydroxide (TMAH) wet etching. Electrical characterizations of the SiNW FET revealed an ambipolar conduction characteristic with an on/off ratio of 10(5)-10(6). CTnI monoclonal antibodies were then covalently immobilized on the SiNW surfaces. By integrating with a homemade biosensor measurement system, the biosensor exhibited rapid and sensitive response to cTnI proteins. The current response showed a nature of logarithm relationship against the cTnI concentration from 46 ng/mL down to 0.092 ng/mL. Moreover, an anti-interference capability of the fabricated biosensor was also assessed. By utilizing the top-down fabrication method, this work provides an efficient way for the cTnI proteins detection with an enormous potential of mass-production, which definitely facilitate the practical applications.


Context, attention, and the switch between habit and goal-direction in behavior.
This article reviews recent findings from the author's laboratory that may provide new insights into how habits are made and broken. Habits are extensively practiced behaviors that are automatically evoked by antecedent cues and performed without their goal (or reinforcer) "in mind." Goal-directed actions, in contrast, are instrumental behaviors that are performed because their goal is remembered and valued. New results suggest that actions may transition to habit after extended practice when conditions encourage reduced attention to the behavior. Consistent with theories of attention and learning, a behavior may command less attention (and become habitual) as its reinforcer becomes well-predicted by cues in the environment; habit learning is prevented if presentation of the reinforcer is uncertain. Other results suggest that habits are not permanent, and that goal-direction can be restored by several environmental manipulations, including exposure to unexpected reinforcers or context change. Habits are more context-dependent than goal-directed actions are. Habit learning causes retroactive interference in a way that is reminiscent of extinction: It inhibits, but does not erase, goal-direction in a context-dependent way. The findings have implications for the understanding of habitual and goal-directed control of behavior as well as disordered behaviors like addictions.


Carotid artery stenting in clinical practice: does sex matter? Results from the carotid artery stenting registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK).
Carotid artery stenting (CAS) is increasingly used for treatment of severe carotid artery stenosis, but only few procedural risk factors for complications of CAS are clearly defined yet. A possible impact of the patient's gender on the outcome of patients undergoing CAS has not been investigated properly and only little information about this topic is available so far. We analysed data of the German prospective, multicenter CAS Registry of the Arbeitsgemeinschaft leitende kardiologische Krankenhausärzte. From July 1996 to May 2009 5130 patients underwent CAS at 35 German hospitals and were enrolled into the prospective ALKK CAS Registry. Therefrom 1443 (28.1%) patients were female. There was no significant time-related difference in the proportion of women undergoing CAS over the years. Women undergoing CAS were significantly older than men (73 years vs. 70 years, p < 0.01) and had a longer in hospital stay in comparison to men (p < 0.01). The majority of patients treated with CAS was between 60 and 80 years of age (∼73%). No significant differences between women and men could be found regarding in-hospital events like death (0.5% vs. 0.5%, p = 0.99), major or minor stroke (1.7% vs. 1.6%, p = 0.97; 1.0% vs. 1.6%, p = 0.12), TIA (2.8% vs. 2.6%, p = 0.64), amaurosis fugax (0.3% vs. 0.5%, p = 0.25) , intracranial bleeding (0.5% vs. 0.3%, p = 0.43), myocardial infarction (0.1% vs. 0.0%, p = 0.48) or all non-fatal strokes and all death (3.0% vs. 3.4%, p = 0.47). 30 day event rates did not show gender related differences in the combined endpoint of the outcome of patients undergoing CAS, as well (♀ n = 31/882 [3.5%] vs. ♂ n = 109/2273 [4.8%], p = 0.12). Our results do not suggest any gender-related differences in success rates and complications in CAS. In clinical practice approximately 30% of patients treated with CAS are women. The institutions and people who participated in the ALKK CAS Registry are listed in Zahn et al.16 The authors have no funding, financial relationships, or conflicts of interest to disclose.


Cancer gene expression signatures - the rise and fall?
A 'gene expression signature' can be defined as a single or a combined gene expression alteration with validated specificity in terms of diagnosis, prognosis or prediction of therapeutic response. Since the publication of the first signature in the late 90s, high-throughput gene expression analysis has revolutionised genetics over the last 15 years. The scientific community has used this new technology to find responses to these fundamental questions; from understanding tumour biology, to prediction of progression, and treatments to which it will respond. Nevertheless, legitimate excitement about the attractiveness of molecular technologies and the promise of discovery-based research should not overlook adherence to the rules of evidence, otherwise it may result in claims that are not meaningful and lead to disappointment. This review will thus focus on the approaches developed to answer these three fundamental questions and the results evidenced both at biological and clinical level. On looking at this huge amount of data that have become increasingly minute, and at times contradictory, we discuss how gene expression signature improve our understanding of cancer biology, our ability to predict progression and response, and finally, our capacity to treat cancers more efficiently.


Oral Inoculation of Point-of-Lay Hens with the New South Wales Outbreak Strain of Salmonella Enteritidis Phage Type 12 Causes Infection, but Minimal Histopathology.
An outbreak of food poisoning in New South Wales (NSW) Australia in 2018, caused by Salmonella enterica serovar Enteritidis phage type 12 (PT12), was traced to eggs consumed from a NSW layer flock. This was the first report of Salmonella Enteritidis infection in NSW layer flocks, despite ongoing environmental monitoring. Clinical signs and mortalities were minimal in most flocks, although seroconversion and infection were demonstrated in some flocks. An oral dose-response challenge study with Salmonella Enteritidis PT12 was undertaken in commercial point-of-lay hens. Cloacal swabs collected at 3, 7, 10, and 14 days postinoculation and caeca, liver, spleen, ovary, magnum, and isthmus tissues collected at necropsy at either 7 or 14 days were processed for Salmonella isolation (AS 5013.10-2009 from ISO6579:2002). Histopathology was performed on the above tissues, as well as lung, pancreas, kidney, heart, and additional intestinal and reproductive tract tissues. Salmonella Enteritidis was consistently detected in cloacal swabs between 7 and 14 days postchallenge. The Salmonella Enteritidis PT12 isolate successfully colonized the gastrointestinal tract, liver, and spleen of all hens orally challenged with 107, 108, and 109 Salmonella Enteritidis, and less consistently colonized their reproductive tracts. On histopathology, mild lymphoid hyperplasia in the liver and spleen, along with hepatitis, typhlitis, serositis, and salpingitis, was observed at 7 and 14 days postchallenge, with a greater proportion of affected birds in the two higher dose groups. Diarrhea and culture of Salmonella Enteritidis from heart blood were not detected in challenged layers. The NSW isolate of Salmonella Enteritidis PT12 was able to invade and colonize the birds' reproductive tracts as well as a wide range of other tissues, indicating the potential for these naive commercial hens to contaminate their eggs.


Target-specific delivery of peptide-based probes for PET imaging.
Positron emission tomography (PET) is one of the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with various diseases. The principal goal of PET imaging is to visualize, characterize, and measure biological processes at the cellular, subcellular, and molecular level in living subjects with non-invasive procedures. PET imaging takes advantage of the traditional diagnostic imaging techniques and introduces positron-emitting probes to determine the expression of indicative molecular targets at different stages of disease. During the last decade, advances in molecular biology have revealed an increasing number of potential molecular targets, including peptide receptors and peptide-related biomolecules. With the help of sophisticated bioconjugation and radiolabeling techniques, numerous peptide-based agents have been developed and evaluated for delivery of PET radionuclides to the specific molecular targets in preclinical and clinical studies. As compared to macromolecules, such as proteins or antibodies, low-molecular-weight peptides have their distinctive advantages and predominantly demonstrate their favorable pharmacokinetics for in vivo PET applications. This review summarizes the criteria of peptide-based PET probes design, the selection of radioisotopes, labeling methods, and provides an overview of the current status and trends in the development of target-specific peptide-based probes with respect to their unique PET imaging applications.


In vitro generation of cytotoxic lymphocytes by tumor extracts of transitional cell carcinoma.
Results of experiments in which in vitro generation of cytotoxic lymphocytes were used are presented. Problems of specificity and levels of cytotoxicity are also briefly discussed.


Selective attention in a multiple-response reaction-time task.
Consistently higher correlations (.74 to .89) were noted between hand and foot RT of 7 subjects assigned to a contralateral group than for another 7 assigned to an ipsilateral group (rs = .80 to .51). Subjects button pressed to onset of a light.


Successful treatment of JAK1-associated inflammatory disease.
Gain-of-function variants of JAK1 drive a rare immune dysregulation syndrome associated with atopic dermatitis, allergy, and eosinophilia. This study sought to describe the clinical and immunological characteristics associated with a new gain-of-function variant of JAK1 and report the therapeutic efficacy of Janus kinase (JAK) inhibition. The investigators identified a family affected by JAK1-associated autoinflammatory disease and performed clinical assessment and immunological monitoring on 9 patients. JAK1 signaling was studied by flow and mass cytometry in patients' cells at basal state or after immune stimulation. A molecular disease signature in the blood was studied at the transcriptomic level. Patients were treated with 1 of 2 JAK inhibitors: either baricitinib or upadacitinib. Clinical, cellular, and molecular response were evaluated over a 2-year period. Affected individuals displayed a syndromic disease with prominent allergy including atopic dermatitis, ichthyosis, arthralgia, chronic diarrhea, disseminated calcifying fibrous tumors, and elevated whole blood histamine levels. A variant of JAK1 localized in the pseudokinase domain was identified in all 9 affected, tested patients. Hyper-phosphorylation of STAT3 was found in 5 of 6 patients tested. Treatment of patients' cells with baricitinib controlled most of the atypical hyper-phosphorylation of STAT3. Administration of baricitinib to patients led to rapid improvement of the disease in all adults and was associated with reduction of systemic inflammation. Patients with this new JAK1 gain-of-function pathogenic variant displayed very high levels of blood histamine and showed a variable combination of atopy with articular and gastrointestinal manifestations as well as calcifying fibrous tumors. The disease, which appears to be linked to STAT3 hyperactivation, was well controlled under treatment by JAK inhibitors in adult patients.


Entrapment of DyP-type peroxidase from Pseudomonas fluorescens Pf-5 into Ca-alginate magnetic beads.
The aim of this study was to investigate the optimal conditions for the immobilization and stabilization of DyP1B dye decolorizing peroxidases type B (DyP1B) from Pseudomonas fluorescens Pf-5 immobilized in Ca-alginate ferromagnetic beads. The immobilized DyP1B was used in the degradation of the Reactive Blue 5 (RB5) synthetic dye. The enzyme was successfully entrapped in a Ca-alginate matrix and showed an encapsulation efficiency of 94%. The concentration of DyP1B (0.8 mg mL-1 ), 2% of alginate and magnetite (10.0 mg mL-1 ) was optimal for immobilization. The immobilized DyP1B showed optimum activity at pH 7.0 and 40 °C compared with pH 5.5 and 30 °C for free peroxidase. Reusability studies showed that after five cycles, the immobilized DyP1B system retained more than 58% of its initial activity. The immobilized DyP1B was able to decolorize RB5 at concentrations of 0.1, 0.05, and 0.01% (w v-1 ) with efficiency rates of about 20, 29, and 45%, respectively. The immobilization of DyP1B in alginate beads with the addition of Fe3 O4 increased its catalytic and applicative potential.


Pediatric Symptom Checklist: screening school-age children for psychosocial dysfunction.
The Pediatric Symptom Checklist (PSC) is a 35-item screening questionnaire that is completed by parents and designed to help pediatricians in outpatient practice identify school-age children with difficulties in psychosocial functioning. The current study assessed the validity of the PSC by screening 300 children in two pediatric practices, a middle-class group practice and an urban health maintenance organization. Validity was established by comparing the results of PSC screening of 48 children with in-depth interview assessments and pediatricians' ratings. Results indicate that the PSC has a specificity of 0.68 and a sensitivity of 0.95. The screening process was well accepted by parents and pediatricians. Several children whose pediatricians' ratings had indicated adequate functioning were identified by the PSC as having substantial psychosocial dysfunction and requiring further evaluation.


Optimized cell type signatures revealed from single-cell data by combining principal feature analysis, mutual information, and machine learning.
Machine learning techniques are excellent to analyze expression data from single cells. These techniques impact all fields ranging from cell annotation and clustering to signature identification. The presented framework evaluates gene selection sets how far they optimally separate defined phenotypes or cell groups. This innovation overcomes the present limitation to objectively and correctly identify a small gene set of high information content regarding separating phenotypes for which corresponding code scripts are provided. The small but meaningful subset of the original genes (or feature space) facilitates human interpretability of the differences of the phenotypes including those found by machine learning results and may even turn correlations between genes and phenotypes into a causal explanation. For the feature selection task, the principal feature analysis is utilized which reduces redundant information while selecting genes that carry the information for separating the phenotypes. In this context, the presented framework shows explainability of unsupervised learning as it reveals cell-type specific signatures. Apart from a Seurat preprocessing tool and the PFA script, the pipeline uses mutual information to balance accuracy and size of the gene set if desired. A validation part to evaluate the gene selection for their information content regarding the separation of the phenotypes is provided as well, binary and multiclass classification of 3 or 4 groups are studied. Results from different single-cell data are presented. In each, only about ten out of more than 30000 genes are identified as carrying the relevant information. The code is provided in a GitHub repository at https://github.com/AC-PHD/Seurat_PFA_pipeline.


Cortical excitability changes correlate with fluctuations in glucose levels in patients with epilepsy.
We used transcranial magnetic stimulation (TMS) to investigate motor cortical excitability changes in relation to blood glucose levels. Twenty-two drug-naïve patients with epilepsy [11 generalized and 11 focal] and 10 controls were studied twice on the same day; first after 12h of fasting and then 2h postprandial. Motor threshold and paired-pulse TMS at a number of short and long interstimulus intervals were measured. Serum glucose levels were measured each time. Decreased long intracortical inhibition was seen in patients and controls during fasting compared to postprandial studies. This effect was much more prominent in patients with generalized epilepsy (with effect sizes of up to 0.8) in whom there was also evidence of increased intracortical facilitation (effect size: 0.3). Cortical excitability varies with fluctuations in blood glucose levels. This variation is more prominent in patients with epilepsy. Decreased glucose levels may be an important physiological seizure trigger.


Piezo-Catalytic Effect on the Enhancement of the Ultra-High Degradation Activity in the Dark by Single- and Few-Layers MoS2 Nanoflowers.
Single- and few-layer MoS2 nanoflowers are first discovered to have a piezo-catalyst effect, exhibiting an ultra-high degradation activity in the dark by introducing external mechanical strains. The degradation ratio of the Rhodamine-B dye solution reaches 93% within 60 s under ultrasonic-wave assistance in the dark.


Modified carbon nitride nanozyme as bifunctional glucose oxidase-peroxidase for metal-free bioinspired cascade photocatalysis.
Nanomaterials-based biomimetic catalysts with multiple functions are necessary to address challenges in artificial enzymes mimicking physiological processes. Here we report a metal-free nanozyme of modified graphitic carbon nitride and demonstrate its bifunctional enzyme-mimicking roles. With oxidase mimicking, hydrogen peroxide is generated from the coupled photocatalysis of glucose oxidation and dioxygen reduction under visible-light irradiation with a near 100% apparent quantum efficiency. Then, the in situ generated hydrogen peroxide serves for the subsequent peroxidase-mimicking reaction that oxidises a chromogenic substrate on the same catalysts in dark to complete the bifunctional oxidase-peroxidase for biomimetic detection of glucose. The bifunctional cascade catalysis is successfully demonstrated in microfluidics for the real-time colorimetric detection of glucose with a low detection limit of 0.8 μM within 30 s. The artificial nanozymes with physiological functions provide the feasible strategies for mimicking the natural enzymes and realizing the biomedical diagnostics with a smart and miniature device.


A novel nanoaggregation detection technique of TNT using selective and ultrasensitive nanocurcumin as a probe.
Here, for the first time, we designed an ultrasensitive nanocurcumin based nanomaterials surface energy transfer (NSET) probe for detection of trace amount of TNT with excellent sensitivity (1 nM) and selectivity over other nitro explosives via nanoaggregation and we found the largest fluorescent enhancement to date for sensing TNT (upto 800 fold).


Cell-surface antigens induced by RNA tumour viruses.
Host animals show an immune response to the surface of cells infected with RNA tumour viruses. An element of this response is due to expression of viral structural antigens, but the major part is due to virus-induced cell-surface antigens (CSAs). This article compares the properties of CSAs of the avian, murine and feline retrovirus systems.


Studies of the mechanism of augmented synthesis of cholesteryl ester in atherosclerotic rabbit aortic microsomes.
A study was undertaken to test the hypothesis that an abnormally high concentration of acyl-CoA:cholesterol acyltransferase in atherosclerotic microsomes is partly responsible for augmented esterification of cholesterol. We approached the problem indirectly by measuring the incorporation of radioactivity into cholesteryl ester from [1-14C]palmityl-CoA in normal microsomes after enrichment of their concentration of microsomal free cholesterol to levels characteristic of atherosclerotic microsomes. Elevation of free cholesterol content induced increased cholesterol esterification approximately linearly over the range studied. The cholesterol-esterifying activity of atherosclerotic microsomes was not greater than that of normal microsomes having the same concentration of cholesterol. The results suggest that, with acyl-CoA constant, augmented cholesterol esterification in atherosclerotic microsomes is an effect of high microsomal cholesterol concentrations and not due to an increase in the concentration of the enzyme.


MRI of the normal orbit and optic pathway.
In recent years MRI has made increasingly important contributions to the evaluation of the orbit and optic pathway. The unique ability of MRI to demonstrate soft tissue contrast allows exquisite demonstration of anatomic detail. MRI technique and normal anatomy are reviewed. Today, optimal ophthalmologic work-up is often incomplete without the critical input of the radiologist.


Cisplatin chronotherapy and disulfiram rescue reduce toxicity without interfering with anticancer activity: animal findings and preliminary clinical experiences.
Cisplatin-induced mortality and nephrotoxicity are each predictably worse when the drug is given at certain points within the circadian schedule. Oral disulfiram protects rats from toxic effects at some circadian stages but not others. This manuever does not diminish the anticancer activity of cisplatin in these rats. Human beings given 2 g of oral disulfiram and high doses of cisplatin at the circadian stage associated with least cisplatin nephrotoxicity (prospectively determined potassium excretion acrophase) suffer little or no kidney damage. Disulfiram administration apparently does not interfere with the antineoplastic activity of cisplatin in humans. This is the first demonstration of the feasibility of assignment of treatment time according to a measure of the patient's 'internal clock' as assessed by pretreatment marker rhythmometry. It also establishes the feasibility of giving disulfiram to human beings.


MicroRNAs from saliva of anopheline mosquitoes mimic human endogenous miRNAs and may contribute to vector-host-pathogen interactions.
During blood feeding haematophagous arthropods inject into their hosts a cocktail of salivary proteins whose main role is to counteract host haemostasis, inflammation and immunity. However, animal body fluids are known to also carry miRNAs. To get insights into saliva and salivary gland miRNA repertoires of the African malaria vector Anopheles coluzzii we used small RNA-Seq and identified 214 miRNAs, including tissue-enriched, sex-biased and putative novel anopheline miRNAs. Noteworthy, miRNAs were asymmetrically distributed between saliva and salivary glands, suggesting that selected miRNAs may be preferentially directed toward mosquito saliva. The evolutionary conservation of a subset of saliva miRNAs in Anopheles and Aedes mosquitoes, and in the tick Ixodes ricinus, supports the idea of a non-random occurrence pointing to their possible physiological role in blood feeding by arthropods. Strikingly, eleven of the most abundant An. coluzzi saliva miRNAs mimicked human miRNAs. Prediction analysis and search for experimentally validated targets indicated that miRNAs from An. coluzzii saliva may act on host mRNAs involved in immune and inflammatory responses. Overall, this study raises the intriguing hypothesis that miRNAs injected into vertebrates with vector saliva may contribute to host manipulation with possible implication for vector-host interaction and pathogen transmission.


Rapid method for screening enoate reductase activity in yeasts.
Old Yellow Enzymes (OYEs, EC 220.127.116.11) are flavin-dependent oxidoreductases that catalyze the asymmetric reduction of electron-poor alkenes (enoate reductase activity). Since OYEs are involved in detoxification of acrolein, a high-throughput method for selecting yeasts expressing high enoate reductase activity, based on their acrolein resistance, was developed. The screening method was based on the measurement of growth in acrolein-supplemented medium, in 96-well microtiter plate cultures. A quantitative descriptor (Acrolein Resistance Factor=ARF) was firstly designed for quantifying the influence of both acrolein concentration and time of exposure on yeast growth. Besides, the efficiency of bioconversion of ketoisophorone (KIP) was exploited to measure OYE activity. In order to validate the method, ARF was correlated with the bioconversion of KIP on thirty yeast strains, belonging to 7 genera. With only a few exceptions, all strains exhibiting the highest ARF also displayed the maximum OYE activity. The presence of OYE genes in the strains showing OYE activity was confirmed by PCR amplification. Based on the results herein reported, this method should be profitably used as a fast screening procedure aimed at selecting outstanding strains for whole-cell bioconversions and could open many possibilities for the isolation and the biocatalytic exploitation of new OYEs from yeasts.


T-cell subsets in multiple sclerosis: relationships between peripheral blood and cerebrospinal fluid.
We contemporarily studied cerebrospinal fluid (CSF) and peripheral blood (PB) T-cell subsets, defined by monoclonal antibodies, in 29 patients with multiple sclerosis (MS) and 10 patients with other neurological diseases (OND). All subjects showed a clear-cut prevalence of CSF T-cells. Similarly, T-helper and T-suppressor subsets tended to show higher percentages in CSF in almost all subjects except relapsing MS, who were characterized by low percentages of T-suppressors in PB and even much lower percentages in CSF. Helper/suppressor ratios were found to be almost similar in the two body compartments of OND patients, lower in CSF than in PB of chronic progressive MS, always higher in CSF than in PB of relapsing MS. MS patients in remission showed both patterns of progressive MS and OND patients. Our results demonstrate that the loss of PB T-suppressor in relapsing MS is not due to a migration of such cells into CSF. Furthermore, regarding T-lymphocyte subsets, a typical CSF/PB pattern characterizes relapsing MS from other patients.


"Risk assessment for periodontal disease associated tooth loss among rural and urban population of 35-44, 45-54, 55-64 and 65-74 years age groups of Barabanki district, Uttar Pradesh, India: An epidemiological study.
The aim of the study was to assess the risk for periodontal disease-associated tooth loss among rural and urban population of Barabanki district, Uttar Pradesh, India. A cross-sectional study was done on 1200 urban and rural adults (632 males and 568 females) aged 35-74 years. Data were collected, followed by clinical examination for missing teeth. One-way analysis of variance with Bonferroni post hoc test, Chi-square test, and Student's t-test were used for statistical analysis. Statistical significance was set at P ≤ 0.05. The mean number of periodontal disease-associated tooth loss in the study population was 4.2 ± 7.4. A significant association was found between the place of residence and tooth loss (3.5 ± 6.8 urban; 4.7 ± 7.8 rural), with rural adults showing greater tooth loss compared to urban adults (P < 0.01). Tooth loss increased significantly with age, ranging from mean number of 1.2 teeth in 35-44 years old to 11.5 teeth among 65-74 years old (P < 0.001). Gender showed a significant difference (P < 0.01) in tooth loss between males (4.7 ± 7.7) and females (3.6 ± 6.9). A significant association for tooth loss was also found with respect to the level of education and socioeconomic status (P < 0.001). A decrease in the mean number of missing teeth with increasing education and better socioeconomic status was observed, which was statistically significant (P < 0.001). The insights gained illustrate that tooth loss was 57% in rural and urban Barabanki district population, and the significant risks identified were age, illiterate, marital status, and low socioeconomic status.


The flavonoid luteolin induces nitric oxide production and arterial relaxation.
Luteolin, a flavone present in many foods and medicinal plants, may have beneficial effects on various human chronic diseases. In the present study, we investigated the hypothesis that luteolin can directly act on vascular endothelial cells (ECs), leading to nitric oxide (NO) production and subsequent vascular relaxation. Rat aortic rings were mounted in organ bath. Luteolin was added cumulatively, and vessel relaxation of rat aortic rings precontracted with phenylephrine (PE) or potassium was recorded. Endothelial nitric oxide synthase (eNOS) phosphorylation at Ser1177 and NO production from aortic rings and primary human aortic endothelial cells (HAECs) exposed to luteolin were measured by using Western blot and fluorometric assay, respectively. Luteolin dose-dependently (10-100 μmol/L) elicited relaxation of PE- or potassium-contracted aortic rings. The vasorelaxation effect of luteolin was attenuated by the eNOS inhibitor, N-nitro-L-arginine methyl ester, suggesting that this luteolin action is at least partially mediated by activating eNOS activity. We further found that luteolin dose-dependently (10-100 μmol/L) increased eNOS phosphorylation at Ser1177 (up to 1.9-fold) in isolated rat rings. Consistently, exposure of HAECs to luteolin also increased eNOS phosphorylation and NO production. Luteolin may be a vascular protective agent by directly acting on vascular ECs to stimulate NO-dependent vascular dilatation.


Detection of soluble interleukin-2 receptor and soluble intercellular adhesion molecule-1 in the effusion of otitis media with effusion.
We measured sIL-2R, TNF-alpha and sICAM-1 in the sera and middle ear effusions (MEEs) of patients with otitis media with effusion (OME). Although there was no signmcant difference between the sIL-2R levels of the serous and mucoid MEEs, they were significantly higher than serum sIL-2R levels of OME patients and healthy controls. TNF-alpha levels of the mucoid MEEs were significantly higher than those of the serous type. However, TNF-alpha was rarely detected in the sera of OME patients or healthy controls. We observed significant differences between the serous and mucoid MEEs with respect to their sICAM-1 levels, which were also higher than serum slCAM-1 levels of OME patients and healthy controls. Our findings suggested that IL-2, TNF-alpha and ICAM-1 could be significantly involved in the pathogenesis of OME through the cytokine network.


Do non-weight-bearing knee radiographs for chronic knee pain result in increased follow-up imaging?
While weight-bearing radiographs are considered the optimal method for evaluation of joint spaces in osteoarthritis, non-weight-bearing radiographs are often performed. The purpose of this study is to evaluate the rate of follow-up radiographs in patients receiving non-weight-bearing radiographs for chronic knee pain in the outpatient setting, compared with patients receiving weight-bearing radiographs. Consecutive patients who received non-weight-bearing knee radiographs for chronic knee pain between January 1, 2018, and June 15, 2019, were included. Exclusion criteria included trauma, concern for infection or tumor, and post-surgical radiographs. An age- and sex-matched control group of 100 patients who received weight-bearing knee radiographs was compiled. The proportion of follow-up radiographs within 1 year was compared between the study and control groups with chi-squared tests. Four hundred non-weight-bearing knee radiographic examinations were included. There were 74/400 (18.5%) follow-up radiographs within 12 months. All follow-up radiographs were weight-bearing. In the control group, 4/100 (4%) had follow-up weight-bearing radiographs within 1 year (p < 0.001). Outpatients who underwent non-weight-bearing knee radiographs for chronic pain had a higher frequency of repeat imaging than those who initially underwent weight-bearing knee radiographs. These results suggest that non-weight-bearing knee radiographs are of lower clinical utility compared with weight-bearing radiographs.


Increased oxidative stress and severe arterial remodeling induced by permanent high-flow challenge in experimental pulmonary hypertension.
Involvement of inflammation in pulmonary hypertension (PH) has previously been demonstrated and recently, immune-modulating dendritic cells (DCs) infiltrating arterial lesions in patients suffering from idiopathic pulmonary arterial hypertension (IPAH) and in experimental monocrotaline-induced PH have been reported. Occurrence of perivascular inflammatory cells could be linked to local increase of oxidative stress (OS), as it has been shown for systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still to be determined. We hypothesized, that augmented blood-flow could increase OS and might thereby contribute to DC/inflammatory cell-recruitment and smooth-muscle-cell-proliferation. We applied a monocrotaline-induced PH-model and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were assigned to following groups: control, monocrotaline-exposure (MCT), monocrotaline-exposure/pneumonectomy (MCT/PE). Hemodynamic exploration demonstrated most severe effects in MCT/PE, corresponding in histology to exuberant medial and adventitial remodeling of pulmonary muscular arteries, and intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES, fractalkine) in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase-1 were significantly elevated, while HO-1 showed maximal expression in MCT with significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE. Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a highly increased number of interstitial and perivascular CXCR4/SDF1 pathway-recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were produced in endothelial cells, medial smooth muscle and perivascular leucocytes of hypertensive vasculature. Immunolabeling for OX62, CD68 and actin revealed adventitial and medial DC- and monocyte-infiltration; in MCT/PE, medial smooth muscle cells were admixed with CD68+/vimentin+ cells. Our experimental findings support a new concept of immunologic responses to increased OS in MCT/PE-induced PAH, possibly linking recruitment of dendritic cells and OS-producing mast-cells to characteristic vasculopathy.


CHEK2 1100DELC germline mutation: a frequency study in hereditary breast and colon cancer Brazilian families.
CHEK2 encodes a cell cycle checkpoint kinase that plays an important role in the DNA damage repair pathway, activated mainly by ATM (Ataxia Telangiectasia Mutated) in response to double-stranded DNA breaks. A germline mutation in CHEK2, 1100delC, has been described as a low penetrance allele in a significant number of families with breast and colorectal cancer in certain countries and is also associated with increased risk of contralateral breast cancer in women previously affected by the disease. About 5%-10% of all breast and colorectal cancers are associated with hereditary predisposition and its recognition is of great importance for genetic counseling and cancer risk management. Here, we have assessed the frequency of the CHEK2 1100delC mutation in the germline of 59 unrelated Brazilian individuals with clinical criteria for the hereditary breast and colorectal cancer syndrome. A long-range PCR strategy followed by gene sequencing was used. The 1100delC mutation was encountered in the germline of one (1.7%) individual in this high risk cohort. This indicates that the CHEK2 1100delC is not commonly encountered in Brazilian families with multiple diagnoses of breast and colorectal cancer. These results should be confirmed in a larger series of families and further testing should be undertaken to investigate the molecular mechanisms underlying the hereditary breast and colorectal cancer phenotype.


The signal-to-noise characteristics of rod-cone interaction.
1. The influence of rods on cone-mediated vision was assessed in eight human observers. To this end, increment threshold functions were obtained by determining thresholds of a cone-detected test flash (25 ms duration, 655 nm wave-length, 13' diameter) as a function of the illuminance of larger, 500 ms duration, rod-detected masking flashes. The type of photoreceptor influenced by each stimulus was carefully checked by means of a series of control procedures involving action spectra and selective rod adaptation.2. When the rod mask was 512 nm in wave-length, 40' in diameter, and less than one scotopic td in illuminance, increment threshold functions show that [Formula: see text], where I(Cth) is cone test threshold, I(R) is rod mask illuminance, and D is a dark noise term similar to that used by Barlow (1956). Further increases in I(R) have no additional influences on cone test threshold until threshold is influenced by the combined action of the mask on both rods and cones. If I(R) is expressed in terms of scotopic flux rather than illuminance, the functional relationship obtained with all rod masks </= 40' diameter and </= 580 nm wave-length is identical.3. Over the range of illuminance where a square-root relationship is obtained, probability of seeing functions show that a signal-to-noise mechanism limits the detectability of the cone test flash. These findings suggests a quantitative model in which cones produce a signal in a detector which is proportional to the illuminance of the cone test flash. Within a neural locus designated E (excitatory spatial summator), a response is produced which over at least a 40' diameter area, is proportional to the scotopic flux of the rod mask. E, however, feeds into a gain box, S, which saturates at illuminance levels at least 3 log(10) units less than usual estimates of rod saturation. Other than saturation, S behaves in a linear fashion.4. As diameter increases beyond 60', rod masks of equal scotopic illuminance have progressively less influence on cone test threshold; rod masks > 2 degrees have negligible influence on cone test threshold. We propose that I (inhibitory spatial summator), a neural locus which responds to scotopic flux provided over a very large area, attenuates the activity of E. The combined action of E and I is designated a rod channel. The response of cones and the rod channel summate at a detector. Within the detector, cone signals are distinguished from rod-related activity and intrinsic dark noise on the basis of signal-to-noise discriminations.5. The neural substrate for this rod channel most probably involves the combined action of several neurones which synapse within the inner plexiform layer of the retina. The relationship of this rod channel to other perceptual phenomena is discussed.


A common pathophysiology for sudden cot death and sleep apnoea. "The vacuum-glossoptosis syndrome".
Several congenital and acquired conditions, characterized by upper airway narrowing, may result in respiratory, cardiac, and sleep disturbances. In all these conditions the leading clinical feature is the occurrence of cyclic obstructive apnoea, mainly during sleep. The common pathogenic mechanism for the airway occlusion seems to be a backward displacement of the tongue and mandible, favoured by the muscle relaxation which occurs during sleep and by gravity in the supine position. A constant factor determining the glossoptosis is the pharyngeal vacuum occurring in these conditions as a result of inspiratory efforts in face of a narrowed upper airway. The response to this type of obstruction is age-dependent, since only in early infancy may these apnoeic spells be life-threatening. A similar pathophysiology is suggested for sudden cot death, which could be considered as a peculiar presentation of this "vacuum-glossoptosis syndrome". This hypothesis could explain why sudden cot death is often associated with nasopharyngitis and occurs always in infancy, almost invariably during sleep.


Structure and synthesis of intracellular proteoglycan in HL-60 human leukemic promyelocytes.
The structure, biosynthesis, and metabolism of proteoglycans in the HL-60 human promyelocytes were studied by metabolic labeling in culture with [35S]sulfate, [3H]glucosamine, [3H]serine, and [3H]leucine. These cells synthesize a single predominant species of intracellular proteoglycan with an approximate molecular weight of 100,000. The cells contain about 1 microgram of proteoglycan/million cells. The proteoglycan is turned over within the cells in two apparent pools with half-lives of about 0.6 and 27 h, respectively. The fast pool represents secretion into medium in an apparently intact form, whereas the slow pool represents intracellular degradation to free chondroitin sulfate chains and smaller fragments. The proteoglycan contains a protein core with an apparent Mr on gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of about 20,000-30,000. To the core protein are attached an average of six or seven chondroitin sulfate chains, each with an Mr of about 10,000. The chondroitin sulfate chains contain approximately 85% 4-sulfated and approximately 15% nonsulfated disaccharides. The chondroitin sulfate attachment region of the core protein is essentially resistant to trypsin and elastase, whereas the remainder of the protein core is readily degraded by proteases. The size of the chondroitin sulfate attachment region peptide generated by trypsin was estimated to be approximately 5 kDa. Based on the molecular size, distribution of amino acids, protease susceptibility, and the extent of O-glycosylation, we propose that the intracellular proteoglycan characterized in this study is the translation product of a proteoglycan gene reported to be present in these cells (Stevens, R.L., Avraham, S., Gartner, M.C., Bruns, G.A., Austen, K.E., and Weis, J.H. (1988) J. Biol. Chem. 263, 7287-7291).


TCOF1 upregulation in triple-negative breast cancer promotes stemness and tumour growth and correlates with poor prognosis.
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor prognosis. By performing multiomic profiling, we recently uncovered super-enhancer heterogeneity between breast cancer subtypes. Our data also revealed TCOF1 as a putative TNBC-specific super-enhancer-regulated gene. TCOF1 plays a critical role in craniofacial development but its function in cancer remains unclear. Overall survival and multivariant Cox regression analyses were conducted using the METABRIC data set. The effect of TCOF1 knockout on TNBC growth and stemness was evaluated by in vitro and in vivo assays. RNA-seq and rescue experiments were performed to explore the underlying mechanisms. TCOF1 is frequently upregulated in TNBC and its elevated expression correlates with shorter overall survival. TCOF1 depletion significantly inhibits the growth and stemness of basal-like TNBC, but not of mesenchymal-like cells, highlighting the distinct molecular dependency in different TNBC subgroups. RNA-seq uncovers several stem cell molecules regulated by TCOF1. We further demonstrate that KIT is a downstream effector of TCOF1 in mediating TNBC stemness. TCOF1 expression in TNBC is regulated by the predicted super-enhancer. TCOF1 depletion potently attenuates the growth and stemness of basal-like TNBC. Expression of TCOF1 may serve as a TNBC prognostic marker and a therapeutic target.


Analgesic effects of antibiotics in rats.
Studies in forelimb-deafferented rats suggest that treatment with certain antibiotics can decrease pain sensation. To test this hypothesis, the analgesic effects of nine randomly selected antibiotics were studied in rats by using a constant-temperature hotplate. The results show that several antibiotics have antinociceptive properties, and two of them, chloramphenicol and ampicillin, can produce analgesia in a dose range used in human therapy (100 mg/kg). This analgesia is comparable to salicylate and ketoprofen analgesia but lower than pethidine's one. The analgesia is long lasting with chloramphenicol (10 h or more). These antinociceptive properties cannot be attributed to sedation because amphetamine-induced hyperactivity, measured in an open field, is not sensitive to injection of the most sensitive antibiotics.


Degenerative medial meniscus posterior root tear and non-root tear do not show differences in joint survival and clinical outcome after partial meniscectomy.
No comparative studies of outcomes between degenerative medial meniscus posterior root tear (MM PRT) and non-root tear (NRT) have been conducted. This study aimed to compare joint survival and clinical outcome between MM PRT and MM NRT after partial meniscectomy with proper control of confounding factors. One hundred and ten patients each in MM PRT and MM NRT groups who underwent arthroscopic partial meniscectomy were retrospectively evaluated through propensity score matching. Joint survival was assessed on the basis of surgical and radiographic failures. Clinical outcomes were assessed using the Lysholm score. The confounding variables were well balanced between the groups, with standardized mean differences of < 0.2 after propensity score matching. Failures occurred in 30 (27.3%) and 35 patients (31.8%) in the MM PRT group and MM NRT group, respectively. The estimated mean survival times were 12.5 years (95% confidence interval [CI] 11.5-13.5) and 11.7 years (10.7-12.7), respectively. There were no significant differences in the overall survival rate and Lysholm score between the two groups (n.s.). In middle-aged patients with degenerative MM PRT, joint survival and clinical outcome showed comparable results with those with MM NRT after partial meniscectomy. Arthroscopic partial meniscectomy is one of the effective treatments for MM PRT with consideration of various patient factors. III.


FvSO regulates vegetative hyphal fusion, asexual growth, fumonisin B1 production, and virulence in Fusarium verticillioides.
Hyphal anastomosis is a hallmark of filamentous fungi and plays vital roles including cellular homoeostasis, interhyphal communication and nutrient translocation. Here we identify a gene, FvSO, in Fusarium verticillioides, a filamentous ascomycete causing maize ear and stalk rot and producing fumonisin mycotoxins. FvSO, like its Neurospora crassa homologue SO, is required for vegetative hyphal fusion. It is also essential for normal vegetative growth, sporulation, and pathogenesis. FvSO encodes a predicted WW domain protein and shares 70 % protein sequence identity with N. crassa SO. FvSO deletion mutants (ΔFvSO) had abnormal distribution of conidia size, and conidia of ΔFvSO germinated much later and slower than wild type. ΔFvSO was deficient in hyphal anastomosis, had slower radial growth and produced less fungal biomass than wild type. ΔFvSO were unable to perform anastomosis, a key feature of filamentous fungi. Interestingly, production of fumonisin B1 by ΔFvSO was significantly reduced compared to wild type. Additionally, ΔFvSO was nonpathogenic to corn ears, stalks and seedlings, likely due to defective growth and development. In conclusion, FvSO is essential for vegetative hyphal fusion and is required for normal vegetative growth and sporulation, normal levels of fumonisin production and pathogenicity in F. verticillioides. The pleiotropic nature of ΔFvSO phenotypes suggests that FvSO is likely involved in certain signalling pathways that regulate multiple cellular functions.


Safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor during concurrent chemoradiotherapy for small-cell lung cancer: a retrospective, cohort-controlled trial.
To investigate pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) safety and efficacy in preventing hematological toxicity during concurrent chemoradiotherapy (CCRT) for small-cell lung cancer (SCLC). We retrospectively assessed 80 SCLC patients treated with CCRT from January 2013 to December 2018 who received PEG-rhG-CSF within 48 hours after the end of chemotherapy, defined as prophylactic use, as the experimental group. An additional 80 patients who were not treated with PEG-rhG-CSF were matched 1:1 by the propensity score matching method and served as the control group. The main observations were differences in hematological toxicity, neutrophil changes, febrile neutropenia (FN) incidence and adverse reactions. Progression-free survival (PFS) and overall survival (OS) were analyzed with regular assessment and follow-up. The leukocyte, neutrophil, erythrocyte, and platelet counts and hemoglobin level decreased after CCRT, but the experimental group had slightly higher leukocyte and neutrophil counts than the control group (P < 0.05). The incidences of grade III-IV leukopenia (18.75% vs. 61.25%) and neutropenia (23.75% vs. 67.5%) in the experimental group were significantly lower than those in the control group (P < 0.05). The absolute neutrophil count was 4.17 ± 0.79 (× 109/L) on day 1 and peaked 6.81 ± 2.37 (× 109/L) on day 10 in the experimental group; the value in the control group was 2.81 ± 0.86 (× 109/L) on day 1. It decreased significantly and reached the minimum 0.91 ± 0.53 (× 109/L) on day 10 (P < 0.05). The experimental group had a lower FN incidence than the control group (P < 0.05). There was also no significant acute esophagitis or pulmonary toxicity. The treatment had no significant effect on PFS (11.4 months vs. 8.7 months, P = 0.958) or OS (23.9 months vs. 17.3 months, P = 0.325) over an 18.6-month median follow-up time. PEG-rhG-CSF has good efficacy and safety in preventing hematological toxicity in SCLC patients during CCRT and has no significant effects on PFS or OS.


Design of ultrathin CoAl-LDHs/ZnIn2S4 with strong interfacial bonding and rich oxygen vacancies for highly efficient hydrogen evolution activity.
Designing a semiconductor-based heterostructure photocatalyst is very important way to enhance the hydrogen production activity. Here, a novel 2D/2D CoAl-LDHs/ZnIn2S4 S-scheme heterostructure with an ultrathin structure was synthesized by electrostatic attraction between CoAl-LDHs and ZnIn2S4 nanosheets. The presence of oxygen vacancies in the monolayer CoAl-LDHs nanosheet promotes the formation of Co-SX bonds, which serve as charge transfer channels at the interface of the CoAl-LDHs/ZnIn2S4 heterostructure. The ultrathin CoAl-LDHs/ZnIn2S4 exhibits broadened light absorption in the near-infrared range due to the occurrence of Co-SX chemical bonds. The CoAl-LDHs/ZnIn2S4 with a mass ratio of 1:2 demonstrated the highest photocatalytic hydrogen evolution activity (1563.64 μmol g-1 h-1) under the simulated sunlight, which is 4.6 and 9.7 times than that of the ZnIn2S4 and CoAl-LDHs/ZnIn2S4(bulk), respectively. The enhanced photocatalytic activity of ultrathin 2D/2D CoAl-LDHs/ZnIn2S4 should attributed to the shorter carriers path that benefit from the ultrathin structure and the quicker photogenerated charge transfer and the S-scheme migration pathway accelerated by the charge channel of Co-SX bonds. These new ideas should be inspiring for the design and construction of heterostructures for higher photocatalytic hydrogen evolution activity.


An Economic Evaluation of the Impact of Using Rapport-Based Interviewing Approaches With Child Sexual Abuse Suspects.
Two studies examined whether rapport-based interviewing with child sexual abuse (CSA) suspects provides greater interview yield that could result in overall cost-savings to the investigation. First, multi-level modelling was applied to 35 naturalistic CSA suspect interviews to establish whether rapport-based interviewing techniques increase "yield" - defined as information of investigative value. The Observing Rapport Based Interviewing Technique (ORBIT coding manual was used to code interviews; it includes an assessment of both interpersonal adaptive and maladaptive rapport-based interviewer engagement as well as motivational interviewing (MI) strategies. The impact of these two strands (interpersonal and MI) on extracting information of investigative value (including strengthening a case for court and safeguarding) were examined. Adaptive interpersonal strategies increased case strengthening and safeguarding yield, with motivational interviewing having the largest impact on safeguarding yield. Both strategies increase the likelihood of gaining additional types of economic yield. Maladaptive interviewer strategies reduced case strengthening and different types of economic yield. In study two, literature-based economic estimates were applied to establish the potential cost benefits from following national ORBIT rapport training. Further training in adaptive and motivational interviewing could contribute cost savings between £19 and £78 million (annual unit costs) increasing to £238-£972 million (lifetime costs) for online CSA across England and Wales; and £157-£639 million (annual unit costs) increasing to £2-£8 billion (lifetime costs) for all CSA. Failure to commit training resource to this, or an alternative strategy, could mean the cost burden attributable to maladaptive interviewing (between £1 and £6 million for online CSA and £12 and £48 million for all CSA) is not successfully averted.


Aspartame as a dietary trigger of headache.
Many dietary factors have been implicated as possible precipitants of headache. There have been recent differences of opinion with regard to the effect of the artificial sweetener aspartame as a precipitant of headache. To assess the importance of aspartame as a dietary factor in headache, 190 consecutive patients of the Montefiore Medical Center Headache Unit were questioned about the effect of alcohol, carbohydrates and aspartame in triggering their headaches. Of the 171 patients who fully completed the survey, 49.7 percent reported alcohol as a precipitating factor, compared to 8.2 percent reporting aspartame and 2.3 percent reporting carbohydrates. Patients with migraine were significantly more likely to report alcohol as a triggering factor and also reported aspartame as a precipitant three times more often than those having other types of headache. The conflicting results of two recent placebo-control studies of aspartame and headache are discussed. We conclude that aspartame may be an important dietary trigger of headache in some people.


How race affects evidence accumulation during the decision to shoot.
The biasing role of stereotypes is a central theme in social cognition research. For example, to understand the role of race in police officers' decisions to shoot, participants have been shown images of Black and White males and instructed to shoot only if the target is holding a gun. Findings show that Black targets are shot more frequently and more quickly than Whites. The decision to shoot has typically been modeled and understood as a signal detection process in which a sample of information is compared against a criterion, with the criterion set for Black targets being lower. We take a different approach, modeling the decision to shoot as a dynamic process in which evidence is accumulated over time until a threshold is reached. The model accounts for both the choice and response time data for both correct and incorrect decisions using a single set of parameters. Across four studies, this dynamic perspective revealed that the target's race did not create an initial bias to shoot Black targets. Instead, race impacted the rate of evidence accumulation with evidence accumulating faster to shoot for Black targets. Some participants also tended to be more cautious with Black targets, setting higher decision thresholds. Besides providing a more cohesive and richer account of the decision to shoot or not, the dynamic model suggests interventions that may address the use of race information in decisions to shoot and a means to measure their effectiveness.


Incidence, associated factors and evolution of non-severe functional mitral regurgitation in patients with severe aortic stenosis undergoing aortic valve replacement.
In order to improve the prognosis, repair of severe mitral regurgitation should be undertaken at the same time as aortic valve replacement in patients with severe aortic valve stenosis. However, mitral regurgitation may be secondary to pressure overload or ventricular dysfunction and improve after surgery. To assess the incidence of non-severe functional mitral regurgitation before and after isolated aortic valve replacement and determine its influence on the postoperative course. The clinical and surgical characteristics were compared in a cohort of 577 consecutive patients who underwent isolated aortic valve replacement. The mean age was 68.4+/-9.2 years (44% women). Non-severe functional mitral valve regurgitation was detected prior to surgery in 26.5% of the patients. These patients were older (p=0.009), more often had ventricular dysfunction (p=0.005) and pulmonary hypertension (0.002), and had been admitted more frequently for heart failure (0.002), with fewer of them conserving sinus rhythm (p<0.001). Additionally, the pre-surgery existence of mitral regurgitation was associated with greater morbidity and mortality (10.5% vs 5.6%; p=0.025). The mitral regurgitation disappeared or improved prior to hospital discharge in 56.2% and 15.6%, respectively. Independent factors predicting this improvement were the presence of coronary lesions (OR 3.7, p=0.038), and the absence of diabetes (OR 0.28, p=0.011) and pulmonary hypertension (0.33, p=0.046). The presence of intermediate degree mitral regurgitation in patients undergoing isolated aortic valve replacement increases morbidity and mortality. However, a high percentage of those who do survive experience disappearance or improvement of the mitral regurgitation.