Effects of a Case Management Program for Women With Pregnancy-Induced Hypertension.
Pregnancy-induced hypertension (PIH) is a leading cause of maternal and fetal morbidity and mortality. Although case management programs have been proposed to improve maternal and fetal outcomes in high-risk pregnancies, limited data are available regarding the effect of case management on women with PIH. The aim of this study was to evaluate the effect of an antepartum case management program on stress, anxiety, and pregnancy outcomes in women with PIH. A quasi-experimental research design was employed. A convenience sample of women diagnosed with PIH, including preeclampsia, was recruited from outpatient clinics at a medical center in southern Taiwan. Sixty-two women were assigned randomly to either the experimental group (n = 31) or the control group (n = 31). The experimental group received case management for 8 weeks, and the control group received routine clinical care. Descriptive statistics, independent t or Mann-Whitney U tests, chi-square or Fisher's exact tests, paired t test, and generalized estimating equations were used to analyze the data. The average age of the participants was 35.1 years (SD = 4.5). No significant demographic or clinical differences were found between the control and experimental groups. The results of the generalized estimating equations showed significantly larger decreases in stress and anxiety in the experimental group than in the control group. No significant differences were identified between the two groups with respect to infant birth weeks, infant birth weight, average number of medical visits, or frequency of hospitalization. The nurse-led case management program was shown to have short-term positive effects on the psychosocial outcomes of a population of Taiwanese patients with PIH. These results have important clinical implications for the healthcare administered to pregnant women, particularly in terms of improving the outcomes in those with PIH.


How to Recognize, Correct, and Avoid Intraoperative Complications During Anterior Cruciate Ligament Reconstructions.
Technical complications are a leading cause of graft failure following anterior cruciate ligament reconstructions. Complications can occur during any phase of the procedure, from graft harvesting to tunnel preparation to graft fixation. Predicting potential causes of technical difficulty and developing strategies to avoid potential pitfalls can limit the number of intraoperative complications. If adverse events do occur intraoperatively, prompt recognition and treatment can lead to favorable outcomes. It is important to discuss strategies to understand potential complications and develop tactics to avoid and correct adverse events that can occur during anterior cruciate ligament reconstruction.


WEB Treatment of Intracranial Aneurysms: Feasibility, Complications, and 1-Month Safety Results with the WEB DL and WEB SL/SLS in the French Observatory.
Safety analyses in the French Observatory have shown that treatment of intracranial aneurysms by using flow disruption with the Woven EndoBridge Device (WEB) is safe, with low morbidity and no mortality. The objective of this study was to analyze treatment feasibility, complications, and safety results in patients treated with the Woven EndoBridge Device Dual-Layer (WEB DL) and Woven EndoBridge Device Single-Layer/Single-Layer Sphere (WEB SL/SLS) in the French Observatory. Patients with bifurcation aneurysms were included in this prospective, multicenter good clinical practices study. A medical monitor independently analyzed procedural and clinical data. The study started with the WEB DL, and secondarily, the WEB SL/SLS was authorized in the study. Between November 2012 and January 2014, 10 French centers included 62 patients with 63 aneurysms. Thirty patients with 31 aneurysms were treated with the WEB DL, and 32 patients with 32 aneurysms, with the WEB SL/SLS. The percentage of anterior communicating artery aneurysms treated with WEB SL/SLS was significantly higher (37.5%) compared with WEB DL (12.9%) (P = .04). The WEB SL/SLS was more frequently used in aneurysms of <10 mm than the WEB DL (respectively, 96.9% and 67.7%; P = .002). Morbidity was similar in both groups (WEB DL, 3.3%; WEB SL/SLS, 3.1%), and mortality was 0.0% in both groups. This comparative study shows increased use of WEB treatment in ruptured, small, and anterior communicating artery aneurysms when using WEB SL/SLS. There was a trend toward fewer thromboembolic complications with the WEB SL/SLS. With both the WEB DL and WEB SL/SLS, the treatment was safe, with low morbidity and no mortality.


New academic partnerships in global health: innovations at Mount Sinai School of Medicine.
Global health has become an increasingly important focus of education, research, and clinical service in North American universities and academic health centers. Today there are at least 49 academically based global health programs in the United States and Canada, as compared with only one in 1999. A new academic society, the Consortium of Universities for Global Health, was established in 2008 and has grown significantly. This sharp expansion reflects convergence of 3 factors: (1) rapidly growing student and faculty interest in global health; (2) growing realization-powerfully catalyzed by the acquired immune deficiency syndrome epidemic, the emergence of other new infections, climate change, and globalization-that health problems are interconnected, cross national borders, and are global in nature; and (3) rapid expansion in resources for global health. This article examines the evolution of the concept of global health and describes the driving forces that have accelerated interest in the field. It traces the development of global health programs in academic health centers in the United States. It presents a blueprint for a new school-wide global health program at Mount Sinai School of Medicine. The mission of that program, Mount Sinai Global Health, is to enhance global health as an academic field of study within the Mount Sinai community and to improve the health of people around the world. Mount Sinai Global Health is uniting and building synergies among strong, existing global health programs within Mount Sinai; it is training the next generation of physicians and health scientists to be leaders in global health; it is making novel discoveries that translate into blueprints for improving health worldwide; and it builds on Mount Sinai's long and proud tradition of providing medical and surgical care in places where need is great and resources few.


LC-MS/MS analysis of apical and basolateral plasma membranes of rat renal collecting duct cells.
We used biotinylation and streptavidin affinity chromatography to label and enrich proteins from apical and basolateral membranes of rat kidney inner medullary collecting ducts (IMCDs) prior to LC-MS/MS protein identification. To enrich apical membrane proteins and bound peripheral membrane proteins, IMCDs were perfusion-labeled with primary amine-reactive biotinylation reagents at 2 degrees C using a double barreled pipette. The perfusion-biotinylated proteins and proteins bound to them were isolated with CaptAvidin-agarose beads, separated with SDS-PAGE, and sliced into continuous gel pieces for LC-MS/MS protein identification (LTQ, Thermo Electron Corp.). 17 integral and glycosylphosphatidylinositol (GPI)-linked membrane proteins and 44 non-integral membrane proteins were identified. Immunofluorescence confocal microscopy confirmed ACVRL1, H(+)/K(+)-ATPase alpha1, NHE2, and TauT expression in the IMCDs. Basement membrane and basolateral membrane proteins were biotinylated via incubation of IMCD suspensions with biotinylation reagents on ice. 23 integral and GPI-linked membrane proteins and 134 non-integral membrane proteins were identified. Analyses of non-integral membrane proteins preferentially identified in the perfusion-biotinylated and not in the incubation-biotinylated IMCDs revealed protein kinases, scaffold proteins, SNARE proteins, motor proteins, small GTP-binding proteins, and related proteins that may be involved in vasopressin-stimulated AQP2, UT-A1, and ENaC regulation. A World Wide Web-accessible database was constructed of 222 membrane proteins (integral and GPI-linked) from this study and prior studies.


Joint demosaicing and denoising.
The output image of a digital camera is subject to a severe degradation due to noise in the image sensor. This paper proposes a novel technique to combine demosaicing and denoising procedures systematically into a single operation by exploiting their obvious similarities. We first design a filter as if we are optimally estimating a pixel value from a noisy single-color (sensor) image. With additional constraints, we show that the same filter coefficients are appropriate for color filter array interpolation (demosaicing) given noisy sensor data. The proposed technique can combine many existing denoising algorithms with the demosaicing operation. In this paper, a total least squares denoising method is used to demonstrate the concept. The algorithm is tested on color images with pseudorandom noise and on raw sensor data from a real CMOS digital camera that we calibrated. The experimental results confirm that the proposed method suppresses noise (CMOS/CCD image sensor noise model) while effectively interpolating the missing pixel components, demonstrating a significant improvement in image quality when compared to treating demosaicing and denoising problems independently.


[Role of probiotics in Obstetrics and Gynecology].
The human microbiota is estimated to be 2.5-3.0 kg. Bacterial colonization starts during delivery, due to fetal contact with vaginal and intestinal maternal microorganisms. The oligosaccharides in human breast milk stimulate the growth of bacteria, which provide the optimal environment for intestinal mucosal immunity development. Additionally, breast milk has its own microbiota and it is altered in mastitis. The vagina is another important microenvironment. Vaginal dysbiosis leads to bacterial vaginosis and vaginal candidiasis, both of them very frequent in reproductive life. The probiotics are a potential and encouraging treatment for all microbiota alterations. Nevertheless, additional studies are required to confirm the benefits of probiotics.


Malignant triton tumor of the gluteal region in a patient unaffected by neurofibromatosis: A case report.
Malignant triton tumor (MTT) is a rare variant of malignant peripheral nerve sheath tumor (MPNST) made up of both malignant schwannoma cells and malignant rhabdomyoblasts. A 26-years-old male patient was admitted with an asymptomatic gluteal mass. Magnetic resonance imaging showed heterogeneous soft tissue mass and he underwent open biopsy. Malignant peripheral nerve sheath tumor was diagnosed. He was given adjuvant chemotherapy following the removal of the tumor with hip disarticulation. The tumor was diagnosed as "malignant triton tumor" based on pathological examination including immunohistochemical studies. There were no signs of metastasis but recurrence was observed at 9 months follow up. MTT is usually associated with Neurofibromatosis 1 and located in head, neck region. In this case sporadic involvement of gluteal region and aggressive behavior of the lesion despite radical surgery was demonstrated.


CB1-Dependent Long-Term Depression in Ventral Tegmental Area GABA Neurons: A Novel Target for Marijuana.
The VTA is necessary for reward behavior with dopamine cells critically involved in reward signaling. Dopamine cells in turn are innervated and regulated by neighboring inhibitory GABA cells. Using whole-cell electrophysiology in juvenile-adolescent GAD67-GFP male mice, we examined excitatory plasticity in fluorescent VTA GABA cells. A novel CB1-dependent LTD was induced in GABA cells that was dependent on metabotropic glutamate receptor 5, and cannabinoid receptor 1 (CB1). LTD was absent in CB1 knock-out mice but preserved in heterozygous littermates. Bath applied Δ9-tetrahydrocannabinol depressed GABA cell activity, therefore downstream dopamine cells will be disinhibited; and thus, this could potentially result in increased reward. Chronic injections of Δ9-tetrahydrocannabinol occluded LTD compared with vehicle injections; however, a single exposure was insufficient to do so. As synaptic modifications by drugs of abuse are often tied to addiction, these data suggest a possible mechanism for the addictive effects of Δ9-tetrahydrocannabinol in juvenile-adolescents, by potentially altering reward behavioral outcomes.SIGNIFICANCE STATEMENT The present study identifies a novel form of glutamatergic synaptic plasticity in VTA GABA neurons, a currently understudied cell type that is critical for the brain's reward circuit, and how Δ9-tetrahydrocannabinol occludes this plasticity. This study specifically addresses a potential unifying mechanism whereby marijuana could exert rewarding and addictive/withdrawal effects. Marijuana use and legalization are a pressing issue for many states in the United States. Although marijuana is the most commonly abused illicit drug, the implications of legalized, widespread, or continued usage are speculative. This study in juvenile-adolescent aged mice identifies a novel form of synaptic plasticity in VTA GABA cells, and the synaptic remodeling that can occur after Δ9-tetrahydrocannabinol use.


[Eosinophilia and lymphatic filariasis in French Polynesia].
An important hypereosinophilia is usually regarded as an interesting argument of presumption in lymphatic filariasis. This present report concerns 278 Polynesians people infected with Wuchereria bancrofti pacifica. Six kinds of patients were analysed: carriers of microfilarias, patients with elephantiasis, with lymphangitis attacks, new infections, carriers of microfilariasis recently treated with Diethylcarbamazine and, at least, 100 fellows without filariasis. The results which were observed differ, in some aspects, from the usually admitted ideas.


Use of single nucleotide polymorphisms (SNP) and real-time polymerase chain reaction for bone marrow engraftment analysis.
Allogeneic bone marrow transplant engraftment assays use polymorphisms in the human genome to determine the relative percentages of donor and recipient cells present in the recipient. We describe a novel posttransplant assay approach using single nucleotide polymorphisms (SNPs), the most common type of polymorphism in humans. Using samples of defined genotype, we used real-time polymerase chain reaction (PCR) and allele-specific fluorescent TaqMan probes to assay a SNP of the cytochrome P450 CYP2C9 gene. Standard curves of chimeric mixes showed a linear relationship between the ratio of two alleles and the ratio of their respective fluorophore emission, except for mixes with a low percentage (< 5%) of the less common allele. We validated the SNP real-time PCR assay by comparing it to Southern hybridization analysis, analyzing DNA mixes in a blinded fashion with both methods. The correlation between the two methods was high. We have produced a statistical model that varies allele frequency to predict how many SNPs would be required to produce a functional SNP panel. Additional development will be necessary to produce such a panel of highly informative SNPs for clinical use. A real-time PCR SNP assay may ultimately provide more accurate quantification and shortened turnaround time compared to current post-engraftment assays.


CADASIL as a Useful Medical Model and Genetic Form of Vascular Depression.
The main magnetic resonance imaging (MRI) findings of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are white matter hyperintensities (WMHs), lacunar infarctions, and cerebral microbleeds (CMBs). The purpose of this study was to investigate the effects of these three neuroimaging markers of CADASIL on depression to determine whether CADASIL is a useful medical model supporting the vascular depression hypothesis. Eighty-four subjects with CADASIL, aged 34-86 years, participated in this study. They underwent comprehensive clinical evaluation, including 3T MRI and genotyping of NOTCH3. The effects of WMH, lacunar infarctions, and CMBs were analyzed by path analyses and multivariate logistic regression analyses. Patients with CADASIL exhibited frequencies of 17.9% for major depressive disorder (MDD) and 10.7% for minor depressive disorder. The frequency of MDD increased from 5.0% to 46.2% as WMH volume increased from first quartile to fourth quartile. WMH volume (OR: 1.03, 95% CI: 1.003-1.06) in patients with CADASIL was associated with the current depressive disorder. Path analyses demonstrated that only WMH volume was associated with the Korean version of the short form Geriatric Depression Scale score, Center for Epidemiologic Studies Depression Scale score, and 17-item Hamilton depression scale score. The effects of lacunar infarctions and CMBs on depression were not significant in path analyses and multivariate logistic regression analyses. This study demonstrates that WMHs are closely associated with depression in patients with CADASIL. This supports that CADASIL might be a useful medical model and genetic form of vascular depression.


The assessment of cardiac function with tissue Doppler imaging in fetuses with congenital diaphragmatic hernia.
Introduction: This study aimed to evaluate the cardiac function of fetuses with congenital diaphragmatic hernia by conventional echocardiography and spectral tissue Doppler imaging (s-TDI) and to evaluate the relationship between cardiac function and the severity of pulmonary hypoplasia. We also aimed to investigate the effect of diaphragmatic hernia side on fetal cardiac function.Methods: Fetal cardiac function were evaluated in 28 fetuses (20 with left-sided and 8 with right-sided) complicated with isolated congenital diaphragmatic hernia (CDH) and 56 gestational age matched control in this single center prospective study. s-TDI measurements were obtained at the right atrioventricular valve annulus. The annular peak velocities and their ratios, the time periods of cardiac cycle and myocardial performance index were calculated.Results: In comparison to controls, significantly prolonged isovolumetric contraction time (ICT') and isovolumetric relaxation time (IRT') and, significantly shortened ejection time (ET') were observed in fetuses with CDH by s-TDI. Fetuses with CDH also had higher myocardial performance index (MPI') z-scores compared to controls. There were no significant differences in terms of s-TDI cardiac function parameters between fetuses with right- and left-sided CDH. In correlation analysis, a significant positive correlation was found between ET' value and o/e LHR.Conclusion: The signs of both systolic and diastolic altered function were observed in fetuses with CDH with s-TDI independent of the side of the hernia, and a significant positive correlation was observed between fetal cardiac systolic function and the severity of pulmonary hypoplasia.


Identification of virulence mutants of the fungal pathogen Cryptococcus neoformans using signature-tagged mutagenesis.
Cryptococcus neoformans var. neoformans is an important opportunistic fungal pathogen of patients whose immune system has been compromised due to viral infection, antineoplastic chemotherapy, or tissue transplantation. As many as 13% of all AIDS patients suffer a life-threatening cryptococcal infection at some time during the course of their HIV disease. To begin to understand the molecular basis for virulence in Cryptococcus neoformans var. neoformans serotype A, we have employed signature-tagged mutagenesis (STM) to identify mutants with altered virulence in a mouse model. The critical parameters of signature-tagged mutagenesis in C. neoformans are explored. Data are presented showing that at least 100 different strains can be mixed together in a single animal with each participating in the infection and that there is no apparent interaction between a virulent strain and an avirulent strain in our animal model. Using signature-tagged mutagenesis, we identified 39 mutants with significantly altered growth in a competitive assay. Molecular analyses of these mutants indicated that 19 (49%) contained an insertion in the actin promoter by homologous recombination from a single crossover event, creating a duplication of the actin promoter and the integration of single or multiple copies of the vector. Analysis of the chromosomal insertion sites of those mutants that did not have an integration event in the actin promoter revealed an approximately random distribution among the chromosomes. Individual challenge of the putative mutants in a mouse model revealed five hypovirulent mutants and one hypervirulent mutant.


R-Spondin 3 Regulates Mammalian Dental and Craniofacial Development.
Development of the teeth requires complex signaling interactions between the mesenchyme and the epithelium mediated by multiple pathways. For example, canonical WNT signaling is essential to many aspects of odontogenesis, and inhibiting this pathway blocks tooth development at an early stage. R-spondins (RSPOs) are secreted proteins, and they mostly augment WNT signaling. Although RSPOs have been shown to play important roles in the development of many organs, their role in tooth development is unclear. A previous study reported that mutating Rspo2 in mice led to supernumerary lower molars, while teeth forming at the normal positions showed no significant anomalies. Because multiple Rspo genes are expressed in the orofacial region, it is possible that the relatively mild phenotype of Rspo2 mutants is due to functional compensation by other RSPO proteins. We found that inactivating Rspo3 in the craniofacial mesenchyme caused the loss of lower incisors, which did not progress beyond the bud stage. A simultaneous deletion of Rspo2 and Rspo3 caused severe disruption of craniofacial development from early stages, which was accompanied with impaired development of all teeth. Together, these results indicate that Rspo3 is an important regulator of mammalian dental and craniofacial development.


Management of Crohn's disease of the ileoanal pouch with infliximab.
The occurrence of Crohn's disease (CD) in a patient with an ileal-pouch anastomosis (IPAA) often results in severe morbidity and significant chance of reservoir loss. We report our experience of the use of infliximab in these patients. Medical records of 26 patients with an IPAA and CD-related complications were reviewed. The median time between the IPAA and the diagnosis of CD was 4.5 yr (range 0.1-16 yr). The main reasons for changing the original ulcerative colitis diagnosis to CD were complex perianal or pouch fistulizing disease in 14 patients (54%), prepouch ileitis in five (19%), and both prepouch ileitis and complex fistula in seven (27%). Patients received one to three doses of infliximab over 8 wk as induction therapy. Subsequently the patients received a variable number of maintenance infusions. At a short term follow-up, 16/26 patients (62%) had a complete response, six of 26 (23%) had a partial response, and four of 26 (15%) had no response. Information regarding long term follow-up was available in 24 patients. After a median follow-up of 21.5 months (range 3-44 months), eight patients (33%) either had their pouch resected or had a persistent diverting ileostomy. The pouch was functional in 16/24 (67%) patients, with either good (n = 7) or acceptable (n = 7) clinical results in 14/24 (58%). Of those 14 patients, 11 were under long term, on demand, or systematic maintenance treatment with infliximab. Infliximab is beneficial in both the short and long term treatment of patients with an IPAA performed for a presumed diagnosis of ulcerative colitis who subsequently develop CD-related complications. Good pouch function requires long term treatment with infliximab in most patients.


Grief and joy: emotion word comprehension in the dementias.
Word comprehension deficits in neurodegenerative conditions are most striking in the syndrome of semantic dementia. Tests of word comprehension typically examine concrete and abstract nonemotion words. Whether or not understanding of words describing emotion concepts (e.g., insulted, fascinated) is also impaired in the dementias has not been systematically investigated. Patients with semantic dementia (SD; n = 8), behavioral-variant frontotemporal dementia (bvFTD; n = 8), Alzheimer's disease (AD; n = 12), as well as healthy controls (n = 15) completed newly designed emotion word comprehension tasks. Participants also undertook the Graded Synonyms Test, an abstract and concrete nonemotion word comprehension measure. Degradation of knowledge about negative and positive emotion words was most impaired in SD. Correlation analyses in the SD group also showed that knowledge of emotion words correlated with the understanding of abstract nonemotion words. The bvFTD group was impaired only when making associations for emotion words. The AD cohort did not differ from controls on any measures of word comprehension. Impairment in word knowledge is greatest in the syndrome of SD, compared with bvFTD and AD, and includes concrete words, abstract words as well as emotion words. Importantly, word comprehension deficits affect positive and negative emotions.


[Detection of lymphoproliferative response in monkeys innoculated with dengue 4 virus].
A group of 6 Cynomolgus monkeys was immunized with dengue 4 virus (H247 standard strain). 60 days after innoculation the cellular proliferation against the same serotype as well as against hetereologous serotypes 1 and 2 was measured. A proliferative response predominantly of the specific serotype and some cross reactivity were detected. These results showed a behavior of primates similar in some extent to that of human beings and mice regarding the specific serotype and cross serotype response to dengue virus.


Immobilization of Heteroatom-Doped Carbon Dots onto Nonpolar Plastics for Antifogging, Antioxidant, and Food Monitoring Applications.
This work presents the facile synthesis of heteroatom-doped fluorescent carbon quantum dots (C-dots), which could serve as an antioxidant. Herein, nitrogen, phosphorous, and sulfur codoped carbon dots (NPSC-dots) have been synthesized by a single-step hydrothermal strategy. Owing to the radical scavenging activity of the NPSC-dots, they were tested against several methods as well as in practical applications. The antioxidant ability of the NPSC-dots was efficiently utilized on plastic films by coating with these NPSC-dots. For the very first time, NPSC-dots were immobilized onto nonpolar plastic films (polypropylene) via photochemical covalent grafting to extend the shelf life of food items or storage without affecting the quality of plastic films. The NPSC-dot-coated PP film with negligible deterioration of transparency was extensively studied using scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier transform infrared (FTIR) analysis, X-ray photoelectron spectroscopy (XPS), contact angle measurement, and thermogravimetric analysis (TGA). The fluorescent character, antioxidant ability, and durability under different solvent systems of the coated film were examined. Also, the coated films were extensively and rigorously evaluated against simulated drastic environmental conditions to ensure the durability and antifogging application.


Study into the effect of microfluidisation processing parameters on the physicochemical properties of wheat (Triticum aestivum L.) bran.
The physicochemical properties of wheat bran have an effect on its technofunctional and nutritional profile. The possibility to induce physicochemical modifications in wheat bran using microfluidisation was investigated. An I-optimal experimental design was used to investigate the effect of microfluidisation processing parameters (pressure, number of passes, bran concentration and initial particle size) on important properties of wheat bran (particle size, microstructure, chemical composition, water retention capacity (WRC), extractability, viscosity and sedimentation). With the parameters used in this study, microfluidisation reduced wheat bran median particle size to 14.8 μm and disintegrated starch granules from the attached endosperm. This coincided with an increased extractability of starch and arabinoxylan. While the initial particle size was of minor importance, a higher pressure, larger number of passes and lower bran concentration during microfluidisation resulted in a smaller particle size, higher WRC and extractability, and an increased viscosity and stability in a 2% wheat bran suspension.


High-dose hydroxocobalamin achieves biochemical correction and improvement of neuropsychiatric deficits in adults with late onset cobalamin C deficiency.
Cobalamin C (cblC) deficiency is the most common inborn error of intracellular cobalamin metabolism caused by pathogenic variant(s) in MMACHC and manifests with methylmalonic acidemia, hyperhomocysteinemia, and hypomethioninemia with a variable age of presentation. Individuals with late-onset cblC may be asymptomatic until manifesting neuropsychiatric symptoms, thromboembolic events, and renal disease. Although hydroxocobalamin provides a foundation for therapy, optimal dose regimen for adult patients has not been systematically evaluated. We report three adult siblings with late-onset cblC disease, and their biochemical and clinical responses to high-dose hydroxocobalamin. The 28-year-old proband presented with severe psychosis, progressive neurological deterioration, and deep venous thrombosis complicated by a pulmonary embolism. MRI studies identified lesions in the spinal cord, periventricular white matter, and basal ganglia. Serum homocysteine and methylmalonic acid levels were markedly elevated. Hydroxocobalamin at standard dose (1 mg/day) initially resulted in partial metabolic correction. A regimen of high-dose hydroxocobalamin (25 mg/day) together with betaine and folic acid resulted in rapid and sustainable biochemical correction, resolution of psychosis, improvement of neurological functions, and amelioration of brain and spinal cord lesions. Two siblings who did not manifest neuropsychiatric symptoms or thromboembolism achieved a satisfactory metabolic control with the same high-dose regimen. Hydroxocobalamin injection was then spaced out to 25 mg weekly with good and sustainable metabolic control. All three patients are compound heterozygotes for c.271dupA p.Arg91LysfsX14 and c.389A > G p.Tyr130Cys. This study highlights the importance of evaluating intracellular cobalamin metabolism in adults with neuropsychiatric manifestations and/or thromboembolic events, and demonstrates that high-dose hydroxocobalamin achieves rapid and sustainable metabolic control and improvement in neuropsychiatric outcomes in adults with late-onset cblC disease.


Dual loyalties: Everyday ethical problems of registered nurses and physicians in combat zones.
When healthcare personnel take part in military operations in combat zones, they experience ethical problems related to dual loyalties, that is, when they find themselves torn between expectations of doing caring and military tasks, respectively. This article aims to describe how Swedish healthcare personnel reason concerning everyday ethical problems related to dual loyalties between care and military tasks when undertaking healthcare in combat zones. Abductive qualitative design. Individual interviews with 15 registered nurses and physicians assigned for a military operation in Mali. The participants signed up voluntarily, and requirements for informed consent and confidentiality were met. The research was approved by the Regional Ethics Review Board in Gothenburg (D no. 816-14; 24 November 2014). Three main categories emerged: reasons for not undertaking combat duties, reasons for undertaking combat duties and restricted loyalty to military duties, and 14 subcategories. Reasons for not undertaking combat duties were that it was not in their role, not according to ethical codes or humanitarian law or a breach towards patients. Reasons for undertaking combat duties were that humanitarian law does not apply or has to be treated pragmatically or that it is a case of force protection. Shortage of resources and competence were reasons for both doing and not doing military tasks. Under some circumstances, they could imagine undertaking military tasks: when under threat, if unseen or if not needed for healthcare duties. These discrepant views suggest a lack of a common view on what is ethically acceptable or not, and therefore we suggest further normative discussion on how these everyday ethical problems should be interpreted in the light of humanitarian law and ethical codes of healthcare personnel and following this, further training in ethical reflection before going on military operations.


Spindle and epithelioid cell nevus (Spitz nevus). Natural history following biopsy.
A clinical follow-up study of 49 cases of spindle and epithelioid cell nevus is presented to address the question about the potential for local recurrence. Only 19 (39%) of the 49 lesions were initially excised en toto, and the remainder (30 cases) had positive margins; six of the latter spindle and epithelioid cell nevi were reexcised, and no evidence of a residual nevus was found in five of the six cases. There were no recurrences in the 49 patients during an average follow-up period of 5.0 years (range, 1 to 10 years). The rarity of recurrent spindle and epithelioid cell nevus would justify a conservative approach to management, with clinical follow-up alone recommended after a subtotal excision, when the pathologic diagnosis is unequivocal.


[Whole-body MRI in children with langerhans cell histiocytosis for the evaluation of the skeletal system].
The usefulness of whole-body MRI (WB-MRI) for the detection of skeletal lesions in patients with Langerhans cell histiocytosis should be documented on the basis of case presentations. In six patients with histologically proven Langerhans cell histiocytosis, 14 WB-MRI examinations were performed to evaluate the skeletal system within disease staging (6 primary, 8 follow-up examinations). The examinations were performed on a 1.5 Tesla, 32-channel whole-body scanner. The examination protocol consisted of T 1-weighted and STIR sequences in coronal and sagittal orientation. For comparison, radiographs of the initial skeletal lesions and those that were additionally detected on WB-MRI were available. In 4 patients no additional skeletal lesions were found on WB-MRI besides the initial lesion leading to the diagnosis of unifocal single system disease. In 2 patients WB-MRI was able to identify additional skeletal lesions. In a 5 S year-old boy with the primary lesion located in the cervical spine, a second lesion was detected in the lumbar spine on the initial scan and in the skull and proximal femur during follow-up examination. In a 12 year-old girl with a primary lesion of the thoracic spine, WB-MRI diagnosed additional lesions in the pelvic bone and the tibia. In both patients the diagnosis of multifocal skeletal involvement led to chemotherapy. During follow-up examination, the healing response under therapy could be demonstrated. Comparison with conventional imaging showed that especially lesions located in the spine or the pelvis were not detectable on radiographs even when knowing the MR results. The extent of skeletal involvement in Langerhans cell histiocytosis has crucial impact on therapy and prognosis. Whole-body MRI has been reported to be an established method for the evaluation of disseminated skeletal disease with distinct advantages over conventional radiography and bone scintigraphy. Our results suggest that WB-MRI should also be the imaging modality of choice for the assessment of skeletal involvement in children with Langerhans cell histiocytosis.


The effect of grain shape and material on the nonlocal rheology of dense granular flows.
Nonlocal rheologies allow for the modeling of granular flows from the creeping to intermediate flow regimes, using a small number of parameters. In this paper, we report on experiments testing how particle properties affect the model parameters used in the Kamrin & Koval cooperative nonlocal model, using particles of three different shapes (circles, ellipses, and pentagons) and three different materials, including one which allows for the measurement of stresses via photoelasticity. Our experiments are performed on a quasi-2D annular shear cell with a rotating inner wall and a fixed outer wall. Each type of particle is found to exhibit flows which are well-fit by nonlocal rheology, with each particle having a distinct triad of the local, nonlocal, and frictional parameters. While the local parameter b is always approximately unity, the nonlocal parameter A depends sensitively on both the particle shape and material. The critical stress ratio μs, above which Coulomb failure occurs, varies for particles with the same material but different shape, indicating that geometric friction can dominate over material friction.


Molecular basis of ligand recognition and transport by glucose transporters.
The major facilitator superfamily glucose transporters, exemplified by human GLUT1-4, have been central to the study of solute transport. Using lipidic cubic phase crystallization and microfocus X-ray diffraction, we determined the structure of human GLUT3 in complex with D-glucose at 1.5 Å resolution in an outward-occluded conformation. The high-resolution structure allows discrimination of both α- and β-anomers of D-glucose. Two additional structures of GLUT3 bound to the exofacial inhibitor maltose were obtained at 2.6 Å in the outward-open and 2.4 Å in the outward-occluded states. In all three structures, the ligands are predominantly coordinated by polar residues from the carboxy terminal domain. Conformational transition from outward-open to outward-occluded entails a prominent local rearrangement of the extracellular part of transmembrane segment TM7. Comparison of the outward-facing GLUT3 structures with the inward-open GLUT1 provides insights into the alternating access cycle for GLUTs, whereby the C-terminal domain provides the primary substrate-binding site and the amino-terminal domain undergoes rigid-body rotation with respect to the C-terminal domain. Our studies provide an important framework for the mechanistic and kinetic understanding of GLUTs and shed light on structure-guided ligand design.


Radioimmunotherapy in non-Hodgkin's lymphoma: focus on 90Y-ibritumomab tiuxetan (Zevalin).
Radioimmunotherapy (RIT), in which a radionuclide conjugated to an antibody directed towards a tumor associated antigen (the radioimmunoconjugate) is administered in a therapeutic regimen, represents a significant addition to the treatment of non-Hodgkin's lymphoma (NHL). RIT offers several advantages for this heterogenous disease, foremost being the ability to kill tumor cells adjacent to cells to which the radioimmunoconjugate is bound (the cross-fire effect). Thus, RIT is cytotoxic to tumor cells that may be inaccessible to the antibody, or do not express the target antigen in sufficient quantities for antibody binding. The radioimmunoconjugate 90Y-ibritumomab tiuxetan is directed against the B-cell antigen, CD20. Phase II and III clinical trials with this agent report overall response rates of 74% to 83% (complete response rates 15% to 51%) in patients with relapsed or refractory, indolent or transformed NHL, including patients refractory to rituximab. Median durations of response range up to 13.9 months. A variety of RIT approaches are under investigation to improve outcomes in patients with NHL, including the use of radioimmunoconjugates combined with chemotherapy, and myeloablative therapeutic strategies.


Cytotoxicity of Cichorium intybus L. metabolites (Review).
Cichorium intybus L. (Chicory) is a widely distributed, edible, perennial, herbaceous member of the Asteraceae family. Besides its use in modern Chinese herbal medicine, its ethnomedicinal use is evident in the text from ancient Greece, Egypt and China. It is also used as a food and coffee substitute, which is mainly responsible for its extensive domestication. In recent decades, cytotoxic studies of C. intybus extracts have shown its antitumor potential. These studies also identified metabolite constituents including guaianolides, 6‑methoxyflavone, eudesmanolides, germacranolides, polyacetylene, sterol, anthocyanin, delphinidin, 3,4‑dihydroxyphenethyl and other novel compounds. Many of these phytometabolites have shown positive cytotoxic activities in vitro, and antitumor action in vivo and in clinical trials, demonstrating the potential of C. intybus metabolites as antitumor drugs. Structural activity relationship studies have further confirmed these bioactivities. In this review, we focused on the phytochemicals of C. intybus with reported cytotoxicity and potential antitumor properties. We also discuss their specificity towards tumor cells, structural activity relationship, the involved signaling pathways and molecular mechanism, with the expectation of the future development of efficient and targeted antitumor therapeutic strategies.


Immersion events in residential swimming pools. Evidence for an experience effect.
--Drowning and near-drowning in residential swimming pools are leading causes of morbidity and mortality for young children. We tested the hypothesis that the period immediately after a pool is acquired is a time of high risk for these events. This study was also designed to provide population-based data on swimming pool immersion events, regardless of severity. --We conducted a mail survey of a probability sample of Sacramento County, California, households with in-ground swimming pools in January 1988; 80% of eligible subjects responded. Onset of exposure to a pool was defined as the month in which (1) the responding household had a pool installed, or (2) the responding household first occupied a residence with a pool. Exposures began in 1959 through 1987. --The home swimming pool immersion event rate was 11 per 1000 pool-years. The rate per 1000 pool-years was higher for the first 6 months of exposure than thereafter (0 to 6 months, 44; 7 to 24 months, 14; greater than 24 months, seven), but 77% of events occurred outside the high-risk period. For households whose exposures began in 1984 through 1987, the immersion event rate was 51 per 1000 pool-years overall and 123 per 1000 pool-years for the first 6 months of pool exposure; these increases probably represent underreporting of earlier events. In this group, 48% of events occurred outside the high-risk period. The family swimming pool accounted for 91% of immersion events at the respondents' homes. --The residential swimming pool is an important hazard for pool-owning households. The first 6 months of exposure constitute a high-risk period, but many immersion events occur later. Pool drowning prevention programs may focus on newly acquired swimming pools and their owners but should be as broad as possible to maximize their effectiveness.


Advances in research on the prenatal development of skeletal muscle in animals in relation to the quality of muscle-based food. I. Regulation of myogenesis and environmental impact.
Skeletal muscle development in vertebrates - also termed myogenesis - is a highly integrated process. Evidence to date indicates that the processes are very similar across mammals, poultry and fish, although the timings of the various steps differ considerably. Myogenesis is regulated by the myogenic regulatory factors and consists of two to three distinct phases when different fibre populations appear. The critical times when myogenesis is prone to hormonal or environmental influences depend largely on the developmental stage. One of the main mechanisms for both genetic and environmental effects on muscle fibre development is via the direct action of the growth hormone-insulin-like growth factor (GH-IGF) axis. In mammals and poultry, postnatal growth and function of muscles relate mainly to the hypertrophy of the fibres formed during myogenesis and to their fibre-type composition in terms of metabolic and contractile properties, whereas in fish hyperplasia still plays a major role. Candidate genes that are important in skeletal muscle development, for instance, encode for IGFs and IGF-binding proteins, myosin heavy chain isoforms, troponin T, myosin light chain and others have been identified. In mammals, nutritional supply in utero affects myogenesis and the GH-IGF axis may have an indirect action through the partitioning of nutrients towards the gravid uterus. Impaired myogenesis resulting in low skeletal myofibre numbers is considered one of the main reasons for negative long-term consequences of intrauterine growth retardation. Severe undernutrition in utero due to natural variation in litter or twin-bearing species or insufficient maternal nutrient supply may impair myogenesis and adversely affect carcass quality later in terms of reduced lean and increased fat deposition in the progeny. On the other hand, increases in maternal feed intake above standard requirement seem to have no beneficial effects on the growth of the progeny with myogenesis not or only slightly affected. Initial studies on low and high maternal protein feeding are published. Although there are only a few studies, first results also reveal an influence of nutrition on skeletal muscle development in fish and poultry. Finally, environmental temperature has been identified as a critical factor for growth and development of skeletal muscle in both fish and poultry.


[Submucosal endoscopic dissection].
Endoscopic submucosal dissection (ESD) is a novel technique that increases the therapeutic spectrum for early-stage malignant lesions (T1mN0) of gastrointestinal tract. To review the current training requirements, indications and devices for ESD. A PubMed search and selection for manuscripts between 2005 and 2009 was performed. Kew words used were of "endoscopic submucosal dissection", "indications", "training" and "devices". Indications for ESD in early gastrointestinal cancer are: I) Well differentiated and limited to mucosa: a) Non ulcerated: no matters size and shape or, b) Ulcerated: less than 3 cm; II) Poorly-differentiated limited to mucosa: non ulcerated and less than 2 cm; III) Invading submucosa: well differentiated, less than 3 cm with a maximum depth of 500 µm. The most frequently used technique to elevate submucosa is injection of isotonic saline solution with epinephrine and indigo. Technology is evolving with new devices for increasing safety. Training should include at least 30 animal models before attempting to perform the procedure in patients. ESD is an endoscopic procedure with well established indications that require a special training. Its use in well selected cases is safe and can replace a surgical procedure or other therapeutic modalities.


Networks of triboelectric nanogenerators for harvesting water wave energy: a potential approach toward blue energy.
With 70% of the earth's surface covered with water, wave energy is abundant and has the potential to be one of the most environmentally benign forms of electric energy. However, owing to lack of effective technology, water wave energy harvesting is almost unexplored as an energy source. Here, we report a network design made of triboelectric nanogenerators (TENGs) for large-scale harvesting of kinetic water energy. Relying on surface charging effect between the conventional polymers and very thin layer of metal as electrodes for each TENG, the TENG networks (TENG-NW) that naturally float on the water surface convert the slow, random, and high-force oscillatory wave energy into electricity. On the basis of the measured output of a single TENG, the TENG-NW is expected to give an average power output of 1.15 MW from 1 km(2) surface area. Given the compelling features, such as being lightweight, extremely cost-effective, environmentally friendly, easily implemented, and capable of floating on the water surface, the TENG-NW renders an innovative and effective approach toward large-scale blue energy harvesting from the ocean.


Safety and Efficacy of Bis-Glyceryl Ascorbate (Amitose DGA) to Prevent Hand-Foot Skin Reaction in Patients With Renal Cell Carcinoma Receiving Sunitinib Therapy: Protocol for a Phase I/II, Uncontrolled, Single-Arm, Open-Label Trial.
Hand-foot skin reaction (HFSR) is a serious side effect induced by multiple-tyrosine kinase inhibitors (TKIs). HFSR can cause treatment interruption or decreased dosing. HFSR also markedly decreases quality of life and is associated with the therapeutic efficacy of multiple-TKIs. Therefore, the management and prevention of HFSR is an important issue; however, an effective method for its prevention has not been established. Specific ascorbic acid derivatives can reverse multiple-TKI-induced keratinocyte growth and pathological changes in vitro. This study was designed to evaluate the safety of bis-glyceryl ascorbate (Amitose DGA), a novel, hydrosoluble, and moisturizing ascorbic acid derivative, in patients with renal cell carcinoma (RCC) receiving sunitinib therapy. This study was also designed to evaluate Amitose DGA's preventive efficacy for sunitinib-induced HFSR. This is a Phase I/II, single-center, uncontrolled, single-arm, open-label trial. We will recruit a total of 30 patients with RCC receiving sunitinib therapy, with a 2-week-on and 1-week-off schedule. The participants will apply Amitose DGA-containing cream over both palmar and plantar surfaces within two treatment cycles (ie, 6 weeks) of sunitinib in combination with a general moisturizing agent, in addition to standard-of-care processes. Safety assessments will include dermatological abnormalities, clinical laboratory tests, and incidence of adverse events. Efficacy assessments will include development of HFSR and therapeutic outcomes associated with sunitinib. Recruitment to the study began in August 2017 and is ongoing in Japan. To date, 21 subjects have been recruited. Study completion is expected in 2021. This is the first clinical study of Amitose DGA-containing cream in patients with RCC who are receiving sunitinib therapy. The single-center, single-arm, open-label design was selected to maximize subject exposure and increase the likelihood of achieving our study endpoints. The results will provide valuable and preliminary evidence of the effects of Amitose DGA-containing cream on HFSR. UMIN Clinical Trials Registry UMIN000027209; https://upload.umin.ac.jp/cgi-open-bin/ctr /ctr_view.cgi?recptno=R000031174. DERR1-10.2196/14636.


Prediction of breast tumor size by mammography and sonography--A breast screen experience.
Concise preoperative assessment of breast Tumor size is important when considering surgical approach and the staging of breast cancer. A retrospective study of 400 uni-focal, invasive ductal carcinomas compared the accuracy of sonographic and mammographic measuring modalities with histological size. Sub-groups for tumor size, type and grade, with other variables, were also considered in intra-modal correlations of lesion dimension. Mammography (R2=0.74), although slightly over estimating tumor size, appeared to be more useful than sonography (R2=0.60) following logistical analysis of the data. Correlational significance for both imaging modalities decreased for tumors larger than 20mm. Sonography under estimated lesions in over 50% of cases; the average underestimate being 9.9 mm, and ranging from 1mm to 30 mm. Consideration of both imaging measurements in cohort should improve the accuracy of radiological reporting of pre-surgical tumor size.


Effect of the alpha-glucosidase inhibitor acarbose on control of glycemia in dogs with naturally acquired diabetes mellitus.
To evaluate effect of acarbose on control of glycemia in dogs with diabetes mellitus. Prospective randomized crossover controlled trial. 5 dogs with naturally acquired diabetes mellitus. Dogs were treated with acarbose and placebo for 2 months each: in 1 of 2 randomly assigned treatment sequences. Dogs that weighed < or = 10 kg (22 lb; n = 3) or > 10 kg (2) were given 25 or 50 mg of acarbose, respectively, at each meal for 2 weeks, then 50 or 100 mg of acarbose, respectively, at each meal for 6 weeks, with a 1-month interval between treatments. Caloric intake, type of insulin, and frequency of insulin administration were kept constant, and insulin dosage was adjusted as needed to maintain control of glycemia. Serum glucose concentrations, blood glycosylated hemoglobin concentration, and serum fructosamine concentration were determined. Significant differences in mean body weight and daily insulin dosage among dogs treated with acarbose and placebo were not found. Mean preprandial serum glucose concentration, 8-hour mean serum glucose concentration, and blood glycosylated hemoglobin concentration were significantly lower in dogs treated with insulin and acarbose, compared with insulin and placebo. Semisoft to watery feces developed in 3 dogs treated with acarbose. Acarbose may be useful as an adjunctive treatment in diabetic dogs in which cause for poor glycemic control cannot be identified, and insulin treatment alone is ineffective.


In vivo accumulation of the same anti-melanoma T cell clone in two different metastatic sites.
In a patient with progressing metastatic melanoma, we showed that the same autologous tumor-cytolytic CD8+ tumor infiltrating lymphocyte (TIL) clone accumulated in two separate metastatic sites. This clone, which represented three of eight independently derived clones from a tumor deposit on the skin of the abdomen, also represented two of eight clones derived from a skin lesion on the shoulder. This clone could be identified by its use of a unique TCRBV2-nD1n-J1S6 sequence, and could also be detected by single-stranded conformational polymorphism (SSCP) as the dominant TCRBV2-expressing clone among CD8+ TILs propagated from both shoulder and abdominal lesions. Using SSCP analysis, we also demonstrated that this clone was dominant in the fresh tumor tissue and in all TILs in which CD8+ were strongly represented, including several separate but parallel cultures. The SSCP pattern for this clone was not apparent among CD4+ TILs or CD8+ peripheral blood mononuclear cells. The SSCP analysis of the tumor tissue prior to in vitro culture is an indication that the selection for this anti-tumor cytotoxic T cell clone was a reflection of its in vivo accumulation. Thus, we provide evidence that melanomas are immunogenic and able to select for cytotoxic antitumor-specific TIL clones that are expanded in vivo and can circulate to accumulate in different tumor sites. However, because these clones were isolated from progressing tumor metastases, the accumulation of these specific cytotoxic T cells was not sufficient to contain tumor growth.


Classification, assessment, prevalence, and effect of personality disorder.
Personality disorders are common and ubiquitous in all medical settings, so every medical practitioner will encounter them frequently. People with personality disorder have problems in interpersonal relationships but often attribute them wrongly to others. No clear threshold exists between types and degrees of personality dysfunction and its pathology is best classified by a single dimension, ranging from normal personality at one extreme through to severe personality disorder at the other. The description of personality disorders has been complicated over the years by undue adherence to overlapping and unvalidated categories that represent specific characteristics rather than the core components of personality disorder. Many people with personality disorder remain undetected in clinical practice and might be given treatments that are ineffective or harmful as a result. Comorbidity with other mental disorders is common, and the presence of personality disorder often has a negative effect on course and treatment outcome. Personality disorder is also associated with premature mortality and suicide, and needs to be identified more often in clinical practice than it is at present.


Towards a simple objective framework for the investigation and treatment of cancer cachexia: the Glasgow Prognostic Score.
Progress in the treatment of progressive involuntary weight loss in patients with cancer (cancer cachexia) remains dismally slow. Cancer cachexia and its associated clinical symptoms, including weight loss, altered body composition, poor functional status, poor food intake, and poorer quality of life, have long been recognised as indicators of poorer prognosis in the patient with cancer. In order to make some progress a starting point is to have general agreement on what constitutes cancer cachexia. In recent years a plethora of different definitions and consensus statements have been proposed as a framework for investigation and treatment of this debilitating and terminal condition. However, there are significant differences in the criteria used in these and all include poorly defined or subjective criteria and their prognostic value has not been established. The aim of the present review was to examine the hypothesis that a systemic inflammatory response accounts for most of the effect of cancer cachexia and its associated clinical symptoms on poor outcome in patients with cancer. Furthermore, to put forward the case for the Glasgow Prognostic Score to act a simple objective framework for the investigation and treatment of cancer cachexia.


Sialic acids in human health and disease.
The surfaces of all vertebrate cells are decorated with a dense and complex array of sugar chains, which are mostly attached to proteins and lipids. Most soluble secreted proteins are also similarly decorated with such glycans. Sialic acids are a diverse family of sugar units with a nine-carbon backbone that are typically found attached to the outermost ends of these chains. Given their location and ubiquitous distribution, sialic acids can mediate or modulate a wide variety of physiological and pathological processes. This review considers some examples of their established and newly emerging roles in aspects of human physiology and disease.


Heterogeneity in vaccine immune response: the role of immunogenetics and the emerging field of vaccinomics.
Recent advances in the fields of immunology, genetics, molecular biology, bioinformatics, and the Human Genome Project have allowed for the emergence of the field of vaccinomics. Vaccinomics encompasses the fields of immunogenetics and immunogenomics as applied to understanding the mechanisms of heterogeneity in immune responses to vaccines. In this study, we examine the role of HLA genes, cytokine genes, and cell surface receptor genes as examples of how genetic polymorphism leads to individual and population variations in immune responses to vaccines. In turn, this data, in concert with new high-throughput technology, inform the immune-response network theory to vaccine response. Such information can be used in the directed and rational development of new vaccines, and this new golden age of vaccinology has been termed "predictive vaccinology", which will predict the likelihood of a vaccine response or an adverse response to a vaccine, the number of doses needed and even whether a vaccine is likely to be of benefit (i.e., is the individual at risk for the outcome for which the vaccine is being administered?).


Clinical efficacy of Vestibular Incision Subperiosteal Tunnel Access (VISTA) for treatment of multiple gingival recession defects: a systematic review, meta-analysis and meta-regression.
This study investigated the efficacy of Vestibular Incision Subperiosteal Tunnel Access (VISTA) compared to other methods for treating multiple adjacent gingival recessions (MAGRs) through a systematic review and meta-analysis. A systematic literature search was performed through June 2023, to identify clinical trials investigating VISTA for root coverage on MAGRs. A meta-analysis with meta-regression model was employed on the primary outcomes of mean and complete root coverages (MRC, CRC), comparing VISTA with other techniques. Clinical efficacy of various graft materials was assessed. Fourteen studies were included, 8 of which met the criteria for quantitative assessment. The cumulative MRC (88.15% ± 20.79%) and CRC (67.85% ± 21.72%) of VISTA were significantly higher compared to the tunneling technique (SMD = 0.83 (95% CI [0.36, 1.30], p < 0.01). The baseline recession depth showed a negative correlation with CRC, whereas baseline keratinized gingiva width exhibited a positive correlation with this outcome. The VISTA technique, particularly with acellular dermal matrix (ADM) or connective tissue graft (CTG) materials, offers superior outcomes compared to the tunneling technique. The capacity of platelet-rich fibrin (PRF) to substitute for connective tissue graft (CTG) in VISTA-root coverage was noteworthy, provided there is adequate keratinized tissue width. VISTA in concert with acellular dermal matrix or CTG resulted in improved root coverage, surpassing the outcomes achieved through tunneling. PRF emerged as a viable alternative to CTG, when used in conjunction with VISTA, demonstrating comparable mean root coverage. This is particularly evident in situations where sufficient keratinized gingiva is available and when patient comfort is taken into consideration.


Online teaching and learning in higher education: Lessons learned in crisis situations.
In the year 2020, the Covid-19 pandemic turned both private and public life upside down. Teaching and learning at higher education institutions worldwide had to move online on very short notice. This Special Issue focuses on the academic practice of online teaching and learning in higher education in the current time of crisis. Online teaching and learning has been a prominent research topic for the last three decades, but online study programs at universities are still scarce. In this synthesis article, our considerations about online teaching and learning in higher education are positioned in the broad framework of communities of practice (CoPs). We establish a relationship between CoP-concepts and the integrative framework for learning activities involving technology in higher education (the C♭ model), as proposed by Sailer and colleagues in this Special Issue. We continue with some initial thoughts on online teaching and learning in higher education in general, and emergency online teaching and learning more specifically. After an overview of the international research compiled in this Special Issue, we derive a number of general insights on online teaching and learning in higher education, emphasizing, for instance, scaffolding of regulation processes or communication platforms as potential artifacts of an online teaching and learning CoP.


Wavelet-based protocols for ion channel electrophysiology.
Fluctuation-induced phenomena caused by both random and deterministic stimuli have been previously studied in a variety of contexts. They are based on the interplay between the spectro-temporal patterns of the signal and the kinetics of the system it is applied to. The aim of this study was to develop a method for designing fluctuating inputs into nonlinear system which would elicit the most desired system output and to implement the method to studies of ion channels. We describe an algorithm based on constructing the input as a superposition of wavelets and optimizing it according to a selected cost functional. The algorithm is applied to ion channel electrophysiology where the input is the fluctuating voltage delivered through a patch-clamp experimental apparatus and the output is the whole-cell ionic current. The algorithm is optimized to aid selection of Markov models of the gating kinetics of the voltage-gated Shaker K+ channel and tested by comparison of numerically obtained ionic currents predicted by different models with experimental data obtained from the Shaker K+ channels. Other applications and optimization criteria are also suggested. The method described in this paper can be useful in development and testing of models of ion channel gating kinetics, developing voltage inputs that optimize certain nonequilibrium phenomena in ion channels, such as the kinetic focusing, and potentially has applications to other fields.


Global surveillance, travel, and trade during a pandemic
Pandemics have had very important consequences in human history. Lots of people lost their lives and countries have been intensively affected in terms of socioeconomic problems. Unfortunately, avoidance of pandemics and limiting the spread are still currently not always possible. Maybe the most important factor for this is the increasing frequency of traveling. Increasing airline traveling rate also increases the rate of spread. Global organizations like the World Health Organization and United Nations are trying to play a supreme role over the countries. Pandemics do not have borders; therefore, efforts should be given globally, definition of pandemic should be established as soon as possible, and protective measures should be shared with countries. If these are not done, severe health consequences and serious economic problems are inevitable.


A phylogenetic approach to RNA structure prediction.
Methods based on the Mutual Information statistic (MI methods) predict structure by looking for statistical correlations between sequence positions in a set of aligned sequences. Although MI methods are often quite effective, these methods ignore the underlying phylogenetic relationships of the sequences they analyze. Thus, they cannot distinguish between correlations due to structural interactions, and spurious correlations resulting from phylogenetic history. In this paper, we introduce a method analogous to MI that incorporates phylogenetic information. We show that this method accurately recovers the structures of well-known RNA molecules. We also demonstrate, with both real and simulated data, that this phylogenetically-based method outperforms standard MI methods, and improves the ability to distinguish interacting from non-interacting positions in RNA. This method is flexible, and may be applied to the prediction of protein structure given the appropriate evolutionary model. Because this method incorporates phylogenetic data, it also has the potential to be improved with the addition of more accurate phylogenetic information, although we show that even approximate phylogenies are helpful.


Clinical characteristics and referral pattern of patients with left ventricular dysfunction and significant coronary artery disease undergoing radionuclide imaging.
Many observational studies that predict patient outcomes have examined the use of myocardial perfusion imaging results. However, a referral pattern for radionuclide testing could bias these analyses and should be determined. These patients may also differ with regard to the extent of coronary artery disease (CAD). All of these differences must be incorporated into proper outcomes examinations. We sought to identify the nuclear perfusion imaging referral pattern for patients with left ventricular (LV) dysfunction and significant CAD. Patients with LV dysfunction and CAD (n = 2951) meeting our inclusion criteria were compared by receipt or absence of radionuclide perfusion testing within 6 months before or after angiography. Pearson chi2 and Kruskal-Wallis analyses were used to examine differences in baseline characteristics and catheterization results, whereas logistic regression modeling was applied to predict nuclear imaging referral before and after catheterization. Precatheterization nuclear cohort patients were more likely to be minority patients (odds ratio [OR], 1.34; P =.0083) with previous cardiac revascularization (OR, 2.27; P =.0001), Charlson comorbidity index greater than 1 (OR, 1.146; P =.0091), and heart failure symptoms (OR, 1.62; P =.0001) than those without imaging. They were less likely to have a myocardial infarction (OR, 0.464; P =.0001). After catheterization, the nuclear patients were more likely to have had congestive heart failure (OR, 1.452; P =.0019), a myocardial infarction (OR, 1.353; P =.0371), an ejection fraction lower than 30% (OR, 1.058; P =.0002), and prior revascularization (OR, 1.880; P =.0001). In addition, they had fewer diseased vessels (OR, 0.731; P =.0001). Bias exists in nuclear referral for patients with LV dysfunction and significant CAD and must be considered when interpreting observational studies on this topic.


Water-Templated, Polysaccharide-rich Bioartificial 3D Microarchitectures as Extra-Cellular Matrix Bioautomatons.
This is the first report of exploiting the "quasi-spherical" shape of water molecules for recapitulating a true human extracellular matrix (ECM). Herein, water behaved as a quasi-spherical porogen, for engineering polysaccharide-rich and chemically defined 3D-microarchitecture, with semi-interpenetrating networks (S-IPNs). Furthermore, their viscoelastic behavior along with a heterogeneous, fibroporous morphology, facilitated instructive, self-remodeling of the bioartificial scaffolds, thence effectively permitting and promoting the growth of 3D tumor spheroids of divergent origins. The hybrid composites displayed reproducible, uniform tumor spheroids with a Z-depth of ∼65 ± 2 μm in case of human adenocarcinoma (DLD-1) and ∼54 ± 3 μm for human glioblastoma cells (U-251) (vs. nonuniform spheroids, on Agarose matrix). Thereafter, their capacity for anticancer drug screening was examined using limited cancer drugs. The conflicting drug screening results for Etoposide's reduced efficacy on glioblastoma cells cultured on our 3D matrix could be ascribed to decreased drug access and thus lower ingression. Nonetheless, adenocarcinoma's resistance to Camptothecin was paralleled. Moreover, their potential for real-time, high-content, phenotypic precision oncology was affirmed by the exceptional transparency of the synthesized composite. Since this 3D microarchitecture typifies ECM bioautomaton, this matrix can also be wielded for precision oncology.


MOSS-Multi-Modal Best Subset Modeling in Smart Manufacturing.
Smart manufacturing, which integrates a multi-sensing system with physical manufacturing processes, has been widely adopted in the industry to support online and real-time decision making to improve manufacturing quality. A multi-sensing system for each specific manufacturing process can efficiently collect the in situ process variables from different sensor modalities to reflect the process variations in real-time. However, in practice, we usually do not have enough budget to equip too many sensors in each manufacturing process due to the cost consideration. Moreover, it is also important to better interpret the relationship between the sensing modalities and the quality variables based on the model. Therefore, it is necessary to model the quality-process relationship by selecting the most relevant sensor modalities with the specific quality measurement from the multi-modal sensing system in smart manufacturing. In this research, we adopted the concept of best subset variable selection and proposed a new model called Multi-mOdal beSt Subset modeling (MOSS). The proposed MOSS can effectively select the important sensor modalities and improve the modeling accuracy in quality-process modeling via functional norms that characterize the overall effects of individual modalities. The significance of sensor modalities can be used to determine the sensor placement strategy in smart manufacturing. Moreover, the selected modalities can better interpret the quality-process model by identifying the most correlated root cause of quality variations. The merits of the proposed model are illustrated by both simulations and a real case study in an additive manufacturing (i.e., fused deposition modeling) process.


Positive and negative regulation of phosphoinositide 3-kinase-dependent signaling pathways by three different gene products of the p85alpha regulatory subunit.
Phosphoinositide (PI) 3-kinase is a key mediator of insulin-dependent metabolic actions, including stimulation of glucose transport and glycogen synthesis. The gene for the p85alpha regulatory subunit yields three splicing variants, p85alpha, AS53/p55alpha, and p50alpha. All three have (i) a C-terminal structure consisting of two Src homology 2 domains flanking the p110 catalytic subunit-binding domain and (ii) a unique N-terminal region of 304, 34, and 6 amino acids, respectively. To determine if these regulatory subunits differ in their effects on enzyme activity and signal transduction from insulin receptor substrate (IRS) proteins under physiological conditions, we expressed each regulatory subunit in fully differentiated L6 myotubes using adenovirus-mediated gene transfer with or without coexpression of the p110alpha catalytic subunit. PI 3-kinase activity associated with p50alpha was greater than that associated with p85alpha or AS53. Increasing the level of p85alpha or AS53, but not p50alpha, inhibited both phosphotyrosine-associated and p110-associated PI 3-kinase activities. Expression of a p85alpha mutant lacking the p110-binding site (Deltap85) also inhibited phosphotyrosine-associated PI 3-kinase activity but not p110-associated activity. Insulin stimulation of two kinases downstream from PI-3 kinase, Akt and p70 S6 kinase (p70(S6K)), was decreased in cells expressing p85alpha or AS53 but not in cells expressing p50alpha. Similar inhibition of PI 3-kinase, Akt, and p70(S6K) was observed, even when p110alpha was coexpressed with p85alpha or AS53. Expression of p110alpha alone dramatically increased glucose transport but decreased glycogen synthase activity. This effect was reduced when p110alpha was coexpressed with any of the three regulatory subunits. Thus, the three different isoforms of regulatory subunit can relay the signal from IRS proteins to the p110 catalytic subunit with different efficiencies. They also negatively modulate the PI 3-kinase catalytic activity but to different extents, dependent on the unique N-terminal structure of each isoform. These data also suggest the existence of a mechanism by which regulatory subunits modulate the PI 3-kinase-mediated signals, independent of the kinase activity, possibly through subcellular localization of the catalytic subunit or interaction with additional signaling molecules.


Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?
The current approach of morbidity control of schistosomiasis, a helminth disease of poverty with considerable public health and socioeconomic impact, is based on preventive chemotherapy with praziquantel. There is a pressing need for new drugs against this disease whose control entirely depends on this single drug that has been widely used over the past 40 years. We argue that a broader anthelminthic approach supplementing praziquantel with new antischistosomals targeting different parasite development stages would not only increase efficacy but also reduce the risk for drug resistance. Repositioning drugs already approved for other diseases provides a shortcut to clinical trials, as it is expected that such drugs rapidly pass the regulatory authorities. The antischistosomal properties of antimalarial drugs (e.g., semisynthetic artemisinins, synthetic trioxolanes, trioxaquines and mefloquine) and of drugs being developed or registered for other purposes (e.g., moxidectin and miltefosin), administered alone or in combination with praziquantel, have been tested in the laboratory and clinical trials. Another avenue to follow is the continued search for new antischistosomal properties in plants. Here, we summarise recent progress made in schistosomiasis chemotherapy, placing particular emphasis on repositioning of existing drugs against schistosomiasis.


Rehabilitative skilled forelimb training enhances axonal remodeling in the corticospinal pathway but not the brainstem-spinal pathways after photothrombotic stroke in the primary motor cortex.
Task-specific rehabilitative training is commonly used for chronic stroke patients. Axonal remodeling is believed to be one mechanism underlying rehabilitation-induced functional recovery, and significant roles of the corticospinal pathway have previously been demonstrated. Brainstem-spinal pathways, as well as the corticospinal tract, have been suggested to contribute to skilled motor function and functional recovery after brain injury. However, whether axonal remodeling in the brainstem-spinal pathways is a critical component for rehabilitation-induced functional recovery is not known. In this study, rats were subjected to photothrombotic stroke in the caudal forelimb area of the primary motor cortex and received rehabilitative training with a skilled forelimb reaching task for 4 weeks. After completion of the rehabilitative training, the retrograde tracer Fast blue was injected into the contralesional lower cervical spinal cord. Fast blue-positive cells were counted in 32 brain areas located in the cerebral cortex, hypothalamus, midbrain, pons, and medulla oblongata. Rehabilitative training improved motor performance in the skilled forelimb reaching task but not in the cylinder test, ladder walk test, or staircase test, indicating that rehabilitative skilled forelimb training induced task-specific recovery. In the histological analysis, rehabilitative training significantly increased the number of Fast blue-positive neurons in the ipsilesional rostral forelimb area and secondary sensory cortex. However, rehabilitative training did not alter the number of Fast blue-positive neurons in any areas of the brainstem. These results indicate that rehabilitative skilled forelimb training enhances axonal remodeling selectively in the corticospinal pathway, which suggests a critical role of cortical plasticity, rather than brainstem plasticity, in task-specific recovery after subtotal motor cortex destruction.


Nihilism in the 1990s: the true mortality of congenital diaphragmatic hernia.
Reported survival in congenital diaphragmatic hernia (CDH) fails to allow for case selection bias. This study reports the incidence of CDH in a geographically defined population over 11 years and assesses the effect of new therapies (high-frequency oscillatory ventilation, extracorporeal membrane oxygenation, inhaled nitric oxide, and delayed surgery) on survival when case selection is avoided. A retrospective review of cases from a regional case registry, the Northern Region Congenital Anomaly Survey, was conducted. A total of 185 cases were identified. Mortality was 62% and did not vary significantly during the study period. Mortality was unaffected by the introduction of new therapies. There was a significant inverse correlation between the rate of elective termination and survival of live borns. The presence of an additional anomaly increased mortality to 79%. The mortality of CDH when complete case ascertainment is achieved is unaffected by new therapies. The survival rate is principally determined by the rate of antenatal termination and the incidence of associated anomalies. Reports of improved survival of CDH should be interpreted with caution, as variations in outcome are more likely to be explained by case selection artifact.


Complications after laparoscopic and open subtotal colectomy for inflammatory colitis: a case-matched comparison.
The aim of this study was to compare the early postoperative outcome of patients undergoing laparoscopic subtotal colectomy with those undergoing open subtotal colectomy for colitis refractory to medical treatment. A retrospective observational study was carried out of patients who underwent subtotal colectomy for refractory colitis, at a single centre, between 2006 and 2012. Patients were matched for age, gender, American Society of Anesthesiology (ASA) grade, urgency of operation and immunosuppressant/modulator treatment. The primary outcome measure was the number of postoperative complications, classified using the Clavien-Dindo scale. Secondary end-points included procedure duration, laparoscopic conversion rates, blood loss, 30-day readmission rates and length of hospital stay. Ninety-six patients were included, 39 of whom had laparoscopic surgery. Thirty-two of these were matched to similar patients who underwent an open procedure. The overall duration of the procedure was longer for laparoscopic surgery than for open surgery (median: 240 vs 150 min, P < 0.005) but estimated blood loss was less (median: 75 vs 400 ml, P < 0.005). In the laparoscopic group, 23 patients experienced 27 complications, and in the open surgery group, 23 patients experienced 30 complications. Most complications were minor (Grade I/II), and the distribution of complications, by grade, was similar between the two groups. There was no statistically significant difference in 30-day readmission rates between the laparoscopic and open groups (five readmissions vs eight readmissions, P = 0.536). Length of hospital stay was 4 days shorter for laparoscopic surgery, but this difference was not statistically significant (median: 7 vs 11 days, P = 0.159). In patients requiring colectomy for acute severe colitis, laparoscopic surgery reduced blood loss but increased operating time and was not associated with a reduction in early postoperative complications, length of hospital stay or readmission rates.


Airway microbiome research: a modern perspective on surveillance cultures?
The incidence of ventilator-associated pneumonia (VAP) is estimated to be around 10% in a high-risk population. Over the last decade, major improvements have been made in the prevention of VAP, with great cost-effectiveness. However, we still do not understand the exact pathogenesis of VAP. A better understanding might explain why some patients develop ventilator-associated tracheobronchitis, while others develop VAP even though they are infected with the same types of pathogens. Microbiome research has been a hot topic in translational medicine over the past decade. Slowly, microbiome research has also been introduced to the intensive care setting. One of the areas where it may influence our pathophysiological considerations is in VAP. The adapted island has been proposed for the colonization and infection of the respiratory tract. In this model, not only the immigration of bacteria into the lung is important, but elimination and regional growth factors are of equal significance. The importance of these factors can be supported by epidemiological studies. Several small observational studies on the development of the pulmonary microbiome during mechanical ventilation also support this theory. We speculate on the consequences of the newest insights in microbiome research on the prevention and targeted treatment of VAP. We conclude that there is still a strong need for more in-depth analyses of the changes in the microbial composition of the pulmonary microbiome during mechanical ventilation and with the development of VAP.


Lateral switch to IFN beta-1a 44 mcg may be effective as escalation switch to fingolimod in selected persons with relapsing remitting multiple sclerosis: a real-world setting experience.
The efficacy of lateral and escalation switch is a challenge in MS. We compared in a real-world setting the efficacy of switching to IFN beta-1a 44 mcg or to fingolimod in persons with relapsing remitting MS (pwRRMS) who failed with others injectable IFNs or glatiramer acetate. retrospective analysis of 24 months prospectively-collected data at the MS center of the University of Catania, Italy was performed. Patients who were switched to IFN-beta 1a 44 mcg or fingolimod were analyzed using propensity-score covariate adjustment model within demographic (e.g. age and gender) and disease (e.g. timing of pre-switch relapse) characteristics. Switching-time was considered the starting-time of the observation. 43 pwRRMS on IFN beta-1a 44 mcg and 49 pwRRMS on fingolimod were included. Baseline characteristics differed for EDSS score and number of T2 lesions (higher in group on fingolimod). At 24 months of follow up, both groups showed no differences in the survival curves of reaching a first new relapse, new T2 and Gd+ MRI brain lesions, even corrected for the propensity score covariate adjustment. lateral switch to IFN beta-1a 44 mcg and escalation switch to fingolimod showed same ability in influencing RRMS disease activity at 24 months.


Self-reported prior night's sleep quantity on baseline symptom factors and computerized neurocognitive testing in high school athletes.
Little is known regarding sleep and baseline concussion performance and symptoms in athletes. We explored the effects of self-reported prior night's sleep quantity on baseline symptoms and computerized neurocognitive testing in high school athletes. A retrospective analysis of 958 high school athletes between the ages of 13-19 years was completed on Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) performance. Participants were categorized into two groups based on self-reported prior night's sleep quantity: <8 h (n = 524; 55%) and ≥8 h (n = 434; 45%). Measures consisted of baseline total symptom score, symptom factors (vestibular-somatic, sleep-arousal, affective, and cognitive-sensory), and ImPACT composite scores (verbal and visual memory, visual-motor speed, reaction time, and impulse control). Significant differences were found on all baseline symptom factors (ps < .02) and total symptom scores (p < .001) with greater symptom reporting in the <8 h prior night's sleep group. No group differences were observed between duration and composite scores of verbal memory (p = .49), visual memory (p = .94), visual-motor speed (p = .38), reaction time (p = .50), or impulse control (p = .81). High school athletes who report <8 h of sleep the night prior to baseline concussion testing reported greater symptoms across all symptom factors. Clinicians should consider inadequate sleep the night prior to concussion testing to ensure accurate, valid assessments, especially on symptom reporting scales.


[CD23 positive, BCL2 rearrangement-negative germinal centre lymphomas].
Acknowledgeing that the group of follicular lymphomas is to be regarded as very heterogeneous, a group of follicular lymphomas has been delineated in recent years that was characterised by an often diffuse growth (without formation of evident follicular structures) as well as expression of CD23 in the lymphoma cells and the absence of the classic BCL2 translocation. Further characteristics are a preferred inguinal localisation of the lymphomas and a localised stage with a good prognosis. Genetically, this lymphoma group is characterised by a high rate of either STAT6 or SOCS1 mutations.The ICC classification took this development into account by introducing the provisional entity CD23 positive, BCL2 rearrangement-negative germinal centre lymphoma. Further studies must now show how exactly this entity can be defined (combination of morphology, immunohistochemical phenotype, focus on genetic alterations) in order to pave the way towards a uniform classification and a better clinical characterisation of these cases - especially with regard to possible new therapeutic treatment options.


DNA-dependent transregulation by IE1 of Autographa californica nuclear polyhedrosis virus: IE1 domains required for transactivation and DNA binding.
IE1 is the principal early transregulator of Autographa californica multicapsid nuclear polyhedrosis virus (AcMNPV). The 582-residue protein stimulates viral transcription and binds as a dimer to 28-bp palindromic repeats (28-mers) comprising the AcMNPV homologous region (hr) transcription enhancers. To define IE1 domains responsible for hr-dependent transactivation, we first constructed a series of IE1 fusions to the DNA binding domain of the yeast GAL4 transactivator. In transfection assays, GAL4-IE1 fusions stimulated transcription from a TATA-containing AcMNPV promoter only upon cis linkage to GAL4 DNA binding sites. IE1 N-terminal residues 8 to 118 were sufficient for GAL4-binding-site-dependent transactivation. To identify IE1 residues required for hr interaction, we tested a series of IE1 mutations for 28-mer binding by using electrophoretic mobility shift assays. Deletion of IE1 residues other than the N-terminal transactivation domain eliminated 28-mer binding. Of 14 insertion mutations, only IE1(I425) and IE1(I553) failed to bind the 28-mer either as homodimers or as heterodimers with functional IE1. In contrast to insertion IE1(I425), IE1(I553) also failed to compete with wild-type IE1 for DNA binding and suggested a defect in oligomerization. Consistent with loss of oligomerization, substitutions within a hydrophobic repeat (residues 543 to 568) at the IE1 C terminus abolished 28-mer binding and demonstrated that this helix-loop-helix-like domain is required for DNA interaction. These data confirm that IE1 contains separable domains for transactivation and oligomerization-dependent DNA binding. Furthermore, they support a model wherein hr-mediated transactivation by IE1 involves sequence-specific DNA binding that contributes to transcriptional stimulation by interaction with components of the basal transcription complex.


Induction of orientation of bacterial cellulose microfibrils by a novel terpenoid from Acetobacter xylinum.
1. The bacterium Acetobacter xylinum produces extracellular cellulose microfibrils that form a pellicle in the medium enmeshing the bacterial cells. These microfibrils may show some localized alignment, which can be seen as birefringence when the culture is viewed between crossed Polaroid sheets. 2. An increase in birefringence can be induced by the addition of small amounts of certain classes of lipids, particularly sterols, to the cultures. 3. A crude lipid extract from Acetobacter cells induced greatly increased birefringence when added to fresh cultures of this organism. 4. When the bacterial lipids were fractionated, most of the activity was recovered in a complex, polar lipid. The lipid is secreted into the medium during growth and is unstable. The non-saponifiable portion of this lipid is shown to be a 1:1 mixture of a saturated and a monounsaturated C(35) tetrahydroxy terpene with a hopane ring system in the accompanying paper by Förster et al. (1973). The saturated molecule is referred to as tetrahydroxybacteriohopane. 5. Tetrahydroxybacteriohopane is itself capable of inducing birefringence in cultures as is 22-hydroxyhopane, which was also isolated from the non-saponifiable fraction of the total lipids. 6. The mechanism of induction of birefringence (orientation of microfibrils) is not known. This is unlikely to be a specific effect, since all the above compounds are active (intact lipid, tetrahydroxybacteriohopane, 22-hydroxyhopane), as are other classes of lipid. It is suggested, however, that a common mechanism may be involved and that similar compounds may be concerned with control of microfibril alignment in the cells of higher plants.


Are monotherapy options reasonable for T3 prostate cancer?
In 1997, we believe that either surgery, radiation, or hormonal monotherapy are unlikely to be adequate therapy alone for clinical stage T3 prostate cancer and that primary treatment strategies should use combination therapy. Combination therapies have been investigated in an effort to lessen the impact of monotherapy failure, and combination therapy trials have been shown to diminish the incidence of local failure and increase the time to progression. To gauge the role that irradiation or surgical monotherapy may play in clinical stage T3 disease, this article analyzes series that report local and distant disease control.


[Hepatitis B prevention and risk of HIV infection in children injured by discarded needles and/or syringes].
Main aim: to study the application of mixed prophylaxis against Hepatitis B viral infection (HB) in children injured by discarded needles and/or syringes. Secondary aim: to find in the group under study the incidence of HIV infection caused by these accidents. Descriptive study. 12 de octubre University Hospital, Madrid. Children injured by discarded needles and/or syringes and referred to the Preventive Medicine Service between May 1988 and April 1995 (7 years). 1) Serological study for HB and HIV; 2) application to unprotected children of HB mixed prophylaxis (specific Immunoglobulin--IGHB--plus vaccination) and 3) Post-vaccination serological check-ups for HB and HIV at 6 and 12 months from the incident. 249 children, whose average age was 5.8 +/- 3.37, were seen (158 boys, 63.5% and 91 girls, 36.5%). 189 (75.9% of the total) received a dose of IGHB and 171 (71.8%) completed the HB vaccinations. Post-vaccination serological check-ups covered 144 children (84.2%). 101 children (40.6%) completed the HIV check-ups. No HIV infection was detected. 1) HB mixed prophylaxis in children without serological protection is adequate for dealing with these incidents. 2) The risk of HIV infection should not be discounted, but is probably very slight. 3) The procedure should be put into practice in PC, with some shortening of HIV follow-up periods, as a measure to improve compliance.


Seven retinal specializations in the tubular eye of the deep-sea pearleye, Scopelarchus michaelsarsi: a case study in visual optimization.
The deep-sea pearleye, Scopelarchus michaelsarsi (Scopelarchidae) is a mesopelagic teleost with asymmetric or tubular eyes. The main retina subtends a large dorsal binocular field, while the accessory retina subtends a restricted monocular field of lateral visual space. Ocular specializations to increase the lateral visual field include an oblique pupil and a corneal lens pad. A detailed morphological and topographic study of the photoreceptors and retinal ganglion cells reveals seven specializations: a centronasal region of the main retina with ungrouped rod-like photoreceptors overlying a retinal tapetum; a region of high ganglion cell density (area centralis of 56.1 x 10(3) cells per mm2) in the centrolateral region of the main retina; a centrotemporal region of the main retina with grouped rod-like photoreceptors; a region (area giganto cellularis) of large (32.2+/-5.6 microm2), alpha-like ganglion cells arranged in a regular array (nearest neighbour distance 53.5+/-9.3 microm with a conformity ratio of 5.8) in the temporal main retina; an accessory retina with grouped rod-like photoreceptors; a nasotemporal band of a mixture of rod- and cone-like photoreceptors restricted to the ventral accessory retina; and a retinal diverticulum comprised of a ventral region of differentiated accessory retina located medial to the optic nerve head. Retrograde labelling from the optic nerve with DiI shows that approximately 14% of the cells in the ganglion cell layer of the main retina are displaced amacrine cells at 1.5 mm eccentricity. Cryosectioning of the tubular eye confirms Matthiessen's ratio (2.59), and calculations of the spatial resolving power suggests that the function of the area centralis (7.4 cycles per degree/8.1 minutes of arc) and the cohort of temporal alpha-like ganglion cells (0.85 cycles per degree/70.6 minutes of arc) in the main retina may be different. Low summation ratios in these various retinal zones suggests that each zone may mediate distinct visual tasks in a certain region of the visual field by optimizing sensitivity and/or resolving power.


Organization of Kenyon cells in subdivisions of the mushroom bodies of a lepidopteran insect.
The mushroom bodies are paired structures in the insect brain involved in complex functions such as memory formation, sensory integration, and context recognition. In many insects these centers are elaborate, sometimes comprising several hundred thousand neurons. The present account describes the mushroom bodies of Spodoptera littoralis, a moth extensively used for studies of olfactory processing and conditioning. The mushroom bodies of Spodoptera consist of only about 4,000 large-diameter Kenyon cells. However, these neurons are recognizably similar to morphological classes of Kenyon cells identified in honey bees, Drosophila, and cockroaches. The spodopteran mushroom body is equipped with three major divisions of its vertical and medial lobe, one of which, the gamma lobe, is supplied by clawed class II Kenyon cells as in other described taxa. Of special interest is the presence of a discrete tract (the Y tract) of axons leading from the calyx, separate from the pedunculus, that innervates lobelets above and beneath the medial lobe, close to the latter's origin from the pedunculus. This tract is comparable to tracts and resultant lobelets identified in cockroaches and termites. The article discusses possible functional roles of the spodopteran mushroom body against the background of olfactory behaviors described from this taxon and discusses the possible functional relevance of mushroom body structure, emphasizing similarities and dissimilarities with mushroom bodies of other species, in particular the fruit fly, Drosophila melanogaster.


Another idea for the treatment of patients with borderline personality disorder.
We are not suggesting that casting is appropriate for all patients with BPD, nor are we suggesting that patients need be casted for prolonged periods of time. In the 3 stated cases, the patients were desperate to have some behaviour modification introduced into their lives and welcomed the procedure. In all these cases, comorbidity existed. Because marked skin damage and open wounds often occur, other specialists with expertise in wound healing and joint mobility maintenance need to be involved. We were fortunate to have the services of a plastic surgeon with a special interest in psychiatric disorders. We believe that psychiatrists should be aware of this technique as a possible strategy to be used in very specific circumstances. It appears, in our short series of 3 cases, to have benefits in very specific cases. If it appears that casting may be helpful, our recommendations are as follows: 1. The behaviours should be thoroughly evaluated, and all alternative managements should be reviewed. 2. Reasonable rapport needs to be established between the patient and the major therapists so that compliance can be assured. 3. Other specialists should be consulted, such as plastic surgeons, who have the expertise to manage prolonged casting. 4. Along with casting, appropriate medications and psychotherapy must be in place for a balanced approach to management.