Shifting livelihood strategies in northern Nigeria - extensified production and livelihood diversification amongst Fulani pastoralists.
This paper presents an in-depth investigation of the livelihood strategies of Fulani pastoralists in north central Nigeria. Results show a diversified crop-livestock system aimed at spreading risk and reducing cattle offtake, adapted to natural resource competition and insecurity by extensification, with further diversification into off-farm activities to spread risk, increase livelihood security and capture opportunities. However, significant costs were associated with extensification, and integration of crop and livestock enterprises was limited. Mean total income per capita in the study area was $554 or $1.52/person/day with 42% of households earning less than 1.25/person/day. Income levels were positively correlated with income diversity and price received per animal sold, rather than herd size. The outcomes of this livelihood strategy were favourable across the whole community, but when individual households are considered, there was evidence of moderate economic inequality in total income, cash income and herd size (Gini coefficient 0.32, 0.35 and 0.43 respectively). The poorest households were quite vulnerable, with low assets, income and income diversity. Implications for sustainability are discussed given the likelihood that the negative trends of reduced access to natural resources and insecurity will continue.


The influence of exercise on serum enzyme levels in the horse.
A group of clinically normal horses was subjected to controlled strenuous exercise. Elevated serum concentrations of lactic dehydrogenase, aldolase and creatine kinase were observed after exercise but no significant change in serum glutamic-oxalacetic transaminase was noted. These changes were reduced by repeated exposure to exercise suggesting that measurement of serum enzyme elevations, particularly creatine kinase, might be a useful index of fitness in the horse. Administration of prednisolone prior to exercise also reduced these changes. Since the serum enzyme concentrations had returned to normal within 72 hours of exercise, and since the cytoplasmic enzyme glutamic oxalacetic transaminase was not released from the tissues this supported the hypothesis that efflux of intracellular enzymes into the circulation was due to a temporary selective change in cell membrane permeability rather than to tissue necrosis.


Unbalanced overexpression of the mutant allele in murine Patched mutants.
Inherited mutations of Patched (PTCH) in the nevoid basal cell carcinoma syndrome (NBCCS) lead to several developmental defects and contribute to tumor formation in a variety of tissues. PTCH mutations have been also identified in sporadic tumors associated with NBCCS including basal cell carcinoma (BCC) and medulloblastoma. Mice heterozygous for Ptch recapitulate the typical developmental symptoms of NBCCS and develop rhabdomyosarcoma (RMS) and medulloblastoma. PTCH is assumed to act as a tumor suppressor gene although inactivation of both alleles has been demonstrated only in a fraction of tumors. We have investigated the status of Ptch in RMS of heterozygous Ptch neo67/+ mice. Although the wild-type Ptch allele was retained in tumor tissue, the high levels of Ptch mRNA in these tumors result from overexpression of the mutant Ptch transcript. Our results suggest that the wild-type Ptch allele might be selectively silenced in RMS tissue or, alternatively, that haploinsufficiency of Ptch is sufficient to promote RMS formation in mice.


Demonstration of electromagnetic enhancement correlated to optical absorption of single plasmonic system coupled with molecular excitons using ultrafast surface-enhanced fluorescence.
The relationship between the electromagnetic (EM) enhancement of the optical responses of molecules and plasmon resonance has been investigated using Rayleigh scattering or the extinction spectra of plasmonic systems coupled with molecular excitons. However, quantum optics predicts that the EM enhancement of such optical responses, e.g., fluorescence, Raman, and their nonlinear counterparts, is related directly to optical absorption and indirectly to Rayleigh scattering and extinction. To demonstrate this prediction, a micro-spectroscopic method for obtaining Rayleigh scattering, extinction, absorption, and EM enhancement is developed using single-coupled plasmonic systems composed of silver nanoparticle dimers and dye molecules. The EM enhancement is derived from ultrafast surface-enhanced fluorescence. An evaluation of the spectral relationships demonstrates that the EM enhancement can be reproduced better by absorption than by Rayleigh scattering or extinction. This reproduction is phenomenologically confirmed by numerical calculations based on classical electromagnetism, indicating the importance of absorption spectroscopy in coupled plasmonic systems for evaluating EM enhancement.


Pain management in periodontal therapy using local anesthetics and other drugs: an integrative review.
Surgical and non-surgical periodontal procedures often lead to postoperative pain. Clinicians use pharmacological methods such as anesthetics, anti-inflammatory drugs, and analgesics for relief. However, the multitude of options makes it challenging to select the best approach for routine dental care. This review aimed to describe previous studies regarding the pharmacological management used for pain control during periodontal procedures as well as factors that may interfere with patients' perception of pain. We included studies (period of 2000-2023, whose approach corresponded to the pharmacological protocols used for preoperative, trans-operative, and postoperative pain control in adult patients undergoing surgical and non-surgical periodontal therapy. A total of 32 studies were included in the analysis, of which 17 (53%) were related to anesthetic methods and 15 (47%) were related to therapeutic protocols (anti-inflammatory/analgesic agents). These studies predominantly involved nonsurgical periodontal procedures. Studies have reported that factors related to age, type of procedure, and anxiety can influence pain perception; however, only seven of these studies evaluated anxiety. Numerous methods for pain control can be applied in periodontal therapy, which are accomplished through anesthetic methods and/or therapeutic protocols. Factors such as anxiety, age, and type of procedure are related to pain perception in patients. Thus, it is the responsibility of dentists to evaluate each clinical situation and define the best protocol to follow based on the literature.


Current management of locally advanced head and neck cancer: the combination of chemotherapy with locoregional treatments.
This review will discuss the evolution of the role of chemotherapy in the treatment of locally advanced head and neck cancer (HNC), over the last few decades. Studies were identified by searching PubMed electronic databases. Surgery followed by radiotherapy (RT) or definitive RT are potentially curative approaches for locally advanced HNC. While chemotherapy itself is not curative, it can improve cure rates when given as an adjunct to RT. The benefit of combining chemotherapy with RT is related to the timing of the chemotherapy. Several prospective randomized trials have demonstrated that concurrent delivery of chemotherapy and RT (CRT) is the most promising approach, given that locoregional recurrence is the leading pattern of failure for patients with locally advanced HNC. Induction chemotherapy before CRT has not been shown to be superior to CRT alone and the added toxicity may negatively impact the compliance with CRT. Sequential chemotherapy administration, in the form of induction chemotherapy followed by RT or CRT, has been successful as a strategy for organ preservation in patients with potentially resectable laryngeal and hypopharyngeal cancer. Systemic chemotherapy delivered concurrently with RT is used as a standard treatment for locally advanced HNC.


Gastrointestinal uptake and fate of cadmium in rainbow trout acclimated to sublethal dietary cadmium.
Adult rainbow trout were pre-exposed to a sublethal concentration of dietary Cd (500 mg/kg dry wt.) for 30 days to induce acclimation. A gastrointestinal dose of radiolabeled Cd (276 microg/kg wet wt.) was infused into the stomach of non-acclimated and Cd-acclimated trout through a stomach catheter. Repetitive blood samples over 24 h and terminal tissue samples were taken to investigate the gastrointestinal uptake, plasma clearance kinetics, and tissue distribution of Cd. Only a small fraction of the infused dose (non-acclimated: 2.4%; Cd-acclimated: 6.6%) was internalized across the gut wall, while most was bound in the gut tissues (10-24%) or remained in the lumen (16-33%) or lost from the fish (approximately 50%) over 24 h. Cadmium loading during pre-exposure produced a profound increase of total Cd in the blood plasma (approximately 28-fold) and red blood cells (RBC; approximately 20-fold). The plasma Cd-time profiles consisted of an apparent rising (uptake) phase and a declining (clearance) phase with a maximum value of uptake in 4 h, suggesting that uptake of gastrointestinally infused Cd was very rapid. Acclimation to dietary Cd did not affect plasma Cd clearance (approximately 0.5 ml/min), but enhanced new Cd levels in the plasma (but not in the RBC), and resulted in a longer half-life for plasma Cd. Tissue total and new Cd levels varied in different regions of the gastrointestinal tract, and overall levels in gut tissues were much greater than in non-gut tissues, reflecting the Cd exposure route. Dietary Cd, but not the infused Cd, greatly increased total Cd levels of all gut tissues in the order posterior-intestine (640-fold) > cecae (180-fold) > mid-intestine (94-fold) > stomach (53-fold) in Cd-acclimated fish relative to naïve fish. Among non-gut tissues in the Cd-acclimated fish, the great increases of total Cd levels were observed in the liver (73-fold), kidney (39-fold), carcass (35-fold), and gills (30-fold). The results provide some clear conclusions that may be useful for environmental risk assessment of dietary Cd exposure in fish.


The amphibian octavo-lateralis system and its regressive and progressive evolution.
The phylogenetic and ontogenetic changes in the octavolateralis system of sarcopterygian fish and tetrapods, presumed to be important for the formation of an amphibian auditory system, are reviewed. The lateral line system shows rudimentation of lines and loss of ampullary electroreceptors in many amphibians; in some amphibians it never develops. The metamorphic changes of the lateral-line system show different patterns in the different amphibian lineages with metamorphic retention in most urodeles and metamorphic loss in most anurans. The multitude of both ontogenetic and phylogenetic changes of the lateral line system among amphibians do exclude any prediction as to how this system might have changed in ancestral amniotes. The most important auditory epithelium of the tetrapod inner ear, the basilar papilla, seems to be primitively present in all tetrapods and Latimeria. In two amphibian lineages there is a trend towards rudimentation and loss of the basilar papilla. Only in the third order, the anurans, a tympanic ear develops and the inner ear shows a progressive evolution of the auditory epithelia. Together with the known differences in the periotic labyrinth of amphibians and amniotes, this scenario suggests a parallel evolution of the amniotic and anuran auditory periphery. All mechanoreceptive hair cells of the lateral line system and the inner ear appear to receive a common and bilateral efferent innervation. Among amphibians this pattern is represented only in some urodeles, whereas anurans show a derived pattern with loss of a bilateral component and presumably also of a common neuromast/inner ear component. Changes in the rhombencephalic nuclei which receive octavo-lateralis afferent fibers show a trend towards development of auditory nuclei only in the anuran lineage. The phylogenetic appearance of an auditory nucleus in this lineage coincides with the complete absence of formation of ampullary electroreceptors. In contrast, the earlier claim of a correlation between a metamorphic loss of the lateral line system and the formation of an auditory nucleus is not supported by more recent data: an auditory nucleus develops in anurans already prior to metamorphosis and is present in all anurans even when they retain the neuromast system. In anurans with a metamorphic loss of the neuromasts, the second order neurons degenerate as well. This independence of the auditory and the second order lateral line nuclei is further substantiated by their separate projection to other brain areas, like the torus semicircularis of the midbrain, and their functional properties.(ABSTRACT TRUNCATED AT 400 WORDS)


[Effects of shenmai injection on the clinical efficacy of noninvasive ventilation in patients with severe respiratory failure caused by chronic obstructive pulmonary disease].
To study the effect of Shenmai Injection (SMI) on the clinical efficacy of noninvasive positive-pressure ventilation (NPPV) in treating patients with severe respiratory failure (RF) caused by chronic obstructive pulmonary disease (COPD). Patients in the control group (n=23) were treated with conventional therapy plus NPPV, and those in the treatment group (n=25) received the same treatment but with intravenous infusion of SMI 30 ml once a day additionally. The treatment lasted for 10 days. Arterial oxygen saturation (SaO2) was continuously monitored in all patients, arterial blood gas values was determined before treatment and at the 6th hour, the 24th hour, the 3rd day and the 7th day after treatment, and consciousness, breath, heart rate and severity of dyspnea were observed during the treating period. All patients in the treatment group were markedly improved and discharged from hospital, while in the control group 20 were improved and discharged from hospital, but the other 3 failed to be remitted and received the conventional invasive mechanical ventilation. The duration of hospitalization and ventilation were 11.3 +/- 2.5 d and 5.8 +/- 2.8 d in the treatment group, and 13.2 +/- 2.7 d and 7.5 +/- 3.0 d in the control group, showing significant difference in the two indexes between the two groups (P < 0.05). The dyspnea score and the arterial blood gas values determined on the 3rd and 7th day were significantly improved in the treatment group than those in the control group (P < 0.05 or P < 0.01). The incidence of endotracheal intubation caused adverse reaction, such as facial-skin crush wound, abdominal distention and contaminated infection in the treatment group was obviously lessened as compared with the control group. SMI could shorten the duration of hospitalization and mechanical ventilation, reduce trachea cannulation, and decrease the incidence of complications and adverse reactions in the patients with severe RF due to COPD treated with NPPV.


Hydrogen sulfide therapy in brain diseases: from bench to bedside.
Hydrogen sulfide (H2S) has been recognized and studied for nearly 300 years, but past researches mainly focus on its toxicity effect. During the past two decades, the majority of researches have reported that H2S is a novel endogenous gaseous signal molecule in organisms, and play an important role in various systems and diseases. H2S is mainly produced by three enzymes, including cystathionine β-synthase, cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase along with cysteine aminotransferase. H2S had been firstly reported as a neuromodulator in the brain, because of its essential role in the facilitating hippocampal long-term potentiation at physiological concentration. It is subsequently reported that H2S may have relevance to neurologic disorders through antioxidative, anti-inflammatory, anti-apoptotic and additional effects. Recent basic medical studies and preclinical studies on neurologic diseases have demonstrated that the administration of H2S at physiological or pharmacological levels attenuates brain injury. However, the neuroprotective effect of H2S is concentration-dependent, only a comparatively low dose of H2S can provide beneficial effect. Herein, we review the neuroprotevtive role of H2S therapy in brain diseases from its mechanism to clinical application in animal and human subjects, and therefore provide the potential strategies for further clinical treatment.


Effect of combined long-term starvation and γ-irradiation on membrane fatty acids and cell surface hydrophobicity of Salmonella enterica serovar Typhimurium.
This study was carried out to explore the adaptive mechanisms of Salmonella enterica serovar Typhimurium, in particular the implication of fatty acids (FA) in the remodeling of membrane lipid composition to overcome the combined effects of long-term starvation and γ-irradiation stresses. In addition, cell surface hydrophobicity was also evaluated. The bacterial strains (control and starved) were treated with a nonlethal γ-irradiation dose of 0.5 kGy and sublethal doses of 1 kGy. Gas chromatography analysis showed that the FA composition of starved and γ-irradiated cells was modified. However starvation combined with γ-irradiation induced more modifications in the FA composition than γ-irradiation or starvation alone. Indeed, the unsaturated FA-to-saturated FA ratio decreased significantly for both strains compared with γ-irradiated cells, as main consequence of the cyclic FA formation. Our results showed that starvation, irradiation, or combined stresses significantly influenced the hydrophobicity, and this may have affected the virulence state of Salmonella Typhimurium cells. This study represents one of the few to demonstrate the modifications on bacterial membrane as a cellular response to survive to the ionizing radiation combined with long-term starvation stress.


The persistence of carbon in the African forest understory.
Quantifying carbon dynamics in forests is critical for understanding their role in long-term climate regulation1-4. Yet little is known about tree longevity in tropical forests3,5-8, a factor that is vital for estimating carbon persistence3,4. Here we calculate mean carbon age (the period that carbon is fixed in trees7) in different strata of African tropical forests using (1) growth-ring records with a unique timestamp accurately demarcating 66 years of growth in one site and (2) measurements of diameter increments from the African Tropical Rainforest Observation Network (23 sites). We find that in spite of their much smaller size, in understory trees mean carbon age (74 years) is greater than in sub-canopy (54 years) and canopy (57 years) trees and similar to carbon age in emergent trees (66 years). The remarkable carbon longevity in the understory results from slow and aperiodic growth as an adaptation to limited resource availability9-11. Our analysis also reveals that while the understory represents a small share (11%) of the carbon stock12,13, it contributes disproportionally to the forest carbon sink (20%). We conclude that accounting for the diversity of carbon age and carbon sequestration among different forest strata is critical for effective conservation management14-16 and for accurate modelling of carbon cycling4.


Feasibility study of range-based registration using daily cone beam CT for intensity-modulated proton therapy.
Proton dose coverage is sensitive to proton beam range. The current practice of CT number-based registration for patient positioning focuses on matching the target and is not sufficient for proton therapy because the proton range depends on the medium traversed by the beam. Patient body deformations and anatomical changes result in range deviation in the target. We propose proton range-based registration to minimize the range deviation. The range was calculated from cone beam-computed tomography (CBCT) of the patient on couch, and the range deviation was the difference of the calculated range from that on the initial (day 1) CBCT. In the investigated prostate cases in which the main cause of range deviation was the rotation of femur bones, and in the investigated abdomen cases in which the main cause of range deviation was body growth and anatomic change, our range-based registration was used to obtain the optimal beam angle by minimizing the range deviation. The new angle was limited to be ±5° from that planned to prevent potentially increased dose to the organs at risk. To demonstrate the benefit of range-based registration, we investigated the range at the voxels on the surface of the target volume. The calculation error of range deviation due to CBCT scatter was investigated by using solid water phantoms with different thicknesses. Range-based registration using both CBCTs and CTs was performed in cases of two patients with pelvic rhabdomyosarcoma and one patient with upper abdominal tumor. The range was represented by the water-equivalent thickness to shorten the computation for online application purposes. In the phantom study, the calculation error of range deviation due to CBCT scatter was within 2 mm for a 1-cm thickness change (the mean range deviation was 0.8 mm). In the CT study of the prostate cases, the range deviation (mean ± root-mean-square deviation) on the contour in each slice was efficiently reduced from 3.6 ± 2.8 mm to 2.1 ± 1.4 mm, with most slices being within 3 mm; in the CT study of the abdomen cases, the range deviation of the whole set was reduced from 4.4 ± 1.9 mm to 3.5 ± 2.1 mm. Both the mean and root-mean-square deviation of the range deviation on each treatment day were decreased. The dose coverage on the target was improved and the dose on the OARs was only slightly changed. Range-based registration can efficiently mitigate range deviation due to patient positioning and anatomical changes. It can shorten patient positioning time and reduce the patient's dose from CBCT.


Maternal serum cytokine levels and risk of bipolar disorder.
Prenatal exposure to influenza has previously been associated with increased risk of bipolar disorder (BD), an association that may be mediated by maternal cytokines. The objective of this study was to determine the association between maternal levels of cytokines measured during each trimester of pregnancy and the risk of BD in offspring. We conducted a case-control study nested in the Child Health and Development Study, a birth cohort that enrolled pregnant women in 1959-1966. Potential cases with DSM-IV-TR bipolar I disorder, bipolar II disorder, BD not otherwise specified, and BD with psychotic features were ascertained through electronic medical records, a public agency database, and a mailing to the cohort. Diagnoses were confirmed by clinical interview. Nine cytokines (IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and GM-CSF) were measured simultaneously by Luminex assays in archived prenatal maternal serum samples from 85 cases and 170 matched controls. Data were analyzed using conditional logistic regression. In the overall study sample, there were no significant associations between prenatal maternal cytokine levels and BD after adjustment for confounders. The risk of BD without psychotic features was decreased among subjects with higher maternal levels of first trimester log-transformed IL-4 (OR (95% CI)=0.76 (0.58, 0.98); p=0.04) and third trimester log-transformed IL-6 (OR (95% CI)=0.64 (0.42, 0.98); p=0.04). In conclusion, higher levels of prenatal maternal cytokines were not associated with increased risk for BD. Further studies with larger samples are necessary to confirm the finding.


Photonic Generation of High Power, Ultrastable Microwave Signals by Vernier Effect in a Femtosecond Laser Frequency Comb.
Optical frequency division of an ultrastable laser to the microwave frequency range by an optical frequency comb has allowed the generation of microwave signals with unprecedently high spectral purity and stability. However, the generated microwave signal will suffer from a very low power level if no external optical frequency comb repetition rate multiplication device is used. This paper reports theoretical and experimental studies on the beneficial use of the Vernier effect together with the spectral selective filtering in a double directional coupler add-drop optical fibre ring resonator to increase the comb repetition rate and generate high power microwaves. The studies are focused on two selective filtering aspects: the high rejection of undesirable optical modes of the frequency comb and the transmission of the desirable modes with the lowest possible loss. Moreover, the conservation of the frequency comb stability and linewidth at the resonator output is particularly considered. Accordingly, a fibre ring resonator is designed, fabricated, and characterized, and a technique to stabilize the resonator's resonance comb is proposed. A significant power gain is achieved for the photonically generated beat note at 10 GHz. Routes to highly improve the performances of such proof-of-concept device are also discussed.


Development of a High-Content Orthopoxvirus Infectivity and Neutralization Assays.
Currently, a number of assays measure Orthopoxvirus neutralization with serum from individuals, vaccinated against smallpox. In addition to the traditional plaque reduction neutralization test (PRNT), newer higher throughput assays are based on neutralization of recombinant vaccinia virus, expressing reporter genes such as β-galactosidase or green fluorescent protein. These methods could not be used to evaluate neutralization of variola virus, since genetic manipulations of this virus are prohibited by international agreements. Currently, PRNT is the assay of choice to measure neutralization of variola virus. However, PRNT assays are time consuming, labor intensive, and require considerable volume of serum sample for testing. Here, we describe the development of a high-throughput, cell-based imaging assay that can be used to measure neutralization, and characterize replication kinetics of various Orthopoxviruses, including variola, vaccinia, monkeypox, and cowpox.


Raman spectroscopy and related techniques in biomedicine.
In this review we describe label-free optical spectroscopy techniques which are able to non-invasively measure the (bio)chemistry in biological systems. Raman spectroscopy uses visible or near-infrared light to measure a spectrum of vibrational bonds in seconds. Coherent anti-Stokes Raman (CARS) microscopy and stimulated Raman loss (SRL) microscopy are orders of magnitude more efficient than Raman spectroscopy, and are able to acquire high quality chemically-specific images in seconds. We discuss the benefits and limitations of all techniques, with particular emphasis on applications in biomedicine--both in vivo (using fiber endoscopes) and in vitro (in optical microscopes).


The bovine B and C blood group systems are not likely to be the orthologues of human RH: an interesting twist in the comparative map.
We tested the hypothesis that either the bovine B or C blood group system is the orthologue of human RH. A comparative linkage mapping strategy was applied, using blood typing and restriction fragment length polymorphism (RFLP) analysis of four loci linked to RH on HSA1; PGD, FGR, ALPL and FUCA1. Four sires with a total of 255 half-sib offspring were used for the linkage analysis. Strong support for linkage between ALPL, FUCA1 and FGR was obtained for all sire families (lod scores > 11 for all pairwise comparisons). This new linkage group was assigned to bovine synteny group U17 based on previous somatic cell mapping of the FGR locus. The most favoured order is ALPL-FUCA1-FGR (2.18:1), with ALPL and FGR 5.4 CM and 6.3 CM, respectively, from FUCA1. The B and C blood group systems and PGD were genetically independent of each other and all other markers, indicating that neither B nor C is likely to be the bovine orthologue of human RH. However, given available comparative mapping data, there is some chance that the bovine orthologue of RH is on bovine synteny group U6. Although gene order appears to be conserved with humans, the differences in recombination rates between these three loci in cattle, humans and mice strongly suggest that it is not possible to use human map distances to predict map distances in cattle, making it imperative that bovine gene mappers continue to emphasize adding type I markers to the bovine linkage map.


Genetic and environmental influences on ethanol consumption: perspectives from preclinical research.
Alcohol use disorders (abuse and dependence, AUD) are multifactorial phenomena, depending on the interplay of environmental and genetic variables. This review describes current developments in animal research that may help (a) develop gene therapies for the treatment of alcoholism, (b) understand the permissive role of stress on ethanol intake, and (c) elucidate why exposure to ethanol early in life is associated with a greater risk of AUD. The polymorphisms found in liver alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) affect the elimination of ethanol and the susceptibility to ethanol intake. A highly active ADH protects against alcoholism, an effect related to a presteady state burst in arterial acetaldehyde. Social stressors, such as repeated early maternal separation or social defeat, exert a permissive effect on ethanol intake, perhaps by altering the normal development of the hypothalamic-pituitary-adrenal axis. Ethanol exposure during gestation, infancy, or adolescence increases the likelihood of AUD later in life. Early perception of ethanol's positive and negative (anti-anxiety) reinforcing effects may play a role in this phenomenon. The review underscores the advantages of using preclinical animal models of AUD and highlights points of intersection between the topics to help design a more integrated approach for the study of alcohol-related problems.


Nitric Oxide Mediates Molybdenum-Induced Antioxidant Defense in Wheat under Drought Stress.
Molybdenum (Mo) has been reported to alleviate drought stress by enhancing antioxidant defense in plants, but the underlying mechanism remains unclear. Here, we hypothesized that Mo mediates nitric oxide (NO)-induced antioxidant defense through Mo-enzymes, particularly by nitrate reductase (NR) in wheat under drought stress. The 30-day-old wheat seedlings cultivated in -Mo (0 μM Mo) and +Mo (1 μM Mo) Hoagland solutions were detached and then pretreated with Mo-enzyme inhibitors, NO scavengers, NO donors or their combinations according to demands of complementary experiment under 10% polyethylene glycol 6000 (PEG)-stimulated drought stress (PSD). Mo supplementation increased the activities and transcripts of antioxidant enzymes, decreased H2O2 and MDA contents, and elevated NO production, implying that Mo-induced antioxidant defense may be related to NO signal. Complementary experiment showed that NO production was induced by Mo, while suppressed by Mo-enzyme inhibitors and NO scavengers, but restored by NO donors, suggesting that Mo-induced increase of NO production may be due to the regulation by Mo-enzymes. Further experiment indicated that the increased activities and transcripts of antioxidant enzymes induced by Mo were suppressed by Mo-enzyme inhibitors and NO scavengers, and NO donors could eliminate their suppressing effects. Moreover, Mo application increased NR activity and inhibitors of Mo-enzymes inhibited NR activity in wheat leaves under PSD, suggesting that NR might involve in the regulation of Mo-induced NO production. These results clearly indicate that NO mediates Mo-induced antioxidant defense at least partially through the regulation of NR.


Posterior cranial fossa dermoid in association with craniovertebral and cervical spinal anomaly: report of two cases.
Two patients, a 12-year-old girl and an 8-year-old boy, with congenital craniovertebral anomaly and Klippel-Feil syndrome also had a posterior cranial fossa dermoid. The association of these two discrete pathological lesions in the same individual is extremely rare. As both lesions are related to an embryological disorder, issues regarding the possible stage of dysgenesis are analyzed. The treatment options in such cases are discussed.


[Active constituents of Commelina communis L].
According to the pharmacological results five compounds were isolated from the herb of Commelina communis. Based on physico-chemical constants and spectral data, four of them were identified as n-triacontanol, p-hydroxycinnamic acid, daucosteril and D-mannitol. p-hydroxycinnamic acid shows antibacterial activity and D-mannitol shows antitussive effect.


Management of renal angiomyolipoma by selective arterial embolization.
4 Patients with renal angiomyolipomas are presented. One of them had tuberous sclerosis with synchronous bilateral tumors. All the patients were symptomatic, 2 of them with retroperitoneal hemorrhage. In all patients selective arterial embolization was performed. Permanent control of the symptoms was successful in 2 patients. In 1 patient temporary resolution of the symptoms was observed, and a second embolization was required. Retroperitoneal bleeding in 1 patient continued and nephrectomy was undertaken.


Race Matters: Analyzing the Relationship between Colorectal Cancer Mortality Rates and Various Factors within Respective Racial Groups.
Colorectal cancer (CRC) is the third leading cause of mortality due to cancer (with over 50,000 deaths annually), representing 9% of all cancer deaths in the United States (1). In particular, the African-American CRC mortality rate is among the highest reported for any race/ethnic group. Meanwhile, the CRC mortality rate for Hispanics is 15-19% lower than that for non-Hispanic Caucasians (2). While factors such as obesity, age, and socio-economic status are known to associate with CRC mortality, do these and other potential factors correlate with CRC death in the same way across races? This research linked CRC mortality data obtained from the National Cancer Institute with data from the United States Census Bureau, the Centers for Disease Control and Prevention, and the National Solar Radiation Database to examine geographic and racial/ethnic differences, and develop a spatial regression model that adjusted for several factors that may attribute to health disparities among ethnic/racial groups. This analysis showed that sunlight, obesity, and socio-economic status were significant predictors of CRC mortality. The study is significant because it not only verifies known factors associated with the risk of CRC death but, more importantly, demonstrates how these factors vary within different racial groups. Accordingly, education on reducing risk factors for CRC should be directed at specific racial groups above and beyond creating a generalized education plan.


Forensic age estimation by the Schmeling method: computed tomography analysis of the medial clavicular epiphysis.
The variability of anthropometric measures, such as the degree of ossification, among societies should be taken into account when estimating age. The degree of ossification of the medial clavicle can be determined with thin-section computed tomography (CT), which is one of the methods recommended by the Study Group on Forensic Age Diagnostics of the German Association of Forensic Medicine. The purpose of this retrospective study was to investigate the applicability of thin-section CT analysis of the degree of ossification of the medial clavicle in a Turkish population. We evaluated the CT images (1-mm slice thickness) of 503 patients (362 male, 141 female; age, 10-35 years) using the Schmeling five-stage method. The Spearman's correlation analysis revealed a positive correlation between age and ossification stage in both male and female patients (total group: rho = 0.838, p < 0.001; male: rho = 0.831, p < 0.001; female: rho = 0.856, p < 0.001). The linear regression analysis results indicated that the ossification stage of the medial clavicle is a good predictor when estimating age (r (2) = 0.735 for all patients, 0.734 for male patients, 0.741 for female patients). Sex differences in ossification stages were observed only for stage 1 and 4 ossification. We believe that future research could expand the database on this topic and contribute to improvements in this measurement method.


Ectopic expression of a Chlamydomonas mt+-specific homeodomain protein in mt- gametes initiates zygote development without gamete fusion.
The molecular mechanisms that activate expression of zygote genes after fertilization are obscure. In animals, receptor-ligand interactions during sperm-egg membrane fusion as well as delivery of putative regulatory molecules by the sperm into the egg cytoplasm are proposed to activate zygote development and subsequent transcription of zygote genes. The mechanisms of activation of zygote development in higher plants also are mysterious, in part because of the difficulty of isolating female gametes of higher plants. In the unicellular, biflagellated green alga Chlamydomonas, the early steps in zygote development are much more accessible to investigation. Within minutes after mating type plus (mt+) and mating type minus (mt-) gametes fuse, expression of several zygote-specific transcripts is induced independently of protein synthesis. Here, we show that ectopic expression in mt- gametes of an mt+ gamete-specific, homeodomain protein, GSP1, induces a zygote-like phenotype and activates expression of zygote genes. One of the genes, zsp2, expressed in these "haploid zygotes" encodes a zygote cell surface adhesion molecule that promotes formation of multicellular aggregates. In total, expression of six out of seven zygote genes examined was induced by ectopic expression of GSP1. Our experiments show that in addition to contributing their genomes to the zygote cytoplasm, gametes also deliver proteins that can activate gene transcription.


Creatine phosphokinase in rat mast cells.
The soluble cytoplasmic fraction of an homogenate from peritoneal rat mast cells, demonstrated a considerable amount of catalytic activity which promotes the transfer of phosphate from creatine phosphate to ADP. The plasma membrane, mitochondrial and microsomal fractions show negligible amounts of the catalyst. Enzyme activity is maximal at 37 degrees showing little activity below 17 degrees or above 45 degrees. The enzyme is strongly Mg2+-dependent, whereas it is only slightly activated by Ca2+. pH values between 7 and 8 are optimal and the enzyme is irreversibly inactivated below pH 4. The overall behaviour of the catalyst indicates it to be a creatine phosphokinase (CPK), an enzyme considered important to muscle and nerve tissues. The CPK is probably not encapsulated within the mast cells' perigranular membranes and is retained in the soluble cytoplasm during exocytosis. The possible role of CPK, as to whether it is assisting in maintaining proper levels of intracellular ATP during exocytosis, and/or whether it is associated with components of the mast cells' contractile apparatus, is discussed.


In vitro effect of isoprinosine on rabies virus.
The in vitro effect of isoprinosine, an antiviral compound, was evaluated on ERA and VA319 rabies viral strains. Isoprinosine diminished the number of immunofluorescent cells, viral titers, and structures involved in rabies virus replication. Mechanism of antiviral action was probably mediated by modification of the polyribosome conformation and function.


Moving beyond the stigma: the impression formation benefits of exercise for individuals with a physical disability.
This study examined whether the positive impressions formed by others of able-bodied exercisers extend to people with a physical disability. Participants (226 women and 220 men) read a description of a man or woman with a spinal cord injury who was described as an exerciser, nonexerciser, or control, and then rated the target (i.e., the person being described in the vignette) on 17 personality and 9 physical dimensions. Results revealed significantly more favorable ratings for the exerciser than both the nonexerciser and control on almost all dimensions. Additionally, the male control target was rated more favorably than the female counterpart on three personality and two physical attributes. Evidently, the exerciser stereotype may undermine negative impressions of people with physical disabilities.


Social tuning of the self: consequences for the self-evaluations of stereotype targets.
These experiments examined how social interactions with individuals who ostensibly have stereotype-relevant views affect the self-evaluations of stereotype targets. Participants believed they were going to interact, or actually interacted, with a person who ostensibly had stereotype-consistent or stereotype-inconsistent views about their social group. Consistent with shared reality theory, participants' self-evaluations (Experiments 1, 2, and 3) and behavior (Experiment 2) corresponded with the ostensible views of the other person when affiliative motivation was high. This occurred even when it was likely to be detrimental to participants' nonaffiliative outcomes (Experiment 3). Experiment 4 showed that self-evaluative shift away from the ostensible views of another person was a function of social distance motives, also consistent with shared reality theory.


TT2, TT8, and TTG1 synergistically specify the expression of BANYULS and proanthocyanidin biosynthesis in Arabidopsis thaliana.
Genetic analyses have demonstrated that together with TTG1, a WD-repeat (WDR) protein, TT2 (MYB), and TT8 (bHLH) are necessary for the correct expression of BANYULS (BAN). This gene codes for the core enzyme of proanthocyanidin biosynthesis in Arabidopsis thaliana seed coat. The interplays of TT2, TT8, and their closest MYB/bHLH relatives, with TTG1 and the BAN promoter have been investigated using a combination of genetic and molecular approaches, both in yeast and in planta. The results obtained using glucocorticoid receptor fusion proteins in planta strongly suggest that TT2, TT8, and TTG1 can directly activate BAN expression. Experiments using yeast two- and three-hybrid clearly demonstrated that TT2, TT8, and TTG1 can form a stable ternary complex. Furthermore, although TT2 and TT8 were able to bind to the BAN promoter when simultaneously expressed in yeast, the activity of the complex correlated with the level of TTG1 expression in A. thaliana protoplasts. In addition, transient expression experiments revealed that TTG1 acts mainly through the bHLH partner (i.e. TT8 or related proteins) and that TT2 cannot be replaced by any other related A. thaliana MYB proteins to activate BAN. Finally and consistent with these results, the ectopic expression of TT2 was sufficient to trigger BAN activation in vegetative parts, but only where TTG1 was expressed. Taken together, these results indicate that TT2, TT8, and TTG1 can form a ternary complex directly regulating BAN expression in planta.


Reducing the Allergenicity of Shrimp Tropomyosin and Allergy Desensitization Based on Glycation Modification.
Shrimp is a major allergic food that could trigger severe food allergy, with the most significant and potent allergen of shrimp referred to as tropomyosin (TM). Glycation modification (Maillard reaction) could reportedly weaken the allergenicity of TM and generate hypoallergenic TM, while up to now, there is still a lack of investigations on the hypoallergenic glycated tropomyosin (GTM) as a candidate immunotherapy for desensitizing the shrimp TM-induced allergy. This study analyzed the effects of glycation modification on decreasing the allergenicity of TM and generated hypoallergenic GTM and how GTM absorbed to the Al(OH)3 function as a candidate immunotherapy for desensitizing allergy. As the results, in comparison to TM, the saccharides of smaller molecular sizes could lead to more advanced glycation end products in GTMs than saccharides of greater molecular sizes, and TM glycated by saccharides of different molecular sizes (glucose, maltose, maltotriose, maltopentaose, and maltoheptaose) exhibited lower allergenicity as a hypoallergen upon activating the allergic reactions of the mast cell and mouse model, while TM glycated by maltose had insignificant allergenicity changes upon activating the allergic reactions of the mast cell and mouse model. In addition, the hypoallergenic GTM + Al(OH)3 was efficient as a candidate immunotherapy; this work intended to offer preclinical data to promote GTM + Al(OH)3 as a candidate allergen-specific immunotherapy for desensitizing the allergy reactions for patients allergic to shrimp food.


Verification of a Proposed Clinical Electroacoustic Test Protocol for Personal Digital Modulation Receivers Coupled to Cochlear Implant Sound Processors.
Guidelines established by the AAA currently recommend behavioral testing when fitting frequency modulated (FM) systems to individuals with cochlear implants (CIs). A protocol for completing electroacoustic measures has not yet been validated for personal FM systems or digital modulation (DM) systems coupled to CI sound processors. In response, some professionals have used or altered the AAA electroacoustic verification steps for fitting FM systems to hearing aids when fitting FM systems to CI sound processors. More recently steps were outlined in a proposed protocol. The purpose of this research is to review and compare the electroacoustic test measures outlined in a 2013 article by Schafer and colleagues in the Journal of the American Academy of Audiology titled "A Proposed Electroacoustic Test Protocol for Personal FM Receivers Coupled to Cochlear Implant Sound Processors" to the AAA electroacoustic verification steps for fitting FM systems to hearing aids when fitting DM systems to CI users. Electroacoustic measures were conducted on 71 CI sound processors and Phonak Roger DM systems using a proposed protocol and an adapted AAA protocol. Phonak's recommended default receiver gain setting was used for each CI sound processor manufacturer and adjusted if necessary to achieve transparency. Electroacoustic measures were conducted on Cochlear and Advanced Bionics (AB) sound processors. In this study, 28 Cochlear Nucleus 5/CP810 sound processors, 26 Cochlear Nucleus 6/CP910 sound processors, and 17 AB Naida CI Q70 sound processors were coupled in various combinations to Phonak Roger DM dedicated receivers (25 Phonak Roger 14 receivers-Cochlear dedicated receiver-and 9 Phonak Roger 17 receivers-AB dedicated receiver) and 20 Phonak Roger Inspiro transmitters. Employing both the AAA and the Schafer et al protocols, electroacoustic measurements were conducted with the Audioscan Verifit in a clinical setting on 71 CI sound processors and Phonak Roger DM systems to determine transparency and verify FM advantage, comparing speech inputs (65 dB SPL) in an effort to achieve equal outputs. If transparency was not achieved at Phonak's recommended default receiver gain, adjustments were made to the receiver gain. The integrity of the signal was monitored with the appropriate manufacturer's monitor earphones. Using the AAA hearing aid protocol, 50 of the 71 CI sound processors achieved transparency, and 59 of the 71 CI sound processors achieved transparency when using the proposed protocol at Phonak's recommended default receiver gain. After the receiver gain was adjusted, 3 of 21 CI sound processors still did not meet transparency using the AAA protocol, and 2 of 12 CI sound processors still did not meet transparency using the Schafer et al proposed protocol. Both protocols were shown to be effective in taking reliable electroacoustic measurements and demonstrate transparency. Both protocols are felt to be clinically feasible and to address the needs of populations that are unable to reliably report regarding the integrity of their personal DM systems.


Remimazolam dosing for intraoperative sedation in elderly patients undergoing hip replacement with combined spinal-epidural anesthesia.
The aim of the study was to investigate the 50% and 95% effective doses (ED50 and ED95) of remimazolam for intraoperative sedation in elderly patients undergoing hip replacement with combined spinal-epidural anesthesia (CSEA). We retrospectively analyzed the clinical data of 50 patients who underwent hip replacement with CSEA in our hospital from October 2021 to June 2022. There were 29 males and 21 females, aged 60-80 years old, with body mass indexes (BMI) ranging from 18 to 24 kg/m2, and American Society of Anesthesiologists (ASA) classifications of I or II. The modified Dixon sequential method was used to determine the dose of remimazolam for each patient. Each patient's initial dose was 0.1 mg/kg/h, and the dose gradient was 0.01 mg/kg/h. The bispectral index (BIS) and the modified observer's assessment of alertness/sedation score (MOAA/S) were used to evaluate the sedation of the patient. An MOAA/S score ≤3 and a BIS <85 at three or more time points during surgery indicated the sedation was satisfactory. The induction dose of the next patient was adjusted by 0.01 mg/kg/h based on the level of sedation achieved, and the study was terminated after eight crossovers. The ED50 and ED95 of remimazolam for sedation of elderly patients undergoing hip replacement with CSEA are 0.212 mg/kg/h (95% CI: 0.121-0.231 mg/kg/h) and 0.288 mg/kg/h (95% CI: 0.254-0.884 mg/kg/h), respectively. Two patients experienced transient bradycardia, five experienced hypoxemia, three experienced postoperative nausea, and three experienced postoperative delirium. No patients experienced adverse reactions such as injection pain, hypotension, vomiting, delayed awakening, or emergence agitation. The ED50 and ED95 of remimazolam for sedation of elderly patients undergoing hip replacement with CSEA are 0.212 mg/kg/h and 0.288 mg/kg/h, respectively.


The REVAMP natural experiment study: the impact of a play-scape installation on park visitation and park-based physical activity.
Designing parks that optimise visitation and support visitors to be active is important for public health. Yet there is very little evidence about whether playground refurbishment achieves these objectives. This study examined the impact of the installation of a play-scape in a large metropolitan park in Melbourne, Australia. Natural experiment study (intervention vs control). At both parks, park visitation and physical activity were assessed before (T1, 2013) and after the intervention at 12 (T2, 2014) and 24 months (T3, 2015). At each time point, measures included: observations of park visitors using the System for Observing Play and Recreation in Communities on four weekdays and four weekend days, objective monitors to record usage of the walking paths and the number of cars entering the park; and intercept surveys with adult park visitors. Cross-sectional surveys were conducted with local residents at T1 and T3. The observational data showed a 176% increase in park visitor counts from T1 to T2 (Incidence Rate Ratio (IRR) = 2.76, 95% CI = 1.04-7.33), at the intervention park relative to the control park. The intervention park had a 119% increase in counts of visitors observed engaging in MVPA from T1 to T2 (IRR = 2.19, 95% CI = 1.14-4.20), and a 128% increase from T1 to T3 (IRR = 2.28, 95% CI = 1.19-4.38), relative to the control park. The relative increases in visitation at the intervention park play-scape compared with the control park playground were highly statistically significant from both T1 to T2 (IRR = 18.12, 95% CI = 5.51-59.59) and T1 to T3 (IRR = 15.05, 95% CI = 4.61-49.16). Similarly, there was a significant interaction between time and park with regard to the number of visitors observed engaging in MVPA in the play-scape/playground areas. The intercept survey data showed an increased odds of children's regular visitation to the intervention park at T2 (OR = 2.67, 95% CI = 1.08, 6.64), compared with T1, relative to the control park. The remaining results from the intercept survey, objective monitors and resident surveys showed no significant differences in visitation between the two parks. These findings confirm that a well-designed play-scape installation has the potential to increase park visitation and encourage visitors to be physically active. Current controlled trial ISRCTN50745547 .


SARS-CoV-2 detection in formalin-fixed paraffin-embedded tissue specimens from surgical resection of tongue squamous cell carcinoma.
In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pathologists can be exposed to infection handling surgical specimens. Guidelines related to safety procedures in the laboratory have been released. However, there is a lack of studies performed on biopsy and surgical resection specimens. Here we report the detection of SARS-CoV-2 in formalin-fixed paraffin-embedded samples from surgical resection of tongue squamous cell carcinoma of a patient who developed COVID-19 postsurgery. RNA of SARS-CoV-2 strain was detected in the tumour and the normal submandibular gland samples using real-time PCR-based assay. No viral RNA was found in metastatic and reactive lymph nodes. We demonstrated that SARS-CoV-2 RNA can be detected in routine histopathological samples even before COVID-19 disease development. These findings may give important information on the possible sites of infection or virus reservoir, and highlight the necessity of proper handling and fixation before sample processing.


Ginkgo Biloba Extract Is Comparable With Donepezil in Improving Functional Recovery in Alzheimer's Disease: Results From a Multilevel Characterized Study Based on Clinical Features and Resting-State Functional Magnetic Resonance Imaging.
Background: Ginkgo biloba extract (GBE) and donepezil have been reported to be effective in patients with Alzheimer's disease (AD). Nonetheless, how these drugs impact spontaneous brain activities and how they consequently improve functional recovery are currently unclear. Objectives: This study was to explore the efficacy of GBE vs. donepezil and their add-on efficacy on functional recovery and the adaption of spontaneous brain activities following pharmacologic treatment in patients with AD. Methods: Patients with AD were enrolled and assigned to the GBE group (n = 50), the donepezil group (n = 50), or the combined group (n = 50). Neuropsychological assessments, including minimum mental state examination (MMSE), Alzheimer's disease assessment scale-cognition (ADAS-Cog), instrumental activity of daily living (IADL), geriatric depression scale (GDS), neuropsychiatric inventory (NPI), and quality of life in Alzheimer's disease (QOL-AD), were conducted at baseline, 1 month, 3 months, and 6 months. Resting-state functional magnetic resonance imaging (rs-fMRI) was collected to compare the amplitude of low-frequency fluctuation (ALFF), percent amplitude of fluctuation (PerAF), regional homogeneity (ReHo), and degree centrality (DC) at baseline and 6 months. Results: No major significant differences were detected in all comparisons between groups across all follow-up time points. For intragroup comparison, MMSE and ADAS-Cog scores differed significantly across all follow-ups in three groups. The combined group showed significant improvement of GDS scores between baseline and 6 months (p = 0.007). The GBE group (p = 0.044) and donepezil group (p = 0.012) demonstrated significant improvement of NPI scores between baseline and 6 months. Significant correlations were observed between IADL and ALFF in the right gyrus rectus (p = 0.03) and in the left superior cerebellum gyrus (p = 0.01), between GDS and ALFF in the right middle temporal gyrus (p = 0.01), between NPI and PerAF in the left fusiform gyrus (p = 0.03), and between MMSE and ReHo in right superior frontal gyrus (p = 0.04). Conclusion: GBE was comparable with donepezil in the improvement of functional recovery in patients with AD while the combined application of GBE and donepezil seems unnecessary. GBE-mediated improvement of functional recovery was characterized by decreased ALFF values in the right gyrus rectus and decreased PerAF values in the left fusiform gyrus. These featured variations of imaging metrics in specific brain regions may serve as biomarkers in the monitoring of the therapeutic efficacy of GBE.


Simultaneous determination of procaine, lidocaine, ropivacaine, tetracaine and bupivacaine in human plasma by high-performance liquid chromatography.
A simple and sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method has been developed and validated for simultaneous quantification of five local anesthetics in human plasma: procaine, lidocaine, ropivacaine, tetracaine and bupivacaine. In an ice-water bath, 500 microL plasma sample, containing 100 microg/mL neostigmine methylsulfate as anticholinesterase, was spiked with carbamazepine as internal standard and alkalized by sodium hydroxide. Liquid-liquid extraction with ethyl ether was used for plasma sample preparation. The chromatographic separation was achieved on a Kromosil ODS C18 column with a mobile phase consisting of 30 mM potassium dihydrogen phosphate buffer (0.16% triethylamine, pH adjusted to 4.9 with phosphoric acid) and acetonitrile (63/37, v/v). The detection was performed simultaneously at wavelengths of 210 and 290 nm. The chromatographic analysis time was 13 min per sample. The calibration curves of all five analytes were linear between 0.05 and 5.0 microg/mL (r(2) > or = 0.998). Precision ranged from 1.4% to 7.9% and accuracy was between 91.7% and 106.5%. The validated method is applicable for simultaneous determination of procaine, lidocaine, ropivacaine, tetracaine and bupivacaine for therapeutic drug monitoring and pharmacokinetic study.


MATE CHOICE IN THE SAILFIN MOLLY, POECILIA LATIPINNA.
We examined both female and male mate choice in the sailfín molly, Poecilia latipinna. Female mollies preferred larger males over smaller ones when comparing males from their own populations. Although the expression of this preference depends on a female's receptive state, the level of female preference does not appear to be associated with any other attribute of the female or of the males. When presented with males of the same size from different populations, females preferred native over foreign males in some but not all population combinations. These results cannot be explained by a bias for higher size-specific rates of courtship displays that is shared by all females. Males preferred larger over smaller females; larger males exhibited stronger preferences, and preference for the larger female also increased as the disparity in size between the two object females increased. We found no evidence that males preferred native over foreign females when encountered singly or in size-matched combinations. These results indicate that discrimination among populations arises because females exercise divergent directional preferences for size-specific trait values that are associated with differences among males in these values. This result implies an active role for sexual selection in contributing to the maintenance of the behavioral or morphological distinctions among males observed within and among populations.


RNA sequencing analysis of hepatocellular carcinoma identified oxidative phosphorylation as a major pathologic feature.
Dysregulation of expression of functional genes and pathways plays critical roles in the etiology and progression of hepatocellular carcinoma (HCC). Next generation-based RNA sequencing (RNA-seq) offers unparalleled power to comprehensively characterize HCC at the whole transcriptome level. In this study, 17 fresh-frozen HCC samples with paired non-neoplastic liver tissue from Caucasian patients undergoing liver resection or transplantation were used for RNA-seq analysis. Pairwise differential expression analysis of the RNA-seq data was performed to identify genes, pathways, and functional terms differentially regulated in HCC versus normal tissues. At a false discovery rate (FDR) of 0.10, 13% (n = 4335) of transcripts were up-regulated and 19% (n = 6454) of transcripts were down-regulated in HCC versus non-neoplastic tissue. Eighty-five Kyoto Encyclopedia of Genes and Genomes pathways were differentially regulated (FDR, <0.10), with almost all pathways (n = 83) being up-regulated in HCC versus non-neoplastic tissue. Among the top up-regulated pathways was oxidative phosphorylation (hsa00190; FDR, 1.12E-15), which was confirmed by Database for Annotation, Visualization, and Integrated Discovery (DAVID) gene set enrichment analysis. Consistent with potential oxidative stress due to activated oxidative phosphorylation, DNA damage-related signals (e.g., the up-regulated hsa03420 nucleotide excision repair [FDR, 1.14E-04] and hsa03410 base excision repair [FDR, 2.71E-04] pathways) were observed. Among down-regulated genes (FDR, <0.10), functional terms related to cellular structures (e.g., cell membrane [FDR, 3.05E-21] and cell junction [FDR, 2.41E-07], were highly enriched, suggesting compromised formation of cellular structure in HCC at the transcriptome level. Interestingly, the olfactory transduction (hsa04740; FDR, 1.53E-07) pathway was observed to be down-regulated in HCC versus non-neoplastic tissue, suggesting impaired liver chemosensory functions in HCC. Our findings suggest oxidative phosphorylation and the associated DNA damage may be the major driving pathologic feature in HCC.


Hypomyelinating disorders: An MRI approach.
In recent years, the concept of hypomyelinating disorders has been proposed as a group of disorders with varying systemic manifestations that are identified by MR findings of absence or near absence of the T2 hypointensity that develops in white matter as a result of myelination. Initially proposed as a separate group because they were the largest single category of undiagnosed leukodystrophies, their separation as a distinct group that can be recognized by looking for a specific MRI feature has resulted in a marked increase in their diagnosis and a better understanding of the different causes of hypomyelination. This review will discuss the clinical presentations, imaging findings on standard MRI, and new MRI-related techniques that allow a better understanding of these disorders and proposed methods for quantifying the myelination as a potential means of assessing disease course and the effects of proposed treatments. Disorders with hypomyelination of white matter, or hypomyelinating disorders (HMDs), represent the single largest category among undiagnosed genetic leukoencephalopathies (Schiffmann and van der Knaap, 2009; Steenweg et al., 2010). This group of inborn errors of metabolism is characterized by a magnetic resonance imaging (MRI) appearance of reduced or absent myelin development: delay in the development of T2 hypointensity and, often, T1 hyperintensity in the white matter of the brain. The concept of hypomyelination was first conceptualized by (Schiffmann and van der Knaap, 2009; Steenweg et al., 2010; Schiffmann et al., 1994) in a series of papers that showed that these MRI characteristics were easily recognized, were different from the MRI characteristics of dysmyelinating and demyelinating disorders, and that the combination of these imaging findings with specific other clinical and imaging features could be used to make diagnoses with some confidence. In this manuscript, we will discuss the physiologic and genetic bases of hypomyelinating disorders, as well as their classification, clinical manifestations and imaging characteristics.


Finite Element Parametric Design of Hallux Valgus Orthosis Based on Orthogonal Analysis.
To design appropriate orthosis for hallux valgus, a difficult foot condition that affects a quarter of the body's bones, we need to clarify the numerical biomechanical features, which have not been established in previous biomechanical studies. Therefore, we constructed a finite element model of the bunion foot to investigate the orthopaedic force compensation mechanism. A patient with moderate hallux valgus was recruited. CT imaging data in DICOM format were extracted for three-dimensional foot model reconstruction. In conjunction with the need for rapid design of bunion orthosis, a metatarsal force application sizing method based on an orthogonal test design was investigated. The orthogonal test design was used to obtain the hallux valgus angle (HVA) and the inter metatarsal angle (IMA) data for different force combinations. Based on the extreme difference analysis and analysis of variance of the test results, the influence of different force combinations on the bunion angle was quickly determined. The results showed that the stress concentration occurred mainly in the first metatarsal bone. The distribution trend was in the medial and lateral middle of the bone and gradually decreased to the dorsal base of the bone body. The greatest stress occurs in the cartilage between the phalanges and metatarsals. In 25 groups of simulation experiments, HVA was reduced from 27.7° to 13°, and IMA was reduced from 12.5° to 7.3°. Applying detailed orthopaedic force collocation to the first metatarsal column can effectively restore the mechanics and kinematics of hallux valgus, and provide a reference for the treatment of bunion valgus and the design of orthopaedic devices.


[Value of pulmonary hemodynamic exploration during muscular exercise in chronic bronchitis?].
The value of pulmonary haemodynamic tests during physical exercise in chronic bronchitis was shown by the comparison of two groups of patients. In the first group (n=24) the PAP during exercise is lower than 30 torr. In the second it was over 30 torr. The PAP at rest was always lower than 20 torr. The load was 40 to 50 watts, i.e. an average O2 consumption of 500-600 ml.mm-1 m-2. The cardiac output doubled on average in exercise. Both groups varied markedly in their PAP at rest: 13.6 +/- 1.7 torr for the first group and 15.8 +/- 2.4 for the second (p less than 0.001). In fact differences in pressure during exercise (I=25.0 +/- 3.4 torr; II=39.6 +/- 7.4 torr, p less than 0.001) could be explained mainly by the differences of pulmonary vascular resistances (I=0.91 +/- 0.37; II=1.47 +/- 0.61, p less than 0.005): they tended to fall during effort in the first group and increased slightly in the second; and by the much higher increase in the pulmonary "capillary" pressure during exercise in the second group (I=12.5 +/- 4.4 torr; II=19.7 +/- 72 torr, p less than 0.001). The cardiac output during rest and exercise was equal in both groups. The haemo-dynamic "recovery delay" was much higher in the second group. The spirographic shortage was on the whole identical in both groups. PaO2 on average was higher in group I (p less than 0.05) where it improved during exercise (p less than 0.01). The PaO2 of the second group did improve during exercise. The haemodynamic differences were concomitant with the differences in gas exchanges during effort, of well known prognostic significance. As the "foretelling" of PAP in effort from the PAP at rest was quite poor, it appeared that haemodynamic test in effort has a real value in contributing efficiently to the differenciation of the degree in severeness. The threshold of 30 torr for PAP in exercise (and for the load mentioned above) seemed a good discriminating factor.


The regenerative response of cardiac interstitial cells.
Understanding how certain animals are capable of regenerating their hearts will provide much needed insights into how this process can be induced in humans in order to reverse the damage caused by myocardial infarction. Currently, it is becoming increasingly evident that cardiac interstitial cells play crucial roles during cardiac regeneration. To understand how interstitial cells behave during this process, we performed single-cell RNA sequencing of regenerating zebrafish hearts. Using a combination of immunohistochemistry, chemical inhibition, and novel transgenic animals, we were able to investigate the role of cell type-specific mechanisms during cardiac regeneration. This approach allowed us to identify a number of important regenerative processes within the interstitial cell populations. Here, we provide detailed insight into how interstitial cells behave during cardiac regeneration, which will serve to increase our understanding of how this process could eventually be induced in humans.


Seasonal shifts in sex ratios are mediated by maternal effects and fluctuating incubation temperatures.
Sex-specific maternal effects can be adaptive sources of phenotypic plasticity. Reptiles with temperature-dependent sex determination (TSD) are a powerful system to investigate such maternal effects because offspring phenotype, including sex, can be sensitive to maternal influences such as oestrogens and incubation temperatures.In red-eared slider turtles (Trachemys scripta), concentrations of maternally derived oestrogens and incubation temperatures increase across the nesting season; we wanted to determine if sex ratios shift in a seasonally concordant manner, creating the potential for sex-specific maternal effects, and to define the sex ratio reaction norms under fluctuating temperatures across the nesting season.Eggs from early and late season clutches were incubated under a range of thermally fluctuating temperatures, maternally derived oestradiol concentrations were quantified via radioimmunoassay, and hatchling sex was identified. We found that late season eggs had higher maternal oestrogen concentrations and were more likely to produce female hatchlings. The sex ratio reaction norm curves systematically varied with season, such that with even a slight increase in temperature (0.5°C), late season eggs produced up to 49% more females than early season eggs.We found a seasonal shift in sex ratios which creates the potential for sex-specific phenotypic matches across the nesting season driven by maternal effects. We also describe, for the first time, systematic variation in the sex ratio reaction norm curve within a single population in a species with TSD.


Imaging input and output of neocortical networks in vivo.
Neural activity manifests itself as complex spatiotemporal activation patterns in cell populations. Even for local neural circuits, a comprehensive description of network activity has been impossible so far. Here we demonstrate that two-photon calcium imaging of bulk-labeled tissue permits dissection of local input and output activities in rat neocortex in vivo. Besides astroglial and neuronal calcium transients, we found spontaneous calcium signals in the neuropil that were tightly correlated to the electrocorticogram. This optical encephalogram (OEG) is shown to represent bulk calcium signals in axonal structures, thus providing a measure of local input activity. Simultaneously, output activity in local neuronal populations could be derived from action potential-evoked calcium transients with single-spike resolution. By using these OEG and spike activity measures, we characterized spontaneous activity during cortical Up states. We found that (i) spiking activity is sparse (<0.1 Hz); (ii) on average, only approximately 10% of neurons are active during each Up state; (iii) this active subpopulation constantly changes with time; and (iv) spiking activity across the population is evenly distributed throughout the Up-state duration. Furthermore, the number of active neurons directly depended on the amplitude of the OEG, thus optically revealing an input-output function for the local network. We conclude that spontaneous activity in the neocortex is sparse and heterogeneously distributed in space and time across the neuronal population. The dissection of the various signal components in bulk-loaded tissue as demonstrated here will enable further studies of signal flow through cortical networks.


Meaning is Not a Reflex: Context Dependence of Spatial Congruity Effects.
In two experiments, Brookshire, Ivry, and Casasanto (2010) showed that words with positive and negative emotional valence can activate spatial representations with a high degree of automaticity, but also that this activation is highly context dependent. Lebois, Wilson-Mendenhall, and Barsalou (2015) reported that they "aimed to replicate" our study but found only null results in the "Brookshire et al. replication" conditions. Here we express concerns about three aspects of this paper. First, the study was not an attempt to replicate ours; it was a different study that adapted our method. Second, Lebois et al. did not accurately represent our theoretical position. Third, Lebois et al.'s main conclusion, that spatial congruity effects depend on the task context, was not supported by their data. Despite these concerns, we agree with Lebois et al.'s overall message that spatial aspects of words' meanings are activated differently in different contexts. This was a main conclusion of our study as well.


Effects of depth of neuromuscular blockade on the BIS-guided propofol requirement: A randomized controlled trial.
Deep neuromuscular blockade is considered beneficial for improving the surgical space condition during laparoscopic surgery. Adequacy of the surgical space condition may affect the anesthetists' decision regarding titration of depth of anesthesia. We investigated whether deep neuromuscular blockade reduces the propofol requirement under bispectral index monitoring compared to moderate neuromuscular blockade. Adult patients undergoing elective laparoscopic colorectal surgery were randomly allocated to a moderate or deep group. A train-of-four count of 1-2 in the moderate group, and a post-tetanic count of 1-2 in the deep group, were maintained by continuous infusion of rocuronium. The induction and maintenance of anesthesia were achieved by target-controlled infusion of propofol and remifentanil. The dose of propofol was adjusted to maintain the bispectral index in the range of 40-50. The remifentanil dose was titrated to maintain the systolic blood pressure to within 20% of the ward values. A total of 82 patients were included in the analyses. The mean±SD dose of propofol was 7.54 ± 1.66 and 7.42 ± 1.01 mg·kg-1·h-1 in the moderate and deep groups, respectively (P = .104). The mean±SD dose of remifentanil was 4.84 ± 1.74 and 4.79 ± 1.77 μg kg-1 h-1 in the moderate and deep groups, respectively (P = .688). In comparison to the moderate group, the deep group showed significantly lower rates of intraoperative patient movement (42.9% vs 22.5%, respectively, P = .050) and additional neuromuscular blocking agent administration (76% vs 53%, respectively, P = .007). Postoperative complications, including pulmonary complications, wound problems and reoperation, were not different between the two groups. Deep neuromuscular blockade did not reduce the bispectral index-guided propofol requirement compared to moderate neuromuscular blockade during laparoscopic colon surgery, despite reducing movement of the patient and the requirement for a rescue neuromuscular blocking agent. Clinicaltrials.gov (NCT03890406).


Engineered Gut Symbiotic Bacterium-Mediated RNAi for Effective Control of Anopheles Mosquito Larvae.
Anopheles mosquitoes are the primary vectors for the transmission of malaria parasites, which poses a devastating burden on global public health and welfare. The recent invasion of Anopheles stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. To address this issue, we developed a new approach for mosquito larvae control using gut microbiota-mediated RNA interference (RNAi). We engineered a mosquito symbiotic gut bacterium, Serratia fonticola, by deleting its RNase III gene to produce double-stranded RNAs (dsRNAs) in the mosquito larval gut. We found that the engineered S. fonticola strains can stably colonize mosquito larval guts and produce dsRNAs dsMet or dsEcR to activate RNAi and effectively suppress the expression of methoprene-tolerant gene Met and ecdysone receptor gene EcR, which encode receptors for juvenile hormone and ecdysone pathways in mosquitoes, respectively. Importantly, the engineered S. fonticola strains markedly inhibit the development of A. stephensi larvae and leads to a high mortality, providing an effective dsRNA delivery system for silencing genes in insects and a novel RNAi-mediated pest control strategy. Collectively, our symbiont-mediated RNAi (smRNAi) approach offers an innovative and sustainable method for controlling mosquito larvae and provides a promising strategy for combating malaria. IMPORTANCE Mosquitoes are vectors for various diseases, imposing a significant threat to public health globally. The recent invasion of A. stephensi in Africa has made malaria eradication more challenging due to its outdoor biting behavior and widespread resistance to insecticides. RNA interference (RNAi) is a promising approach that uses dsRNA to silence specific genes in pests. This study presents the use of a gut symbiotic bacterium, Serratia fonticola, as an efficient delivery system of dsRNA for RNAi-mediated pest control. The knockout of RNase III, a dsRNA-specific endonuclease gene, in S. fonticola using CRISPR-Cas9 led to efficient dsRNA production. Engineered strains of S. fonticola can colonize the mosquito larval gut and effectively suppress the expression of two critical genes, Met and EcR, which inhibit mosquito development and cause high mortality in mosquito larvae. This study highlights the potential of exploring the mosquito microbiota as a source of dsRNA for RNAi-based pest control.


Management Perspective of Wilson's Disease: Early Diagnosis and Individualized Therapy.
Wilson's disease (WD) is an inherited disease caused by mutations in ATP7B and is characterized by the pathological accumulation of copper in the liver and brain. Common clinical manifestations of WD include a wide range of liver disease and neurological symptoms. In some patients, psychiatric symptoms may be the only manifestation at the time of diagnosis. The clinical features of WD are highly variable and can mimic any disease of internal medicine. Therefore, for unexplained medical diseases, the possibility of WD should not be ignored. Early diagnosis and treatment can improve the prognosis of WD patients and reduce disability and early death. Gene sequencing is becoming a valuable method to diagnose WD, and if possible, all WD patients and their siblings should be genetically sequenced. Copper chelators including D-penicillamine, trientine, and dimercaptosuccinic acid can significantly improve the liver injury and symptoms of WD patients but may have a limited effect on neurological symptoms. Zinc salts may be more appropriate for the treatment of asymptomatic patients or for the maintenance treatment of symptomatic patients. High-quality clinical trials for the drug treatment of WD are still lacking, therefore, individualized treatment options for patients are recommended. Individualized treatment can be determined based on the clinical features of the WD patients, efficacy and adverse effects of the drugs, and the experience of the physician. Liver transplantation is the only effective method to save patients with acute liver failure or with severe liver disease who fail drug treatment.


Decreasing the frequency and rate of wet brewers grains supplementation did not impact growth but reduced humoral immune response of preconditioning beef heifers.
This study evaluated growth and measurements of innate and humoral immunity of preconditioning beef heifers supplemented with wet brewers grains (WBG) at 2 supplementation rates and frequencies. At 14 d after weaning (d 0), Angus heifers ( = 36; 213 ± 2 kg BW and 254 ± 7 d of age) were stratified by BW and age and randomly assigned to 1 of 12 drylot pens (3 heifers/pen). Treatments were randomly assigned to pens, in a 2 × 2 factorial design, and consisted of heifers provided ground tall fescue hay ad libitum (55% TDN and 12% CP of DM) and supplemented with WBG (75% TDN and 36% CP of DM) either daily (7X) or 3 times weekly (3X; Monday, Wednesday, and Friday) at 0.5 or 1.0% of BW (DM basis) for 42 d. Heifers were vaccinated against infectious bovine rhinotracheitis (IBR), bovine viral diarrhea virus (BVDV), Mannheimia haemolytica, and Clostridium on d 14 and 28. Individual BW was measured before feeding on d 0 and 42 following 12 h of feed and water withdrawal. Blood samples were collected via jugular venipuncture 4 h after WBG supplementation on d 14, 15, 16, 17, 21, 28, 29, 30, 31, 35, and 42. Heifers fed WBG 3X had less hay DMI (2.6 ± 0.16 vs. 3.2 ± 0.16 kg/d; < 0.0001) but greater total DMI (5.6 ± 0.16 vs. 3.8 ± 0.16 kg/d; < 0.0001) than 7X heifers on days that all heifers received WBG supplementation. However, overall hay and total DMI was not affected ( ≥ 0.40) by supplementation frequency. Therefore, ADG, BW, and G:F from d 0 to 42 did not differ among treatments ( ≥ 0.29). Plasma concentrations of haptoglobin on d 15 and cortisol on d 14 were greater for 3X heifers vs. 7X heifers ( ≤ 0.04). Heifers fed WBG at 0.5% of BW tended to have greater plasma cortisol concentrations on d 15, 17, and 35 ( ≤ 0.09) than heifers fed at 1.0% of BW. Serum BVDV-1a titers were greater ( = 0.04) for 7X heifers vs. 3X heifers on d 42 (4.2 ± 0.28 vs. 3.3 ± 0.28 log), whereas serum titers against BVDV-2 and IBR were greater for heifers fed WBG at 1.0% of BW vs. heifers fed WBG at 0.5% of BW (7.6 vs. 6.7 and 3.3 vs. 2.8 ± 0.19 log, respectively). In summary, decreasing WBG supplementation frequency (7 vs. 3 times weekly) or rate (1.0 vs. 0.5% of BW) for recently weaned beef heifers did not affect growth but decreased vaccine-induced antibody production against pathogens associated with bovine respiratory disease during a 42-d preconditioning period.


[Establishment and use of infectious bacterial artificial chromosome (BAC) DNA clones of animal herpesviruses].
Since the first description of the cloning und mutagenesis of a herpesviral genome in 1997, a number of herpesviral DNA's have been cloned as bacterial artificial chromosomes (BACs). Herpesvirus BAC's are established by introduction of a mini F origin of replication into the viral genome, which can as such be maintained und manipulated in Escherichia coli as a single copy extrachromosomal DNA. Herpesvirus DNA's cloned as BAC's are accessible to the DNA repair und mutagenesis apparatus encoded by E. coli, which can be exploited for the generation und subsequent analysis of virus mutants. One of the advantages of BAC cloning und mutagenesis is that it is independent of virus growth in cultured cells, thereby minimizing the risk of compensatory mutations. Here we summarize BAC's that have been established for Herpesviruses of livestock, among them Bovine Herpesvirus Type 1 (BHV-1), Equine Herpesvirus Type 1 (EHV-1), Marek's Disease Virus (MDV), Pseudorabies Virus (PRV). Special emphasis is put on the exploitation of herpesviral BAC's for the analysis of virus replication und vaccine developments.


Chlorido(1H-imidazole-κN)bis-(triphenyl-phosphane-κP)copper(I).
In the title complex, [CuCl(C(3)H(4)N(2))(C(18)H(15)P)(2)], the coordination geometry around Cu(I) is distorted tetra-hedral formed by two triphenyl-phosphane ligands, an imidazole ligand and a chloride group. An intra-molecular C-H⋯Cl inter-action occurs. The crystal packing is stabilized by inter-molecular N-H⋯Cl hydrogen bonds, which form an extended chain parallel to [010].


Quantitative and qualitative feed restriction on growth characteristics of male broiler chickens.
Four experiments were conducted to evaluate the quantitative and qualitative feed restriction on the performance of male broiler chickens. In the first experiment, broilers fed identical pelleted diets were feed-restricted from 5 to 42 d by giving 95, 90, or 85% of the feed consumed ad libitum by control birds the previous day. In a second experiment, broilers were fed pellet or mash diets from 1 to 7 wk. In Experiments 3 and 4, broilers were feed-restricted to 90% of the ad libitum intake of a control group during different intervals. Results from Experiment 1 indicated that live body weight at 42 d was significantly different between unrestricted and restricted broilers (P < 0.01). A reduction in mortality was noted when feed intake was reduced (P < 0.05). In the second experiment, broilers fed mash had lower body weights and breast meat yields at 42 and 49 d (P < 0.05). Cumulative mortality at 42 and 49 d was reduced in broilers fed mash (P < 0.05). Results from Experiment 3 indicated that body weight and mortality were not significantly different (P > 0.05) at 42 d across treatments. There was a significant (P < 0.01) linear improvement on feed conversion at 42 d due to duration of feed restriction. Breast meat yield at 42 d was less in broilers subjected to mild feed restriction (P > 0.05) (Experiments 3 and 4). Broilers appeared able to recover from mild feed restriction, and there was always an associated reduction in mortality.


Development of an enzyme linked immunosorbent assay for detection of cyathane diterpenoids.
So-called cyathane type diterpenoids are produced as secondary metabolites by basidiomycetes. Based on their antibacterial, fungicidal, and cytotoxic properties, cyathane type terpenoids represent interesting target compounds in fungal biotechnology. An indirect competitive enzyme linked immunosorbent assay has been developed for detection of cyathane type diterpenoids. Rabbit polyclonal antibodies were raised against a mixture of striatal A and B conjugated to bovine serum albumin. The conditions for direct attachment of the hapten striatal B to a solid phase by passive adsorption were optimized. The cross reactivities of the striatals A, C and D, of the striatins A and B, and of the erinacines C and P to striatal B were determined. The validation study showed that the ELISA was precise and sensitive. The average IC50 of striatal B was 36.0 ng mL-1 with an inter-assay coefficient of variation (CV) of 13.2% (n = 5). Recoveries from striatal B spiked samples in the assay were in the range of 97.3 - 125.9%. A good correlation between the striatal B concentration measured by the ELISA and by HPLC-DAD (y = 1.1122× - 0.1585, R2 = 0.9942) was obtained from linear regression analysis. The suitability of the ELISA for detection of cyathane type diterpenoids in submerged cultures and fruiting bodies of H. erinaceus was studied. It showed cross reactivity with supernatants from submerged cultures and extracts thereof, but did not show cross reactivity with extracts from fruiting bodies. The developed method is appropriate for qualitative and quantitative detection of cyathane diterpenoids in complex mixtures. Due to its high sensitivity and specificity, it represents an ideal screening method for discovering new cyathane diterpenoids and new potential producers of them.


Autoantibodies in Indian-Asians with insulin-dependent diabetes in the UK.
Classical insulin-dependent diabetes mellitus (IDDM) is relatively uncommon in Indian-Asians whether in India or in the UK and this may be related to immunogenetic factors. We have studied the presence or absence of islet cell antibodies and other auto-antibodies in 36 subjects with IDDM and 41 controls, all of Indian origin. Islet cell antibodies (ICA-IgG) were found in 8 subjects with IDDM but in none of the controls. Four of the 8 patients with ICA-IgG also possessed the complement fixing variety (CF-ICA). There was no definite association between possession of ICA and HLA-DR antigens. Thyroid antibodies were commoner in patients (22%) compared with controls (7%) as were parietal cell antibodies (8.3% vs 4.8%). None of the patients or controls had adrenal antibodies. The frequency of organ-specific antibodies in Indian-Asians with IDDM is similar to that of white Caucasians. The overall frequency of ICA is, however, lower than that reported for white Caucasians although the temporal distribution is similar. We conclude that even though the prevalence of IDDM in Indian-Asians is lower than in white Caucasians there is no evidence that different immunological mechanisms are involved in the pathogenesis of IDDM in the two groups.


Character of Localization and Microenvironment of Solvatochromic Reichardt's Betaine Dye in Sodium n-Dodecyl Sulfate and Cetyltrimethylammonium Bromide Micelles: Molecular Dynamics Simulation Study.
The problem of using surfactant micellar aqueous solutions as reaction media centers on estimating the polarity of the micellar pseudophase. The most popular approach is the utilization of solvatochromic dyes. Among the last, the strongest ones are the dipolar pyridinium N-phenolate dyes. The complication of such approach, however, consists in the nonuniform character of the environment of the indicator fixed in the micellar pseudophase. The aim of this study is to reveal the character of localization and orientation of the standard solvatochromic pyridinium N-phenolate dye, 4-(2,4,6-triphenylpyridinium-1-yl)-2,6-diphenylphenolate, the so-called Reichardt's dye, within the micellar pseudophase of an anionic (sodium n-dodecyl sulfate, SDS) and cationic (cetyltrimethylammonium bromide, CTAB) surfactants using MD simulations. The locus and hydration of the dye are found to be dependent on the surfactant nature. New approaches are proposed to quantitatively describe the state of the dye within the pseudophase. The results confirm the experimental data, which indicate the higher polarity of the interfacial region in the case of the SDS micelles. Because this dye is also used as an interfacial acid-base probe, the corresponding study is simultaneously performed for its protonated, i.e., cationic form. The neutral and protonated forms of the dye are found to be localized and hydrated in a different way in both SDS and CTAB micelles. This should be taken into account when using the Reichardt's dye as an acid-base indicator for estimating the electrical surface potential of micelles. The presented approach may be recommended to shed light upon the locus of other solvatochromic and acid-base indicators in micelles and micellar-like aggregates.


The Biochemical Profile of Post-Mortem Brain from People Who Suffered from Epilepsy Reveals Novel Insights into the Etiopathogenesis of the Disease.
Epilepsy not-otherwise-specified (ENOS) is one of the most common causes of chronic disorders impacting human health, with complex multifactorial etiology and clinical presentation. Understanding the metabolic processes associated with the disorder may aid in the discovery of preventive and therapeutic measures. Post-mortem brain samples were harvested from the frontal cortex (BA8/46) of people diagnosed with ENOS cases (n = 15) and age- and sex-matched control subjects (n = 15). We employed a targeted metabolomics approach using a combination of proton nuclear magnetic resonance (1H-NMR) and direct injection/liquid chromatography tandem mass spectrometry (DI/LC-MS/MS). We accurately identified and quantified 72 metabolites using 1H-NMR and 159 using DI/LC-MS/MS. Among the 212 detected metabolites, 14 showed significant concentration changes between ENOS cases and controls (p < 0.05; q < 0.05). Of these, adenosine monophosphate and O-acetylcholine were the most commonly selected metabolites used to develop predictive models capable of discriminating between ENOS and unaffected controls. Metabolomic set enrichment analysis identified ethanol degradation, butyrate metabolism and the mitochondrial beta-oxidation of fatty acids as the top three significantly perturbed metabolic pathways. We report, for the first time, the metabolomic profiling of postmortem brain tissue form patients who died from epilepsy. These findings can potentially expand upon the complex etiopathogenesis and help identify key predictive biomarkers of ENOS.


Changes in Thyroid Hormone Levels Within the Normal and/or Subclinical Hyper- or Hypothyroid Range Do Not Affect Circulating Irisin Levels in Humans.
Both thyroid hormones and irisin increase energy expenditure and induce browning of adipose tissue. However, irisin physiology and regulation remain largely unknown, and existing data are mainly derived from observational studies. In this study, we aimed to elucidate whether changes in thyroid-axis hormones alter circulating irisin levels in humans, thereby exerting a direct downstream effect on serum irisin. Samples from a cross-sectional evaluation and two interventions were utilized, including patients who had previously undergone thyroidectomy. In the cross-sectional study, 96 consecutively enrolled subjects were divided into a euthyroid group and a subclinical hyperthyroid group, according to their serum thyrotropin (TSH) levels (TSH cutoff 0.3 mIU/L). In interventional study A, 34 patients who had undergone thyroidectomy due to thyroid cancer were withdrawn from their thyroxine replacement treatment for five weeks. In interventional study B, 13 patients underwent a recombinant human TSH stimulation protocol, and blood samples were drawn at baseline, day 3 (i.e., at least 24 hours after the second intramuscular injection), day 5, and day 10. Irisin concentrations were not associated with thyroid-axis hormones (i.e., TSH, free thyroxine, and free triiodiothyronine) cross-sectionally in either the overall cohort or in the euthyroid and/or subclinical hyperthyroid subgroups (p > 0.05). There was no significant difference between euthyroid and subclinical hyperthyroid subjects (p = 0.60). Levothyroxine withdrawal did not result in any changes in irisin concentrations (p = 0.33). Recombinant human TSH stimulation did not induce any significant changes in circulating irisin (p = 0.60). Changes in thyroid-axis hormone levels within the physiological or supraphysiological range do not affect circulating irisin levels in humans. Therefore, their metabolic effects are most likely independent of each other. Other regulators of irisin levels should be identified in the future.


Automated Comparison of Pathology Reports for On-the-job Assessment of Residents.
The clinical competency of residents at teaching hospitals is always under scrutiny. Ideally, assessment should reflect competency on-the-job, under realistic circumstances, and include evaluating their medical reports. Currently, the assessment is done manually by the attending physicians, which adds to the cognitive load. In this study, we developed an automated system for assessing medical resident's pathology reports. Our system used natural language processing (NLP) techniques to identify different lexical and semantic similarity scores at sentence level as well as chunk level. We then used supervised learning to classify the reports into three categories- No Change (NC), Minor Changes (MiC), and major changes (MaC), reflecting how much the attending physician's report differs from that of the resident. Our system was able to classify the reports with an accuracy of 73.6%. Although moderately successful, our work shows the potential and future of automated assessment systems in the biomedical domain.


Solving a four-destination traveling salesman problem using Escherichia coli cells as biocomputers.
The Traveling Salesman Problem involves finding the shortest possible route visiting all destinations on a map only once before returning to the point of origin. The present study demonstrates a strategy for solving Traveling Salesman Problems using modified E. coli cells as processors for massively parallel computing. Sequential, combinatorial DNA assembly was used to generate routes, in the form of plasmids made up of marker genes, each representing a path between destinations, and short connecting linkers, each representing a given destination. Upon growth of the population of modified E. coli, phenotypic selection was used to eliminate invalid routes, and statistical analysis was performed to successfully identify the optimal solution. The strategy was successfully employed to solve a four-destination test problem.


The predictive value of race as a clinical prognostic factor among patients with clinically localized prostate cancer: a multivariate analysis of positive surgical margins.
Several investigators have reported that African-American men with clinically localized prostate cancer have poorer survival than do white men. In addition, prostate cancer in African-American men is commonly diagnosed at a more advanced stage of disease. Is race or ethnicity predictive of outcome of clinically localized prostate cancer? It has been reported that the presence of positive surgical margins significantly influences time to progression independently of other prognostic factors. Therefore, we have elected to conduct a multivariate analysis of clinical factors including race as potential predictors of positive surgical margin outcome. We studied 369 consecutive men (120 African-American and 249 white) who had radical prostatectomies at a single institution. Comparisons by race of Gleason score, stage, presence of positive surgical margins, and mean preoperative prostate-specific antigen (PSA) level were carried out. Our data demonstrate that African-American men have more pathologically locally advanced prostate cancer than do white American men: 69% among blacks compared with 57% among whites. However, the difference in rate of positive surgical margins between blacks and whites is statistically significant: 58% among blacks versus 40% among whites (P = 0.002). Four factors were predictive of positive surgical margins: preoperative PSA level, race, clinical stage, and Gleason score. We have demonstrated that race is an independent predictor of positive surgical margins among patients with clinically localized prostate cancer and should be included in treatment decisions. In addition, the risk of positive surgical margins increases noticeably when PSA is greater than 10 ng/mL.