A Strain Distribution Sensing System for Bone-Implant Interfaces Based on Digital Speckle Pattern Interferometry.
This paper aims to provide an effective measurement method for the distribution of deformations and strains focusing on the response to external loading of bone-implant interfaces. To achieve this target, a novel speckle interference imaging method is proposed by introducing phosphate buffer saline medium, in which the samples were completely placed into a phosphate buffer saline solution medium to stable the water molecules. The stability of interferometry imaging is analyzed by using the concepts of co-occurrence matrix and moment of inertia. A series of experiments to measure load-driven deformation and strain in the bone-implant interface was carried out, and the experiments results were analyzed and discussed. It shows that the proposed method is feasible and effective for the no-contact strain measurements of biomaterials in a physiological condition. The proposed strain distribution sensing system will contribute to evaluating computational simulations and improving selection of implant designs and materials.


History, clinical findings and outcome of horses with radiographical signs of equine odontoclastic tooth resorption and hypercementosis.
The progression of equine odontoclastic tooth resorption and hypercementosis (EOTRH) has not been completely evaluated, and currently, the only effective treatment is extraction of severely affected teeth. We aim to describe how the disease relates to the history and clinical findings and to report on the outcome in individual horses. This case series comprises data collected from 20 horses (age 14-29 years old) with radiographic findings of EOTRH in their incisor and/or canine teeth. Most horses affected with EOTRH in this study were admitted for dental problems, but some for other complaints such as colic. Of the 288 teeth evaluated radiographically, 224 teeth were abnormal. Radiographic findings were most frequently located in the apical aspect and reserve crown of the teeth, and lesions were also commonly found in clinically normal teeth. Histopathology of extracted teeth showed inflammation in the periodontal ligament and revealed that resorption often extended to the dentine. Some owners were unwilling to allow extraction of their horses' severely affected teeth, even though this treatment has been shown to increase the wellbeing of the horse. As EORTH is a life-long condition, the progression of the disease has to be continuously monitored and the treatments adjusted accordingly.


Bacterial bloodstream infections in the allogeneic hematopoietic cell transplant patient: new considerations for a persistent nemesis.
Bacterial bloodstream infections (BSI) cause significant transplant-related morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). This manuscript reviews the risk factors for and the bacterial pathogens causing BSIs in allo-HCT recipients in the contemporary transplant period. In addition, it offers insight into emerging resistant pathogens and reviews clinical management considerations to treat and strategies to prevent BSIs in allo-HCT patients.


Microtubule nucleation by γ-tubulin complexes and beyond.
In this short review, we give an overview of microtubule nucleation within cells. It is nearly 30 years since the discovery of γ-tubulin, a member of the tubulin superfamily essential for proper microtubule nucleation in all eukaryotes. γ-tubulin associates with other proteins to form multiprotein γ-tubulin ring complexes (γ-TuRCs) that template and catalyse the otherwise kinetically unfavourable assembly of microtubule filaments. These filaments can be dynamic or stable and they perform diverse functions, such as chromosome separation during mitosis and intracellular transport in neurons. The field has come a long way in understanding γ-TuRC biology but several important and unanswered questions remain, and we are still far from understanding the regulation of microtubule nucleation in a multicellular context. Here, we review the current literature on γ-TuRC assembly, recruitment, and activation and discuss the potential importance of γ-TuRC heterogeneity, the role of non-γ-TuRC proteins in microtubule nucleation, and whether γ-TuRCs could serve as good drug targets for cancer therapy.


New function of the CD44 gene: Lipid metabolism regulation in bovine mammary epithelial cells.
The CD44 gene encodes a cell-surface glycoprotein that participates in a variety of biological processes such as cell interactions, adhesion, hematopoiesis, and tumor metastasis. We compared the transcriptome in bovine mammary epithelial cells (bMEC) of Chinese Holstein dairy cows producing milk of high and low fat contents. Our results suggest that CD44 might be a candidate gene affecting milk fat synthesis. In the present study, the overexpression of the CD44 gene increased the contents of intracellular triglycerides (TG) and cholesterol (CHOL), whereas knockdown of the CD44 gene decreased bMEC CHOL and TG contents. Gas chromatography analysis of fatty acid composition showed that the contents of α-linolenic acid, palmitic acid, and cis-8,11,14-eicosatrienoic acid were altered due to changes in the level of expression of the CD44 gene. Additionally, elaidic acid, palmitoleic acid, tridecanoic acid, and oleic acid were markedly reduced in the CD44 gene overexpression group compared with the control group. On the contrary, cis-5,8,11,14-eicosatetraenoic acid and stearic acid were markedly increased in the CD44 knockdown group compared with the control group. And RT2 Profiler PCR array (Qiagen, CLAB24070A Frankfurt, Germany) further suggested that overexpression or knockdown of the CD44 gene altered expression levels of functional genes associated with lipid metabolism. The present data indicate that CD44 plays a key regulatory role in lipid metabolism in bMEC.


Highly Siderophile Elements and Coupled Fe-Os Isotope Signatures in the Temagami Iron Formation, Canada: Possible Signatures of Neoarchean Seawater Chemistry and Earth's Oxygenation History.
Banded iron formations (BIFs) were deposited before and concurrent with the Great Oxidation Event at ∼2.33 Ga. They provide useful archives that document the transformation of the Precambrian hydrosphere from anoxic to progressively oxygenated conditions. Their formation involves removal of oceanic Fe by either inorganic or biologically promoted Fe2+ oxidation, or both. To evaluate depositional settings, elemental sources that affect seawater chemistry, and oxidation pathways, we present the first combined highly siderophile element (HSE) and Fe-Os isotope study for the ∼2.7 Ga Temagami BIF, Abitibi Greenstone Belt, Ontario (Canada). HSE abundances and 187Os/188Os ratios show no systematic variation between alternating magnetite and (meta)chert bands of the Temagami BIF. Whereas HSE concentrations mostly resemble modern crustal values, present-day 187Os/188Os ratios range from ∼0.17 to ∼10.8. Magnetite samples define a regression line corresponding to an age of 2661 ± 126 Ma. A chondrite-like 187Os/188Os initial value is in agreement with earlier studies on Neoarchean marine sediments and is thought to reflect seawater composition, which, unlike modern oceans, is dominated by mantle-like 187Os inventory most likely derived from deep-sea hydrothermal vents. Our δ56Fe data vary from about +0.6‰ to +0.9‰ and define a sawtooth-like pattern between alternating magnetite and (meta)chert layers. Partial oxidation of hydrothermally sourced Fe(II) and a lack of microbially mediated dissimilatory iron reduction provide the most plausible explanation for the positive δ56Fe values. Notably, our δ56Fe data for Temagami are in accord with trends defined by literature results for other Algoma-type BIFs that were deposited throughout the Archean.


Sox11 modulates neocortical development by regulating the proliferation and neuronal differentiation of cortical intermediate precursors.
Neural precursor cells play important roles in the neocortical development, but the mechanisms of neural progenitor proliferation, neuronal differentiation, and migration, as well as patterning are still unclear. Sox11, one of SoxC family members, has been reported to be essential for embryonic and adult neurogenesis. But there is no report about the roles of Sox11 in corticogenesis. In order to investigate Sox11 function during cortical development, loss of function experiment was performed in this study. Knockdown of Sox11 by Sox11 siRNA constructs resulted in a diminished neuronal differentiation, but enhanced proliferation of intermediate progenitors. Accompanied with the high expression of Sox11 in the postmitotic neurons, but low expression of Sox11 in the dividing neural progenitors, all the observations indicate that Sox11 induces neuronal differentiation during the neocortical development.


Effect of Exercise and Oral Niacinamide Mononucleotide on Improving Mitochondrial Autophagy in Alzheimer's Disease.
Oral niacinamide mononucleotide (NMN) and aerobic exercise have been shown to enhance niacinamide adenine dinucleotide (NAD+) in the body. NAD+ plays a critical role in the body and can directly and indirectly affect many key cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cell aging, and immune cell function. It is noteworthy that the level of NAD+ decreases gradually with increasing age. Decreased levels of NAD+ have been causally associated with a number of diseases associated with aging, including cognitive decline, cancer, metabolic diseases, sarcopenia, and frailty. Many diseases related to aging can be slowed down or even reversed by restoring NAD+ levels. For example, oral NMN or exercise to increase NAD+ levels in APP/PS1 mice have been proven to improve mitochondrial autophagy, but currently, there is no regimen combining oral NMN with exercise. This review summarizes recent studies on the effect of oral NMN on the enhancement of NAD+ in vivo and the improvements in mitochondrial autophagy abnormalities in AD through aerobic exercise, focusing on (1) how oral NMN improves the internal NAD+ level; (2) how exercise regulates the content of NAD+ in the body; (3) the relationship between exercise activation of NAD+ and AMPK; (4) how SIRT1 is regulated by NAD+ and AMPK and activates PGC-1α to mediate mitochondrial autophagy through changes in mitochondrial dynamics. By summarizing the results of the above four aspects, and combined with the synthesis of NAD+ in vivo, we can infer how exercise elevates the level of NAD+ in vivo to mediate mitochondrial autophagy, so as to propose a new hypothesis that exercise interferes with Alzheimer's disease (AD).


Vitamin E in the prevention of vancomycin-induced nephrotoxicity.
The use of vancomycin, as a key therapeutic choice for treatment of hazardous infections, may be associated with nephrotoxicity. The proposed mechanism is the indirect production of reactive oxygen species and oxidative stress. The purpose of this study was to investigate the effect of vitamin E as an antioxidant agent in the prevention of vancomycin-induced nephrotoxicity. In a matched-groups interventional study, patients who received vancomycin for any indication were assigned to vitamin E (n = 30) and control (n = 60) groups. The patients in experimental group received 400 units of oral vitamin E per day for 10 days started concurrently with vancomycin, while the patients in control group received vancomycin alone. Serum level of creatinine, blood urea nitrogen (BUN), creatinine clearance (CrCl), and 24-h urine output were determined and recorded before the start of interventions, every other day during therapy, and 12 h after the last dose of vancomycin in 10th day of therapy for all patients. Also, the rate of acute kidney injury (AKI) in the two groups was recorded. Finally, the mean values of the measured parameters were compared between the groups. Treatment with vitamin E for 10 days resulted in a significant reduction of BUN (from 17.5 ± 7.8 mg/dL at baseline to 11.4 ± 4.8 mg/dL at the end; P < 0.001) along with slightly non-significant increase of CrCl (from 84.7 ± 18.9 mL/min at baseline to 91.3 ± 19.5 mL/min at the end; P = 0.301) in comparison to the control group. However, CrCl decreased significantly in the control group. Vitamin E had no significant effect on 24-h urine output. Regarding vancomycin-induced AKI, 12 cases were observed in the control group, while no case was reported in experimental group (P = 0.041). This study showed the beneficial effect of add-on therapy of vitamin E besides vancomycin in reducing AKI, which could be considered as a new potential prophylactic therapy for vancomycin-induced nephrotoxicity.


Prokineticin receptor 2 (Prokr2) is essential for the regulation of circadian behavior by the suprachiasmatic nuclei.
The suprachiasmatic nucleus (SCN), the brain's principal circadian pacemaker, coordinates adaptive daily cycles of behavior and physiology, including the rhythm of sleep and wakefulness. The cellular mechanism sustaining SCN circadian timing is well characterized, but the neurochemical pathways by which SCN neurons coordinate circadian behaviors remain unknown. SCN transplant studies suggest a role for (unidentified) secreted factors, and one potential candidate is the SCN neuropeptide prokineticin 2 (Prok2). Prok2 and its cognate prokineticin receptor 2 (Prokr2/Gpcr73l1) are widely expressed in both the SCN and its neural targets, and Prok2 is light-regulated. Hence, they may contribute to cellular timing within the SCN, entrainment of the clock, and/or they may mediate circadian output. We show that a targeted null mutation of Prokr2 disrupts circadian coordination of the activity cycle and thermoregulation. Specifically, mice lacking Prokr2 lost precision in timing the onset of nocturnal locomotor activity; and under both a light/dark cycle and continuous darkness, there was a pronounced temporal redistribution of activity away from early to late circadian night. Moreover, the coherence of circadian behavior was significantly reduced, and nocturnal body temperature was depressed. Entrainment by light is not, however, dependent on Prokr2, and bioluminescence real-time imaging of organotypical SCN slices showed that the mutant SCN is fully competent as a circadian oscillator. We conclude that Prokr2 is not necessary for SCN cellular timekeeping or entrainment, but it is an essential link for coordination of circadian behavior and physiology by the SCN, especially in defining the onset and maintenance of circadian night.


Pharmacogenetics-based new therapeutic concepts.
Pharmacogenetics, one of the fields of clinical pharmacology, studies how genetic factors influence drug response. If hereditary traits are taken into account appropriately before starting drug treatment, the type of drug and its dosage can be tailored to the individual patient's needs. Pharmacogenetics adds a considerable amount of stringency to the doctor's therapeutic approach. Today, it is the relationship between dosage requirements and genetic variations in drug metabolizing enzymes like cytochrome P450 (CYP) 2D6 and CYP2C19, or in drug transporters like p-glycoprotein, that is substantiated best. A standard dose will bring about more adverse effects than usual if enzymatic activity is lacking or feeble. Sometimes, however, therapeutic response might be better due to higher concentrations: proton pump inhibitors for eradication of Helicobacter pylori are more efficacious in carriers of a deficient CYP2C19 variant. The drug's interaction with its target (e.g. receptor) also depends on genetic factors. In some cases genetic tests can help distinguish between responders and non-responders of a specific drug treatment. The first pharmacogenetic tests are already on the market.


Resveratrol inhibits hypoxia-inducible factor-1α-mediated androgen receptor signaling and represses tumor progression in castration-resistant prostate cancer.
Androgen-dependent prostate cancer inevitably progresses to incurable castration-resistant prostate cancer (CRPC) after androgen deprivation therapy. Because castration-induced hypoxia-inducible factor (HIF)-1α enhances the transcriptional activity of androgen receptor (AR) at low androgen levels mimicking the castration-resistant stage, HIF-1α is expected to be a promising target for suppression of growth of CRPC. We investigated the effect of resveratrol (3,4',5-trihydroxy-trans-stilbene) on the growth of human prostate cancer LNCaP xenografts in castrated male BALB/cSlc-nu/nu mice (5 wk old). The mice were administered a control diet or a resveratrol diet (4 g/kg diet) for 40 d. The resveratrol diet significantly suppressed tumor growth compared to the control diet. In LNCaP xenografts, dietary resveratrol decreased the protein level of HIF-1α, but not the AR coactivator β-catenin, and reduced the mRNA levels of androgen-responsive genes. In the control group, β-catenin was predominantly localized in the nucleus with HIF-1α in LNCaP xenografts, whereas dietary resveratrol inhibited the nuclear accumulation of β-catenin. In hypoxic LNCaP cells at a low androgen level mimicking the castration-resistant stage, hypoxia-induced nuclear accumulation of β-catenin was inhibited by resveratrol. Furthermore, resveratrol repressed the expression level of HIF-1α even in the presence of a proteasome inhibitor and suppressed hypoxia-enhanced AR transactivation. These results indicate that dietary resveratrol represses nuclear localization of β-catenin by decreasing the HIF-1α expression, perhaps in a proteasome-independent manner, and inhibits β-catenin-mediated AR signaling; this contributes to suppression of tumor growth of CRPC.


Day to day issues in the forensic identification practice related to illegal immigration in Italy.
The migratory flows to Europe from the African countries, Asia and Middle East, have hugely intensified in the recent years. In 2016, more than 98,000 out of a total of 260,000 migrants across the Mediterranean Sea arrived in Italy and in May 2017, the trend of arrivals is: Italy +576%; Greece -39% compared to previous years. Some migrants die before touching the sole of the European continent, during the crossing, often afforded with ships, made available by unscrupulous smugglers or criminal organizations, which are unsuitable for this type of transportation. The tremendous occurrence of migrant casualties during the Mediterranean Sea crossing remains underestimated and nobody, country officers or databank, can provide a reliable number of dead bodies in such a large and now, endemic phenomenon. Forensic officers, who intervened to examine migrants' corpses, are ideally required to perform the usual activity and to answer the routine questions about the causes of death by detecting signs of possible crimes and body identification. In practice, several specific issues and limits challenge the activity of the forensic professionals addressed to ascertain both circumstances of death and possible related crimes and the identity of the corpses. Generally speaking, in case of examining up to a few dead bodies in Italy, a complete autopsy is performed, whilst, when several tens or hundreds of corpses are recovered, the lack of resources on one hand and clearer clues on incident, connected crimes, and cause of deaths on the other, push the public prosecutor to limit the request of complete autopsies. In some cases, the dead migrants were identified through visual recognition by relatives, friends, or travel companions. The DVI Interpol protocol is never completely applied to dead migrants for several reasons, mainly for the huge difficulties in retrieving AM data of the missing persons and for some limitations affecting both the primary and the secondary identifiers. The few chances of identification by dental data are further reduced by the systematic lack of an odontologist among the forensic teams charged of the PM; valuable dental data for body identification or for constructing the biological profile of the missing person (age, ancestry, country of provenance/residence, etc.) are likely to be overlooked. This approach implies a clear disparity with the approach applied when corpses of citizens of the EU or other developed countries are involved and undergo identification. The dead migrants' identification activity should be reconsidered for an improvement in the common international effort in accordance to an approach more respectful toward the legal rights and dignity of the dead migrants and their families.


Steroid hormone influence on melanomagenesis.
Disparities in the prognosis and incidence of melanoma between male and female patients have led clinicians to explore the influence of steroid hormones on the development and progression of this malignancy. A better understanding of the disparities of melanoma behavior between sexes and ages could lead to improved prevention and treatment options. There are multiple themes in the literature that unify the physiologic functions of estrogen and androgen receptors; herein we discuss and map their pathways. Overall, it is important to understand that the differences in melanoma behavior between the sexes are multifactorial and likely involve interactions between the immune system, endocrine system, and environment, namely UV-radiation. Melanoma deserves a spot among hormone-sensitive tumors, and if tamoxifen is re-introduced for future therapy, tissue ratios of estrogen receptors should be obtained beforehand to assess their therapeutic predictive value. Because androgens, estrogens, and their receptors are involved in signaling of commonly mutated melanoma pathways, potential synergistic properties of the recently developed molecular kinase inhibitors that target those pathways may exist.


Arsenic bioaccessibility upon gastrointestinal digestion is highly determined by its speciation and lipid-bile salt interactions.
The release of arsenic (As) from a contaminated food matrix during gastrointestinal digestion, i.e., its bioaccessibility, is an important estimator of its bioavailability, and therefore also its health risk. In addition, As toxicity is primarily determined by its speciation and it is not clear how different As species behave during digestion in the upper digestive tract. Here, we evaluated to what extent digestive parameters like gastric pH and bile concentration, but also food matrix constituents affect the bioaccessibility of 8 As species (As(III), As(V), MMA(V), DMA(V), MMA(III), DMA(III), MMMTA(V), DMMTA(V)). Bioaccessibility of all As standards ranged between 85% and 90% under pH 1.8. Bioaccessibility of methylated and thiolated arsenicals was decreased from 85% to 50% with increasing gastric pH to 4, yet an increasing bile salts concentration up to 30 g/L lowered the bioaccessibility of inorganic species from 83% to 70% due to interaction with Fe present in bile salts. With respect to food matrices, we noted that the fiber content did not affect As bioaccessibility, yet the presence of fat resulted in an increased bioaccessibility of both inorganic and organic arsenicals in the presence of bile salts. With respect to inorganic arsenic, the intestinal presence of trivalent Fe appeared to be the predominant factor for bioaccessibility of iAs. These data demonstrate that species dependent bioaccessibility must be considered upon ingestion and gastrointestinal digestion.


Are energy and protein requirements met in hospital?
Malnutrition is a problem within hospitals, which impacts upon clinical outcomes. The present audit assesses whether a hospital menu meets the energy and protein standards recommended by the British Dietetic Association's (BDA) Nutrition and Hydration Digest and determines the contribution of oral nutrition supplements (ONS) and additional snacks. Patients in a UK South West hospital were categorised as 'nutritionally well' or 'nutritionally vulnerable' in accordance with their Malnutrition Universal Screening Tool score. Energy and protein content of food selected from the menu ('menu choice'), menu food consumed ('hospital intake') and total food consumed including snacks ('overall intake') were calculated and compared with the standards. In total, 93 patients were included. For 'nutritionally well' patients (n = 81), energy and protein standards were met by 11.1% and 33.3% ('menu choice'); 7.4% and 22.2% ('hospital intake'); and 14.8% and 28.4% ('overall intake'). For 'nutritionally vulnerable' patients (n = 12), energy and protein standards were met by 0% and 8.3% ('menu choice'); 0% and 8.3% ('hospital intake'); and 8.3% and 16.7% ('overall intake'). Ten percent of patients consumed ONS. Patients who consumed hospital snacks (34%) were more likely to meet the nutrient standards (P ≤ 0.001). The present audit demonstrated that most patients are not meeting the nutrient standards recommended by the BDA Nutrition and Hydration Digest. Recommendations include the provision of energy/protein-dense snacks, as well as menu, offering ONS where clinically indicated, in addition to training for staff. A food services dietitian is ideally placed to lead this, forming a vital link between patients, caterers and clinical teams.


Antiproliferative activity of daidzein and genistein may be related to ERα/c-erbB-2 expression in human breast cancer cells.
In this study, we investigated the antiproliferative activity of the isoflavones daidzein and genistein in three breast cancer cell lines with different patterns of estrogen receptor (ER) and c‑erbB‑2 protein expression (ERα‑positive MCF‑7 cells, c‑erbB‑2‑positive SK‑BR‑3 cells and ERα/c‑erbB‑2‑positive ZR‑75‑1). After treatment at various concentrations (1‑200 µM for 72 h), the effect of daidzein and genistein on the proliferation of different cell types varied; these effects were found to be associated with ERα and c‑erbB‑2 expression. Daidzein and genistein exhibited biphasic effects (stimulatory or inhibitory) on proliferation and ERα expression in MCF‑7 cells. Although 1 µM daidzein significantly stimulated cell growth, ERα expression was unaffected. However, genistein showed marked increases in proliferation and ERα expression after exposure to <10 µM genistein. Notably, the inhibition of cell proliferation by 200 µM genistein was greater compared to that by daidzein at the same concentration. Daidzein and genistein significantly inhibited proliferation of SK‑BR‑3 and ZR‑75‑1 cells in a dose‑dependent manner. In addition, ERα and c‑erbB‑2 expression was reduced by daidzein and genistein in both SK‑BR‑3 and ZR‑75‑1 cells in a dose‑dependent manner. However, the effect of genistein was greater compared to that of daidzein. In conclusion, the isoflavones daidzein and genistein showed anti‑breast cancer activity, which was associated with expression of the ERα and c‑erbB‑2 receptors.


Encoding calamitic mesomorphism in thermotropic lanthanidomesogens.
Peripheral cyanobiphenyl dendrimers impose a microphase organization compatible with smectic mesomorphism, in which the bulky nine-coordinate lanthanide core is located between the decoupled mesogenic sublayers made up of parallel cyanobiphenyl groups.


Coupling between taxonomic and functional diversity in protistan coastal communities.
The study of protistan functional diversity is crucial to understand the dynamics of oceanic ecological processes. We combined the metabarcoding data of various coastal ecosystems and a newly developed trait-based approach to study the link between taxonomic and functional diversity across marine protistan communities of different size-classes. Environmental DNA was extracted and the V4 18S rDNA genomic region was amplified and sequenced. In parallel, we tried to annotate the operational taxonomic units (OTUs) from our metabarcoding dataset to 30 biological traits using published and accessible information on protists. We then developed a method to study trait correlations across protists (i.e. trade-offs) in order to build the best functional groups. Based on the annotated OTUs and our functional groups, we demonstrated that the functional diversity of marine protist communities varied in parallel with their taxonomic diversity. The coupling between functional and taxonomic diversity was conserved across different protist size classes. However, the smallest size-fraction was characterized by wider taxonomic and functional groups diversity, corroborating the idea that nanoplankton and picoplankton are part of a more stable ecological background on which larger protists and metazoans might develop.


Interest in using rectal microbicides among Australian gay men is associated with perceived HIV vulnerability and engaging in condomless sex with casual partners: results from a national survey.
We assessed interest in using rectal microbicides to prevent HIV transmission among gay men in Australia. A national online survey was conducted in 2013. Interest in using rectal microbicides was measured on a seven-item scale (α=0.81). Factors independently associated with greater interest in using a microbicide were identified using multivariate logistic regression. Data were collected from 1223 HIV-negative and untested men. Mean age was 31.3 years (SD=10.8, range 18-65); 77% were born in Australia and 25% reported any condomless anal sex with a casual partner in the previous 6 months. Overall, there was moderate interest in using rectal microbicides (M=3.33, range 1-5). In multivariate analysis, greater interest in using microbicides was independently associated with being born outside Australia (adjusted OR (AOR)=1.59; p=0.009), greater self-perceived likelihood of becoming HIV positive (AOR=3.40; p<0.001), less uncertainty about the efficacy of microbicides (AOR=0.65; p=0.009), any condomless anal sex with casual partners in the previous 6 months (AOR=1.78; p=0.03) and ever having received postexposure prophylaxis (AOR=1.53; p=0.04). Interest in using microbicides was not associated with age, number of male sex partners or the HIV status of regular male partners. Interest in using rectal microbicides was associated with self-perceived vulnerability to HIV, engaging in sexual practices that increase the risk of HIV acquisition and less uncertainty about the efficacy of microbicides. There appears to be a group of men who would benefit from, and are highly motivated to use, a rectal microbicide product.


Generalization of seizures parallels the formation of "dark" neurons in the hippocampus and pontine reticular formation after focal-cortical application of 4-aminopyridine (4-AP) in the rat.
Distribution and time course of the occurrence of "dark" neurons were compared with the EEG activity and behavior of rats during 4-aminopyridine (4-AP) induced epileptic seizures. A crystal of the K(+) channel blocker 4-AP (0.5 mg/kg) was placed onto the exposed parieto-occipital cortex of Halothane-anesthetized rats for 40 min. Thereafter, the anesthesia was discontinued and the behavioral signs of the epileptic seizure activity were observed. The presence of "dark" neurons was demonstrated by the sensitive silver method of Gallyas in rats sacrificed at 0, 3 and 6 h after the end of the 4-AP crystal application. The EEG activity was recorded in the rats with longer survival times. The EEG analysis revealed the generalization of the epileptic seizures. We found that the formation of "dark" neurons in the hippocampus and the pontine reticular formation paralleled the generalization of the seizures.


Aspects of fish conservation in the upper Patos Lagoon basin.
The Patos Lagoon basin is a large (201 626 km(2) ) and complex drainage system in southern Brazil. The lagoon is 250 km long and 60 km wide, covering an area of 10 360 km(2) . The exchange of water with the Atlantic Ocean occurs through a 0·8 km wide and 15 m deep inlet, fixed by 4 km long jetties, at the southernmost part of the Patos Lagoon. The estuarine area is restricted to its southern portion (10%), although the upper limit of saline waters migrates seasonally and year to year, influenced by the wind regime and river discharge. The known number of recorded limnetic fish species is 200, but this number is expected to increase. A higher endemism is observed in fish species occurring in upper tributaries. The basin suffers from the direct impact of almost 7 million inhabitants, concentrated in small to large cities, most with untreated domestic effluents. There are at least 16 non-native species recorded in natural habitats of the Patos Lagoon basin, about half of these being from other South American river basins. Concerning the fishery, although sport and commercial fisheries are widespread throughout the Patos Lagoon basin, the lagoon itself and the estuarine area are the main fishing areas. Landing statistics are not available on a regular basis or for the whole basin. The fishery in the northern Patos Lagoon captures 31 different species, nine of which are responsible for most of the commercial catches, but only three species are actually sustaining the artisanal fishery: the viola Loricariichthys anus: 455 kg per 10 000 m(2) gillnet per day, the mullet Mugil liza: 123 kg per 10 000 m(2) gillnet per day and the marine catfish Genidens barbus: 50 kg per 10 000 m(2) gillnet per day. A decline of the fish stocks can be attributed to inadequate fishery surveillance, which leads to overfishing and mortality of juveniles, or to decreasing water quality because of urban and industrial activities and power production. Global climatic changes also represent a major threat to the Patos system by changing the frequency of El Niño-La Niña-Southern Oscillation (ENSO).


The ionic permeability changes during acetylcholine-induced responses of Aplysia ganglion cells.
ACh-induced depolarization (D response) in D cells markedly decreases as the external Na(+) is reduced. However, when Na(+) is completely replaced with Mg(++), the D response remains unchanged. When Na(+) is replaced with Tris(hydroxymethyl)aminomethane, the D response completely disappears, except for a slight decrease in membrane resistance. ACh-induced hyperpolarization (H response) in H cells is markedly depressed as the external Cl(-) is reduced. Frequently, the reversal of the H response; i.e., depolarization, is observed during perfusion with Cl(-)-free media. In cells which show both D and H responses superimposed, it was possible to separate these responses from each other by perfusing the cells with either Na(+)-free or Cl(-)-free Ringer's solution. High [K(+)](0) often caused a marked hyperpolarization in either D or H cells. This is due to the primary effect of high [K(+)](0) on the presynaptic inhibitory fibers. The removal of this inhibitory afferent interference by applying Nembutal readily disclosed the predicted K(+) depolarization. In perfusates containing normal [Na(+)](0), the effects of Ca(++) and Mg(++) on the activities of postsynaptic membrane were minimal, supporting the current theory that the effects of these ions on the synaptic transmission are mainly presynaptic. The possible mechanism of the hyperpolarization produced by simultaneous perfusion with both high [K(+)](0) and ACh in certain H cells is explained quantitatively under the assumption that ACh induces exclusively an increase in Cl(-) permeability of the H membrane.


Effects of autophagy on the spermatogonia of chronic hypoxic mice.
Varicocele (VC) is a common cause of male infertility. An increasing number of studies have confirmed that chronic hypoxia plays an important role in male infertility caused by VC. Our previous study suggested that autophagy may have a crucial function in VC. Whether autophagy plays an important role in hypoxic spermatogonia remains unknown. We established a new method to study VC by culturing spermatogonia under hypoxic conditions to simulate the chronic hypoxic environment of VC. Moreover, the effects of autophagy on hypoxic spermatogonia were observed by regulating autophagy. Spermatogonia from GC-1 spg mice were cultured in vitro in chronic hypoxic conditions (2% O2, 93% N2, 5% CO2) with a tri-gas incubator. Cells were separately cultured under normal oxygen and hypoxic conditions, and then, the autophagy blocker drug LY294002 was subsequently administered. Cytoactivity and proliferation were tested by CCK8 assays. Cells cultured in hypoxic conditions were divided into the hypoxia for 24 h, 48 h, and 72 h groups and the LY294002+hypoxia for 24 h, 48 h, and 72 h groups. Hoechst staining and flow cytometry/Annexin-V-FITC/PI staining were used to detect cell apoptosis, while transmission electron microscopy was used to observe the structure of the spermatogonia. Western blot analysis was used to observe the expression of Hif-1α, Beclin-1, LC3, SOD2, GPX4, and Cyt C. As the hypoxia time increased, CCK8 detection showed that the cytoactivity of the spermatogonia was suppressed. After administration of the inhibitor LY294002, the inhibition ratio of the spermatogonia increased. As the hypoxia time was prolonged, the apoptosis index of spermatogonia increased. After administration of LY294002, the apoptosis index increased significantly. Transmission electron microscopy showed that there were abundant structurally abnormal mitochondria and autophagosomes and autolysosomes in hypoxic spermatogonia. In addition, LY294002 reduced the expression of autophagosomes and autophagosomes, but the number of abnormal mitochondria and vacuoles in hypoxic cells increased significantly. As the hypoxia time was prolonged, the expression levels of Hif-1α, Beclin-1, LC3 II/LC3-I, and Cyt C increased gradually, but there were no significant changes in SOD2 and GPX4. After administration of LY294002, the expression levels of Beclin-1, LC3 II/LC3-I, and GPX4 significantly decreased, but Cyt C significantly increased. Thus, chronic hypoxia decreases cytoactivity and proliferation of spermatogonia. Moreover, hypoxia damages the mitochondria and other organelles. At the same time, hypoxia activates the autophagic system to clear these damaged organelles. The inhibition of autophagy in spermatogonia under chronic hypoxic conditions prevents the removal of damaged mitochondria and eventually results in a significant decrease in the antioxidant system molecule GPX4, rather than SOD2, and a significant increase in the apoptosis rate.


"Alkaline-earth metals in a box": structures of solvent-separated ion pairs.
During our research on homoleptic organocalcium compounds, we found that fluorenylcalcium complexes show unusual solution behavior and precipitate from nonpolar solvents after addition of THF. Their solid-state structures reveal the unexpected rupture of both metal-carbanion bonds by the polar solvent THF. The crystal structures of five new Mg and Ca solvent-separated ion pairs are described. The compound [Ca(2+)(thf)(6)][Me(3)Si(fluorenyl(-))](2) is the first organometallic complex of a Group 2 element that crystallizes as a completely solvent-separated ion pair. The driving forces for its formation are: 1) the strong Ca-THF bond; 2) the stability of the free [Me(3)Si(fluorenyl)](-) ion; 3) encapsulation of [Ca(2+)(thf)(6)] in a "box", the walls of which consist of anionic fluorenyl ligands and benzene molecules; and 4) the presence of numerous (THF)C- H...pi interactions. The magnesium analogue [Mg(2+)(thf)(6)][Me(3)Si(fluorenyl(-))](2) is isostructural. Bis(7,9-diphenylcyclopenta[a]acenaphthadienyl)calcium also crystallizes as a completely solvent-separated ion pair and can likewise be described as a [Ca(2+)(thf)(6)] species in a box of delocalized anions and benzene molecules. In addition, the structures of two Ph(4)B(-) complexes of Mg and Ca are described. [Mg(2+)(thf)(6)][Ph(4)B(-)](2) crystallizes as a completely solvent-separated ion pair and also shows a solvated metal cation bonded via C-H.pi interactions in a cavity formed by Ph(4)B(-) ions. [(thf)(4)CaBr(+)][Ph(4)B(-)] has a structure in which one of the anionic ligands is still bonded to the Ca atom. Bridging bromide ligands result in the formation of the dimer [(thf)(4)CaBr(+)](2).


Comparison of stool versus rectal swab samples and storage conditions on bacterial community profiles.
Sample collection for gut microbiota analysis from in-patients can be challenging. Collection method and storage conditions are potential sources of variability. In this study, we compared the bacterial microbiota from stool stored under different conditions, as well as stool and swab samples, to assess differences due to sample storage conditions and collection method. Using bacterial 16S rRNA gene sequence analysis, we compared the microbiota profiles of stool samples stored and collected under various conditions. Stool samples (2 liquid, 1 formed) from three different patients at two hospitals were each evaluated under the following conditions: immediately frozen at -80°C, stored at 4°C for 12-48 hours before freezing at -80°C and stored at -20°C with 1-2 thaw cycles before storage at -80°C. Additionally, 8 stool and 30 rectal swab samples were collected from 8 in-patients at one hospital. Microbiota differences were assessed using the Yue and Clayton dissimilarity index (θYC distance) and analysis of molecular variance (AMOVA). Regardless of the storage conditions, the bacterial communities of aliquots from the same stool samples were very similar based on θYC distances (median intra-sample θYC distance: 0.035, IQR: 0.015-0.061) compared to aliquots from different stool samples (median inter-sample θYC distance: 0.93, IQR: 0.85-0.97) (Wilcoxon test p-value: <0.0001). For the stool and rectal swab comparison, samples from different patients, regardless of sample collection method, were significantly different (AMOVA p-values: <0.001-0.029) compared to no significant difference between all stool and swab samples (AMOVA p-value: 0.976). The θYC dissimilarity index between swab and stool samples was significantly lower within individuals (median 0.17, IQR: 0.10-0.27) than between individuals (median 0.93, IQR: 0.85-0.97) (Wilcoxon test p-value: <0.0001), indicating minimal differences between stool and swab samples collected from the same individual over the sampling period. For gastrointestinal microbiota studies based on bacterial 16S rRNA gene sequence analysis, interim stool sample storage at 4 °C or -20 °C, rather than immediate storage at -80 °C, does not significantly alter results. Additionally, stool and rectal swab microbiotas from the same subject were highly similar, indicating that these sampling methods could be used interchangeably to assess the community structure of the distal GI tract.


Biosimilars in oncology: key role of nurses in patient education.
Biosimilars have the potential to lower costs and increase patient access to life-saving cancer therapies. However, lack of familiarity with biosimilars can be a barrier to their adoption, limiting their health and economic benefits. As highly trusted healthcare providers, nurses play integral roles in patient education. This review aims to help prepare nurses to respond to potential questions from patients on biosimilars. The regulation, use and potential benefits of biosimilars are discussed, with a focus on biosimilars in oncology. Overall, biosimilars are highly regulated medicines that provide comparable benefits to available biologics. Nurses can influence the adoption of biosimilars through patient education and can impact the future of the field in their expanding roles within health care systems.


Surface markers on lymphocytes of multiple sclerosis patients.
Peripheral blood lymphocytes of twenty-two multiple sclerosis (MS) patients and thirty-five healthy controls were examined for the presence of surface markers characteristic for B lymphocytes (surface immunoglobulin, receptor for C3 (EAC), reporter for Fc (EA) and the spontaneous rosette-forming capacity characteristic of T cells. The results obtained indicate that the number of B and T cells in MS is similar to controls, as evaluated by the presence of surface immunoglobulin and E rosette-forming capacity. However, a statistically significant reduction in the percentage of lymphocytes bearing C3 receptors has been found in MS patients. It might have resulted from a reduction in the lymphocyte population bearing C3 receptor but no surface immunoglobulin. The EA rosette test revealed the greatest difference between the groups. The difference indicated a reduction in the density of the receptor for 7S Fc on lymphocytes from MS patients. The results obtained are consistent with the hypothesis of an immune deficit in multiple sclerosis.


Metabolic engineering of glycerol production in Saccharomyces cerevisiae.
Inactivation of TPI1, the Saccharomyces cerevisiae structural gene encoding triose phosphate isomerase, completely eliminates growth on glucose as the sole carbon source. In tpi1-null mutants, intracellular accumulation of dihydroxyacetone phosphate might be prevented if the cytosolic NADH generated in glycolysis by glyceraldehyde-3-phosphate dehydrogenase were quantitatively used to reduce dihydroxyacetone phosphate to glycerol. We hypothesize that the growth defect of tpi1-null mutants is caused by mitochondrial reoxidation of cytosolic NADH, thus rendering it unavailable for dihydroxyacetone-phosphate reduction. To test this hypothesis, a tpi1delta nde1delta nde2delta gut2delta quadruple mutant was constructed. NDE1 and NDE2 encode isoenzymes of mitochondrial external NADH dehydrogenase; GUT2 encodes a key enzyme of the glycerol-3-phosphate shuttle. It has recently been demonstrated that these two systems are primarily responsible for mitochondrial oxidation of cytosolic NADH in S. cerevisiae. Consistent with the hypothesis, the quadruple mutant grew on glucose as the sole carbon source. The growth on glucose, which was accompanied by glycerol production, was inhibited at high-glucose concentrations. This inhibition was attributed to glucose repression of respiratory enzymes as, in the quadruple mutant, respiratory pyruvate dissimilation is essential for ATP synthesis and growth. Serial transfer of the quadruple mutant on high-glucose media yielded a spontaneous mutant with much higher specific growth rates in high-glucose media (up to 0.10 h(-1) at 100 g of glucose. liter(-1)). In aerated batch cultures grown on 400 g of glucose. liter(-1), this engineered S. cerevisiae strain produced over 200 g of glycerol. liter(-1), corresponding to a molar yield of glycerol on glucose close to unity.


Genome and Phylogenetic Analysis of Genes Involved in the Immune System of Solea senegalensis - Potential Applications in Aquaculture.
Global aquaculture production continues to increase rapidly. One of the most important species of marine fish currently cultivated in Southern Europe is Solea senegalensis, reaching more than 300 Tn in 2017. In the present work, 14 Bacterial Artificial Chromosome (BAC) clones containing candidate genes involved in the immune system (b2m, il10, tlr3, tap1, tnfα, tlr8, trim25, lysg, irf5, hmgb2, calr, trim16, and mx), were examined and compared with other species using multicolor Fluorescence in situ Hybridization (mFISH), massive sequencing and bioinformatic analysis to determine the genomic surroundings and syntenic chromosomal conservation of the genomic region contained in each BAC clone. The mFISH showed that the groups of genes hmgb2-trim25-irf5-b2m; tlr3-lysg; tnfα-tap1, and il10-mx-trim16 were co-localized on the same chromosomes. Synteny results suggested that the studied BACs are placed in a smaller number of chromosomes in S. senegalensis that in other species. Phylogenetic analyses suggested that the evolutionary rate of immune system genes studied is similar among the taxa studied, given that the clustering obtained was in accordance with the accepted phylogenetic relationships among these species. This study contributes to a better understanding of the structure and function of the immune system of the Senegalese sole, which is essential for the development of new technologies and products to improve fish health and productivity.


Site-specific percutaneous absorption of methyl salicylate and VX in domestic swine.
The site specificity of the percutaneous absorption of methyl salicylate (MeS) and the organophosphate nerve agent VX (O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate) was examined in anaesthetized domestic swine that were fully instrumented for physiological endpoints. Four different anatomical sites (ear, perineum, inguinal crease and epigastrium) were exposed to the MeS and the serum levels were measured over a 6-h time period. The dose absorbed at the ear region was 11 microg cm(-2) with an initial flux of 0.063 microg cm(-2)min(-1), whereas at the epigastrium region the dose absorbed was 3 microg cm(-2) with an initial flux of 0.025 microg cm(-2)min(-1). For this reason further studies were carried out with VX on the ear and the epigastrium only. In animals treated with agent on the epigastrium, blood cholinesterase (ChE) activity began to drop 90 min after application and continued to decline at a constant rate for the remainder of the experiment to ca. 25% of awake control activity. At this time there were negligible signs of poisoning and the medical prognosis was judged to be good. In contrast, the ChE activity in animals receiving VX on the ear decreased to 25% of awake control values within 45 min and levelled out at 5-6% by 120 min. Clinical signs of VX poisoning paralleled the ChE inhibition, progressing in severity over the duration of the exposure. It was judged that these animals would not survive. The dramatic site dependence of agent absorption leading to vastly different toxicological endpoints demonstrated in this model system has important ramifications for chemical protective suit development, threat assessment, medical countermeasures and contamination control protocols.


Production of high affinity autoantibodies in autoimmune New Zealand Black/New Zealand white F1 mice targeted with an anti-DNA heavy chain.
Lupus-prone, anti-DNA, heavy (H) chain "knock-in" mice were obtained by backcrossing C57BL/6 mice, targeted with a rearranged H chain from a VH11(S107)-encoded anti-DNA hybridoma (D42), onto the autoimmune genetic background of New Zealand Black/New Zealand White (NZB/NZW) F1 mice. The targeted female mice developed typical lupus serologic manifestations, with the appearance of transgenic IgM anti-DNA autoantibodies at a young age (2-3 mo) and high affinity, somatically mutated IgM and IgG anti-DNA Abs at a later age (6-7 mo). However, they did not develop clinical, lupus-associated glomerulonephritis and survived to at least 18 mo of age. L chain analysis of transgenic anti-DNA Abs derived from diseased NZB/NZW mouse hybridomas showed a very restricted repertoire of Vkappa utilization, different from that of nonautoimmune (C57BL/6 x BALB/c)F1 transgenic anti-DNA Abs. Strikingly, a single L chain was repetitively selected by most anti-DNA, transgenic NZB/NZW B cells to pair with the targeted H chain. This L chain had the same Vkappa-Jkappa rearrangement as that expressed by the original anti-DNA D42 hybridoma. These findings indicate that the kinetics of the autoimmune serologic manifestations are similar in wild-type and transgenic lupus-prone NZB/NZW F1 mice and suggest that the breakdown of immunologic tolerance in these mice is associated with the preferential expansion and activation of B cell clones expressing high affinity anti-DNA H/L receptor combinations.


Influence of diet quality on nutritional status of school-aged children and adolescents in Zanzibar, Tanzania.
Malnutrition among young children and adolescents poses a serious health challenge in developing countries which results in many health problems during adulthood. Poor diet quality is known as the root cause of malnutrition which is caused by unhealthy food choices and bad eating habits among young children and adolescents. However, limited evidence is available on diet quality and its association with nutrition status among young children and adolescents in Zanzibar. This study examined the diet quality and its relationship with the nutritional status of school-aged children and adolescents in Zanzibar. Data for this study was obtained from the cross-sectional survey of School Health and Nutrition (SHN) conducted in Zanzibar. The survey recruited children aged 5-19 years from 93 schools in Zanzibar. A seven-day food frequency questionnaire (FFQ) was used to assess dietary intake. Prime Dietary Quality Score (PDQS) consisted of 21 food groups was then constructed to assess the diet quality of school-aged children and adolescents. Body mass index (BMI-for-age Z-score) was used as the indicator of nutrition status. Both linear and logistic regression analysis techniques were used to determine the associations between BMI and PDQS. A total data of 2,556 children were enrolled in the survey. The prevalence of thinness was 8.1%, normal 82.1%, overweight 7.2% and obesity 2.6%. The mean (SD) PDQS score was 18.8 (3.2) which ranged from 8 to 33. Consumptions of green leafy vegetables (49.3%), yellow or red fruits (37.8%), legumes (38.3%), fish (36.3%), and vegetable oil (31.5%) were up to three times per week, whereas consumptions of white vegetables (77.3%), cooked vegetables (32.6%), citrus fruits (66.8%), other types of fruits (66.2%), nuts (46.4%), poultry (49.6%), whole grains (61%) and eggs (67.8%) were less than once per week. In terms of unhealthy foods, eating fried foods was reported by 26.3% up to three times per week, and 31.5% reported consuming sweets and ice cream up to three times in the past week. High PDQS was significantly associated with a reduction in BMI of children (p< 0.005). For each unit increase in the consumption of unhealthy foods such as fried foods, cooked vegetables and refined grains there is a significant increase in BMI. The odds of being obese decrease significantly as diet quality increases from the first to third quintile of PDQS (AOR = 0.2, 0.04-0.89 95% CI, p = 0.035). Consumption of high quality diet was found to be associated with a reduction in excessive weight among school-aged children and adolescents in Zanzibar. There is a need for interventions targeting to reduce unhealthy food consumption in school environment. Further research should be conducted to assess diet quality using PDQS among young children and adolescents.


Prolactin regulates tuberoinfundibular dopamine neuron discharge pattern: novel feedback control mechanisms in the lactotrophic axis.
Balance in the body's hormonal axes depends on feedback onto neuroendocrine hypothalamic neurons. This phenomenon involves transcriptional and biosynthetic effects, yet less is known about the potential rapid modulation of electrical properties. Here, we investigated this issue in the lactotrophic axis, in which the pituitary hormone prolactin is tonically inhibited by tuberoinfundibular dopamine (TIDA) neurons located in the hypothalamic arcuate nucleus. Whole-cell recordings were performed on slices of the rat hypothalamus. In the presence of prolactin, spontaneously oscillating TIDA cells depolarized, switched from phasic to tonic discharge, and exhibited broadened action potentials. The underlying prolactin-induced current is composed of separate low- and high-voltage components that include the activation of a transient receptor potential-like current and the inhibition of a Ca(2+)-dependent BK-type K(+) current, respectively, as revealed by ion substitution experiments and pharmacological manipulation. The two components of the prolactin-induced current appear to be mediated through distinct signaling pathways as the high-voltage component is abolished by the phosphoinositide 3-kinase blocker wortmannin, whereas the low-voltage component is not. This first description of the central electrophysiological actions of prolactin suggests a novel feedback mechanism. By simultaneously enhancing the discharge and spike duration of TIDA cells, increased serum prolactin can promote dopamine release to limit its own secretion with implications for the control of lactation, sexual libido, fertility, and body weight.


European Lyme borreliosis clinical spectrum.
At a series of meetings, involving 27 clinicians from 11 countries, case definitions for the diagnosis of Lyme borreliosis in Europe were agreed and are presented here, with appropriate serological criteria, as a diagnostic guide. In a separate study questionnaires directed to clinicians were used to collect information on clinical aspects and risk factors of Lyme borreliosis. Data on the number of Lyme borreliosis patients seen by physicians indicated a low prevalence of the disease in western Europe and a relatively high prevalence in eastern Europe. The most commonly encountered symptom was erythema migrans, followed by neurological manifestations. Cardiac problems were rare. Tick bite was strongly associated with Lyme borreliosis, but the only other significantly associated risk factor was the pastime of gardening.


Effects of flange size on dividing streamlines of exterior hoods in cross drafts.
Effects of flange size on the flow patterns of an exterior circular hood subject to the influence of various uniform cross drafts were studied in an apparatus consisting of hood-model/wind-tunnel assembly. The cross draft to suction velocity ratio covered the range from 0.056 to 0.792. The flange width to hood diameter ratio spanned from 1.2 to 3.0. The hood equipped without flange was also probed. A two-component laser Doppler anemometer was used to measure the velocity field on the symmetry plane. The streamline patterns were obtained from the measured velocity data. The cross draft caused a capture envelope. The boundary of the envelope was described by a dividing streamline. It was found that the flange width presented complex effects on the capture envelope and the dividing streamline. Corresponding to a cross draft to suction velocity ratio, a critical flange width existed. If the flange width was smaller than the critical value, the dividing streamline would terminate at the downstream tip of the flange. The behaviors of the capture envelope and the dividing streamline of the hood in cross draft under different flange widths are presented and discussed.


Pathogenesis of rat colon carcinomas induced by N-methyl-N-nitrosourea.
Colon specimens were obtained from 45 young male and female inbred CDF rats between 11 and 42 weeks after they began to receive intrarectal injections of the carcinogen N-methyl-N-nitrosourea (MNU) 43--108 mg, total dose); specimens were also obtained from 26 control rats. Well-developed tumors from rats receiving MNU generally presented grossly as polyps; histologically, as invasive adenocarcinomas that had not metastasized. These tumors resembled their human counterparts. Focal epithelial atypias were found in grossly normal mucosa both from rats that had not yet developed tumors and from tumor-bearing rats. Such foci typically consisted of low columnar cells with enlarged nuclei, increased number of mitoses, cytoplasmic basophilia, and reduced cytoplasmic mucus. Serial section studies of minute foci of atypia indicated that some of them arose from normal deep crypt cells. Transitions were frequently found between atypical foci and in situ or invasive carcinomas. Less commonly, adenomatous epithelium was identified in the early lesions or within the frank adenocarcinomas. It was concluded that most invasive carcinomas in this rat model originate in foci of epithelial atypia, which are found with increasing frequency in the flat mucosa during treatment with MNU, but that some carcinomas also arise from adenomatous epithelium.


Electroacupuncture improves gait locomotion, H-reflex and ventral root potentials of spinal compression injured rats.
This study explored the effect of electroacupuncture stimulation (EA) on alterations in the Hoffman reflex (H-reflex) response and gait locomotion provoked by spinal cord injury (SCI) in the rat. A compression lesion of the spinal cord was evoked by insufflating a Fogarty balloon located in the epidural space at the T8-9 spinal level of adult Wistar male rats (200-250 gr; n=60). In different groups of SCI rats, EA (frequencies: 2, 50 and 100Hz) was applied simultaneously to Huantiao (GB30), Yinmen (BL37), Jizhong (GV6) and Zhiyang (GV9) acupoints from the third post-injury day until the experimental session. At 1, 2, 3 and 4 post-injury weeks, the BBB scores of the SCI group of rats treated with EA at 50Hz showed a gradual but greater enhancement of locomotor activity than the other groups of rats. Unrestrained gait kinematic analysis of SCI rats treated with EA-50Hz stimulation showed a significant improvement in stride duration, length and speed (p<0.05), whereas a discrete recovery of gait locomotion was observed in the other groups of animals. After four post-injury weeks, the H-reflex amplitude and H-reflex/M wave amplitude ratio obtained in SCI rats had a noticeable enhancement (217%) compared to sham rats (n=10). Meanwhile, SCI rats treated with EA at 50Hz manifested a decreased facilitation of the H-reflex amplitude and H/M amplitude ratio (154%) and a reduced frequency-dependent amplitude depression of the H-reflex (66%). In addition, 50 Hz-EA treatment induced a recovery of the presynaptic depression of the Gs-VRP evoked by PBSt conditioning stimulation in the SCI rat (63.2±8.1%; n=9). In concordance with the latter, it could be suggested that 50 Hz-EA stimulation reduced the hyper-excitability of motoneurons and provokes a partial improvement of the locomotive performance and H reflex responses by a possible recovery of presynaptic mechanisms in the spinal cord of experimentally injured rats.


Understanding Epigenetics in the Neurodegeneration of Alzheimer's Disease: SAMP8 Mouse Model.
Epigenetics is emerging as the missing link among genetic inheritance, environmental influences, and body and brain health status. In the brain, specific changes in nucleic acids or their associated proteins in neurons and glial cells might imprint differential patterns of gene activation that will favor either cognitive enhancement or cognitive loss for more than one generation. Furthermore, derangement of age-related epigenetic signaling is appearing as a significant risk factor for illnesses of aging, including neurodegeneration and Alzheimer's disease (AD). In addition, better knowledge of epigenetic mechanisms might provide hints and clues in the triggering and progression of AD. Intense research in experimental models suggests that molecular interventions for modulating epigenetic mechanisms might have therapeutic applications to promote cognitive maintenance through an advanced age. The SAMP8 mouse is a senescence model with AD traits in which the study of epigenetic alterations may unveil epigenetic therapies against the AD.


Partnership for Diversity: A Multidisciplinary Approach to Nurturing Cultural Competence at an Emerging Medical School.
Fostering cultural competence in higher education institutions is essential, particularly in training future health care workers to care for diverse populations. The opportunity to explore techniques to address diversity and cultural competence at a new medical school was undertaken by a multidisciplinary team of librarians, faculty, staff, and medical students. From 2011 to 2015, the team sponsored a voluntary programming series to promote cultural competence and raise awareness of health care disparities for the medical school. Thirteen events were hosted with 562 participants across all. This approach to diversity proved effective and could be adapted in any higher education setting.


Combined solution of the inverse Stefan problem for successive freezing/thawing in nonideal biological tissues.
A new combined solution of the one-dimensional inverse Stefan problem in biological tissues is presented. The tissue is assumed to be a nonideal material in which phase transition occurs over a temperature range. The solution includes the thermal effects of blood perfusion and metabolic heat generation. The analysis combines a heat balance integral solution in the frozen region and a numerical enthalpy-based solution approach in the unfrozen region. The subregion of phase transition is included in the unfrozen region. Thermal effects of blood perfusion and metabolic heat generation are assumed to be temperature dependent and present in the unfrozen region only. An arbitrary initial condition is assumed that renders the solution useful for cryosurgical applications employing repeated freezing/thawing cycles. Very good agreement is obtained between the combined and an exact solution of a similar problem with constant thermophysical properties and a uniform initial condition. The solution indicated that blood perfusion does not appreciably affect either the shape of the temperature forcing function on the cryoprobe or the location and depth of penetration of the freezing front in peripheral tissues. It does, however, have a major influence on the freezing/thawing cycle duration, which is most pronounced during the thawing stage. The cooling rate imposed at the freezing front also has a major inverse effect on the duration of the freezing/thawing.


Bisphosphonate therapy in multiple myeloma.
Lytic bone lesions, pathological fractures, hypercalcaemia and osteoporosis are common features in patients with multiple myeloma. Adjunctive therapeutic modalities in addition to antimyeloma therapy have been sought to ameliorate these clinical consequences of bone disease. Bisphosphonates appear to be useful in this respect. In addition to correcting hypercalcaemia, they reduce the amount of new bone lesions and pathological fractures in myeloma patients. Bisphosphonates also relieve bone pain. In placebo-controlled studies clodronate (1600-2400 mg/d orally) and pamidronate (90 mg intravenously once every month) have produced clinically significant effects in myeloma patients. Bisphosphonates are a useful adjunct therapy in patients with multiple myeloma.


Erythema and Induration of Bacillus Calmette-Guérin Scar Associated With Multisystem Inflammatory Syndrome in Children in Japan: A Case Report.
Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare febrile disorder with multisystem organ involvement temporally associated with coronavirus 2019 infection (COVID-19) and frequently exhibits features mimicking Kawasaki disease (KD), another febrile disorder in children. The pathogenesis and the full clinical spectrum of MIS-C is poorly understood: It is still unclear whether MIS-C and KD are different syndromes or represent a common spectrum. The erythema and induration of Bacillus Calmette-Guérin (BCG) scar is one of the characteristic findings of KD, and is useful for the diagnosis in countries where BCG vaccination is mandated in infancy. Furthermore, such findings in BCG scar were also reported after SARS-CoV-2 vaccination, which may be related to molecular mimicry. However, there are no reports of changes at the BCG scar in MIS-C cases. Here, we report a case of MIS-C in a 3-year-old Hispanic boy in Japan, with erythema and induration at the BCG scar. The patient received BCG vaccination at 16 months of age in Japan. Four weeks before the onset, he had positive polymerase chain reaction (PCR) results for SARS-CoV-2 following household outbreak, although he was asymptomatic. He presented with fever and gastrointestinal symptoms, followed by the appearance of all six principal findings of complete KD. He exhibited congestive heart failure, following intravenous immunoglobulin (IVIG) therapy. He was diagnosed with MIS-C based on characteristic mucocutaneous and gastrointestinal symptoms, decreased cardiac function, and coagulopathy, in addition to laboratory data consistent with MIS-C. The BCG finding was present from the early stage of the disease. The patient was refractory to two doses of IVIGs, and the third IVIG plus prednisolone resulted in defervescence and improvement in heart failure. No coronary involvement was observed. This is the first case of erythema and induration at the BCG scar associated with MIS-C accompanied by KD features, which may give clinical and mechanistic insights in the understanding of the disease. Since the full spectrum of MIS-C is still evolving and both of them are syndromes with overlapped clinical features, further studies are warranted for deep phenotyping of MIS-C with KD features relative to KD in countries with mandatory BCG programs in infancy.


Words and wordlessness in the psychoanalytic situation.
The difference between words and wordlessness in the psychoanalytic situation is examined in the context of a detailed clinical example. Various pairs of terms that have been used to account for this difference are mapped onto it: word and act, thought and feeling, public and private experience. Each of these sets of differences suggests certain relations between consciousness and the unconscious, and each implies a position about the nature of language. All three prove to be incomplete or inadequate ways of accounting for the difference between words and wordlessness in the clinical setting. The divergence, though, is well described by the difference between self-reflection and unformulated experience. Reflection is then presented as situated in the unformulated background meanings that contextualize it. It is because of this contextual embeddedness that self-reflection can have the kind of depth, resonance, power, and nuance more commonly associated with the nonverbal. In the creation of an explicit meaning, we simultaneously reconfigure the wordless background, thereby creating new possibilities for other meanings.


Weight management and weight loss strategies of professional jockeys.
Jockeys are required to maintain very low body weight and precise weight control during competition. This study examined the weight loss and weight management strategies of professional horseracing jockeys in the state of Victoria, Australia. An anonymous, self-completed questionnaire was administered (55% response rate, n = 116). Almost half (43%) reported that maintaining riding weight was difficult or very difficult, with 75% routinely skipping meals. In preparation for racing, 60% reported that they typically required additional weight loss, with 81% restricting food intake in the 24 hours prior to racing. Additionally, sauna-induced sweating (29%) and diuretics (22%) were frequently employed to further aid in weight loss prior to racing. These rapid weight loss methods did not differ between the 51% of jockeys who followed a weight management plan compared to those who did not. The impact of these extreme weight loss practices on riding performance and health remains unknown.


Nitric oxide-independent effects of tempol on sympathetic nerve activity and blood pressure in DOCA-salt rats.
The role of sympathetic nerves and nitric oxide (NO) in tempol-induced cardiovascular responses was evaluated in urethane-anesthetized sham and deoxycorticosterone acetate (DOCA)-salt-treated (DOCA-salt) rats. Tempol (30-300 micromol/kg iv), a superoxide (O) scavenger, decreased renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) in DOCA-salt and sham rats. The antioxidants tiron and ascorbate did not alter MAP, HR, or RSNA in any rat. Tempol responses were unaffected after sham rats were treated with N(G)-nitro-L-arginine (L-NNA, 13 mg/kg). In DOCA-salt rats, L-NNA reduced tempol-induced depressor responses but not the inhibition of HR or RSNA. Tempol did not significantly decrease MAP, HR, or RSNA after hexamethonium (30 mg/kg iv) treatment in any rat. Dihydroethidine histochemistry revealed increased O levels in arteries and veins from DOCA-salt rats. Tempol treatment in vitro reduced O levels in arteries and veins from DOCA-salt rats. In conclusion, tempol-induced depressor responses are mediated largely by NO-independent sympathoinhibition in sham and DOCA-salt rats. There is an additional interaction between NO and tempol that contributes to depressor responses in DOCA-salt rats.


Body Mass Index Requirements for Gender-Affirming Surgeries Are Not Empirically Based.
Body mass index (BMI) requirements for gender affirmation surgery (GAS) are ubiquitous and vary across providers. Requirement variation is not surprising given little data to suggest an association between BMI and GAS outcomes. Implementation of subjective BMI requirements limits access to GAS and negatively impacts patient health and safety. We outline the literature on BMI and GAS outcomes, discuss clinical utility of GAS, and summarize dangers of prescribing weight loss as a prerequisite for surgery. We propose that providers use empirically supported indices of health and comorbidity instead of BMI to determine surgical eligibility for all patients considering GAS.


A wheat cytochrome P450 enhances both resistance to deoxynivalenol and grain yield.
The mycotoxin deoxynivalenol (DON) serves as a plant disease virulence factor for the fungi Fusarium graminearum and F. culmorum during the development of Fusarium head blight (FHB) disease on wheat. A wheat cytochrome P450 gene from the subfamily CYP72A, TaCYP72A, was cloned from wheat cultivar CM82036. TaCYP72A was located on chromosome 3A with homeologs present on 3B and 3D of the wheat genome. Using gene expression studies, we showed that TaCYP72A variants were activated in wheat spikelets as an early response to F. graminearum, and this activation was in response to the mycotoxic Fusarium virulence factor deoxynivalenol (DON). Virus induced gene silencing (VIGS) studies in wheat heads revealed that this gene family contributes to DON resistance. VIGS resulted in more DON-induced discoloration of spikelets, as compared to mock VIGS treatment. In addition to positively affecting DON resistance, TaCYP72A also had a positive effect on grain number. VIGS of TaCYP72A genes reduced grain number by more than 59%. Thus, we provide evidence that TaCYP72A contributes to host resistance to DON and conclude that this gene family warrants further assessment as positive contributors to both biotic stress resistance and grain development in wheat.


[Diagnosis of allergic diseases].
This study presents the general rules of diagnosing allergic diseases, which can be reduced to answers for the following three questions: is the patient allergic? (does he/she belong to the group of people at risk for allergy?). If so, then; what is he/she allergic to? And again, if the answer is positive, then: does the substance he/she is allergic to, gives the reasons for the symptoms? As it follows from the above-mentioned questions, besides determining the disease, the main goal of allergy diagnostics is to recognize the allergen responsible for the symptoms. In order to attain this, several widely recognized tests are performed (skin prick tests, allergen specific IgE, skin patch tests, allergen challenge tests, etc.). Some doctors use the testing methods which have not been scientifically proven to be effective and accurate. As a matter of fact, many patients in Poland are tested with unverified (ALCAT) or negatively verified methods (allergen specific IgG4) as well as by means of alternative medicine (acupuncture, BICOM).


Neighborhood Disadvantage and Preterm Delivery in Urban African Americans: The Moderating Role of Religious Coping.
Evidence suggests that neighborhood disadvantage predicts preterm delivery (PTD). However, the design of most existing studies precludes within-group analyses, which would allow the identification segments of the population at highest risk, as well as preventive factors. African Americans (AA) are disproportionately affected by PTD, are disproportionately concentrated in disadvantaged neighborhoods, and frequently use religious coping in response to chronic stressors. Our objective was to examine the association between neighborhood disadvantage and PTD, and whether religious coping moderated the associations, among postpartum AA women. Addresses from participants of the Life Influences on Fetal Environments Study (n=1387) were geocoded and linked to data from the American Community Survey. An index of neighborhood disadvantage was derived from a principal components analysis of the following variables: % below poverty, % unemployed, % receiving public assistance income, % college educated, % AA, % female-headed households, % owner occupied homes, median income, and median home value. Three domains of religious coping were assessed: organizational (church attendance), non-organizational (praying for self and asking others for prayer), and personal or subjective (experiences, perceptions, and sentiments about religion), and all were dichotomized as frequent/infrequent or satisfied/not satisfied. Preterm delivery was defined as birth before 37 completed weeks of gestation. Prevalence ratios and 95% confidence intervals were estimated with log binomial regression models. Neighborhood disadvantage did not predict PTD rates in the overall sample. However, there was evidence of moderation by asking others for prayer (P for asking for prayer X disadvantage index interaction term: 0.01). Among women who infrequently asked others for prayer, neighborhood disadvantage was positively associated with PTD rates (adjusted Prevalence ratio: 1.28, 95% Confidence Interval: 1.01, 1.63), and a null association was found for those who frequently asked others for prayer. No evidence of moderation by the other religious coping variables was present. Non-organizational religious coping may buffer against the adverse effects of neighborhood disadvantage on PTD rates, among urban AA women. Future research should examine the mechanisms of the reported relationships.


Psychosocial predictors of consistent condom use among migrant road construction workers in the Southwest Region of Cameroon using the Health Belief Model.
A significant proportion of road construction workers are migrants and prone to HIV infection. This study investigated the psychosocial predictors of consistent condom use among migrant road construction workers in the South-west region of Cameroon using the Health Belief Model (HBM) as the theoretical framework. A cross-sectional survey of a stratified sample of 254 road construction workers was conducted at construction sites along the Kumba-Mamfe road in the South-west region of Cameroon in December 2015. Data were collected using a pretested structured questionnaire and binomial logistic regression was performed to test the strength of association between the independent and the dependent variables using SPSS version 20 at the level 0.05. Only 67 (43.5%) reported consistent condom use. Perception of risk of contracting HIV was also low, 109 (42.9%). None of the constructs of the HBM was significantly associated with consistent condom use. However, perception that road construction workers are prone to HIV (perceived susceptibility) was associated with an increased likelihood of using condom consistently, OR = 2.1 (95% CI 0.72-6.12, p = 0.17); perception that consistent condom use could prevent HIV transmission (perceived benefit) was associated with an increased likelihood of using it consistently, OR = 1.9 (95% CI 0.74-4.80, p = 0.18); perception by workers that they can refuse sex with their partners if they refuse to use condoms (perceived self-efficacy) was associated with an increased likelihood of using condoms consistently, OR = 1.5 (95% CI 0.62-3.53, p = 0.38). However, the perception that condom reduces sexual pleasure (perceived barriers) was associated with a reduced likelihood of using it consistently, OR = 0.84 (95% CI 0.35-2.01, p = 0.698). There were no significant associations between the psycho-social constructs of the HBM and consistent condom use. Therefore, interventions to increase the perception of risk of contracting HIV, which is assumed to be the immediate antecedent of consistent condom use is highly recommended.


Interaction between urokinase receptor and heat shock protein MRJ enhances cell adhesion.
The urokinase-type plasminogen activator receptor (uPAR) has diverse biological functions including roles in proteolysis, cell adhesion and cellular signaling. We identified a heat shock protein MRJ (DNAJB6) as a novel uPAR-interacting protein in a yeast two-hybrid screen and confirmed the interaction and co-localization by GST-pull down assays, and co-immunoprecipitation in cells transfected with MRJ. Endogenous interaction between uPAR and MRJ was also detected in breast cancer MDA-MB-231 cells. Deletion mapping demonstrated that the C-terminal region of MRJ is required to mediate its interaction with uPAR. To understand the biological function of the uPAR-MRJ complex, we determined whether MRJ regulated uPAR mediated adhesion to vitronectin in human embryonic kidney (HEK) 293 cells stably transfected with uPAR. After transfection with full length MRJ, there was a 50% increase in cell adhesion compared to the mock transfected control (p<0.01). This increase in adhesion is dependent on the uPAR/full length MRJ interaction as cells transfected with the mutant construct containing only N-terminal region or C-terminal region of MRJ had no increase in cell adhesion. The observed increase in adhesion to vitronectin by MRJ was also blocked by an anti-uPAR domain I antibody suggesting that the induced adhesion is at least in part contributed by uPAR on the cell surface. These data provide a novel mechanism by which uPAR plays a role in cell adhesion to vitronectin.


Effect of sugammadex on coagulation as detected by rotational thromboelastometry in morbidly obese patients.
Sugammadex, which is used to reverse rocuronium-induced neuromuscular blockade, has a limited and transient effect on activated partial thromboplastin time and prothrombin time. However, no data are available on the effects of sugammadex on coagulation in morbidly obese patients, as assessed by rotational thromboelastometry (ROTEM®). Sixty patients received sugammadex 2 mg/kg or 4 mg/kg to reverse moderate or deep rocuronium-induced neuromuscular blockade (N.=30/group) at the end of surgery under desflurane anesthesia. Arterial blood samples were collected before and 3 min and 30 min after sugammadex administration for ROTEM® analysis, including measurements of clotting time (CT), clot formation time, α angle, and maximum clot firmness in INTEM, EXTEM, and FIBTEM assays. Major and minor bleeding events were also monitored during the postoperative period. Sugammadex 2 and 4 mg/kg has a limited and transient (<30 min) effect on INTEM CTs of 7.7% (P=0.04) and 10.7% (P<0.0001), respectively. There were no relevant effects on other ROTEM® parameters. A multivariate analysis indicated a significant effect of total sugammadex dose (<250, 250-500, >500 mg) on the INTEM CT (P=0.002). A regression analysis showed a positive relationship between sugammadex dose and INTEM CT value at 3 min after administration (coefficient = 0.052 s; 95% CI: 0.005-0.098 s; P=0.03). No major or minor bleeding events were observed in either group during the postoperative period. Sugammadex produces a slight effect on coagulation in morbidly obese patients, without increasing the risk for postoperative bleeding.


Network analysis of genes and their association with diseases.
A plethora of network-based approaches within the Systems Biology universe have been applied, to date, to investigate the underlying molecular mechanisms of various human diseases. In the present study, we perform a bipartite, topological and clustering graph analysis in order to gain a better understanding of the relationships between human genetic diseases and the relationships between the genes that are implicated in them. For this purpose, disease-disease and gene-gene networks were constructed from combined gene-disease association networks. The latter, were created by collecting and integrating data from three diverse resources, each one with different content covering from rare monogenic disorders to common complex diseases. This data pluralism enabled us to uncover important associations between diseases with unrelated phenotypic manifestations but with common genetic origin. For our analysis, the topological attributes and the functional implications of the individual networks were taken into account and are shortly discussed. We believe that some observations of this study could advance our understanding regarding the etiology of a disease with distinct pathological manifestations, and simultaneously provide the springboard for the development of preventive and therapeutic strategies and its underlying genetic mechanisms.


Oral bisphosphonates and colorectal cancer.
Use of oral bisphosphonates has been associated with a decreased risk of colorectal cancer (CRC), but the association may be related to residual confounding by healthy lifestyle or body mass index (BMI). Therefore, we conducted a prospective nested case-control study within the Kaiser Permanente, Northern California health system cohort. In total, 12,505 CRC cases were individually matched to 599,534 controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression models with adjustment for important covariates extracted from the database. Participants who had ever used oral bisphosphonates were less likely than non-users to be diagnosed with CRC (OR 0.82; 95% CI: 0.74, 0.89). Colon and rectum site-specific associations were similar to the overall association. A stronger inverse association for ever use of bisphosphonates was observed for men (OR 0.63; 95% CI: 0.47, 0.85), however when stratified by previous lower endoscopy, the association was only observed in the participants who did not have a previous lower endoscopy (OR 0.73 (0.64, 0.83)). In conclusion, we found that oral bisphosphonate use was associated with a decreased odds of CRC, however this association may be due to residual confounding by BMI or another confounder.


Microbiology and treatment of halitosis.
The prevalence of oral malodor is probably high in the United States, although precise epidemiological data are missing. The many thousands of individuals who experience oral malodor from the overgrowth of proteolytic, anaerobic bacteria on their tongue surfaces can be successfully treated by a regimen that includes tongue brushing, toothbrushing and possibly the usage of mouthrinses containing various agents. Several candidate mouthrinses containing essential oils (Listerine), ZnCl2, or an oil, water and cetylpyridum chloride mouthrinse have reduced the organoleptic scores of individuals with moderate levels of oral malodor in the absence of tongue brushing. Very few long-term data beyond 6 weeks of usage are available. Anecdotal evidence suggests that other agents such as chlorine dioxide may be helpful. These mouthrinses should be marketed as oral deodorants that are analogous in purpose to the usage of deodorant soaps to control and/or eliminate body malodors. In this way the mouthrinse could be considered as a cosmetic by the FDA, provided that there are data on the safety of the various ingredients in the mouthrinse. Mouthrinses containing zinc ions are able to reduce the levels of volatile sulfur compounds by converting these volatile compounds to non-volatile, and therefore, non-malodorous zinc sulfides, and this mode of action would appear to support a cosmetic claim.


Self-Care Practice and Associated Factors among Hypertensive Patients in Debre Tabor Referral Hospital, Northwest Ethiopia, 2020.
Hypertension prevalence is continuously rising and is projected to be 1.56 billion cases by the year 2025. Despite the great progress made in the treatment of hypertension, many patients still do not achieve optimal results and experience devastating complications due to uncontrolled high blood pressure. The aim of this study is to assess self-care practice and associated factors among hypertensive patients. An institution-based cross-sectional study was conducted at Debre Tabor Referral Hospital, Northwest Ethiopia, from October to November 2020. A single population proportion formula and systematic random sampling technique was used to recruit 392 study participants. The data were entered to Epi-Info software version 7.1 and then exported to SPSS version 23 for analysis. A descriptive statistic was expressed as percentage, frequency, and mean. Finally, multivariable logistic regression was used to identify factors associated with dependent variable using a p value of <0.05. A total 392 eligible hypertensive patients participated in the study. The self-care practice among hypertension patients was found to be 54.1%. Urban residency (AOR = 2.17; 95% CI, 1.2-3.9), social support (AOR = 2.12; 95% CI, 1.13-3.39), good knowledge (AOR = 1.83; 95% CI, 1.15-2.91), age between 40 and 64 (AOR = 3.15; 95% CI, 1.19-8.3), age ≥65 (AOR = 3.81; 95% CI, 1.35-10.7), and stress control (AOR = 1.6; 95% CI, 1.06-2.67) were predictors of hypertension self-care practice. Conclusion and Recommendation. The study revealed that almost one out of two hypertension patients had good hypertension self-care practice. Good social support, age greater than 40 years, urban residency, good basic knowledge, and having stress control were positively associated with hypertensive self-care practice.


Cannabis Use Following Total Joint Arthroplasty is Associated With Increased Risks? A Meta-Analysis.
With the increased legalization of cannabis, a new unknown emerges for orthopaedic surgeons and their patients. This systematic review aimed to (1) evaluate complications of cannabis use; (2) determine the effects of cannabis on pain and opioid consumption; and (3) evaluate healthcare utilizations associated with cannabis use among patients undergoing total joint arthroplasty (TJA). A systematic review was performed. A search of the literature was performed in 5 databases. We included studies between January 2012 and July 2022 reporting cannabis use and complications, pain management, opioid consumption, length of stay, costs, or functional outcomes following TJA. A meta-analysis of odds ratios (ORs) and continuous variables was performed. A total of 19 articles were included in our final analysis. Cannabis use was associated with higher odds for deep vein thrombosis (DVT) (OR: 1.46, 95% Confidence Interval [CI]: 1.13 to 1.89) and revisions (OR: 1.47 [95% CI: 1.41 to 1.53]) in total knee arthroplasty (TKA). Cannabis use was associated with similar odds for DVT in total hip arthroplasty (THA) (OR: 1.30 [95% CI: 0.79 to 2.13]), pulmonary embolus in both TKA (OR: 1.29 [95% CI: 0.95 to 1.77]), THA (OR: 0.55 [95% CI: 0.09 to 3.28]), and cardiovascular complications in TKA (OR: 1.97 [95% Cl: 0.93 to 4.14]). Cannabis use did not alter pain scores, opioid consumption, or cost of care in THA (estimate: $2,550.51 [95% CI: $356.58 to $5,457.62]) but was associated with higher costs in TKA (estimate: $3,552.46 [95% CI: $1,729.71 to $5,375.22]). There was no difference in lengths of stay or functional outcomes; however, there may be a potentially increased risk for prosthetic complications, pneumonia, and cerebrovascular accidents among cannabis users. Cannabis use may be associated with an increased risk of DVTs, revisions, pneumonia, cerebrovascular accidents, and cardiac complications after TJA. Higher-level studies are needed to ascertain the impact of cannabis use for patients undergoing TJA.


Fish consumption as a driver of risk-management decisions and human health-based water quality criteria.
The use and interpretation of fish consumption surveys and interviews, the application of fish consumption rates for sediment evaluation and cleanup, and the development of human health water quality criteria (HH WQC) are complex and interrelated issues. The present article focuses on these issues using examples from the United States, although the issues may be relevant for other countries. Some key considerations include the fact that there are many types of fish consumption surveys (e.g., 24-h recall surveys, food frequency questionnaires, creel surveys), and these surveys have different advantages and limitations. Identification of target populations for protection, identification of the species and quantities of fish consumed, and determination of bioaccumulation assumptions are important factors when developing water quality and sediment screening levels and standards. Accounting for the cultural importance of fish consumption for some populations is an even more complex element. Discussions about HH WQC often focus only on the fish consumption rate and may not have broad public input. Some states are trying to change this through extensive public participation efforts and use of probabilistic approaches to derive HH WQC. Finally, there are limits to what WQC can achieve. Solutions beyond the establishment of WQC that target toxics reduction from other sources may provide the greatest improvements to water quality and reductions in human health risks in the future.


Potential of palladium-109-labeled antimelanoma monoclonal antibody for tumor therapy.
Palladium-109, a beta-emitting radionuclide, was chelated to the monoclonal antibody 225.28S to the high molecular weight antigen associated with human melanoma. The radiolabeled antibody maintained its specific in vitro reactivity with cultured human melanoma cells. Injection of the radiolabeled monoclonal antibody into nude mice bearing human melanoma resulted in significant accumulation of the radiolabel in the tumors: 19% injected dose/g; 38:1 and 61:1 tumor-to-blood ratios at 24 and 48 hr, respectively. The localization of the radiolabeled antibody in liver and kidney also was high, but appreciably lower than that achieved in tumor. These results suggest that Pd-109-labeled monoclonal antibody to tumor-associated antigens may have potential applications in tumor immunotherapy.


[Attitude of the pediatric surgeon to antenatal diagnosis of a malformation].
To have found by prenatal ultrasonography a fetal severe malformation implies a complete collaboration between paediatric surgery who must take a decision and the echographist , the obstetrician, the geneticist. The information they give to the parents is a delicate and necessary step. Four kinds of decisions are discussed (termination, provoked delivery, in utero surgery, secondary neo-natal surgery) at the light of medical, psychological, ethical and juridical data.


Q methodology: relevance and application to nursing research.
Q methodology is a unique research tradition with an epistemology and technique that is much more than the Q-sort form of instrumentation used to gather data. Developed to explore and understand the richness of human subjectivity, Q methodology, with its emphasis on the individual, is relevant to many substantive areas of scientific inquiry within nursing. This article presents an overview of the technique and delineates special considerations for implementing Q methodological investigations.


Isolated and Combined Valve Surgery in Elderly Patients: A Comparison of Mid-Term Results.
This study examined mid-term outcomes of valve surgery in the elderly, and focused on the difference in outcomes between isolated and combined valve surgery. From January 2012 to June 2016, 113 consecutive patients aged 75 years and older underwent valve surgery. In all, 60 underwent isolated valve surgery (Group I), and 53 underwent combined valve surgery (Group C) involving the combination of any valve procedures or valve surgery with concurrent other procedure. Short- and mid-term outcomes were compared between the two groups. There was no significant difference in length of intensive care unit stay (2.8 days in Group S vs. 4.2 days in Group C, p = 0.08), hospital stay (16.2 vs. 18.7 days, p = 0.22), and mechanical ventilation (11.2 vs. 15.0 hours, p = 0.28). Neither was there any significant difference in operative mortality (1.6% vs. 5.6%, p = 0.25) nor morbidity (8.3% vs. 9.4%, p = 0.83) between the two groups. Actuarial survival rates at 1 and 3 years were 98.3% in Group S and 92.0% in Group C (log-rank p = 0.126). Once patients have tolerated combined surgery during the early postoperative period, good survival rates equaling those of isolated valve surgery can be expected.


Distribution of peripheral blood mononuclear cell subtypes in patients with West syndrome: Impact of synacthen treatment.
West Syndrome (WS) is an epileptic encephalopathy that typically occurs in infants and is characterized by hypsarrhythmia, infantile spasms, and neurodevelopmental impairment. Demonstration of autoantibodies and cytokines in some WS patients and favorable response to immunotherapy have implicated inflammation as a putative trigger of epileptiform activity in WS. Our aim was to provide additional support for altered inflammatory responses in WS through peripheral blood immunophenotype analysis. Eight WS cases treated with synacthen and 11 age- and sex-matched healthy volunteers were included. Peripheral blood mononuclear cells (PBMC) were isolated and immunophenotyping was performed in pre-treatment baseline (8 patients) and 3 months post-treatment (6 patients) samples. The analysis included PBMC expressing NFκB transcription and NLRP3 inflammasome factors. In pre-treatment baseline samples, switched memory B cells (CD19+IgD-CD27+) were significantly reduced, whereas plasma cells (CD19+CD38+CD138+) and cytotoxic T cells (CD3+CD8+) were significantly increased. Regulatory T and B cell ratios were not significantly altered. Synacthen treatment only marginally reduced helper T cell ratios and did not significantly change other T, B, NK and NKT cell and monocyte ratios. Our findings lend further support for the involvement of inflammation-related mechanisms in WS. New-onset WS patients are inclined to display increased plasma cells in the peripheral blood. Synacthen treatment does not show a beneficial effect on most effector acquired and innate immunity subsets.