Incidence and impact of brain metastasis in patients with hereditary BRCA1 or BRCA2 mutated invasive breast cancer.
Patients with hereditary mutations in BRCA1 or BRCA2 (gBRCA1/2) and breast cancer have distinct tumor biology, and encompass a predilection for brain metastasis (BM). We looked into baseline risk of BMs among gBRCA1/2 patients. Patients with gBRCA1/2, stage I-III invasive breast cancer seen between 2000-2017 with parenchymal BMs. Among gBRCA1 with distant breast cancer recurrence, 34 of 76 (44.7%) were diagnosed with brain metastases compared to 7 of 42 (16.7%) patients with gBRCA2. In the comparator group, 65 of 182 (35.7%) noncarrier triple-negative breast cancer (TNBC) and a distant recurrence experienced BM's. In a competitive risk analysis using death as a competing factor, the cumulative incidence of BMs was similar between gBRCA1 and noncarrier TNBC patients. The time from primary breast cancer diagnosis to detection of BMs was similar between gBRCA1 and noncarrier TNBC patients (2.4 vs 2.2 years). Survival was poor after BMs (7.8 months for gBRCA1 patients vs. 6.2 months for TNBC noncarriers). Brain was a more common site of initial distant recurrence in gBRCA1 patients versus TNBC noncarriers (26.3% vs. 12.1%). Importantly, the presence of BMs, adversely impacted overall survival across groups (HR 1.68 (95% CI 1.12-2.53), hazard ratio for death if a patient had BMs at the time of initial breast cancer recurrence vs. not). In conclusion, breast cancer BMs is common and is similarly frequent among gBRCA1 and noncarrier patients with recurrent TNBC. Our study highlights the importance of improving the prevention and treatment of BMs in patients with TNBC, gBRCA1 carriers, and noncarriers.


Non-fluorescent and yellow chlorophyll catabolites in Japanese plum fruits (Prunus salicina, Lindl.).
Although several chlorophyll metabolites have been shown to exert prominent benefits to human health when consumed, the battery of linear chlorophyll derivatives (phyllobilins) presents in fruits is poorly understood. Yellow chlorophyll catabolites (YCCs) are a new kind of phyllobilins recently identified in senescent leaves, probably arising from an oxidative process of the terminal chlorophyll catabolites, NCCs (non-fluorescent chlorophyll catabolites). This work deals with the characterization by first time of this kind of phytochemicals in edible fruits. Two YCCs have been identified in yellow Japanese plums, one (Ps-YCC1) previously described in the senescent leaves of Cercidiphyllum japonicum Siebold & Zucc. and Ps-YCC2, a chlorophyll catabolite structure described by first time in the edible parts of Japanese plum fruits. These YCCs were characterized by high-resolution MS/MS, describing the specific fragmentation (ring A) and the absence of the typical cleavage of phyllobilins (ring D), as a consequence of the unsaturated bond at C15-16 typical of YCCs, allowing the differentiation from NCCs. To the already known array of phenolic acids, anthocyanins and carotenoids, NCCs and YCCs may contribute to the antioxidant potential of these fruits, a potential that deserves attention and future research, considering the photochemical and photophysical behaviour of this group of tetrapyrrolic breakdown products.


Synthetic nano-LDL with paclitaxel oleate as a targeted drug delivery vehicle for glioblastoma multiforme.
The low density lipoprotein (LDL) receptor has been shown to be upregulated in GBM tumor cells in vitro and is therefore a potential molecular target for the delivery of therapeutic agents. A synthetic nano-LDL (nLDL) particle was developed as a drug delivery vehicle targeted to GBM cells by incorporating a lipophilic prodrug, paclitaxel oleate, into the particle. Nano-LDL containing paclitaxel oleate (nLDL-PO) was constructed by combining a synthetic peptide containing a lipid binding motif and the LDL receptor (LDLR) binding domain of apolipoprotein B-100 with a lipid emulsion consisting of phosphatidyl choline, triolein, and paclitaxel oleate. Paclitaxel oleate incorporated into the core of the lipid particle. nLDL-PO cell survival in GBM cell lines was found to be time, concentration, and cell line dependent. Cell killing was observed with short drug incubations and exhibited saturation at 6 h. nLDL-PO cell survival improved in the presence of the LDL receptor inhibitor, suramin, demonstrating that the drug was delivered via the LDL receptor. Collectively, these data strongly suggest that the synthetic nano-LDLs can incorporate lipophilic drugs and are capable of killing GBM cells. nLDL-PO has the potential to serve as a selective drug delivery vehicle for targeting GBM tumors via the LDL receptor.


Storing energy crops for methane production: effects of solids content and biological additive.
The effect of storage on chemical characteristics and CH4 yield (taking into account loss of VS during storage) of a mixture of grasses and ryegrass, ensiled as such (low solids content) and after drying (medium and high solids) with and without biological additive, were studied in field and laboratory trials. Up to 87% and 98% of CH4 yield was preserved with low solids grass (initial TS 15.6%) and high solids ryegrass (initial TS 30.4%), respectively, after storage for 6months, while under suboptimal conditions at most 37% and 52% of CH4 yield were lost. Loss in CH4 yield was mainly due to VS loss, presumably caused by secondary fermentation as also suggested by increasing pH during storage. Biological additive did not assist in preserving the CH4 yield.


Biotransformation of ginsenoside Rb1 and Rd to four rare ginsenosides and evaluation of their anti-melanogenic effects.
Improving physiological activity of primary ginsenosides through biotransformation is of great significance for food applications. In this study, gynostapenoside XVII, gynostapenoside LXXV, ginsenoside F2, and ginsenoside CK were obtained by enzymolysis of an accessible extract composed of ginsenoside Rb1 and Rd. Their effects on melanin content and tyrosinase activity were compared in vitro, and molecular docking simulation was employed to elucidate the interaction between tyrosinase and individual saponin. The results indicated that four rare ginsenosides decreased tyrosinase activity, melanin content and microphthalmia-associated transcription factor (MITF) expression level, more greatly than their primary ginsenosides, and they were more readily to bind with ASP10 and GLY68 at active site of tyrosinase to inhibit tyrosinase activity as well. These findings suggested that the rare ginsenosides obtained by enzymolysis had excellent anti-melanogenic effect, which could expand the application of ginsenosides in the field of functional foods and health supplements.


Characterization of the new HLA-B*35:482, detected in a potential hematopoietic stem cell donor.
One nucleotide substitution in codon 4 of HLA-B*35:01:01:01 results in a novel allele, HLA-B*35:482.


A novel, Z-scheme ZnO@AC@FeO photocatalyst, suitable for the intensification of photo-mediated peroxymonosulfate activation: Performance, reactivity and bisphenol A degradation pathways.
In this study, the intensification of a UVC-based PMS activation treatment is performed by a novel photocatalyst. Using ZnO nanoparticles coupled with activated carbon (AC), impregnated by ferroferric oxides (FO, magnetite), as an effective Z-scheme photocatalyst (ZACFO), the effective Bisphenol A (BP-A) removal was attained. Several techniques were applied for the characterization of the as-prepared catalyst and proved the successful preparation of ZACFO. The photocatalytic activity of pristine ZnO was significantly improved after its combination with ACFO. It was found that the fabrication of ZACFO heterostructures could inhibit the charge carriers recombination and also accelerate the charge separation of photo-induced e-/h+ pairs. Under this UVC-based photocatalysis-mediated PMS activation system, ZACFO showed an excellent potential as compared to the single constituent catalysts. The complete degradation of 20 mg/L concentration of BP-A was attained in just 20 min with excellent reaction rate constant of 27.3 × 10-2 min-1. Besides, over 60% of TOC was eliminated by the integrated ZACFO/PMS/UV system within 60 min of reaction. The minor inhibition by most matrix components, the high recycling capability with minor metals' leaching and the effectiveness in complex matrices, constitute this composite method an efficient and promising process for treating real wastewater samples. Finally, based on the photo-produced reactive intermediates and by-products identified, the Z-scheme photocatalytic mechanism and the plausible pathway of BP-A degradation were proposed comprehensively. The presence and role of radical and non-radical pathways in the decontamination process of BP-A over ZACFO/PMS/UV system was confirmed.


Reversal of Low-Grade Cerebral Edema After Lactulose/Rifaximin Therapy in Patients with Cirrhosis and Minimal Hepatic Encephalopathy.
Decreased magnetization transfer ratio (MTR) in the brain characterizes cerebral edema (CE) in patients with liver cirrhosis, but the role of treatment on its reversibility has not been studied in patients who have minimal hepatic encephalopathy (MHE). This study was carried to evaluate the reversibility of CE with lactulose and rifaximin treatment in patients with MHE and role of ammonia, pro-inflammatory interleukins (IL-1, IL-6) and tumor necrosis factor (TNF)-α in its pathogenesis. Twenty-three patients with cirrhosis (14 with MHE, 9 without MHE (NMHE)) and 6 healthy controls underwent ammonia, IL-1, IL-6, TNF-α estimation, and MTR in frontal white matter (FWM), parietal white matter (PWM), internal capsule (IC), and basal ganglia (BG). Ammonia was significantly higher in the cirrhosis group compared with controls and in MHE compared with the NMHE group. Ammonia correlated positively with IL-1 and IL-6. MTRs in FWM, PWM, IC, and BG were significantly lower in the MHE group compared with controls and in PWM, IC, and BG compared with the NMHE group. MHE patients showed significant MTR increase in FWM, PWM, and IC with treatment. IL-6 and ammonia had significant negative and significant positive psychometric hepatic encephalopathy score (PHES) correlation with MTR in various regions. This study, for the first time, demonstrated the reversibility of low-grade CE with treatment in patients with MHE. Negative correlation between ammonia, IL-6 levels, and MTR and positive correlation between PHES and MTR in MHE patients suggests the role of inflammation and ammonia in the genesis of low-grade CE.


Ovule survivorship, brood size, life history, breeding systems,and reproductive success in plants.
The percentage of ovules developing into seeds (seed-ovule ratios, S/O ratios) is about 85% in annuals but only approximately 50% in perennials.In both annuals and perennials, these typical S/O ratios occur regardless of the kind of breeding system, although many annuals are normally self-pollinating whereas perennials are virtually all cross-pollinating. The mean number of seeds maturing within individual fruits is defined as brood size, and is correlated with different modes of dispersal and strategies of ovule packging. Annuals also have significantly higher brood sizes (21.7) than perennials (<9.9). Among perennials, woody plants have both lower S/O ratios (32.7%) and brood sizes (3.3) than herbaceous perennials (57.2%, 13.5). S/O ratios appear to be largely determined genetically, whereas resource limitations are perhaps more critical in terms of regulating flower production. Among perennials, increased exposure to predators and pathogens is suggested as the best explanation for theevolution of breeding systems favoring genetic recombination. The maintenance of genetic polymorphisms, however, inevitably increases the frequency of lethal and sub-lethal allelic combinations (and perhaps mutations?), that appear to be responsible for the lower S/O ratios in perennials.


Cost-effectiveness Analysis of Inferior Turbinate Reduction and Immunotherapy in Allergic Rhinitis.
Allergic rhinitis (AR) is a common condition that is frequently associated with atopic inferior turbinate hypertrophy (ITH) resulting in nasal obstruction. Current guidelines support the use of subcutaneous allergen immunotherapy (SCIT) when patients fail pharmacologic management. However, there is a lack of consensus regarding the role of inferior turbinate reduction (ITR), a treatment that we hypothesize is cost-effective compared with other available treatments. We conducted a cost-effectiveness analysis comparing the following treatment combinations over a 5-year time horizon for AR patients presenting with atopic nasal obstruction who fail initial pharmacotherapy: (1) continued pharmacotherapy alone, (2) allergy testing and SCIT, (3) allergy testing and SCIT and then ITR for SCIT nonresponders, and (4) ITR and then allergy testing and SCIT for ITR nonresponders. Results were reported as incremental cost-effectiveness ratios (ICERs). For patients who fail initial pharmacotherapy, prioritizing ITR, either by microdebrider-assisting submucous resection or radiofrequency ablation, before SCIT was the most cost-effective strategy. Probabilistic sensitivity analysis demonstrated that prioritizing ITR before SCIT was the most cost-effective option in 95.4% of scenarios. ITR remained cost-effective even with the addition of concurrent septoplasty. For many AR patients who present with nasal obstruction secondary to atopic inferior turbinate hypertrophy that is persistent despite pharmacotherapy, ITR is a cost-effective treatment that should be considered prior to immunotherapy. N/A - Laryngoscope, 2023 Laryngoscope, 2023.


Are cerebral prostanoids of astroglial origin? Studies on the prostanoid forming system in developing rat brain and primary cultures of rat astrocytes.
Prostanoid forming capacity in vitro and convulsion-induced prostanoid formation in vivo were studied in the developing rat brain. For comparison, prostanoid synthesis in homogenates of primary astrocyte cultures of different ages was also examined. There was no significant prostanoid production in homogenates from primary astrocyte cultures prepared one week after cultivation. Two-week-old astrocyte cultures possessed a prostanoid synthesizing system of high specific activity. The relative proportions of the products were similar to those obtained in brain homogenates of adult rats, prostaglandin D2 (PGD2) being the major product. Prostanoid forming capacity of brain homogenates was low at birth, increased during development and nearly reached adult values by day 21. Generalized convulsions could be evoked by pentylenetetrazol (PTZ) irrespective of age, but convulsion-induced prostanoid formation characteristic of adult rodents did not take place before the third week of postnatal life. The close similarities between the characteristic features of prostanoid synthesis in both brain and astroglial homogenates, together with the coincidence during brain development of the expression of cerebral prostanoid synthesis with the appearance of mature astrocytes suggest that astrocytes are an important source of brain prostanoids.


Glomerular filtration of proteins: clearance of anionic, neutral, and cationic horseradish peroxidase in the rat.
Glomerular permeability to horseradish peroxidase, a protein slightly smaller than rat albumin but similar in shape, was studied in Wistar-Furth rats by using a purified neutral isozyme (HRP; molecular radius, a(e) = 29.8 A) as well as an anionic succinyl-derivative (sHRP a(e) = 31.8 A) and a cationized enzyme (cHRP, a(e) = 30 A). The clearance rate of the proteins was determined over a 20-min period using the amounts of enzyme actually filtered (i.e., protein in the urine and protein reabsorbed by tubules). Fractional clearance of cationic HRP (0.338 +/- 0.019) exceeded that of neutral HRP (0.061 +/- 0.005) by a factor of 5.5 and that of anionic HRP (0.007 +/- 0.000) by a factor of 48. Tubular reabsorption was less than 10% of the filtered load. The experimental results indicate marked charge dependency of the filtration of proteins across the glomerulus. Fractional clearances for these proteins are significantly lower than those reported in the literature for dextrans of similar molecular radii. Other molecular properties such as shape and deformability may explain these differences.


Oral clopidogrel load in aspirin-resistant capsular warning syndrome.
Capsular warning syndrome (CWS) carries a significant risk of permanent stroke. There are no proven therapies for preventing completed stroke in this unstable situation. Clinical observation in two patients with aspirin-resistant CWS treated with a loading dose of oral clopidogrel. Both patients had excellent neurological outcome, although one sustained an asymptomatic brain infarction. High-dose oral clopidogrel plus aspirin merits formal evaluation in high-risk transient brain ischemia such as CWS, preferably in a randomized trial compared to aspirin alone.


Successful correction of depressed scars of the forehead secondary to trauma and morphea en coup de sabre by en bloc autologous dermal fat graft.
Atrophic scars of the forehead can result from various pathologic processes including morphea en coup de sabre as well as trauma. A variety of surgical techniques can be used to correct these atrophic scars. Soft tissue augmentation for correction of atrophic scars of the forehead using en bloc autologous dermal fat graft. Use of en bloc autologous dermal fat graft harvested from the hip and inserted into a pocket created under the atrophic scar in two patients with depressed scars of the forehead. Overcorrection of the scars with en bloc autologous dermal fat grafts resulted in the treated areas becoming level with the adjacent skin within 3 months. Follow-up for a period of 12 months showed a perfectly level and stable graft with no further resorption. En bloc autologous dermal fat grafting appears to be a safe technique that provides excellent cosmetic results for the correction of small to medium depressed scars of the forehead.


Ex vivo expansion and characterization of human corneal endothelium for transplantation: a review.
The corneal endothelium plays a key role in maintaining corneal transparency. Its dysfunction is currently treated with penetrating or lamellar keratoplasty. Advanced cell therapy methods seek to address the persistent global deficiency of donor corneas by enabling the renewal of the endothelial monolayer with tissue-engineered grafts. This review provides an overview of recently published literature on the preparation of endothelial grafts for transplantation derived from cadaveric corneas that have developed over the last decade (2010-2021). Factors such as the most suitable donor parameters, culture substrates and media, endothelial graft storage conditions, and transplantation methods are discussed. Despite efforts to utilize alternative cellular sources, such as induced pluripotent cells, cadaveric corneas appear to be the best source of cells for graft preparation to date. However, native endothelial cells have a limited natural proliferative capacity, and they often undergo rapid phenotype changes in ex vivo culture. This is the main reason why no culture protocol for a clinical-grade endothelial graft prepared from cadaveric corneas has been standardized so far. Currently, the most established ex vivo culture protocol involves the peel-and-digest method of cell isolation and cell culture by the dual media method, including the repeated alternation of high and low mitogenic conditions. Culture media are enriched by additional substances, such as signaling pathway (Rho-associated protein kinase, TGF-β, etc.) inhibitors, to stimulate proliferation and inhibit unwanted morphological changes, particularly the endothelial-to-mesenchymal transition. To date, this promising approach has led to the development of endothelial grafts for the first in-human clinical trial in Japan. In addition to the lack of a standard culture protocol, endothelial-specific markers are still missing to confirm the endothelial phenotype in a graft ready for clinical use. Because the corneal endothelium appears to comprise phenotypically heterogeneous populations of cells, the genomic and proteomic expression of recently proposed endothelial-specific markers, such as Cadherin-2, CD166, or SLC4A11, must be confirmed by additional studies. The preparation of endothelial grafts is still challenging today, but advances in tissue engineering and surgery over the past decade hold promise for the successful treatment of endothelial dysfunctions in more patients worldwide.


Evaluation of brain and cervical MRI abnormality rates in patients with systemic lupus erythematosus with or without neurological manifestations.
Central nervous system (CNS) involvement has been observed in 14-80% of patients with systemic lupus erythematosus (SLE). Magnetic resonance imaging (MRI) is an appropriate method for evaluating CNS involvement in these patients. Clinical manifestations and MRI findings of CNS lupus should be differentiated from other mimicking diseases such as multiple sclerosis (MS). The aim of this study was to evaluate the prevalence and extent of brain and cervical cord MRI lesions of lupus patients. The relationship between neurological signs and symptoms and MRI findings were evaluated as well. Fifty SLE patients who had been referred to the rheumatology clinic of our hospital within 2009 were included in a cross sectional study. All patients fulfilled the revised 1981 American College of Rheumatology (ACR) criteria for SLE. We evaluated the neurological signs and symptoms and brain and cervical MRI findings in these patients. Forty-one patients (82%) were female and nine (18%) were male. The mean age was 30.1 ± 9.3 years. Twenty eight (56%) patients had an abnormal brain MRI. No one showed any abnormality in the cervical MRI. The lesions in 20 patients were similar to demyelinative plaques. Seventeen patients with abnormal brain MRI were neurologically asymptomatic. There was only a significant relationship between neurological motor manifestations and brain MRI abnormal findings. Unlike the brain, cervical MRI abnormality and especially asymptomatic cord involvement in MRI is quite rare in SLE patients. This finding may be helpful to differentiate SLE from other CNS disorders such as MS.


"Living like I am in Thailand": stress and coping strategies among Thai migrant masseuses in Oslo, Norway.
Migrants experience stress before, during and after migrating to a new country, all of which influences their mental wellbeing. In Norway, migration from Thailand is highly gendered as most Thai migrants are women who migrate to live with their Norwegian spouse. Massage shops, often owned by Thai entrepreneurs, are a locale where women use their cultural knowledge to bridge into the local economy. There is little knowledge about Thai migrant masseuses' experience of stress in daily life and associated coping strategies. The objective of this inquiry was to examine stressors and coping strategies among Thai migrant masseuses in Oslo, Norway. We conducted in-depth interviews with 14 Thai migrants who were working as masseuses in Oslo, Norway. We asked participants about their health, experiences of stress, and coping strategies and subsequently analyzed the data using thematic analysis. Stress in participants' lives related to settling in, loneliness, finances and spousal relationships. Of these, relationship conflict was the largest source of stress. Women largely embraced self-coping strategies and utilized Thai cultural practices and Buddhist cognitive thinking. Once relationship conflict became untenable, participants fought to change their situation. Limited fluency in Norwegian, Thai stigma about mental health and limited knowledge of the Norwegian health system were barriers to seeking healthcare. Migrants in our study often adopted "Thainess", the use of Thai cultural practices and Buddhist cognitive thinking, as a strategy for coping with stress. Preferences for self-coping, mental health stigma, and linguistic competency are important considerations when designing mental wellbeing interventions for Thai women. Use of an interpreter or systems navigator can help overcome language barriers. Clinicians can take detailed case histories to better understand Thai patients' stress, coping strategies and wellbeing. Health policy makers could consider network approaches, including using Thai health systems navigators to bridge the health system and Thai communities.


Downregulation of miR-329 promotes cell invasion by regulating BRD4 and predicts poor prognosis in hepatocellular carcinoma.
Increasing evidence indicates that abnormal microRNA (miRNA) expression is related to hepatocellular carcinoma (HCC) development. Our study aimed to elucidate the essential role of miR-329 in HCC progression. Real-time PCR was used to analyze miR-329 and bromodomain containing 4 (BRD4) expression in HCC samples (n = 135). Cell Counting Kit-8 (CCK-8) and flow cytometric analysis were used to investigate cell proliferation and apoptosis. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter and western blot assays. Kaplan-Meier analysis was used to detect the function of miR-329 on the prognosis of HCC patients. miR-329 was decreased in HCC samples and was related to tumor development. Furthermore, miR-329 significantly regulated cell invasion by targeting BRD4 but had no effect on cell proliferation and apoptosis. Moreover, downregulation of miR-329 predicted poor prognosis of HCC patients. miR-329 could control cell invasion via regulating BRD4 expression and may be a prognostic marker in HCC.


Cytotoxicity of ophthalmic solutions with and without preservatives to human corneal endothelial cells, epithelial cells and conjunctival epithelial cells.
The cytotoxicity of a range of commercial ophthalmic solutions in the presence and absence of preservatives was assessed in human corneal endothelial cells (HCECs), corneal epithelia and conjunctival epithelia using in vitro techniques. Cell survival was measured using the WST-1 assay for endothelial cells and the MTT assay for epithelial cells. Commercially available timolol, carteolol, cromoglicate, diclofenac, bromfenac and hyaluronic acid ophthalmic solutions were assessed for cytotoxicity in the presence and absence of preservatives. The preservatives benzalkonium, chlorobutanol and polysorbate were also tested. The survival of cells exposed to test ophthalmic solutions was expressed as a percentage of cell survival in the control solution (distilled water added to media) after 48 h exposure. HCEC survival was 20-30% in ophthalmic solutions diluted 10-fold. The survival of HCEC was significantly greater in all solutions in the absence of preservative than in the presence of preservative. The survival of corneal and conjunctival epithelia was consistent with that of HCECs for all test ophthalmic solutions. The preservatives polysorbate and benzalkonium were highly cytotoxic with cell survival decreasing to 20% at the concentration estimated in commercial ophthalmic solutions. By comparison, the survival of cells exposed to chlorobutanol was 80% or greater. The cytotoxicity of ophthalmic solutions to HCEC, corneal epithelia and conjunctival epithelia decreased in the absence of preservative.


Cloning and expression of cDNA encoding lysyl hydroxylase 1, 2 and 3 in tiger puffer Takifugu rubripes.
Lysyl hydroxylase (LH) catalyzes the hydroxylation of lysine residues in collagens, and contributes to the formation of more stable collagen cross-links. However, in teleost, there is little information about collagen modification enzymes including lysyl oxidase (LOX) family members. Here, we cloned cDNAs encoding LH1, 2 and 3 from tiger puffer Takifugu rubripes. To determine the mRNA expressions of LH family members in a tiger puffer, we performed a northern blot analysis. Results showed that both fgLH1 and fgLH3 mRNAs were almost constitutively expressed in tissues, but highly expressed in muscle and ovary, respectively. However, fgLH2 mRNA was detected only in RT-PCR, indicating that expression level of fgLH2 is very low in tissues. It may be that low expression level of fgLH2 contributes to the fewer contents of stable collagen cross-links in tiger puffer tissues. To further investigate expression profiles of fgLHs, we examined gene expressions in embryos during development. In embryos, expression profiles differ among three fgLHs, indicating that there are functional differences among the three fgLHs. This is the first report that examined gene expression patterns of three LHs in emrbyos and adult tissues in teleost.


The cyclopropene pyrolysis story.
Cyclopropene is the last of the small strained ring hydrocarbons to have its thermal decomposition subjected to intensive investigation. This critical review describes the nearly 40 year history of this investigation largely by gas kinetic methods with chromatographic analysis. These studies have revealed that cyclopropenes can decompose by a variety of mechanisms involving diradicals, vinylcarbenes and vinylidenes. Much detailed information has been obtained about the reactivity of these intermediates which has wider implications for thermal hydrocarbon pyrolysis. Theory has also played a important role. Cyclopropene itself has been shown to be an intermediate in the allene --> propyne rearrangement. The story itself illustrates how the evolution of mechanistic understanding has been anything but straightforward.


Assessing comprehension of the Parenting/Pregnancy Attitudes, Timing, and How Important (PATH) questions through cognitive interviewing.
PATH, "Parenting/Pregnancy Attitudes, Timing, and How Important," is a method for providers to engage in a person-centered discussion about reproductive desires. This study sought to assess patient understanding of and receptivity to PATH questions. Cognitive interviews were conducted with young adult (aged 18-29 years) patients at a federally qualified health center in New York (n = 10). Participants demonstrated clear comprehension and comfort with the PATH questions. These data provide needed person-driven support for the Centers for Disease Control and Prevention and the Society of Family Planning's recommendation to implement PATH questions as a patient-centered method for discussing an individual's reproductive desires.


Transmission of leishmaniasis from human to other vertebrates: a rapid zooanthroponotic evolution.
Research regarding zoonotic diseases often focuses on those diseases that are transferred from animals to humans. However, humans are also transmitting pathogens to animals but research on this topic is not given priority and importance. I have tried to draw the attention of researchers to this area also which is equally important. The aim of this letter was to provide a brief overview of published literature regarding reverse zoonoses or zooanthroponosis in the field of leishmaniasis and highlight the need for future work in this area. Scientific research must be conducted in the field of reverse zoonoses to provide an enriched understanding of emerging disease threats to animals and should not be neglected.


Examination of fetal nasal bone and repeatability of measurement in early pregnancy.
To evaluate the examination and measurement of fetal nasal bone at 10-14 weeks of gestation. The study included 501 fetuses in 496 consecutive pregnant women attending for the routine first-trimester ultrasound examination. The presence or absence of the fetal nasal bone was determined in the mid-sagittal plane and the length was measured by one of four examiners (measurement A; n = 501). A second measurement was taken by the same examiner (B, n = 300) and a different examiner repeated the measurement (C, n = 200) whenever possible. Measurements were made to the nearest 0.1 mm. The duration of one hundred consecutive examinations was recorded, as was that of another 100 consecutive routine first-trimester examinations without measuring the nasal bone. The median nasal bone length was 1.6 (0.8-2.4) mm, the median gestational age was 12 (10-14) weeks and the median crown-rump length (CRL) was 63 (32-90) mm. The fetal profile was examined in all 501 cases and the fetal nasal bone was present in all but one case (99.8%). No transvaginal scans were needed for the examination of nasal bone only. The average time for the sonographic examination (8.3 min) was not significantly different from the average time for first-trimester scans in which the fetal nasal bone was not measured (8.0 min). The fetal nasal bone length increased from 1.1 mm at a CRL of 35 mm to 2.1 mm at a CRL of 90 mm (nasal bone = 0.016 x CRL + 0.619, P < 0.001, r = 0.655). The repeatability coefficient for intraobserver measurements was 0.080 mm and the coefficient for interobserver measurements was similar (0.083 mm). The nasal bone can be detected from 10 weeks of gestation onwards. Consistent visualization and repeatable measurement of fetal nasal bone can be performed by an experienced sonographer in the first trimester without extending the length of time required for scanning or introducing the need for transvaginal sonography.


Connections between photoreceptors and horseradish peroxidase-injected bipolar cells in the carp retina.
We describe two physiologically and morphologically distinct types of on-center bipolar cell in the carp retina. These cells can be distinguished from one another in the following respects: (1) "type I" cells respond to moderate light intensities with a transient depolarization followed by a plateau, while the response of "type II" cells is approximately rectangular in shape; (2) latency of type II cell responses is shorter than that of type I cell responses; (3) mean diameter of type II cell dendritic fields (114 micron) is larger than that of type I cell dendritic fields (65 micron) in the outer plexiform layer; (4) mean diameter of type II cell bodies (7 micron) is smaller than that of type I cell bodies (9 micron); (5) axons of type II cells show extensive arborizations (51 micron), while those of type I cells show a single swelling with a few short collaterals (31 micron) in the proximal half of inner plexiform layer. HRP-injected on- and off-center bipolars were examined by electron microscopy. The dendrites of these bipolar cells invaginate into rod spherules and often occupy the central position of the triad. The dendrites of such bipolar cells also invaginate into cone pedicles, but in quite distinct patterns. Type I on-center bipolars do not send processes to the synaptic ribbons. In contrast, off-center bipolars and type II on-center bipolars send processes to the synaptic ribbons. The dendrites of off-center bipolars occupy the central position of the triad. Although type II on-center bipolar dendrites approach the ribbon very closely, there is usually a process from an off-center bipolar interposed between them.


Retrospective study of intrapartum fever in term pregnancies and adverse obstetric and neonatal outcomes.
Intrapartum fever is a well-known predisposing factor for severe perinatal outcomes. Herein, we explored the intrapartum features, obstetric outcomes, and neonatal outcomes in relation to the extent of intrapartum fever via three group analyses. A retrospective cohort analysis consisting of 575 term, singleton live births in one medical center from January 1st to December 31st, 2020 was carried out. Parturients who had experienced a maximal intrapartum fever of <38.0 °C were compared with two sub-groups of parturients who had experienced respective maximal fevers of 38.0-38.9 °C and ≥39.0 °C. We computed the adjusted risks for adverse perinatal outcomes via multiple logistic regression models to control for confounders. There were statistically remarkable differences among the three groups in 13 items including body mass index, epidural, and WBC before delivery (p < 0.05). In contrast with intrapartum fevers of 37.5-37.9 °C, intrapartum fevers of 38.0-38.9 °C were linked to an elevated risk of neonatal sepsis and neonatal intensive care unit admission with an odds ratio (OR) of 4.28 (95% CI 2.162-8.479) and 1.73 (95% CI 1.125-2.666), nonetheless, the relationship was remarkably higher for intrapartum fever ≥39.0 °C, with an OR of 6.40 (95% CI 2.450-16.725) and 2.23 (95% CI 1.021-4.854). Additionally, intrapartum fevers of 38.0-38.9 °C and ≥39.0 °C were related to remarkably higher risk for operative deliveries (OR 2.24, 95% CI 1.373-3.648; OR 3.59, 95% CI 1.398-9.226; respectively) and histological chorioamnionitis (OR 3.77, 95% CI 2.261-6.271; OR 19.24, 95% CI 7.385-50.111, respectively). Intrapartum fever is an important indicator of adverse perinatal outcomes. The higher the temperature, the higher risk of histological chorioamnionitis, as well as the risk of neonatal sepsis and neonatal intensive care unit admission.


Machine learning to guide clinical decision-making in abdominal surgery-a systematic literature review.
An indication for surgical therapy includes balancing benefits against risk, which remains a key task in all surgical disciplines. Decisions are oftentimes based on clinical experience while guidelines lack evidence-based background. Various medical fields capitalized the application of machine learning (ML), and preliminary research suggests promising implications in surgeons' workflow. Hence, we evaluated ML's contemporary and possible future role in clinical decision-making (CDM) focusing on abdominal surgery. Using the PICO framework, relevant keywords and research questions were identified. Following the PRISMA guidelines, a systemic search strategy in the PubMed database was conducted. Results were filtered by distinct criteria and selected articles were manually full text reviewed. Literature review revealed 4,396 articles, of which 47 matched the search criteria. The mean number of patients included was 55,843. A total of eight distinct ML techniques were evaluated whereas AUROC was applied by most authors for comparing ML predictions vs. conventional CDM routines. Most authors (N = 30/47, 63.8%) stated ML's superiority in the prediction of benefits and risks of surgery. The identification of highly relevant parameters to be integrated into algorithms allowing a more precise prognosis was emphasized as the main advantage of ML in CDM. A potential value of ML for surgical decision-making was demonstrated in several scientific articles. However, the low number of publications with only few collaborative studies between surgeons and computer scientists underpins the early phase of this highly promising field. Interdisciplinary research initiatives combining existing clinical datasets and emerging techniques of data processing may likely improve CDM in abdominal surgery in the future.


Whole Blood Administration for Obstetric-Related Hemorrhage During Prehospital Transport.
Whole blood transfusion has been used for resuscitation in trauma patients; however, case reports of whole blood transfusion for obstetric-related hemorrhage are limited. Whole blood transfusion typically is accomplished with low titer O-positive whole blood, and, despite success in trauma, use in persons with childbearing potential is of concern due to risk of alloimmunization. We present a case series of patients who received low titer O-positive whole blood for obstetric hemorrhage. One patient was Rh-negative and received immune globulin treatment after whole blood transfusion. All patients survived to hospital discharge. None experienced transfusion-related complications. Whole blood can be successfully administered both in and out of the hospital setting, even for obstetric hemorrhage. The benefits of easily administered balanced resuscitation, limited donor exposure, and improved patient outcomes likely outweigh potential alloimmunization, especially in resource-limited settings. Addressing concerns of alloimmunization cannot be accomplished without more research, and we encourage others to investigate using whole blood in this population.


Gentisic acid mitigates gentamicin-induced nephrotoxicity in rats.
The current investigation was considered to evaluate the beneficial effects of gentisic acid (GA) on gentamicin (GEN)-induced nephrotoxicity in rat kidneys through assessment of oxidative stress, inflammatory cytokines, and histopathological changes. Rats were split into five equal groups. Rats were treated with GA (25, 50, and 100 mg/kg/day, p.o.) for 14 consecutive days and GEN (100 mg/kg, i.p.) was administrated from day 8 to day 14 of the experiment. On the 15th day, blood samples were collected to determine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine (Cr) levels. Malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β), and nitric oxide (NO) levels and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were assessed in the renal tissue. Histopathological evaluations were done to confirm the biochemical results. GEN increased the levels of NGAL, KIM-1, BUN, and Cr in serum as well as MDA, NO, GSH, TNF-α, and IL-1β in renal tissue. Moreover, GEN administration reduced the activity of CAT, SOD, and GPx in renal tissue. Nonetheless, the administration of GA before and alongside GEN mitigated these deleterious effects. In conclusion, GA has a beneficial effect on biochemical, inflammatory, and oxidative stress indices against GEN-induced nephrotoxicity.


Correction: The sockeye salmon genome, transcriptome, and analyses identifying population defining regions of the genome.
[This corrects the article DOI: 10.1371/journal.pone.0240935.].


Response to Ursodeoxycholic Acid May Be Assessed Earlier to Allow Second-Line Therapy in Patients with Unresponsive Primary Biliary Cholangitis.
Response to ursodeoxycholic acid (UDCA) in primary biliary cholangitis (PBC) has been traditionally assessed 1 to 2 years after treatment initiation. With the development of new drugs, some patients may benefit from an earlier introduction of second-line therapies. This study aims to identify whether well-validated response criteria could correctly identify individuals likely to benefit from add-on second-line therapy at 6 months. Analysis of a multicenter retrospective cohort which included only patients with clear-cut PBC. 206 patients with PBC (96.6% women; mean age 54 ± 12 years) were included. Kappa concordance was substantial for Toronto (0.67), Rotterdam (0.65), Paris 1 (0.63) and 2 (0.63) criteria at 6 and 12 months, whereas Barcelona (0.47) and POISE trial (0.59) criteria exhibited moderate agreement. Non-response rates to UDCA was not statistically different when assessed either at 6 or 12 months using Toronto, Rotterdam or Paris 2 criteria. Those differences were even smaller or absent in those subjects with advanced PBC. Mean baseline alkaline phosphatase was 2.73 ± 1.95 times the upper limit of normal (× ULN) among responders versus 5.05 ± 3.08 × ULN in non-responders (p < 0.001). After 6 months of treatment with UDCA, the absence of response by different criteria could properly identify patients who could benefit from early addition of second-line therapies, especially in patients with advanced disease or high baseline liver enzymes levels.


Word inversion sensitivity as a marker of visual word form area lateralization: An application of a novel multivariate measure of laterality.
An area within the ventral occipitotemporal cortex (vOTC), the "visual word form area" (VWFA), typically exhibits a strongly left-lateralized response to orthographic stimuli in skilled readers. While individual variation in VWFA lateralization has been observed, the behavioral significance of laterality differences remains unclear. Here, we test the hypothesis that differences in VWFA lateralization reflect differing preferences for holistic orthographic analysis. To examine this hypothesis, we implemented a new multivariate method that uses machine learning to assess functional lateralization, along with a traditional univariate lateralization method. We related these neural metrics to behavioral indices of holistic orthographic analysis (inversion sensitivity). The multivariate measure successfully detected the lateralization of orthographic processing in the VWFA, and as hypothesized, predicted behavioral differences in holistic orthographic analysis. An exploratory whole brain analysis identified further regions with a relationship between inversion sensitivity and lateralization: one near the junction of the inferior frontal and precentral sulci, and another along the superior temporal gyrus. We conclude that proficient native readers of English exhibit differences in cortical lateralization of the VWFA that have significant implications for reading behavior.


Treatment of ventricular arrhythmias by United States cardiologists: a survey before the Cardiac Arrhythmia Suppression Trial results were available.
To define the practice habits of United States cardiologists and the treatment of ventricular arrhythmias, a random sample of 1,000 of 12,000 cardiologists was sent a pretested questionnaire. After follow-up procedures, 252 responded, of which 18% were academically-based, 29% were hospital-based and 53% were office-based. Attitudes about antiarrhythmic drug therapy for the treatment of ventricular arrhythmias were influenced by the presence and severity of cardiac disease, the presence and severity of cardiac disease, the presence of symptoms and the type of ventricular arrhythmias. In this survey, only 1% of cardiologists treated patients with asymptomatic ventricular premature complexes and no heart disease, but 17% treated such patients if unsustained ventricular tachycardia was present. The treatment rate among cardiologists increased to 38% when coronary artery disease with left ventricular dysfunction was present in patients with asymptomatic ventricular premature complexes. The presence of any cardiac disease and symptomatic ventricular arrhythmias increased the treatment rate to 80 to 100%. Approximately 50% of responding physicians treated patients comparable to the Cardiac Arrhythmia Suppression Trial study population with antiarrhythmic drugs. Beta blockers were the most common antiarrhythmic drug class chosen as the most appropriate initial therapy in new patients with ventricular arrhythmias. Whereas no cardiologists thought that amiodarone was appropriate to initiate in new patients with benign or potentially malignant ventricular arrhythmias, as many as 33 to 43% of cardiologists would use amiodarone for refractory patients with such arrhythmias, a response contradictory to the approved labeling for this drug. Less than one half of cardiologists recognize the high potential organ toxicity for quinidine, procainamide and tocainide.(ABSTRACT TRUNCATED AT 250 WORDS)


Correction: Yao, C.A., et al. Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide. Nutrients 2016, 8, 192.
The authors wish to make the following correction to their published paper [...].


The practitioner's perspective: introduction to Ayurvedic herbalism.
Ayurveda, the indigenous holistic healing system of India, is a holistic approach to health and lifestyle management that incorporates diet, exercise, life activity routines, psychotherapeutic practices, massage and botanical medicine. Ayurveda focuses on prevention, applying techniques of self-care to restore health balance quickly and effectively. Ayurveda is one of the four large, long-practiced ethnic herbal medicine systems with large extant literatures (along with Western, Chinese and Unani). It affords valuable clinical insights in its own right. Acquiring a basis in Ayurveda will enhance access to south Asian herbs and indigenous medicinal preparations.


Genetic analysis of glucose tolerance in inbred mouse strains. Evidence for polygenic control.
To determine genetic factors involved in diabetes susceptibility in inbred strains of mice, we initially evaluated differences in fed plasma glucose and insulin concentrations among six strains (AKR/J, C3H/HeJ, C57BL/6J, C57L/J, DBA/2J, and SWR/J). There was considerable variation in fed plasma glucose concentration, with C3H/HeJ mice the most glucose tolerant (174 +/- 7 mg/dl) and C57BL/6J mice the least glucose tolerant (252 +/- 7 mg/dl, P less than .0001 vs. C3H/HeJ mice). Glycosylated hemoglobin of C57BL/6J mice (4.0 +/- 0.06%) was also higher than that of C3H/HeJ mice (3.52 +/- 0.06%, P less than .0001). The fed plasma insulin concentration did not differ between these two strains. Glucose tolerance was further evaluated in overnight-fasted C3H/HeJ and C57BL/6J mice by an intraperitoneal glucose tolerance test (IPGTT). Although fasting plasma glucose did not differ, the most remarkable difference in plasma glucose during IPGTT between C57BL/6J and C3H/HeJ mice was noted at 30 min (489 +/- 29 vs. 227 +/- 20 mg/dl, P less than .001). To determine the number of genes involved in the phenotypic difference in glucose tolerance, C57BL/6J males were crossed with C3H/HeJ females (F1, C3H/HeJ X C57BL/6J), and the F1 hybrid females were backcrossed with C57BL/6J males (backcrossed, F1 X C57BL/6J). Plasma glucose after 30 min on IPGTT was 219 +/- 8 (n = 21), 456 +/- 18 (n = 23), and 292 +/- 13 (n = 23) mg/dl for C3H/HeJ, C57BL/6J, and F1 mice, respectively (P less than .001 for all comparisons).(ABSTRACT TRUNCATED AT 250 WORDS)


Computer analysis of portal hemodynamics after small-diameter portacaval H-grafts: the theoretical basis for partial shunting.
We have previously reported on the clinical results of partial shunting using small-diameter portacaval H-grafts. In this study, we defined the theoretical basis for partial shunting using the Wheatstone bridge model of the splanchnic circulation. The model was modified to include a variable resistance for a portacaval shunt and was programmed as a computer simulation. We calculated portal flow as a function of shunt resistance to determine the resistance necessary to maintain prograde portal flow in patients with portal hypertension. The resistance of 8- and 10-mm portacaval H-grafts, as positioned clinically, was determined using a laboratory apparatus. The experimentally derived values for resistance were inserted into the graph of portal flow predicted by the computer program. Portacaval H-grafts 8 mm in diameter should produce prograde portal flow, 10-mm H-grafts should be borderline, and shunts larger than 10 mm should routinely result in reversed flow. These predictions were confirmed by clinical observations in 29 patients undergoing portacaval H-grafts.


STING: a master regulator in the cancer-immunity cycle.
The aberrant appearance of DNA in the cytoplasm triggers the activation of cGAS-cGAMP-STING signaling and induces the production of type I interferons, which play critical roles in activating both innate and adaptive immune responses. Recently, numerous studies have shown that the activation of STING and the stimulation of type I IFN production are critical for the anticancer immune response. However, emerging evidence suggests that STING also regulates anticancer immunity in a type I IFN-independent manner. For instance, STING has been shown to induce cell death and facilitate the release of cancer cell antigens. Moreover, STING activation has been demonstrated to enhance cancer antigen presentation, contribute to the priming and activation of T cells, facilitate the trafficking and infiltration of T cells into tumors and promote the recognition and killing of cancer cells by T cells. In this review, we focus on STING and the cancer immune response, with particular attention to the roles of STING activation in the cancer-immunity cycle. Additionally, the negative effects of STING activation on the cancer immune response and non-immune roles of STING in cancer have also been discussed.


Structure-Function Assays for Crimean-Congo Hemorrhagic Fever Virus Polymerase.
The recently developed Crimean-Congo hemorrhagic fever virus (CCHFV) reverse genetics systems have paved the way for experiments looking to identify and characterize the roles played by viral and cellular proteins in the CCHFV life cycle. In particular, the development of the noninfectious minigenome and virus-like particle (VLP) systems is a tremendous technological advance, as these systems allow for precisely targeting proteins or nucleic acids and measuring the effects these mutations or treatments have on viral life cycle stages. Importantly, these systems can be used at low-containment levels. Presented are the materials and methods currently available to study CCHFV transcription, replication, and translation in the context of a minigenome or VLP.


Online measurement of tetraethyllead in aqueous samples utilizing monolith-based magnetism-enhanced in-tube solid phase microextraction coupled with chromatographic analysis.
A new procedure that utilizing a preconcentration system based on magnetism-enhanced in-tube solid phase microextraction (ME/IT-SPME) and detection by HPLC with diode array detector (DAD) after liquid desorption from the microextraction column has been developed for the online measurement of tetraethyllead (TEL) in various aqueous samples. In this connection, according to the chemical features of TEL, porous monolith mingled with Fe3O4 nanoparticles were designed and synthesized in a silica capillary, and used as the microextraction column of ME/IT-SPME. To favor the implement of variable magnetic fields during extraction procedure, the as-prepared microextraction column was twined a magnetic coil. Results revealed that the exertion of magnetic field during the adsorption and eluting procedures assisted the extraction of TEL with an enhancement by 52% in extraction efficiency. Under the most beneficial conditions, the developed ME/IT-SPME was online hyphenated with HPLC/DAD to measure trace TEL in various aqueous samples. The limit of detection was 0.082 μg/L and the RSDs for precision were in the range of 6.3-8.5%. The recoveries with low, medium and high fortified levels varied from 80.6% to 95.0% with good repeatability. To the best of knowledge, this is the first study that using IT-SPME to extract TEL and then online quantification with HPLC/DAD.


Colonic adenomatous polyp with focal squamous metaplasia.
A case of adenomatous polyp of the colon with focal squamous metaplasia is reported. Squamous metaplasia has been described in both neoplastic and non-neoplastic conditions of the colon. However, it has not previously been documented to occur in adenomatous polyp. The histogenesis, possible predisposing factors, and clinical significance of the lesion are discussed.


Incidence of cancer after a first episode of idiopathic venous thromboembolism treated with 3 months or 1 year of oral anticoagulation.
A prolonged treatment with oral anticoagulants has been claimed to reduce the incidence of newly diagnosed cancer in the long-term follow-up of patients with venous thromboembolism. In a multicenter prospective study we assessed the incidence of newly diagnosed clinically overt cancer in patients with a first episode of idiopathic venous thromboembolism (VTE) treated with oral anticoagulants for 3 months or 1 year. Consecutive patients with an idiopathic venous thromboembolism who had completed 3 months of oral anticoagulant therapy without having a recurrence, bleeding or newly diagnosed cancer were randomized to discontinue oral anticoagulant therapy or to continue it for nine additional months. Idiopathic venous thromboembolism was defined as thrombosis occurring in the absence of known cancer, known thrombophilia, or temporary risk factors for venous thromboembolism. All patients were followed up for at least 1 year after randomization. A total of 429 patients, 265 patients with DVT and 164 with PE, were followed up for an average of 43.7 months after randomization. A newly diagnosed cancer occurred in 32 patients (7.5%), 13 (6.2%) of the 210 patients treated for 3 months and 19 (8.7%) of the 219 patients treated for 1 year (RR = 0.71, 95% confidence interval 0.36-1.41). The incidence of newly diagnosed clinically overt cancer is not reduced in patients with idiopathic venous thromboembolism treated with 1-year anticoagulant treatment compared with patients treated for 3 months.


A Community Health Worker-Led Positive Psychology Intervention for African American Older Adults With Chronic Pain.
Experiencing structural racism over the life course contributes to disproportionate pain-related disability among African American older adults. Positive STEPS, delivered by community health workers, is a culturally congruent chronic pain self-management intervention that incorporates positive psychology principles and gives attention to social determinants of pain and pain management. We conducted a randomized pilot trial among older adults with chronic musculoskeletal pain in an underserved, primarily African American community (Detroit, Michigan). The 7-week intervention included weekly telephone sessions with a community health worker; web-based videos teaching pain self-management skills; positive activities (e.g., Life Review, Gratitude Jar); and use of wearable activity trackers. Outcomes were measured at baseline and 8-week follow-up. We assessed participant retention, engagement, and satisfaction. Study completers (n = 46; 90% retention) were 93% African American, 89% female, mean 72 years, and completed 5.7 of 7 sessions. Intervention participants versus controls showed greater improvement in PROMIS Pain Interference (4.3-point T-score decrease vs. 0.4-point increase; p = .01) and the Pain Self-Efficacy Questionnaire (p = .007). Furthermore, compared with controls, significantly more intervention participants reported "better" or "much better" global functioning (86% vs. 25%; p = .000) and pain (67% vs. 21%; p = .003) since baseline. Improvements in physical functioning, social participation, and resilience were noted, but differences were not significant. Participant feedback on the intervention was overwhelmingly positive. A community health worker-led chronic pain self-management intervention combining positive activities with self-management skills training demonstrated the potential to enhance pain-related functioning among a vulnerable group of older adults. NCT04321239.


Shipping and storage temperature logger datasets for extended shelf life vacuum packaged chilled beef in the Chinese supply chain.
This article contains temperature logger datasets obtained for refrigerated cartons of Australian vacuum packaged chilled beef stored under near ideal conditions (∼- 1 °C) in Australia (CONTROL) and shipped via land and sea to three destinations in China (China-1, China-2, China-3) described in detail previously [1]. Cartons were stored for 84, 98, 120 and 140 days postslaughter. Temperature data were acquired during shipping and storage using i-buttons (Thermocron-TCS, Baulkham Hills, Australia) and LogTags (TRIX-16, LogTag Australia, Baulkham Hills, Australia).


Failure of rabies postexposure treatment in Thailand.
Three failures of postexposure rabies treatment using imported purified duck embryo cell and Vero cell rabies vaccines are reported from Thailand. Reference is made to eight additional previously reported Thai patients, six of whom had received human diploid cell vaccine. An analysis of these cases reveals that there were serious flaws in management in all of these patients. It is stressed that 45% of human rabies deaths in Thailand occur within 20 days of being bitten and 71% are dead within 28 days. This short incubation period does not allow much time to start immunotherapy. Of Bangkok dogs found to have rabies at autopsy, approximately 8% have a rabies immunization history. Once a dog has bitten a patient immunotherapy should not be delayed in countries with a high incidence of dog rabies. Patients with chronic disease, alcoholics and drug addicts may have an impaired immune response to postexposure rabies vaccines.


Improvement in the anemia of hemodialyzed patients following subtotal parathyroidectomy. Evidence for the role of secondary hyperparathyroidism in the etiology of the anemia of chronic renal failure.
An increase in the blood hemoglobin concentration was found in four of five patients on chronic hemodialysis following subtotal parathyroidectomy performed for the treatment of incapacitating osteodystrophy. In a sixth hemodialyzed patient, there was a striking increase in the hemoglobin level following treatment with 1alpha-hydroxycholecalciferol with suppressed parathyroid overactivity. It is concluded that surgical or "chemical" parathyroidectomy seems to be associated with improvement of the anemia of patients with chronic renal failure.


Organophosphate ester metabolites in human breast milk determined by online solid phase extraction coupled to high pressure liquid chromatography tandem mass spectrometry.
The analysis of metabolites of organophosphate esters (OPEs) in human breast milk is essential to evaluate OPE and OPE metabolite exposure of newborns. In the current study, an analytical method which only needs a small amount of breast milk (100 μl) was developed and validated for six diester metabolites and three hydroxylated metabolites applying salt-induced liquid-liquid extraction (SI-LLE) and dispersive solid phase extraction (d-SPE) for sample preparation and online solid phase extraction coupled to high pressure chromatography tandem mass spectrometry (online-SPE-HPLC-MS/MS) for quantitative measurement. The final method consisted of an extraction with formic acid (FA)/acetonitrile (1:200, v/v) and a cleanup with C18 d-SPE. The final extracts were trapped on a C18 cartridge with application of a wash step of 2 ml 0.1% FA milli-Q/methanol (98:2, v/v). Method detection limits (MDLs) ranging from 21.7 ng/l for BBOEHEP to 500 ng/l for BCIPP and average recoveries ranging from 58% for 5-OH-EHDPHP to 120% for BCIPP were achieved. Thirty-three breast milk samples from the LINC (Linking EDCs in maternal Nutrition to Child health) cohort collected in three distinct areas in The Netherlands were analyzed using the validated method. BCEP, BCIPP, BCIPHPP, BDCIPP, and 5-OH-EHDPHP were not detected in any of the samples, while BBOEP was the most frequently detected metabolite with a concentration range of <MDL to l.47 ng/ml, followed by DPhP and BBOEHEP, detected in ranges of <MDL to 0.09 and <MDL to 0.027 ng/ml. The results indicated that OPEs entering the human body are only to a limited extent excreted via breast milk.


A comprehensive analysis of recent advancements in cancer detection using machine learning and deep learning models for improved diagnostics.
There are millions of people who lose their life due to several types of fatal diseases. Cancer is one of the most fatal diseases which may be due to obesity, alcohol consumption, infections, ultraviolet radiation, smoking, and unhealthy lifestyles. Cancer is abnormal and uncontrolled tissue growth inside the body which may be spread to other body parts other than where it has originated. Hence it is very much required to diagnose the cancer at an early stage to provide correct and timely treatment. Also, manual diagnosis and diagnostic error may cause of the death of many patients hence much research are going on for the automatic and accurate detection of cancer at early stage. In this paper, we have done the comparative analysis of the diagnosis and recent advancement for the detection of various cancer types using traditional machine learning (ML) and deep learning (DL) models. In this study, we have included four types of cancers, brain, lung, skin, and breast and their detection using ML and DL techniques. In extensive review we have included a total of 130 pieces of literature among which 56 are of ML-based and 74 are from DL-based cancer detection techniques. Only the peer reviewed research papers published in the recent 5-year span (2018-2023) have been included for the analysis based on the parameters, year of publication, feature utilized, best model, dataset/images utilized, and best accuracy. We have reviewed ML and DL-based techniques for cancer detection separately and included accuracy as the performance evaluation metrics to maintain the homogeneity while verifying the classifier efficiency. Among all the reviewed literatures, DL techniques achieved the highest accuracy of 100%, while ML techniques achieved 99.89%. The lowest accuracy achieved using DL and ML approaches were 70% and 75.48%, respectively. The difference in accuracy between the highest and lowest performing models is about 28.8% for skin cancer detection. In addition, the key findings, and challenges for each type of cancer detection using ML and DL techniques have been presented. The comparative analysis between the best performing and worst performing models, along with overall key findings and challenges, has been provided for future research purposes. Although the analysis is based on accuracy as the performance metric and various parameters, the results demonstrate a significant scope for improvement in classification efficiency. The paper concludes that both ML and DL techniques hold promise in the early detection of various cancer types. However, the study identifies specific challenges that need to be addressed for the widespread implementation of these techniques in clinical settings. The presented results offer valuable guidance for future research in cancer detection, emphasizing the need for continued advancements in ML and DL-based approaches to improve diagnostic accuracy and ultimately save more lives.


Clarifying the supercomplex: the higher-order organization of the mitochondrial electron transport chain.
The oxidative phosphorylation electron transport chain (OXPHOS-ETC) of the inner mitochondrial membrane is composed of five large protein complexes, named CI-CV. These complexes convert energy from the food we eat into ATP, a small molecule used to power a multitude of essential reactions throughout the cell. OXPHOS-ETC complexes are organized into supercomplexes (SCs) of defined stoichiometry: CI forms a supercomplex with CIII2 and CIV (SC I+III2+IV, known as the respirasome), as well as with CIII2 alone (SC I+III2). CIII2 forms a supercomplex with CIV (SC III2+IV) and CV forms dimers (CV2). Recent cryo-EM studies have revealed the structures of SC I+III2+IV and SC I+III2. Furthermore, recent work has shed light on the assembly and function of the SCs. Here we review and compare these recent studies and discuss how they have advanced our understanding of mitochondrial electron transport.


Renal carbuncle: simulation of tumor response to epinephrine.
A case of renal carbuncle with unusual angiographic findings is presented. The abscess showed abnormal vessels on selective angiogrpahy which were enhanced after intra-arterial epinephrine. New foci of abnormal vessels were also seen on the postepinephrine angiogram.


Usefulness of echocardiographically determined mitral leaflet motion for diagnosis of mitral valve prolapse in 17- and 18-year-old men.
Mitral leaflet motion during systole was studied by echocardiography in 102 healthy young men. Mean posterior maximal leaflet motion was 2 +/- 1 mm behind the CD line on 2-dimensionally (2-D) directed M-mode examination. On the apical 4-chamber cross-sectional view a mean area of 0.34 +/- 0.24 mm2 was contained by the mitral leaflets above the plane of the mitral anulus. Elevated values on the M-mode view (greater than or equal to 4 mm) compared with the 2-D 4-chamber view (greater than or equal to 0.70 mm2) were discordant, with 90% (18 of 20) of the elevated values found in 1 view only. Thus, there is a wide spectrum of mitral leaflet motion in asymptomatic young men. The value of the echocardiogram in diagnosis of mitral valve prolapse is questionable because any cutoff point between normal and abnormal is arbitrary and the degree of motion has not been shown to correlate with morbidity or mortality.


Medical therapy of glaucoma.
Prescribing medical treatment for glaucoma requires a complex decision-making process that involves the patient, the severity of the disease, the therapeutic options available, and their potential side effects. Lowering intraocular pressure, a known risk factor for progression, has been the mainstay of glaucoma treatment. Most patients who are first diagnosed with glaucoma in the United States are started on topical medications. As our understanding of the disease changes and newer treatments become available, glaucoma therapies may need to be reassessed and changed if necessary.


Pseudocoarctation of the aorta.
We report a case of a 50-year-old man with pseudocoarctation of the aorta that we examined with magnetic resonance imaging (MRI) and digital subtraction angiography (DSA). The MR images demonstrated the characteristic "kink" of the aorta and the absence of true coarctation. These appearances were confirmed by DSA, but we believe MRI to be the better method for examining the aorta because it is non-invasive and has the ability to display the mediastinal anatomy in the sagittal plane, in addition to the axial and coronal planes.


Reconstruction of craniofacial bone defects with individual alloplastic implants based on CAD/CAM-manipulated CT-data.
Reconstruction of craniofacial bone defects by intraoperative modelling of autogenous or alloplastic materials may cause undesirable results concerning the implant shape or the long-term maintenance of this shape. Furthermore, the use of alloplastic materials to be modelled intraoperatively may result in an inflammatory tissue response. Therefore the question is raised whether CAD/CAM-techniques may be used for the pre-operative geometric modelling of the implant based on helical computed tomography data. A numerically based 3-dimensional model of the skull defect serves as the basis for a freeform-surfaces design of the implant shape, position and thickness, using modelling tools and programmes developed for industrial CAD/CAM. The precise and individual fit of the implant results from generating its margins by the borders of the defect, whereas the implant surface is generated by the geometry of the non-affected neighbouring bone contours. The implant data run a numerically controlled milling machine to fabricate the individual implant. The reconstruction of post-traumatic defects of the forehead, of post-surgical temporal defects after intracranial haemorrhage, and of a parieto-occipital defect due to ablative tumour surgery are presented as the first clinical experiences of this new method.


Evaluation of 500- and 1,000-mg doses of ciprofloxacin for the treatment of chancroid.
A randomized, double-blind study was performed comparing ciprofloxacin in a 500-mg single dose with 1,000 mg (500-mg doses given 12 h apart) for the treatment of chancroid in Thailand. Haemophilus ducreyi was isolated from 87 (48%) of 180 men with a clinical diagnosis of chancroid. For men with ulcers that were culture positive for H. ducreyi, rates of cure were 100% in the 500-mg group and 98% in the 1,000-mg group. For men with ulcers that were culture negative for H. ducreyi, rates of cure were 93% in the 500-mg group and 96% in the 1,000-mg group. The MIC of ciprofloxacin for 50% of isolates among 85 isolates of H. ducreyi was 0.007 micrograms/ml (range, 0.002 to 0.03 micrograms/ml). No significant adverse effects were detected in either group. These data indicate that both of these treatment regimens are equally effective therapies for chancroid in Thailand.


Structure-activity relationships of mammalian, chicken, and salmon gonadotropin releasing hormones in vivo in goldfish.
Mammalian, chicken, and salmon gonadotropin releasing hormones (GnRHs), and anlogs of each peptide, were injected either alone or in combination with pimozide into goldfish, and the changes in serum gonadotropin (GtH) levels determined. The native peptides had similar potencies in terms of magnitude and duration of the GtH response. Analogs of LHRH that are superactive in mammals are also superactive in goldfish; although [(imBzl)-D-His6, Pro9-NEt]-LHRH is very highly superactive in mammals it has activity similar to [D-Ala6, Pro9-NEt]-LHRH in goldfish. D-Ala6 or (imBzl)-D-His6 substitutions of [Trp7, Leu8, Pro9-NEt]-LHRH are not superactive in goldfish, whereas the D-Arg6 substitution is highly superactive, indicating that there are differences in the factors that make salmon and mammalian GnRH superactive. These results also indicate that the structural modifications that determine superactivity of GnRHs in goldfish differ from what is known for mammals.


Assessment of cord blood hematopoietic cell parameters before and after cryopreservation.
The testing of cord blood (CB) progenitor and stem cell units for transplantation suitability involves enumeration of total nucleated cells before freezing. CD34+ cell counts may also be a means of determining suitability. Studies have been conducted to evaluate how specific storage conditions influence cell counts. CB units were processed by hydroxyethyl starch volume reduction. Cryopreserved-thawed samples were diluted 1:3 without washing. CD34+ cells were measured with three commercially available assay methods. In specific studies, apoptosis-indicating reagents were included. CB units were analyzed for nucleated cells, aldehyde dehydrogenase-containing cells, and progenitor colonies. CD34+ cell levels and nucleated cells were retained during storage in test tubes at 1 to 6 degrees C for 3 days. Cryopreserved-thawed samples showed a reduction in CD34+ cells relative to prefreeze levels with the largest decrease with the Stem-Kit (Beckman Coulter) restricted gating procedure. Prefreeze samples contained minimal numbers of presumed apoptotic cells detected with 7-aminoactinomycin D or SYTO16, but after cryopreservation-thawing there was an increase. Nucleated cell levels determined with a hematology analyzer or flow cytometry were reduced after thawing. Cryopreservation-thawing reduced the percentage of CD34+ cells positive for the presence of aldehyde dehydrogenase and the number of progenitor colonies. These differences were significant. These studies indicate that CD34+ cell counts were maintained when CB samples were stored at 1 to 6 degrees C in test tubes for 3 days. Cryopreservation-thawing resulted in changes in a number of parameters including the percentage of CD34+ cells that were aldehyde dehydrogenase(+) and the number of 7-aminoactinomycin D(+) cells and SYTO16(low) cells.


Nevoid iris melanoma, case report.
The case is presented of a patient with diagnosis of iris nevus in the left eye in youth with a poor follow-up, who referred a decreased visual acuity in that eye. A hyphaema and a 3×4×3mm nodule with irregular pigmentation was observed. Excision of the tumour and histological analysis confirmed the suspicion of iris melanoma in stage Ia. Despite the low grade malignancy of iris melanoma and the low frequency of transformation of iris nevus into melanoma, a follow-up is required for its early diagnosis and treatment.


Effects of recombinant human follicle stimulating hormone on follicle development and ovulation in the mare.
The only gonadotrophin preparation shown to stimulate commercially useful multiple ovulation in mares is equine pituitary extract (EPE); even then, the low and inconsistent ovulatory response has been ascribed to the variable, but high, LH content. This study investigated the effects of an LH-free FSH preparation, recombinant human follicle stimulating hormone (rhFSH), on follicle development, ovulation and embryo production in mares. Five mares were treated twice-daily with 450 i.u. rhFSH starting on day 6 after ovulation, coincident with PGF(2alpha) analogue administration; five control mares were treated similarly but with saline instead of rhFSH. The response was monitored by daily scanning of the mares' ovaries and assay of systemic oestradiol-17beta and progesterone concentrations. When the dominant follicle(s) exceeded 35 mm, ovulation was induced with human chorionic gonadotrophin; embryos were recovered on day 7 after ovulation. After an untreated oestrous cycle to 'wash-out' the rhFSH, the groups were crossed-over and treated twice-daily with 900 i.u. rhFSH, or saline. At the onset of treatment, the largest follicle was <25 mm in all mares, and mares destined for rhFSH treatment had at least as many 10-25 mm follicles as controls. However, neither dose of rhFSH altered the number of days before the dominant follicle(s) reached 35 mm, the number of follicles of any size class (10-25, 25-35, >3 mm) at ovulation induction, the pre- or post-ovulatory oestradiol-17beta or progesterone concentrations, the number of ovulations or the embryo yield. It is concluded that rhFSH, at the doses used, is insufficient to stimulate multiple follicle development in mares.


Regulation of purine biosynthesis in cultured Drosophila melanogaster cells: I.--Conditional activity of hypoxanthine-guanine-phosphoribosyltransferase and 5-nucleotidase.
In cultured cells established from Drosophila melanogaster embryos, and grown in usual medium, no hypoxanthine-guanine-phosphoribosyl transferase (HG-PRT) could be measured, and only traces of 5'-nucleotidase activity were detectable. On the contrary, it was observed that if the same medium is supplemented with purine bases, nucleosides, orotate, glutamine, azaserine or antifolates, de novo purine biosynthesis is inhibited, and HGPRT is detectable, along with an important 5'-nucleotidase activity. Moreover, dialysis or treatment of extracts from cells untreated by purines, with activated charcoal restored HGPRT and 5'-nucleotidase activities. These activities were abolished completely by inosinic acid (IMP) and guanosine 5'-monophosphoric acid (GMP). Similar results were obtained with fly extracts. These results suggest that de novo purine biosynthesis masks HGPRT activity, the endogenous synthesis leading to the accumulation of purine nucleotides which are inhibitors of the HGPRT activity.


Does ICU length of stay influence quality of life?
Patients with prolonged stay in the intensive care unit (ICU) use a disproportionate share of resources. However, it is not known if such treatment results in impaired quality of life (QOL) as compared to patients with a short length of stay (LOS) when taking into account the initial severity of illness. Prospective, observational case-control study in a university hospital surgical and trauma adult ICU. All patients admitted to the ICU during a 1-year period were included. Patients with a cumulative LOS in the ICU > 7 days, surviving up to 1 year after ICU admission and consenting were identified (group L, n = 75) and matched to individuals with a shorter stay (group S). Matching criteria were diagnostic group and severity of illness. Health-related quality of life (HRQOL) was assessed 1 year after admission using the short-form 36 (SF-36) and was compared between groups and to the general population. Further, overall QOL was estimated using a visual analogue scale (VAS) and willingness to consent to future intensive care, and was compared between groups L and S. Based on ANCOVA, a significant difference between groups L and S was noted for two out of eight scales: role physical (P = 0.033) and vitality (P = 0.041). No differences were found for the physical component summary (P = 0.065), the mental component summary (P = 0.267) or the VAS (P = 0.316). Further, there was no difference in expectation to consent to future intensive care (P = 0.149). As compared to the general population, we found similar scores for the mental component summary and for three of eight scales in group L and five of eight scales in group S. When taking into account severity of illness, HRQOL 1 year after intensive care is comparable between patients with a short and a long LOS in the ICU. Thus, prolonged stay in the ICU per se must not be taken as an indicator of future poorer HRQOL. However, as compared to the general population, significant differences, mostly in physical aspects of QOL, were found for both groups of patients.


New records of a rare gibberfish, Gibberichthyslatifrons (Stephanoberyciformes, Gibberichthyidae), from the South China Sea, with comments on morphological characters.
The gibberfish Gibberichthyslatifrons is recorded for the first time from southwestern Taiwan, northern South China Sea, based on the collection of seven adults and subadults from the Dong-gang fish market, Pingtung. These specimens represent the northernmost extent of the adult range of the species, and they fill a distributional gap in the western Pacific Ocean. Our findings suggest that a population of the species has become recently established in the region. Detailed descriptions, otolith morphology, and fresh coloration are provided with comments on the morphological characteristics of the genus.


Pharmacophoric features of drugs with guanylurea moiety: an electronic structure analysis.
Several therapeutically important compounds contain guanylurea (GU) moiety. The appropriate tautomeric state of these species has not been explored, preliminary studies indicated that the traditional representation of this class of compounds use a high energy tautomeric state. In this work, quantum chemical studies (HF, B3LYP, MP2, G2MP2 and CBS-Q methods) were performed on the medicinally important GU based drugs so as to identify their stable tautomeric state and to understand the pharmacophoric features of these drugs. Electronic structure studies suggested that GU-1 is the most stable and preferred isomer among the various ketone and enol isomers of the model GU. This study revealed that the general representation adopted in medicinal chemistry literature (GU-5) is about 10 kcal mol(-1) less stable than the energy minimum tautomeric state; and four other alternate structures are possible with energy less than that of the generally represented structure. Hence, it is advisable to consider the energy minimum tautomeric state (GU-1) in all future studies of GU derivatives. Further, the importance of the correct tautomeric representation was demonstrated using a comparative molecular docking analysis of WHR 1049 in α2A adrenergic receptor target.


Why dermatology is the second least diverse specialty in medicine: How did we get here?
Dermatology is currently the second least diverse medical specialty, after orthopedic surgery, with only a minority of physicians identifying as underrepresented in medicine (UIM). To diversify our specialty, our understanding and recognition of multifactorial barriers to inclusivity such as financial barriers, lack of mentorship, and the implicit bias against minorities UIM is critical. With collaborative efforts by national dermatology organizations, dermatology residency programs, and medical schools to increase the presence of UIM dermatology physicians in the US health care, this important issue continues to receive the attention it deserves.


The influence of summer closure on serious postoperative complications in bariatric surgery.
Bariatric surgery is an effective method of treating obesity, with gastric bypass and sleeve gastrectomy being the most common techniques used worldwide. Despite the technical challenges in these methods, little is known about the effects of summer closure on the incidence of serious postoperative complications in surgeries performed shortly after summer vacation. This has therefore been studied in our large cohort. A retrospective cohort study based on data from the Scandinavian Obesity Surgery Registry was conducted. Patients who underwent a primary gastric bypass or sleeve gastrectomy operation between 2010 and 2019 were included. The rate of serious complications within 30 days after surgery for patients who underwent surgery the first month after summer closure was compared to those who underwent surgery during the rest of the year using the χ2 test and adjusted logistic regression. The study included 42,404 patients, 36,094 of whom underwent gastric bypass and 6310 of whom received sleeve gastrectomy. Summer closure was associated with an increased risk for serious postoperative complications in gastric bypass surgery (adjusted odds ratio (adj-OR) = 1.17; 95% confidence interval (CI): 1.01-1.36). No statistically significant association was seen for sleeve gastrectomy (adj-OR = 1.17; 95% CI: 0.72-1.91), nor in overall complication rate. Summer closure increases the risk of serious postoperative complications in gastric bypass surgery. No statistically significant association was found for sleeve gastrectomy surgery.


Neuroprotective activity of tiagabine in a focal embolic model of cerebral ischemia.
Gamma aminobutyric acid (GABA) agonists have been shown to have neuroprotective effects when used after focal or global cerebral ischemia. In this study, we evaluated the neuroprotective effects of a GABA re-uptake inhibitory agent, tiagabine, on focal ischemic brain injury in an embolic model in rats. Tiagabine, injected at 1 h after embolization, significantly reduced brain infarction volume, measured with 2,3,5-triphenyltetrazolium chloride (TTC) histological assay. There were varying degrees of neuroprotective effect exhibited in the other experimental groups however this did not reach significance. These results suggest that tiagabine is neuroprotective when administrated at an early period after the ischemic brain injury.


Oxidation of galactomannan by laccase plus TEMPO yields an elastic gel.
Chemical modifications of galactomannans are applied to improve and/or modify their solubility, rheological and functional properties, but have limited specificity and are often difficult to control. Enzymatic reactions, catalyzed under mild process conditions, such as depolymerization, debranching and oxidation, represent a viable and eco-friendly alternative. In this study, we describe oxidation of guar galactomannan primary hydroxyl groups by a fungal laccase using the stable radical TEMPO as mediator. Four fungal laccases were investigated from: Trametes versicolor, Myceliophthora thermophila, Thielavia arenaria, Cerrena unicolor. The laccase from T. versicolor was found to efficiently oxidize TEMPO and to be free of mannanase side activity. Oxidation of galactomannan with this enzyme plus TEMPO brought about a ten-fold increase in viscosity of a guar galactomannan solution and altered its rheological profile, by converting a viscous polysaccharide solution into an elastic gel. This structural modification is presumably due to formation of inter-chain hemiacetalic bonds between newly generated carbonyl groups and free OH groups, yielding a cross-linked gel. These findings could be of practical importance, considering that polysaccharides with high viscosity, gelling and elastic properties can find interesting and novel applications as thickeners, viscosifiers and emulsion stabilizers in several industrial applications such as: personal care, oil operations, paper coating, paints, construction and mining.


A critical appraisal of two common "neonatal" experiment subjects.
A comparative study of 11 physiologic variables in 200 piglets and puppies during the first 7 days of life was done. Seven of 11 physiologic variables significantly changed in the 1st wk of the piglets' life. Five of 11 variables significantly changed in the first week of the puppies' life. Six of 11 variables were significantly different when the newborn piglet was compared to the newborn puppy. The rate and/or direction of 7 of 11 physiologic changes during the first day of life were significantly different when the piglet was compared to the puppy. It was concluded that there are marked physiologic differences between: the newborn piglets and the 7 day old piglet; the newborn puppy and the 7 day old puppy; the newborn piglet and the newborn puppy and the "maturation" rate of the piglet and the puppy.


Highly sensitive high-performance liquid chromatography-fluorimetric assay method for carboxypeptidase H activity.
A rapid and sensitive high-performance liquid chromatographic (HPLC)-fluorimetric assay method has been developed for the determination of carboxypeptidase H activity based on the measurement of N-(5-dimethyl-aminonaphthalene-1-sulfonyl)glycine (dansyl-Gly) formed enzymatically from dansyl-Gly-L-Lys or dansyl-Gly-L-Arg. Dansyl-Gly is eluted faster than the substrates with an N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (Hepes) buffer at pH 7.0 containing methanol, but eluted slower with an acidic buffer at pH 4.6. The new HPLC method separates the product and substrate in less than 5 min using an elution buffer at pH 7.0 containing 60% methanol. Using this method carboxypeptidase H activity has been detected in rat sciatic nerves. This HPLC method facilitates the assay of carboxypeptidase H activity in the enzyme samples from various tissues.


A new coumarin isolated from the roots of Heracleum dissectum Ledeb.
A new coumarin named (9 R, 10 R)-9, 10-dihydro-10-hydroxy-9-methoxy-bergapten (1) and 13 known compounds (2-14) were isolated from the roots of Heracleum dissectum Ledeb., in which compounds (2-13) were obtained from H. dissectum for the first time. Their structures were illuminated by HR-ESI MS, 1 D and 2 D NMR, optical rotation and comparison with literatures. All compounds were evaluated against hepatocellular carcinoma HepG2 cell lines and the results showed that candinol C (8) had moderate cytotoxic activity against HepG2 cells with IC50 value at 57.6 ± 1.1 µM.


Protein digestibility (in vitro) of chickpea and blackgram seeds as affected by domestic processing and cooking.
Protein digestibility (in vitro) of grains of chickpea (Cicer arietinum) and blackgram (Vigna mungo) cultivars varied from 48 to 53% and 52 to 58%, respectively. Soaking, cooking (both of unsoaked and soaked seeds), autoclaving and sprouting improved significantly the protein digestibility of all the cultivars of chickpea and blackgram. Autoclaving was found to be most effective followed by cooking and sprouting; cooking of sprouts had only marginal effect. Protein digestibility was higher when soaked instead of unsoaked grains were cooked.


Diagnosis and Management of Rhinosinusitis: Highlights from the 2015 Practice Parameter.
Rhinosinusitis is a commonly diagnosed disease in the USA. Rhinosinusitis is classified as acute, recurrent, or chronic (with or without nasal polyps). While acute rhinosinusitis is diagnosed by history and physical examination, chronic rhinosinusitis and recurrent acute rhinosinusitis are diagnosed based on symptoms and the presence of disease on either a sinus CT scan and/or endoscopy. Management of uncomplicated acute rhinosinusitis includes analgesics, saline irrigation, and/or intranasal steroids. Antibiotics and intranasal steroids are recommended for acute bacterial rhinosinusitis. Intranasal and oral steroids with antibiotics are recommended to treat chronic rhinosinusitis although the evidence for antibiotics is weak. Biologics such as omalizumab and mepolizumab are being investigated for the treatment of chronic rhinosinusitis with nasal polyps. Surgery may be indicated in management of refractory chronic rhinosinusitis and rarely for acute bacterial rhinosinusitis. This review discusses highlights of the updated 2014 practice parameter and up-to-date evidence from other literature sources.


31P NMR Bayesian spectral analysis of rat brain in vivo.
Bayesian spectrum analysis for parameter estimation is a rigorous statistical (non-Fourier-based) method. Herein the Bayesian quadrature NMR model is introduced and applied to analysis of 31P NMR time domain data from in vivo rat brain. Immunity to both the brain spectrum "baseline hump" and the phase twist is demonstrated.


Reassortment and genomic analysis of a G9P[8]-E2 rotavirus isolated in China.
To isolate a prevalent G9P[8] group A rotavirus (RVA) (N4006) in China and investigate its genomic and evolutionary characteristics, with the goal of facilitating the development of a new rotavirus vaccine. The RVA G9P[8] genotype from a diarrhea sample was passaged in MA104 cells. The virus was evaluated by TEM, polyacrylamide gel electrophoresis, and indirect immunofluorescence assay. The complete genome of virus was obtained by RT-PCR and sequencing. The genomic and evolutionary characteristics of the virus were evaluated by nucleic acid sequence analysis with MEGA ver. 5.0.5 and DNASTAR software. The neutralizing epitopes of VP7 and VP4 (VP5* and VP8*) were analyzed using BioEdit ver. 18.104.22.168 and PyMOL ver. 2.5.2. The RVA N4006 (G9P[8] genotype) was adapted in MA104 cells with a high titer (105.5 PFU/mL). Whole-genome sequence analysis showed N4006 to be a reassortant rotavirus of Wa-like G9P[8] RVA and the NSP4 gene of DS-1-like G2P[4] RVA, with the genotype constellation G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1 (G9P[8]-E2). Phylogenetic analysis indicated that N4006 had a common ancestor with Japanese G9P[8]-E2 rotavirus. Neutralizing epitope analysis showed that VP7, VP5*, and VP8* of N4006 had low homology with vaccine viruses of the same genotype and marked differences with vaccine viruses of other genotypes. The RVA G9P[8] genotype with the G9-P[8]-I1-R1-C1-M1-A1-N1-T1-E2-H1 (G9P[8]-E2) constellation predominates in China and may originate from reassortment between Japanese G9P[8] with Japanese DS-1-like G2P[4] rotaviruses. The antigenic variation of N4006 with the vaccine virus necessitates an evaluation of the effect of the rotavirus vaccine on G9P[8]-E2 genotype rotavirus.


Spot blot: a hybridization assay for specific DNA sequences in multiple samples.
Small aliquots of DNA-containing samples from gradient or column fractions are spotted onto agarose plates containing ethidium bromide, and the DNA is visualized qualitatively. After it is overlaid with a thin agarose cover, the DNA is denatured and transferred to nitrocellulose filters for hybridization. This method, called the "spot-blot assay," is particularly convenient when dealing with large numbers of samples.


Bovine holo-lactoferrin inhibits migration and invasion in MDA-MB-231 breast cancer cells.
Breast cancer is the most common malignancy in developed countries and the main cause of deaths in women worldwide. Lactoferrin (Lf) is an iron-binding protein constituted for a single polypeptide chain that is folded into two symmetrical lobes that bind Fe2+ or Fe3+. Lf has the ability to reversibly bind Fe3+ and is found free of Fe3+ (Apo-Lf) or associated with Fe3+ (Holo-Lf) with a different three-dimensional conformation. However, the role of bovine Apo-Lf (Apo-BLf) and bovine Holo-Lf (Holo-BLf) in the migration and invasion induced by linoleic acid (LA) and fetal bovine serum (FBS), as well as in the expression of mesenchymal and epithelial proteins in breast cancer cells has not been studied. Scratch wound assays demonstrated that Holo-BLf and Apo-BLf do not induce migration, however they differentially inhibit the migration induced by FBS and LA in breast cancer cells MDA-MB-231. Western blot, invasion, zymography and immunofluorescence confocal microscopy assays demonstrated that Holo-BLf partly inhibit the invasion, FAK phosphorylation at tyrosine (Tyr)-397 and MMP-9 secretion, whereas it increased the number and size of focal adhesions induced by FBS in MDA-MB-231 cells. Moreover, Holo-BLf induced a slight increase of E-cadherin expression in MCF-7 cells, and inhibited vimentin expression in MCF-7 and MDA-MB-231 breast cancer cells. Holo-BLf inhibits cellular processes that mediate the invasion process in breast cancer cells.


Sphingoid base in pineapple glucosylceramide suppresses experimental allergy by binding leukocyte mono-immunoglobulin-like receptor 3.
The increase in patients suffering from type I hypersensitivity, including hay fever and food allergy, is a serious public health issue around the world. Recent studies have focused on allergy prevention by food factors with fewer side effects. The purpose of this study was to evaluate the effect of dietary glucosylceramide from pineapples (P-GlcCer) on type I hypersensitivity and elucidate mechanisms. Oral administration of P-GlcCer inhibited ear edema in passive cutaneous anaphylaxis reaction. In a Caco-2/RBL-2H3 co-culture system, P-GlcCer inhibited β-hexosaminidase release from RBL-2H3 cells. The direct treatment of P-GlcCer on RBL-2H3 did not affect β-hexosaminidase release, but sphingoid base moiety of P-GlcCer did. These results predicted that sphingoid base, a metabolite of P-GlcCer, through the intestine inhibited type I hypersensitivity by inhibiting mast cell degranulation. In addition, the inhibitory effects of P-GlcCer on ear edema and degranulation of RBL-2H3 cells were canceled by pretreatment of leukocyte mono-immunoglobulin-like receptor 3 (LMIR3)-Fc, which can block LMIR3-mediated inhibitory signals. It was demonstrated that a sphingoid base, one of the metabolites of P-GlcCer, may inhibit mast cell degranulation by binding to LMIR3. The oral administration of P-GlcCer is a novel and attractive food factor that acts directly on mast cells to suppress allergy. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Towards An Advanced Graphene-Based Magnetic Resonance Imaging Contrast Agent: Sub-acute Toxicity and Efficacy Studies in Small Animals.
Current clinical Gd(3+)-based T1 magnetic resonance imaging (MRI) contrast agents (CAs) are suboptimal or unsuitable, especially at higher magnetic fields (>1.5 Tesla) for advanced MRI applications such as blood pool, cellular and molecular imaging. Herein, towards the goal of developing a safe and more efficacious high field T1 MRI CA for these applications, we report the sub-acute toxicity and contrast enhancing capabilities of a novel nanoparticle MRI CA comprising of manganese (Mn(2+)) intercalated graphene nanoparticles functionalized with dextran (hereafter, Mangradex) in rodents. Sub-acute toxicology performed on rats intravenously injected with Mangradex at 1, 50 or 100 mg/kg dosages 3 times per week for three weeks indicated that dosages ≤50 mg/kg could serve as potential diagnostic doses. Whole body 7 Tesla MRI performed on mice injected with Mangradex at a potential diagnostic dose (25 mg/kg or 455 nanomoles Mn(2+)/kg; ~2 orders of magnitude lower than the paramagnetic ion concentration in a typical clinical dose) showed persistent (up to at least 2 hours) contrast enhancement in the vascular branches (Mn(2+) concentration in blood at steady state = 300 ppb, per voxel = 45 femtomoles). The results lay the foundations for further development of Mangradex as a vascular and cellular/ molecular MRI probe.