Paget's disease of nipple with dermal invasion: A case report.
Invasive mammary Paget's disease (MPD) is an extremely rare eczematous eruption on the nipple and areola with an invasion of the dermis by Paget cells. This entity can often be misdiagnosed and overtreated for invasive carcinoma of the breast. A 34-year woman presented with a 2-year history of right nipple eczema and right axillary lump for a month. Breast ultrasound revealed dilated intra-nipple lactiferous duct and an enlarged right axillary lymph node. Histopathology from biopsy revealed MPD with ductal carcinoma in situ (DCIS) whereas final histopathology after right modified radical mastectomy revealed Invasive MPD with DCIS and axillary metastasis. She underwent adjuvant chemotherapy and is under hormonal therapy with complete remission for 18 months. Awareness of invasive MPD is important to avoid misdiagnosis and probable radical treatment. Close follow-up is warranted due to limited knowledge regarding treatment and prognosis of invasive MPD.


Modelling of arsenic (III) removal from aqueous solution using film theory combined Spiegler-Kedem model: pilot-scale study.
Arsenic contamination in drinking water is recognized as major health hazard worldwide. As reported in literature, more than 19% Indians are consuming lethal levels of arsenic for drinking purposes. In this work, arsenic (III) removal was studied using HFN300 polyethersulfone nanofiltration membrane in spiral wound configuration. Various membrane parameters such as hydraulic permeability (4.87 L m-2 h-1 bar-1), mass transfer coefficient (0.957*10-6 m s-1), reflection coefficient (0.9), and solute permeability (2*10-9 m s-1) were estimated using film theory combined Spiegler-Kedem (FTCSK) model. The higher value of reflection coefficient suggested the impervious nature of nanofiltration (NF) membrane used for arsenic (III) solute rejection. The influence of various operating parameters such as transmembrane pressure, initial feed concentration, and feed flowrate on membrane performance was also examined. It was found that arsenic (III) rejection was dependent on pressure and feed concentration. Result showed that more than 96.4% arsenic (III) rejection was achieved for 50 mg L-1 of feed at optimized conditions. As HFN300 membrane was negatively charged at pH 8 and arsenic (III) was available in neutral solute form, electro-migration was not considered for solute rejection mechanism. Solution diffusion with significant coupling between solute and solvent, steric hindrance effect, convection, and solute-membrane affinity interactions were considered dominant factors for the possible solute rejection mechanism. Rejection efficiency (% R) and permeate flowrate (Q2) were simulated and compared with experimental results. It was found that simulated results were in excellent agreement with the experimental results. The maximum error obtained was within 10% for both % R and Q2. This confirms the efficacy of FTCSK model in predicting arsenic (III) removal using NF membrane. The annualized cost per cubic metre of treated water was estimated as 3.32 $/m3. This further confirms the feasibility of using NF process in removing arsenic from contaminated water.


Reconstruction of extensive upper extremity defects using pre-expanded oblique perforator-based paraumbilical flaps.
The pedicled paraumbilical flap is a reliable tissue transfer for hand and forearm reconstruction. However, its size, pedicle length and/or thickness limit its application in resurfacing of extensive defects of the upper limb. To conquer those limitations, this flap was pre-expanded for 10-24 weeks prior to transfer in 25 patients and used as a pedicle flap to cover upper extremity defects. Extensive defects of upper limb were reconstructed by the pre-expanded paraumbilical flaps. The flaps ranged in size from 10 cm × 8 cm to 30 cm × 14 cm. The donor sites were closed directly in all cases. All flaps survived, but two had partial flap necrosis due to venous congestion or infection. With pre-transfer expansion, a large, well-perfused abdominal pedicle flap can be raised and transferred based on the paraumbilical perforators. This pre-expanded flap might be useful in the patients who have the extensive upper limb defects and sufficient time to allow tissue expansion.


cGMP-independent anti-apoptotic effect of nitric oxide on thapsigargin-induced apoptosis in the pancreatic beta-cell line INS-1.
Low concentrations of nitric oxide (NO) produced by constitutive NO synthase (cNOS) in pancreatic beta-cells have been suggested to be a physiological regulator of insulin secretion. In contrast, excessive NO produced by inducible NO synthase is known to mediate beta-cell apoptosis. The aim of the present study was to investigate the effect of low concentrations of NO on beta-cell apoptosis. Apoptosis of the pancreatic beta-cell line INS-1 was quantitatively determined by Annexin V flow cytometry. The 24-h incubation with 1 mM DETA/NO, a long half-life NO donor, induced beta-cell apoptosis, which was insensitive to the soluble guanylate cyclase (sGC) inhibitor ODQ. In contrast, DETA/NO at lower concentrations until 300 microM concentration-dependently decreased the apoptosis induced by thapsigargin, an inhibitor of endoplasmic reticulum Ca2+-ATPase. ODQ did not affect the anti-apoptotic effect of DETA/NO. Moreover, neither the cGMP analogue 8-Br-cGMP nor the sGC activator YC-1 mimicked the anti-apoptotic effect of DETA/NO. These results suggest that low levels of NO protect beta-cells from thapsigargin-induced apoptosis in a cGMP-independent manner.


A unilateral whiteout lung in child with multisystem inflammatory syndrome associated with COVID-19 due to SARS-CoV-2: one case report of a boy.
Multisystem inflammatory syndrome in children (MIS-C) is a relatively new and rare complication of COVID-19. This complication seems to develop after the infection rather than during the acute phase of COVID-19. This report aims to describe a case of MIS-C in an 8-year-old Thai boy who presented with unilateral lung consolidation. Unilateral whiteout lung is not a common pediatric chest radiograph finding in MIS-C, but this is attributed to severe acute respiratory failure. An 8-year-old boy presented with persistent fever for seven days, right cervical lymphadenopathy, and dyspnea for 12 h. The clinical and biochemical findings were compatible with MIS-C. Radiographic features included total opacity of the right lung and CT chest found consolidation and ground-glass opacities of the right lung. He was treated with intravenous immunoglobulin and methylprednisolone, and he dramatically responded to the treatment. He was discharged home in good condition after 8 days of treatment. Unilateral whiteout lung is not a common pediatric chest radiographic finding in MIS-C, but when it is encountered, a timely and accurate diagnosis is required to avoid delays and incorrect treatment. We describe a pediatric patient with unilateral lung consolidation from the inflammatory process.


Classification of Y chromosome polymorphisms by DNA content and C-banding.
A system has been developed using a microscope photometer to measure the DNA content of individual chromosomes. After correcting for the systematic and statistical errors the measured values are highly reproducible. Data are presented of measurements of human Y chromosomes from a cytogenetically normal population. When compared with the C-banding pattern from the same specimens the DNA content is found to change in discrete steps of 1.36 x 10(-14)g or 13.26 x 10(6) bp for each of the Y chromosome polymorphic types.


Evaluation and discussion of handmade face-masks and commercial diving-equipment as personal protection in pandemic scenarios.
Pandemic scenarios like the current Corona outbreak show the vulnerability of both globalized markets and just-in-time production processes for urgent medical equipment. Even usually cheap personal protection equipment becomes excessively expensive or is not deliverable at all. To avoid dangerous situations especially to medical professionals, but also to affected patients, 3D-printer and maker-communities have teamed up to develop and print shields, masks and adapters to help the medical personnel. In this study, we investigate three home-made respiratory masks for filter and protection efficacy and discuss the results and legal aspects. A home-printed respiratory mask with a commercial filter, a scuba-diving mask with a commercial filter and a mask sewn from a vacuum cleaner bag were investigated with 99mTc-labeled NaCl-aerosol, and the respective filter-efficacy was measured under a scintigraphic camera. The sewn mask from a vacuum cleaner bag had a filter efficacy of 69.76%, the 3D-printed mask of 39.27% and the scuba-diving mask of 85.07%. Home-printed personal protection equipment can be a-yet less efficient-alternative against aerosol in case professional masks are not available, but legal aspects of their use and distribution have to be kept in mind in order to avoid compensation claims.


[Study on influence of thermoplastic mask on radiation dermatitis for patients with laryngeal cancer].
To observe the protective effect of thermoplastic mask on radiation dermatitis for patients with laryngeal cancer. Seventy-three patients with laryngeal cancer was recruited in the research and were divided into two group. The test group (38 patients) was treated with opening-window on thermoplastic mask to protect the skin exposure to the radiotherapy. The control group (35 patients) was treated with intact thermoplastic mask. The rate of radio-dermatitis and pain in the skin exposure to the radiotherapy were assessed. The radio-dermatitis and pain of the skin exposure to the radiotherapy in the test group was significantly lower than the control group (P < 0.05). The opening-window on thermoplastic mask can decrease the radio-dermatitis for patients with laryngeal cancer.


Intraoperative Provocative Testing in Patients with Obstructive Hypertrophic Cardiomyopathy Undergoing Septal Myectomy.
Resolution of left ventricular outflow tract (LVOT) obstruction predicts symptom relief postmyectomy. Intraoperative measurement of LVOT gradients thus is essential for surgical guidance. We hypothesized that (1) hypertrophic cardiomyopathy patients have lower LVOT gradients when measured intraoperatively with transesophageal echocardiography (TEE) compared with preoperative measurements with transthoracic echocardiography (TTE) and that (2) intraoperative provocative testing can help evaluate the adequacy of surgical resection. We compared resting LVOT gradients on preoperative TTE to intraoperative TEE. We also compared intraoperative resting and provoked gradients pre- and postresection. Either isoproterenol 10 μg/kg/min or dobutamine 20 μg/kg/min was used. Patients with provoked LVOT gradients >30 mm Hg were considered for further resection based on LVOT/mitral valve morphology and clinical comorbidities. Of 315 patients identified, 293 patients were included in the analysis. There was a statistically significant difference between preoperative TTE and intraoperative TEE resting LVOT gradients (60.9 ± 39.4 mm Hg vs 42.0 ± 30.5 mm Hg, P < .0001). Out of 197 patients who had significant resting obstruction preoperatively, 82 (41.6%) demonstrated mild or no dynamic obstruction under general anesthesia. Provocative testing with both isoproterenol and dobutamine increased peak gradients (116.8 ± 33 mm Hg isoproterenol vs 107.5 ± 33 mm Hg dobutamine, P = .03). Post-cardiopulmonary bypass, seven patients (2.3%) had LVOT gradients > 30 mm Hg at rest, while 63 patients (21.5%) had residual gradients >30 mm Hg only with provocation. Elevated gradients, persistent systolic anterior motion of the mitral valve with near contact, and/or significant mitral regurgitation with provocative testing resulted in return to cardiopulmonary bypass in 41 patients (14%). Resting intraoperative TEE LVOT gradients are significantly lower than preoperative TTE gradients, with systolic anterior motion of the MV and outflow obstruction often not visualized after inducing general anesthesia. Intraoperative pharmacologic provocation can identify patients who may benefit from further surgical intervention, facilitating procedural success.


Characteristics of the Non-Isothermal and Isothermal Crystallization for the β Polymorph in PVDF by Fast Scanning Calorimetry.
Structuring at very high rates has become one of the current and important topics of interest in polymer science, because this is a common protocol in the processing of films or fibers with industrial applicability. This work presents the study by fast scanning calorimetry, FSC, of poly(vinylidene fluoride), paying special attention to the conditions for obtaining the β phase of this polymer, because it is the one technologically more interesting. The results indicate that this β phase of poly(vinylidene fluoride) is obtained when the sample is isothermally crystallized at temperatures below 60 °C. Under non-isothermal conditions, the β polymorph begins to be observed at rates above 400 °C/s, although a coexistence with the α modification is observed, so that exclusively the β phase is obtained only at rates higher than 3000 °C/s.


Long-chain alkanes and ent-labdane-type diterpenes from Gymnosperma glutinosum with cytotoxic activity against the murine lymphoma L5178Y-R.
The antitumor potential of Gymnosperma glutinosum was previously reported using the in vitro and in vivo L5178Y-R lymphoma murine model. The present study was carried out to isolate and identify the cytotoxic compounds present in the Gymnosperma glutinosum leaf hexane extract. Gymnosperma glutinosum was collected in the semi-arid region of Escobedo, State of Nuevo León, México, but it is commonly found in northeastern Mexico; it is traditionally used as a treatment for diarrhea, ulcers and rheumatism. G. glutinosum leaves were extracted with hexane and further fractioned and subfractioned over silica gel by gradient elution with hexane, chloroform, ethyl acetate and methanol. The cytotoxicity of fractions and subfractions was assessed in vitro against L5178Y-R lymphoma cells. Structure elucidation of the active compounds was determined by spectroscopic methods. Fractions and subfractions showed significant (p < 0.05) and concentration-dependent 20% to 56% cytotoxicity against L5178Y-R cells at concentrations ranging from 7.8 µg/mL to 500 µg/mL. The bioassay-guided fractionation of the hexane extract resulted in the isolation and identification of the alkane hentriacontane and the diterpene ent-labd-7-en-13S,14R,15-triol as the metabolites responsible for the activity.


Polysomnographic studies of Lesch-Nyhan syndrome.
Three cases of Lesch-Nyhan syndrome (LNS) were examined by polysomnography to assess the brainstem function, and to determine the causes of the neurological manifestations and sudden death in this syndrome. In the two older cases, the amount of slow wave and rapid eye movement (REM) sleep, the REM density and the frequency of REM bursts were decreased. In the youngest case, symmetrical phasic movements of all four limbs were observed at all sleep stages other than REM sleep. Although movements other than these symmetrical body movements appeared to be normal in this case, the frequency of twitch movements showed an abnormal pattern in each sleep stage in the two older cases. These findings suggest that in the brainstems of younger cases with LNS the REM-non REM generator as well as multiple neurotransmitter systems influencing body movements during sleep remain relatively normal, but become progressively impaired in adult cases. Severe obstructive apnea was observed in one case with hypothyroidism, but there were no respiratory abnormalities in other two cases.


Mitomycin-C induces the apoptosis of human Tenon's capsule fibroblast by activation of c-Jun N-terminal kinase 1 and caspase-3 protease.
To investigate whether mitochondrial dysfunction and mitogen-activated protein kinase family proteins are implicated in apoptotic signaling of human Tenon's capsule fibroblasts (HTCFs) by mitomycin-C. Apoptosis was determined by Hoechst nuclei staining, agarose gel electrophoresis, and flow cytometry in HTCFs treated with 0.4 mg/mL mitomycin-C for 5 minutes. Enzymatic digestion of florigenic biosubstrate assessed the catalytic activity of caspase proteases, including caspase-3, caspase-8, and caspase-9. Phosphotransferase activity of c-Jun N-terminal kinase (JNK) 1 was measured by in vitro immune complex kinase assay using c-Jun(1-79) protein as a substrate. Mitochondrial membrane potential transition (MPT) was measured by flow cytometric analysis of JC-1 staining. Mitomycin-C (0.4 mg/mL) induced the apoptosis of HTCFs, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G(0)/G(1) fraction of cell cycle increase. The catalytic activity of caspase-3 and caspase-9 was significantly increased and was accompanied by cytosolic release of cytochrome c and MPT in response to mitomycin-C. Treatment with mitomycin-C resulted in the increased expression of Fas, FasL, Bad, and phosphorylated p53 and a decreased level of phosphorylated AKT. Treatment with mitomycin-C also increased the phosphotransferase activity and tyrosine phosphorylation of JNK1, whose inhibitor significantly suppressed the cytotoxicity of mitomycin-C. Mitomycin-C induced the apoptosis of HTCFs through the activation of intrinsic and extrinsic caspase cascades with mitochondrial dysfunction. It also activated Fas-mediated apoptotic signaling of fibroblasts. Furthermore, the activation of JNK1 played a major role in the cytotoxicity of mitomycin-C.


Inverse regulation of lipid-peroxidizing and hydroperoxyl lipid-reducing enzymes by interleukins 4 and 13.
12/15-lipoxygenases and phospholipid hydroperoxide glutathione peroxidases are opposite enzymes balancing the intracellular concentration of hydroperoxy lipids. We studied the regulation of both enzymes by interleukins 4 and 13 and found an inverse response. When human lung carcinoma cells A549 were cultured in vitro in the presence of these cytokines, an up-regulation of the 12/15-lipoxygenase and a down-regulation of the phospholipid hydroperoxide glutathione peroxidase were observed. A similar inverse regulation was found in human peripheral monocytes. Interleukin 4-treated A549 cells exhibited an impaired capability of reducing exogenous hydroperoxyl lipids and their levels of endogenous lipid hydroperoxides were markedly increased. To find out whether these regulatory processes also occur in vivo, arachidonic acid oxygenase and phospholipid hydroperoxide glutathione peroxidase activity was assayed in various tissues of transgenic mice that systemically overexpress interleukin 4. In lung, spleen, kidney, and heart, an increased arachidonic acid oxygenase activity was detected when transgenic mice were compared with inbred controls. The phospholipid hydroperoxide glutathione peroxidase activity was impaired in lung, liver, and spleen of the transgenic animals. These data indicate that lipid-peroxidizing and lipid peroxide-reducing enzymes are inversely regulated in various mammalian cells. Up-regulation of the 12/15-lipoxygenase and simultaneous down-regulation of the phospholipid hydroperoxide glutathione peroxidase may lead to an increased oxidizing potential, which is reflected by an augmented intracellular peroxide tone.


Clinical utility and prognostic value of bronchoalveolar lavage galactomannan in patients with hematologic malignancies.
We conducted a single-center retrospective cohort study to determine the performance characteristics of the galactomannan (GM) assay in bronchoalveolar lavage (BAL) in patients with hematologic malignancies. Patients were classified as proven, probable, possible, or no invasive pulmonary aspergillosis (IPA), according to international guidelines. A total of 173 BAL samples from 145 patients were included. There were 5 proven, 7 probable, and 35 possible cases of IPA. Using a GM index cutoff of ≥ 0.5, the sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) of the BAL GM assay were 100%, 78%, 26%, and 100%, respectively. Using a GM index cutoff of ≥ 2.0, the sensitivity and NPV remained 100%, but specificity and PPV increased to 93% and 50%, respectively. The BAL GM assay is a highly sensitive screening test for IPA in patients with hematologic malignancies. Increasing the cutoff value to 2.0 would improve the performance of this assay.


Mutagenesis at the ad-3A and ad-3B loci in haploid UV-sensitive strains of Neurospora crassa. VI. Genetic characterization of ad-3 mutants provides evidence for qualitative differences in the spectrum of genetic alterations between wild-type and nucleotide excision-repair-deficient strains.
Genetic characterization of ad-3B mutants induced in wild-type and UV-sensitive strains has revealed qualitative differences between the spectra of genetic alterations at the molecular level. Ad-3B mutants induced in the two nucleotide excision-repair-deficient strains upr-1 and uvs-2 (Worthy and Epler, 1973) had significantly lower frequencies of nonpolarized complementation patterns and higher frequencies of noncomplementing mutants than ad-3B mutants induced in the wild-type strain in samples induced by either UV, gamma-rays, 4NQO or MNNG. In these same samples ad-3B mutants induced in uvs-4, uvs-5 or uvs-6 did not differ significantly from those induced in the wild-type strain. After ICR-170 treatment, ad-3B mutants induced in the UV-sensitive strains did not differ significantly from those induced in wild-type. The comparisons in the present and previous studies demonstrate that the process of mutation-induction in the ad-3 region is under the control of other loci that not only alter mutant recovery quantitatively (de Serres, 1980; Schüpbach and de Serres, 1981; Inoue et al., 1981a, b) but also qualitatively. These data have important implications for comparative chemical mutagenesis, since the spectrum of genetic alterations produced by a given agent can be modified markedly as a result of defects in DNA repair.


Neuroprotective effects of Longxue Tongluo Capsule on ischemic stroke rats revealed by LC-MS/MS-based metabolomics approach.
The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats. Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment. Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.


Prenatal Exposure to Persistent Organic Pollutants and Anogenital Distance in Children at 18 Months.
Anogenital distance (AGD) is a measure of in utero exposure to hormonally active agents. The aim of the present study was to evaluate the association between prenatal exposure to persistent organic pollutants (POPs) and AGD. POP levels were measured in pregnant women, and the AGD was recorded in 43 offspring at 18 months. We used linear regression models to analyze the association between maternal POP exposure and offspring AGD. We defined the anogenital index (AGI) as AGD divided by weight at 18 months (AGI = AGD / weight at 18 months [mm/kg]) and included this variable in the regression models. AGI measure was 2.35 (0.61) and 1.38 (0.45) in males and females, respectively. AGI was inversely associated with lipid-adjusted concentrations of PBDE-99 (β = -0.28, 95% confidence interval [CI]: -0.51, -0.04) and PBDE-153 (β = -0.61, 95% CI: -1.11, -0.11) in males. We did not find any statistically significant relationship between any POPs and AGI in females. Environmental exposure to POPs may affect genital development and result in reproductive tract alterations with potentially relevant health consequences in maturity.


Identifying 'cause for concern' clients: the role of the health visitor.
'Cause for concern' is an umbrella term used for a multitude of factors that generate concern of some level for the health visitor and often refers to grey or ambiguous situations involving difficult and complex decision-making processes.


Autophagy-Related Protein MAP1LC3C Plays a Crucial Role in Odontogenic Differentiation of Human Dental Pulp Cells.
Autophagy plays important roles in odontogenic differentiation of dental pulp cells (DPCs) in the developmental stage of tooth bud. Few studies have reported the role of autophagy during reparative dentin formation process. The objective of this study was to discover gene expression pattern correlated to autophagy and their role during odontogenic differentiation process in DPCs. After tooth cavities were prepared on the mesial surface of lower first molar crown of rats. Odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining. After tooth cavities were prepared on the mesial surface of lower first molar crown of rats, odontogenic differentiation and reparative dentin formation were assessed based on detection of morphology change with hematoxylin and eosin staining and dentin sialophosphoprotein (DSPP), whereas autophagy inhibitor 3-methyladenine (3MA) reversed. Results of quantitative polymerized chain reaction array of autophagosome formation related genes revealed that GABARAPL2 was prominently upregulated while expression of other ATG8 family members were moderately increased after tooth cavity preparation. In addition, human DPCs incubated in differentiation medium predominantly upregulated MAP1LC3C, which selectively decreased by 3MA but not by autophagy enhancer trehalose. Knock-down of MAP1LC3C using shRNA resulted in strong downregulation of dentin matrix protein 1 and DSPP as well-known odontogenic marker compared to knock-down of MAP1LC3B during odontogenic differentiation process of human DPCs. Our results suggest that MAP1LC3C plays a crucial role in odontogenic differentiation of human DPCs via regulating autophagic flux.


Entangled Assemblages: The Mutual Becoming of Food and More-than-Human Being.
Food and life are intimately entangled. To grasp the underlying complexity of this seemingly simple statement, this article first introduces the approach to food/eating as an assemblage enacted by various heterogeneous components, and further develops it by engaging with actor network theory and material semiotics. Thereafter the focus turns to 'entanglement', as inspired by quantum physics, to elicit the basic dynamics of the entanglement of food and more-than-human beings, conceived of as involving mutual and differential becomings within and among assemblages. The article illustrates these entangled becomings by drawing upon examples from Sri Lanka, which in an intercultural philosophical fashion serve to establish an articulation (in the sense of a connection) between the proposed abstract approach to food and some basic premises of Buddhism and Ayurveda, a South Asian health system. Overall, the article crafts a conceptual toolbox and performs ontological groundwork wherein food and human beings as entangled assemblages provide a productive, refined, and sensitive research apparatus for the intimate study of more-than-human life and organization while also spurring novel theorizations through food/eating.


Structural investigations on an amorphous Se90Te10 alloy produced by mechanical alloying using EXAFS, cumulant expansion and RMC simulations.
We investigated an amorphous Se(90)Te(10) alloy produced by mechanical alloying using two different approaches. First, we used extended x-ray absorption fine structure (EXAFS) spectroscopy and the cumulant expansion method using the Einstein model for the temperature dependence of the cumulants to obtain the cumulants C(*)(1), C(*)(2), and C(*)(3). From these, we found information about the structure of the alloy as well as the thermal and structural disorder, anharmonicity of the effective interatomic pair potentials, thermal expansion of the Se-Se and Se-Te bonds and asymmetry of the partial distribution functions g(Se-Se)(r) and g(Se-Te)(r). The cumulants C(*)(1), C(*)(2), and C(*)(3) also allowed us to reconstruct the g(EXAFS)(ij)(r,T) functions from EXAFS. Then, we made reverse Monte Carlo (RMC) simulations using the total structure factor S(K) obtained from synchrotron x-ray diffraction and the EXAFS oscillations χ(k) on the Se K edge as input data to obtain the g(RMC)(ij)(r) functions. Both methods furnished very similar g(ij)(r) functions, and the structural data obtained from them were also very similar. The results obtained from both methods showed the presence of Se-Te pairs indicating that there is alloying at the atomic level. In addition, we could not find any evidence of the presence of Te clusters in the alloy.


Cytokines in the induction and resolution of experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis is the prototypic T cell-mediated autoimmune disease model. Classically, this disease was viewed in terms of type 1 versus type 2 immunity: the type 1 cytokines IFNgamma and TNFalpha promoting disease, whereas an IL-4-dominated, type 2 response was protective. However, studies in knockout mice do not support this paradigm. More recent data point to important roles for IL-23 and IL-17 (rather than IL-12 and IFNgamma) in the establishment and persistence of the inflammatory lesion. IL-10 appears to be the dominant cytokine mediating recovery. The source of IL-10 includes B cells (most probably in the peripheral lymphoid organs). However, the key IL-10-producing cell within the central nervous system is a CD4+CD25+ T cell population that has regulatory function and is critical to resolution of the disease.


A novel phenotype-genotype correlation with an Arg555Trp mutation of TGFBI gene in Thiel-Behnke corneal dystrophy in a Chinese pedigree.
To investigate the molecular defects in a four-generation Chinese pedigree affected with Thiel-Behnke corneal dystrophy (TBCD). And to further study the relationship between genetic mutation and clinical manifestations. Individuals of the pedigree were recruited for extensive ophthalmic examinations. Histological studies of two corneal buttons obtained from lamellar keratoplasty were conducted. Peripheral blood was collected in EDTA for genomic DNA isolation from leukocytes of all affected and unaffected members. All 17 exons of the TGFBI gene were screened for mutations by polymerase chain reaction and direct DNA sequencing. Clinical examinations revealed a typical pattern of honeycomb-like TBCD. Histopathology study demonstrated eosinophilic deposits that were congo-red-positive and did not stain with periodic acid Schiff or Masson's trichrome. Genetic analysis disclosed a heterozygous p. Arg555Trp mutation resulted from a missense c. 1663C > T nucleotide change in exon 12 of TGFBI gene in all affected members. Morever, a second rare variant in exon 6 of the TGFBI gene (p. Arg257Trp) also cosegregated within this family and has been confirmed to be a single nucleotide polymorphism (SNP) not previously reported. The p. Arg555Trp mutation of the TGFBI gene was associated with TBCD, which revealed a novel phenotype-genotype correlation within the mutational spectrum of phenotypically diverse corneal dystrophies.


Free Energy Dependence of Photoinduced Electron Transfer in Octathiophene-Diimide Dyads.
Donor-acceptor dyads consisting of octathiophene (T8) paired with three (di)imide acceptors (naphthalene diimide (NDI), benzene diimide (BDI), and naphthalimide (NI)) were synthesized and probed for their photoinduced forward electron transfer (ET) and charge recombination kinetics by using ultrafast transient absorption (TA) spectroscopy. The three acceptors have different electron affinities, leading to variation in the energy of the charge-separated state and the driving force (ΔG) for forward ET and charge recombination. Analysis of the TA spectra and kinetics allows assignment of rates for forward ET and charge recombination for each of the oligomers. Electrochemistry and photoluminescence spectroscopy are used to determine the ΔG values for the ET processes. For two of the oligomers (T8NDI and T8BDI), the rates for forward ET and charge recombination are very rapid (k > 3 × 1010 s-1). By contrast, for the third oligomer (T8NI), the rates for both processes are considerably slower (k < 5 × 109 s-1). Analysis of the rate/free energy correlation for the series of oligomers reveals generally good agreement with the Marcus semiclassical theory. In all of the oligomers, the ET reactions are nonadiabatic, in part, due to weak coupling caused by out-of-plane twisting of the phenylene spacer that lies between the T8 segment and the (di)imide acceptors. The rapid ET dynamics for T8NDI and T8BDI are explained as arising due to the processes occurring near the barrierless region (-ΔG ≈ λ) or slightly into the Marcus inverted region (-ΔG > λ). The slower dynamics for T8NI are explained as arising because the forward ET is weakly exothermic, whereas charge recombination is deep into the inverted region. This study is the first to produce experimental results that match a full Marcus bell-shaped curve with ET rates in the normal, barrrierless, and inverted regions in dyads based on a π-conjugated oligomer donor.


Paediatric Nephrology in Africa.
We highlight the unique facets of paediatric nephrology in Africa in terms of the spectrum of kidney diseases, available diagnostic and treatment modalities, kidney healthcare financing options, paediatric nephrology manpower and the contribution of geography and demographics. Paediatric acute kidney injury in Africa is now commonly due to sepsis rather than gastroenteritis. Steroid-sensitive form of nephrotic syndrome is far more common than was two decades ago. The hot arid climate in North Africa and the tropical climate in most of sub-Saharan Africa, and the high rate of consanguinity, sickle cell disease and HIV drive the spectrum of paediatric kidney diseases in the continent. Kidney diseases are often precipitated by infectious triggers associated with poor living conditions and little access to medical care thus resulting in late presentation and often end-stage kidney disease. Although accessibility to kidney care has improved in the continent due to training opportunities provided by international professional organisations, most children still face significant barriers to kidney care because they live in rural areas, governments spend the least on healthcare and the continent has the least density of healthcare practitioners and nephrology trainees.


Medical students' readiness to provide lifestyle counseling for overweight patients.
In order to assess medical students' readiness to engage in lifestyle counseling regarding nutrition, physical activity, and other health behaviors, the authors examined the knowledge, attitudes, and health behaviors of medical students. The authors analyzed questionnaire responses of 290 medical students in their first, second, or third year. Students were generally knowledgeable about cardiovascular disease risk factors, however they were less knowledgeable about body mass index (BMI) and specific nutrition and physical activity recommendations. Students were confident in the ability of physicians to change patients' health behaviors and had positive attitudes about providing lifestyle counseling. The upper-level students held significantly less positive attitudes than the first-year students. Almost half the sample reported regularly making unhealthy dietary choices. Only 23% of the sample met the public health guidelines for accumulating 30 min of moderate activity on at least 5 days a week. Third-year students engaged in significantly less activity than their underclassmen. Although medical students express positive attitudes toward providing lifestyle counseling, they require more instruction in the areas of weight screening, nutrition, and physical activity recommendations in order to be helpful to their patients. Because physicians who practice health behaviors are more likely to provide counseling, it would be beneficial to integrate an emphasis on student health into medical curricula.


Postdialysis serum phosphate equilibrium in hemodialysis patients on a controlled diet and no binders.
Studies evaluating the change in serum phosphate post hemodialysis (HD) demonstrate an initial decline during dialysis but a rebound post dialysis. However, previous studies were done on usual diet and phosphate binders, with limited number of blood draws, confounding conclusions. We determined serum phosphate reduction, rebound, and equilibrium over 48 h in HD patients consuming a controlled, low phosphorus diet without binders. Serum phosphate (mg/dL) was analyzed before and after a HD treatment and frequently during the ensuing 48 h intradialytic period in the clinical research unit. Thirteen subjects were enrolled and had been off phosphate binders for 10 days and consumed a standardized low phosphate (900 mg/day) diet for 3 weeks prior to the assessments. Linear regression was used to determine relationships between the pre-HD serum phosphate, decline post-HD (post-HD drop); and a 48 h area under curve (AUC) using the trapezoidal method as a measure of overall phosphate levels from the end of dialysis to 48 h post dialysis. Repeated Measures ANOVA with Dunnett's posthoc test was used to determine rebound. Five of 13 subjects returned to >90% of their pre-HD serum phosphate within the first 24 h post-HD, and serum phosphate was 94 ± 0.11% (range 63%-113%) by 48 h after the completion of HD. The 48 h AUC of serum phosphate during the interdialytic period was correlated with both pre dialysis phosphorus (r = 0.85; p = 0.0002) and the pre-post drop in serum phosphate during dialysis (r = 0.69; p = 0.0085). In contrast, the net ultrafiltration was not related to the 48 h AUC of serum phosphorus (r = 0.20; p = 0.51). In hemodialysis patients on standard low phosphorus diet and no phosphate binders, the interdialytic serum phosphorus level, assessed as AUC, is determined by the pre dialysis phosphorus and net-change in serum phosphorus during the dialysis treatment, but not the ultrafiltration volume [Correction added on 25 January, after first online publication: In the last sentence of the Abstract, the word "potassium" has been replaced with "phosphorus" to improve accuracy.].


Gender similarities in the brain during mathematics development.
Some scientists and public figures have hypothesized that women and men differ in their pursuit of careers in science, technology, engineering, and mathematics (STEM) owing to biological differences in mathematics aptitude. However, little evidence supports such claims. Some studies of children and adults show gender differences in mathematics performance but in those studies it is impossible to disentangle intrinsic, biological differences from sociocultural influences. To investigate the early biology of mathematics and gender, we tested for gender differences in the neural processes of mathematics in young children. We measured 3-10-year-old children's neural development with functional magnetic resonance imaging (fMRI) during naturalistic viewing of mathematics education videos. We implemented both frequentist and Bayesian analyses that quantify gender similarities and differences in neural processes. Across all analyses girls and boys showed significant gender similarities in neural functioning, indicating that boys and girls engage the same neural system during mathematics development.


Pressure overload leads to an increase of cardiac resident stem cells.
Recent studies suggest that the mammalian heart possesses some capacity for cardiac regeneration. This regenerative capacity is primarily documented postnatally and after myocardial infarction or pressure overload. Although the cell type that mediates endogenous regeneration is unclear, cardiac stem cells might be considered as potential candidates. To determine the number of c-kit + cardiac resident cells under conditions of pressure overload, we evaluated specimens derived from n = 8 patients with pressure overloaded single right ventricles in comparison to n = 4 explanted hearts from patients with dilated cardiomyopathy and n = 14 biopsies from children after heart transplantation. The age of the patients ranged from 16 days to 19 years. For quantification of cardiac stem cells, c-kit+/mast cell tryptase-/CD45- cells were counted and expressed as percent of the total nuclei. In specimens from patients with dilated cardiomyopathy, 0.13 ± 0.09% c-kit +/mast cell tryptase-/CD45- cells were detected. However, in specimens from patients with pressure overloaded single right ventricles, the numbers of c-kit+/mast cell tryptase-/CD45- cells were significantly higher (0.41 ±0.24%, p < 0.05). Under conditions of pressure overload, the right ventricle shows an approximately three-fold increase in c-kit+/mast cell tryptase-/CD45- cardiac resident cells. Despite the fact that this increased number of c-kit+ cells is not sufficient to prevent the failing heart from congestive heart failure, understanding the mechanism that leads to an increase of presumably cardiac resident stem cells under conditions of pressure overload might help to develop new strategies to enhance endogenous repair.


Cost-effectiveness of pharmacist-led care versus usual care in type 2 diabetic Jordanians: a Markov modeling of cardiovascular diseases prevention.
Cardiovascular diseases (CVDs) are responsible for one third of global deaths and the main cause of death among Jordanians. Pharmacist-led care was outlined previously as a cost-effective approach in the management of chronic illness; however, this is not well studied in low to middle-income countries. To assess the cost-effectiveness of pharmacist-led care versus usual care in preventing CVDs in Type 2 Diabetes Mellitus (T2DM). A Markov model of one-year cycle length and 10-year time horizon was constructed to simulate 10-year CVD events, mortality, and costs for two hypothetical cohorts; usual care and pharmacist-led care, respectively, of Jordanian patients suffering from T2DM. Public health provider perspective was adopted. Outcomes examined were incremental costs, LYGs, and incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analysis (PSA) assessed the robustness of the results. The pharmacist-led care generated an additional 0.3 LYG/patient at an additional cost of JD1,238.78 (US$1,747.24) comparing to the usual care in the 10-year base-case analysis. Deterministic and PSA supported the robustness of base-case findings, indicating that pharmacist-led care is cost-effective. The findings outline long-term clinical and economic benefits of expanding clinical pharmacist's roles in direct patient care services.


SARS-CoV-2 spike codon mutations and risk of hospitalization after antispike monoclonal antibody therapy in solid organ transplant recipients.
Neutralizing antispike monoclonal antibody (mAb) therapies were highly efficacious in preventing coronavirus disease 2019 (COVID-19) hospitalization. While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants may harbor spike protein mutations conferring reduced in vitro susceptibility to these antibodies, the effect of these mutations on clinical outcomes is not well characterized. We conducted a case-control study of solid organ transplant recipients who received an antispike mAb for treatment of mild-to-moderate COVID-19 and had an available sample from initial COVID-19 diagnosis for genotypic sequencing. Patients whose SARS-CoV-2 isolate had at least one spike codon mutation conferring at least fivefold decreased in vitro susceptibility were classified as resistant. Overall, 9 of 41 patients (22%) had at least one spike codon mutation that confers reduced susceptibility to the antispike mAb used for treatment. Specifically, 9 of 12 patients who received sotrovimab had S371L mutation that was predicted to confer a 9.7-fold reduced susceptibility. However, among 22 patients who required hospitalization, 5 had virus with resistance mutation. In contrast, among 19 control patients who did not require hospitalization, 4 also had virus-containing resistance mutations (p > 0.99). In conclusion, spike codon mutations were common, though mutations that conferred a 9.7-fold reduced susceptibility did not predict subsequent hospitalization after treatment with antispike mAb.


Multiway clustering with time-varying parameters.
This paper proposes a clustering approach for multivariate time series with time-varying parameters in a multiway framework. Although clustering techniques based on time series distribution characteristics have been extensively studied, methods based on time-varying parameters have only recently been explored and are missing for multivariate time series. This paper fills the gap by proposing a multiway approach for distribution-based clustering of multivariate time series. To show the validity of the proposed clustering procedure, we provide both a simulation study and an application to real air quality time series data.


Effect of low speed drilling on osseointegration using simplified drilling procedures.
Our aim was to find out whether simplified drilling protocols would provide biological responses comparable to those of conventional drilling protocols at the low rotational speed of 400rpm. Seventy-eight root form endosseous implants with diameters of 3.75, 4.2, and 5mm were placed into canine tibias and allowed to heal for 3 and 5 weeks. After the dogs had been killed, the samples of implanted bone were retrieved and processed for non-decalcified histological sectioning. Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) analyses were made on the histological sections. Implants treated by the simplified protocol resulted in BIC and BAFO values comparable to those obtained with the conventional drilling protocol, and there were no significant differences in the technique or diameter of the drilling. The results suggest that the simplified procedure gives biological outcomes comparable to those of the conventional procedure.


Testosterone induces renal tubular epithelial cell death through the HIF-1α/BNIP3 pathway.
The morbidity of nephrolithiasis is 2-3 times higher in males than in females, suggesting that androgen plays a key role in nephrolithiasis. The death of renal tubular epithelial cells (TECs) is an important pathophysiological process contributing to the development of nephrolithiasis. Therefore, the aim of this study is to investigate whether androgen directly induces TECs apoptosis and necrosis and its underlying mechanisms in kidney stone formation. We compared serum testosterone level between male and female healthy volunteers and kidney stone patients. The in vivo nephrolithiasis model was established using glyoxylic acid, and calcium deposits were detected by van Kossa staining. In the in vitro study using mouse TECs (TCMK-1 cells) and human TECs (HK-2 cells), apoptosis, necrosis, and the expression of BH3-only protein Bcl-2-like 19 kDa-interacting protein 3 (BNIP3) were examined incubated with different doses of testosterone using flow cytometry. Levels of apoptosis-related proteins transfected with the BNIP3 siRNA were examined by western blotting. The mitochondrial potential (ΔΨm) was detected by JC-1 staining and flow cytometry. We monitored BNIP3 expression in the testosterone-induced TECs injury model after treatment with hypoxia inducible factor 1α (HIF-1α) and/or hypoxia inducible factor 2α (HIF-2α) inhibitors to determine the upstream protein regulating BNIP3 expression. Additionally, ChIP and luciferase assays were performed to confirm the interaction between HIF-1α and BNIP3. Both male and female patients have significantly higher testosterones compared with healthy volunteers. More calcium deposits in the medulla were detected in male mice compared to female and castrated male mice. Testosterone induced TECs apoptosis and necrosis and increased BNIP3 expression in a dose-dependent manner. Testosterone also increased Bax expression, decreased Bcl-2 expression and induced a loss of ΔΨm. This effect was reversed by BNIP3 knockdown. HIF-1α inhibition significantly decreased BNIP3 expression and protected TECs from testosterone-induced apoptosis and necrosis. HIF-2α inhibition, however, did not influence BNIP3 expression or TECs apoptosis or necrosis. Finally, HIF-1α interacted with the BNIP3 promoter region. Based on these results, testosterone induced renal TECs death by activating the HIF-1α/BNIP3 pathway.


A family of hydrogels based on ureido-linked aminopolyol-derived amphiphiles and bolaamphiphiles: synthesis, gelation under thermal and sonochemical stimuli, and mesomorphic characterization.
This article describes the systematic preparation of a novel family of carbohydrate amphiphiles and bolaamphiphiles in which hydrophilic and hydrophobic units are connected via a ureido or bis(ureido) moiety. The sugar core is derived from aminopolyols such as D-glucamine (1), N-methyl-D-glucamine (2), or the sugar-like species tris(hydroxymethyl)aminomethane (3). The O-unprotected derivatives behave as self-organizing nonionic surfactants with good water gelation ability, which can be induced under thermal or ultrasound-driven stimuli. In addition, some derivatives of 1 and 2, and rarely 3 also formed lyotropic liquid crystals with lamellar or hexagonal structures that exhibit low-temperature transitions.


Facilitation of the dorsal root potentials by volleys spreading caudally and cranially in the spinal cord.
Conditioning volleys spreading along 3 segments of the cord produce larger facilitation of bilateral dorsal root potentials in sacral cord than volleys in neighbouring dorsal roots used to evoke the testing depolarization. Contralateral potentials are more facilitated by volleys descending from lumbar than ascending from caudal segments.


Cardiovascular actions of the kappa-agonist, U-50,488H, in the absence and presence of opioid receptor blockade.
1. The cardiovascular actions of U-50,488H, a kappa-receptor agonist, were studied in rat isolated perfused hearts, and in anaesthetized rats, over concentrations or doses generally above those required to produce kappa-receptor-mediated effects. 2. U-50,488H dose-dependently decreased left-ventricular peak systolic pressure and beating rate in vitro and reduced blood pressure and heart rate in vivo. 3. Over the concentration range of 1-30 microM in vitro, and the dose-range of 0.5-32 mumol kg-1 in vivo, U-50,488H prolonged the P-R, QRS and Q-T intervals of the ECG. 4. The effects of U-50,488H were not antagonized by an opioid receptor antagonist, naloxone (1 microM or 8 mumol kg-1). Similarly, the opioid receptor antagonist, MR 2266, at 8 mumol kg-1 did not significantly reduce the cardiovascular actions of U-50,488H in vivo. 5. The actions of U-50,488H on responses to electrical stimulation were also studied. Over the dose range of 0.5-32 mumol kg-1, U-50,488H altered thresholds and effective refractory period. It had a biphasic action on thresholds for induction of ventricular fibrillation. Thresholds were decreased at lower doses (0.5-4 mumol kg-1) but increased at higher doses (8-32 mumol kg-1). The effects of lower doses were blocked by naloxone. Effective refractory period and threshold pulse width only increased with dose. 6. In conclusion, U-50,488H at high concentration, had direct depressant actions on cardiac contractility, electrical excitability and the ECG. These depressant effects were not antagonized by the opioid receptor antagonists, naloxone and MR 2266, and probably do not involve opioid receptors. Furthermore, some of the observed effects were those expected to result from sodium channel blockade.


The combined method: a novel access technique for fetal endoscopic surgery.
To develop practical and less invasive techniques for fetal endoscopic surgery, new methods of lifting the uterine wall to allow fetal surgery without maternal laparotomy were developed and assessed. Fetal endoscopic surgical procedures, including tracheostomy and umbilical vascular cannulation, were performed using one of the three methods to enter the uterus without maternal laparotomy in pregnant goats (n = 6; 105 to 115 days' gestation): (1) direct uterine lifting with an air-cushion device; (2) indirect uterine lifting, in which the uterine wall was fixed to the maternal abdominal wall using balloon tip ports inserted percutaneously by Seldinger's method, then the maternal abdomen was lifted mechanically; and (3) combined method, in which low pressure CO2 (5 mm Hg for initial inflation and 2 mm Hg for maintenance) was insufflated into the uterus in addition to the indirect uterine lifting cited above. The direct uterine lifting caused massive injury of myometrium and uterine membranes. The creation of intrauterine space and the protection of the membranes were not accomplished effectively by the indirect uterine lifting only. The combined method provided the adequate intrauterine space and excellent endoscopic visibility for completion of the endoscopic procedures with minimal uterine injury. The fetal endoscopic surgery may be accomplished simply and safely by the combined method, a novel technique of uterine lifting to allow fetal surgery without maternal laparotomy.


Lymph: (Fe)rrying Melanoma to Safety.
Lymph nodes are typically the first clinically detectable site of metastasis in melanoma, but the mechanisms that determine this preference are not well understood. An article in Nature reports that the unique composition of lymph may protect melanoma cells from ferroptosis-a form of iron-dependent cell death, thereby increasing metastatic efficiency.


Telehealth diabetes services for non-English speaking patients.
Several studies have shown the use of telehealth in diabetes management to be as efficacious as traditional clinic visits; however, these studies focused on English-speaking populations. The primary objective of this study was to evaluate whether telehealth is an effective approach for participation in pharmacist collaborative diabetes management services among non-English-speaking or limited English proficiency (LEP) patients at a federally qualified health center (FQHC). The secondary objective was to evaluate glycated hemoglobin (A1c) as a clinical outcome in patients participating in telehealth versus in-person visits. This study was a retrospective chart review. Patients were non-English-speaking or LEP adults (≥ 18 years of age) with a diagnosis of type-2 diabetes (T2D) referred for pharmacist collaborative diabetes management services by a medical provider. This study reviewed patient participation and A1c values over 6 months (May to October) of 2 consecutive years (2019 and 2020). In this study, 40 patients in 2019 and 50 patients in 2020 met the inclusion criteria. In 2019, the primary visit model was in-person and 123 total visits were scheduled with a pharmacist. In 2020, the primary visit model was telehealth and 143 total visits were scheduled. In 2019, there were 28 no-show visits, which accounted for 22.8% of total visits. In 2020, there were 27 no-show visits, which accounted for 18.9% of total visits. The mean change in A1c from baseline to follow-up was found to decrease by 1.0% in 2019 and 0.95% in 2020. We concluded that telehealth participation in pharmacist-provided collaborative T2D services and decrease in A1c were similar during telehealth compared with in-person visits among non-English-speaking and LEP patients at a FQHC. However, further studies with larger sample sizes are necessary to determine the overall impact of telehealth in non-English-speaking or LEP patients.


Development and validation of a liquid chromatography-mass spectrometry (LC-MS) assay for the determination of the anti-cancer agent N-[2-(dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide (SN 28049).
N-[2-(Dimethylamino)ethyl]-2,6-dimethyl-1-oxo-1,2-dihydrobenzo[b]-1,6-naphthyridine-4-carboxamide (SN 28049) is a potent topoisomerase II poison being developed to treat solid tumours. A reliable and sensitive LC-MS method has been developed and validated for the determination of SN 28049 in plasma using a structurally similar internal standard. This method had acceptable intra- and inter-assay accuracy (95-105%) and precision (R.S.D.<6.5%) over the range 0.062-2.5 microM (using a 100 microl sample), and had a lower limit of quantitation of 0.062 microM. Both aqueous and plasma solutions of SN 28049 were stable during short-term (24h at room temperature or 4 degrees C) and long-term storage (8 months at -80 degrees C), and following freezing and thawing (three cycles). The method was applied to study the pharmacokinetics of SN 28049 in mice after iv administration (8.9 mg/kg; n=3 mice per time point). The maximum plasma concentration achieved was 1.22+/-0.05 microM, and concentrations were measurable up to 12h post-administration. A bi-exponential concentration-time curve was observed with an elimination half-life of 2.3+/-0.2h (mean+/-S.E.), a volume of distribution of 34.5+/-2.2l/kg, and a plasma clearance of 12+/-0.5l/h/kg.


A predictive algorithm to identify ever smoking in medical claims-based epidemiologic studies.
To develop and validate an algorithm to estimate probability of ever smoking using administrative claims. Using population-based samples of Medicare-aged individuals (121,278 Behavioral Risk Factor Surveillance System survey respondents and 207,885 Medicare beneficiaries), we developed a logistic regression model to predict probability of ever smoking from demographic and claims data. We applied the model in 1,657,266 additional Medicare beneficiaries and calculated area under the receiver operating characteristic curve (AUC) using presence or absence of a tobacco-specific diagnosis or procedure code as our "gold standard." We used these "gold standard" and lung/laryngeal cancer codes to over-ride predicted probability as 100%. We calculated Spearman's rho between probability from this full algorithm and smoking assessed in prior Parkinson disease studies, by substituting our observed and prior ("true") smoking-Parkinson disease odds ratios into the attenuation equation. The predictive model contained 23 variables, including basic demographics, high alcohol consumption, asthma, cardiovascular disease and associated risk factors, selected cancers, and indicators of routine medical usage. The AUC was 67.6% (95% confidence interval 67.5%-67.7%) comparing smoking probability to tobacco-specific diagnosis or procedure codes. Spearman's rho for the full algorithm was 0.82. Ever smoking might be approximated in administrative data for use as a continuous, probabilistic variable in epidemiologic analyses.


Efficacy of hypolipidemic treatment in inhibition of experimental atherosclerosis: the effect of nicotinic acid and related compounds.
The hypolipidemic and antiatherogenic effects of different nicotinic acid derivatives were studied. Five rabbit groups maintained on an atherogenic diet were given simultaneously various nicotinic acid derivatives (50 mg/kg body weight/day): nicotinic acid, Xantinol-nicotinate, beta-pyridylcarbinol or Pirozadil (bis-3,4,5-trimethoxybenzoate, 2,6-pyridindiyldimethylene). All 4 compounds showed a clear hypocholesterolemic and antiatherogenic effect, as measured by serum cholesterol, and by planimetric evaluation of the aortic lesions in terms of percent surface area affected in the aortas and coronary lumen. The simultaneously observed elevation of the HDL/LDL cholesterol ratio of the aortic tissue possibly indicates an antiatherogenic effect of these changes.


Eudesmane-type sesquiterpene derivatives from Laggera alata.
Ten eudesmane-type sesquiterpene derivatives (1-10), including six cuauhtemone derivatives (1-6), one di-norsesquiterpene (3-oxo-di-nor-eudesma-4-en-11-oic acid, 7), and three eudesmane glycosides (alatoside F-H, 8-10) were isolated from the whole plants of Laggera alata together with 12 known compounds. Their structures were elucidated on the basis of extensive spectroscopic analysis, acid hydrolysis, and compounds 1 and 7 were studied by single-crystal X-ray diffraction analysis. The absolute configuration of 1 was determined by the application of the modified Mosher's method. All of the isolated eudesmane-type sesquiterpenes were evaluated for their cytotoxic activities on six human cancer cell lines, but all of the compounds were inactive on the tested cell lines in the concentration of 100 μg/mL.


Mechanical performance of acrylic bone cements containing different radiopacifying agents.
The effect that three different radiopacifying agents, two of them inorganic (BaSO4, ZrO2) and one organic (an iodine containing monomer, IHQM) have on the static and dynamic mechanical properties of acrylic bone cements was studied. Compressive and tensile strength, fracture toughness and fatigue crack propagation were evaluated. The effect of the inorganic fillers depends on their size and morphology. In relation to the radiolucent cement, the addition of zirconium dioxide improved significantly the tensile strength, the fracture toughness and the fatigue crack propagation resistance. In contrast, the addition of barium sulphate produced a decrease of the tensile strength, but did not affect the fracture toughness and improved the crack propagation resistance. When the iodine containing monomer was used, although the tensile strength and the fracture toughness increased, the fatigue crack propagation resistance remained as low as it was for the radiolucent cement.


Radionuclide esophageal transit study in detection of esophageal motor dysfunction: comparison with motility studies (manometry)
Radionuclide esophageal transit study (RETS) has been developed to assess motor function of the esophagus. The purpose of this study was to compare RETS to esophageal motility studies (EMS) in detection of motility disorders. A total of 109 consecutive patients without previous history of surgery on the esophagus underwent both RETS and EMS within one month of each other. Final diagnosis was divided into three categories: I--primary esophageal motor disorders (n = 39); II--reflux disease (n = 48); and III--non-cardiac chest pain and/or dysphagia (n = 22). Using EMS as the standard, the results of RETS were as follows: sensitivity for detection of motor dysfunction was 97%, 92%, and 77% for Groups I, II, and III, respectively, while specificity was 91% for Group II and 100% for Group III. Global sensitivity was 92% and specificity was 88%. No clinically significant motor disorders were missed by RETS. In conclusion, RETS is a useful noninvasive test for the screening of patients with symptoms thought to be of esophageal origin.


Processing of polarized light by squid photoreceptors.
Behavioural tests have demonstrated that cephalopods can discriminate light polarized in different planes, and the receptors have been localized by electrophysiological studies of the eye. Discrimination of the plane of polarization is a consequence of both the structure of the microvilli in the outer segments of the photoreceptors and the orientation of the photosensitive chromophore on these membranes. However, between the depolarizing receptor response resulting from photoreception and the behaviour of the animal, nothing is known about neuronal processing of polarized light by cephalopods. Here we show that some squid photoreceptors discriminate the plane of polarization within the spike train, and that any particular plane is seen as a variable intensity. Given the well known orthogonal orientation of microvilli in outer segments of adjacent photoreceptors and the physiological preference for one of two mutually perpendicular planes of polarization by single photoreceptors, we conclude that cephalopod vision is based on two complementary views of the world, each determined by the transformation of polarization-sensitive receptors into complementary intensity scales. A visual system based on this transformation would lead to enhanced contrast underwater and visualization of object details obscured by confounding highlights.


SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation.
Germ cell division and differentiation require intimate contact and interaction with the surrounding somatic cells. Luteinizing hormone (LH) triggers epidermal growth factor (EGF)-like growth factors to promote oocyte maturation and developmental competence by activating EGF receptor (EGFR) in somatic cells. Here, we showed that LH-EGFR signaling-activated sphingosine kinases (SphK) in somatic cells. The activation of EGFR by EGF increased S1P and calcium levels in cumulus-oocyte complexes (COCs), and decreased the binding affinity of natriuretic peptide receptor 2 (NPR2) for natriuretic peptide type C (NPPC) to release the cGMP-mediated meiotic arrest. These functions of EGF were blocked by the SphK inhibitor SKI-II, which could be reversed by the addition of S1P. S1P also activated the Akt/mTOR cascade reaction in oocytes and promoted targeting protein for Xklp2 (TPX2) accumulation and oocyte developmental competence. Specifically depleting Sphk1/2 in somatic cells reduced S1P levels and impaired oocyte meiotic maturation and developmental competence, resulting in complete female infertility. Collectively, SphK-produced S1P in somatic cells serves as a functional transmitter of LH-EGFR signaling from somatic cells to oocytes: acting on somatic cells to induce oocyte meiotic maturation, and acting on oocytes to improve oocyte developmental competence.


Cognitive impairment improves the predictive validity of physical frailty for mortality in patients with advanced heart failure referred for heart transplantation.
The aim of this study was to identify whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty provides better outcome prediction in patients with advanced heart failure referred for heart transplantation (HT). Beginning in March 2013, all patients with advanced heart failure referred to our Transplant Unit have undergone a physical frailty assessment using the Fried frailty phenotype. Cognition was assessed with the Montreal Cognitive Assessment and depression with the Depression in Medical Illness questionnaire. We assessed the value of 4 composite frailty measures: physical frailty (PF ≥ 3 of 5 = frailty), "cognitive frailty" (CogF ≥ 3 of 6 = frail), "depressive frailty" (DepF ≥ 3 of 6 = frail), and "cognitive-depressive frailty" (ComF ≥ 3 of 7 = frail) in predicting outcomes. Frailty was assessed in 156 patients (109 men, 47 women), aged 53 ± 13 years, and with a left ventricular ejection fraction of 27% ± 14%. Inclusion of cognitive impairment or depression in the definition of frailty increased the proportion classified as frail from 33% using PF to 42% using ComF. During follow-up, 28 patients died before ventricular assist device implantation or HT. Frailty was associated with significantly lower ventricular assist device- and HT-free survival, with CogF best capturing early mortality: 12-month survival for non-frail and frail cohorts was 81% ± 5% vs 58% ± 10% (p < 0.02) using PF and 85% ± 5% vs 56% ± 9% (p < 0.002) using CogF. Combining the Depression in Medical Illness score with PF or CogF did not strengthen the relationship between frailty and mortality. The addition of cognitive impairment to the assessment of PF strengthened its capacity to identify advanced heart failure patients referred for HT who are at high risk of early death.


Different Course of Immune Reactions and Endothelial Cell Loss after Penetrating Low-Risk Keratoplasty and Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Dystrophy.
The aim of this study was to compare the incidence of immune reactions and endothelial cell loss after penetrating keratoplasty (PKP) vs. Descemet membrane endothelial keratoplasty (DMEK) in patients with Fuchs endothelial dystrophy (FED). In the present retrospective study, a total of 962 surgeries (225 excimer laser PKP and 727 DMEK) of 700 patients performed between 28.06.2007 and 27.08.2020 in the Department of Ophthalmology at Saarland University Medical Center UKS were statistically evaluated. On the one hand, the prevalence and the temporal course of the immune reactions that occurred were analysed using the Kaplan-Meier method, as well as the effect of the immune reactions on the endothelial cells and corneal thickness. Secondly, endothelial cell density, pleomorphism, and polymegethism of the endothelial cells were evaluated for the time points U1 = preoperative, U2 = 6 weeks postoperative, U3 = 6 to 9 months postoperative, U4 = 1 to 2 years postoperative, and U5 = 5 years postoperative. In addition, statistical tests were carried out for differences between the two types of surgery and in the longitudinal course. A total of 54 immune reactions occurred during the observed period, whereby the probability of such a reaction was significantly greater in the PKP group with 8.9% than in the DMEK group with 4.5% (p = 0.011). The comparison of the two Kaplan-Meier curves also showed a significant difference between the two surgical techniques in the log-rank test (p = 0.012). The endothelial cell loss due to the immune reaction was only significant in PKP (p = 0.003). For all surgical procedures, endothelial cell density decreased significantly with time in both surgical techniques (p < 0.0001 in each case), but more strongly with DMEK than with PKP (p < 0.0001). Furthermore, this cell density was significantly higher with PKP than with DMEK for the whole observation time (p < 0.0001). Polymegethism decreased significantly in the DMEK group (p < 0.0001). Pleomorphism was significantly higher, on average, in DMEK than in PKP (p < 0.0001). The prognosis of DMEK in patients with FED seems to be more favourable after immune reactions than that of PKP, as not only were immune reactions less frequent, but they were also milder. However, endothelial cell density was significantly higher in the PKP group during the entire follow-up.


Acute myocardial infarction and 30-year coronary aneurysm follow-up by serial angiography in a young adult with Kawasaki disease.
The number of adult patients with coronary artery disease caused by Kawasaki disease (KD) is gradually increasing, but some patients drop out of clinical follow-up. However, careful, long-term follow-up and establishment of an optimal treatment strategy are needed in these patients, as well as cooperation between pediatric and adult cardiologists. We report a case of acute myocardial infarction in a young adult patient with KD whose serial coronary angiography was followed up for over 30 years. Successful reperfusion therapy was performed with thrombus aspiration, rotational atherectomy, and implantation of a drug-eluting stent.


Feelings of fear, sadness, and loneliness during the COVID-19 pandemic: Findings from two studies in the UK.
During the COVID-19 pandemic, exposure to COVID-related stimuli, has been enormous. Exposure to threat-related stimuli, can have a significant impact on people's wellbeing particularly in relation to COVID-related anxiety. The present research comprises two empirical studies. In Study 1, a newly developed Emotional Stroop Task (EST) and an Image Rating Task (IRT) were used to assess, automatic and non-automatic affective responses to COVID-related words and images during the first wave of the pandemic in the UK general population. In Study 2, the same tasks were used to evaluate the affective responses of University students during the second wave of the pandemic. Additionally, loneliness and pro-social behaviours were explored in relation COVID-related anxiety in the same population. Overall, the results showed that automatic affective responses as measured by interference effects on the EST, remained unaffected during the pandemic. However, non-automatic affective responses to COVID-related images measured by the IRT, indicated that participants rated these images as more fearful sadder and higher in anger, compared to non-COVID negative images matched for arousal and negativity and this was more evident in people with high COVID-anxiety. Trait anxiety was related to higher levels of loneliness, more prosocial behaviour and higher intentions to help others, while COVID-related anxiety mediated these effects, suggesting that for high levels of trait anxiety, participants were more likely to have helped someone in need during the pandemic when their COVID-anxiety levels were low.


Reproductive and endocrinological effects of Benign Prostatic Hyperplasia and finasteride therapy in dogs.
Benign prostatic hyperplasia (BPH) is one of the most important reproductive disorders in aging dogs. Therapeutic measures include orchiectomy and pharmacological treatment, leading to reduction of prostate volume and clinical signs. One of the most common drugs used in BPH treatment is finasteride, but data regarding its possible side effects are scarce. Thus, the aim of this study was to evaluate the effects of BPH and short-term (2 months) finasteride therapy on clinical, endocrinological, and reproductive parameters in dogs. Dogs were allocated into four experimental groups: Non-affected (n = 5), BPH (n = 5), Non-Affected-Finasteride (n = 5) and BPH-Finasteride (n = 5) groups. Dogs were evaluated monthly during 2 months by a complete breeding soundness examination, B-mode ultrasound and Doppler ultrasonography of the testicular artery, hormonal profile (testosterone, estrogen and dihydrotestosterone) and oxidative profile of the prostatic fluid. After 2 months, dogs were gonadectomized and testicles were subjected to histologic analysis. Finasteride treatment reduced dihydrotestosterone concentrations, without negative influence on semen quality and also reverted testicular hemodynamics changes of BPH. On the other hand, BPH was accompanied by significant changes in testosterone and estrogen concentrations and semen quality, mainly related to sperm kinetics alterations. In conclusion, BPH dogs have important hormonal and sperm alterations, however, short-term finasteride treatment (2 months) was able to reduce overall effects of BPH, thus representing a method of therapy for BPH treatment.


The Use of Augmented Reality to Improve Safety of Anterior Petrosectomy: Two-Dimensional Operative Video.
An anterior petrosectomy (AP) provides access to the upper petroclival region, but approach-related complications include seizures and temporal lobe hematomas.1 Moreover, the floor of the middle fossa contains multiple critical neurovascular structures, and drilling Kawase's quadrilateral must be performed carefully to avoid iatrogenic injury. In particular, the cochlea, carotid artery, and the contents of the internal acoustic canal are vulnerable because there are no locational cues to help the surgeon define their borders.2-4 In this video, we demonstrate the use of an augmented reality (AR) to protect critical structures during drilling of an AP. The illustrative case involves a 70-year-old woman with difficulty walking caused by a petrotentorial meningioma. The 3-dimensional, virtual reality rendering (Surgical Theater SRP7.4.0, Cleveland, Ohio, USA) of her patient-specific anatomy was enhanced by "painting" the cochlea, petrous carotid, labyrinthine, and the plane of the internal acoustic canal. This process takes 30-60 minutes, and the resulting rendering was used for surgical rehearsal to optimize the AP for tumor exposure. At surgery, our unique AR technique projects the painted anatomic landmarks into the eye-piece of the navigation-tracked microscope (Surgical Theater Sync AR v.3.8.0). Drilling is performed while the critical structures are visible in AR, superimposed on the patient's anatomy in real-time. The AP in surgery mimicked the one practiced during rehearsal and provided exposure to our patient's tumor. After surgery, the patient awoke without injury to her hearing, balance, or facial movements. By providing visual locational cues to the surgeon, we believe that AR improves the safety to the critical neurovascular structures during AP.


From cytogenetics to cytogenomics: whole-genome sequencing as a first-line test comprehensively captures the diverse spectrum of disease-causing genetic variation underlying intellectual disability.
Since different types of genetic variants, from single nucleotide variants (SNVs) to large chromosomal rearrangements, underlie intellectual disability, we evaluated the use of whole-genome sequencing (WGS) rather than chromosomal microarray analysis (CMA) as a first-line genetic diagnostic test. We analyzed three cohorts with short-read WGS: (i) a retrospective cohort with validated copy number variants (CNVs) (cohort 1, n = 68), (ii) individuals referred for monogenic multi-gene panels (cohort 2, n = 156), and (iii) 100 prospective, consecutive cases referred to our center for CMA (cohort 3). Bioinformatic tools developed include FindSV, SVDB, Rhocall, Rhoviz, and vcf2cytosure. First, we validated our structural variant (SV)-calling pipeline on cohort 1, consisting of three trisomies and 79 deletions and duplications with a median size of 850 kb (min 500 bp, max 155 Mb). All variants were detected. Second, we utilized the same pipeline in cohort 2 and analyzed with monogenic WGS panels, increasing the diagnostic yield to 8%. Next, cohort 3 was analyzed by both CMA and WGS. The WGS data was processed for large (> 10 kb) SVs genome-wide and for exonic SVs and SNVs in a panel of 887 genes linked to intellectual disability as well as genes matched to patient-specific Human Phenotype Ontology (HPO) phenotypes. This yielded a total of 25 pathogenic variants (SNVs or SVs), of which 12 were detected by CMA as well. We also applied short tandem repeat (STR) expansion detection and discovered one pathologic expansion in ATXN7. Finally, a case of Prader-Willi syndrome with uniparental disomy (UPD) was validated in the WGS data. Important positional information was obtained in all cohorts. Remarkably, 7% of the analyzed cases harbored complex structural variants, as exemplified by a ring chromosome and two duplications found to be an insertional translocation and part of a cryptic unbalanced translocation, respectively. The overall diagnostic rate of 27% was more than doubled compared to clinical microarray (12%). Using WGS, we detected a wide range of SVs with high accuracy. Since the WGS data also allowed for analysis of SNVs, UPD, and STRs, it represents a powerful comprehensive genetic test in a clinical diagnostic laboratory setting.


Correlation of particle properties with cytotoxicity and cellular uptake of hydroxyapatite nanoparticles in human gastric cancer cells.
Three types of hydroxyapatite nanoparticles (HAPNs) were synthesized employing a sonochemistry-assisted microwave method by changing microwave power (from 200 to 300W) or using calcination treatment: L200 (200W, lyophilization), L300 (300W, lyophilization) and C200 (200W, lyophilization & calcination). Their physiochemical properties were characterized and correlated with cytotoxicity to human gastric cancer cells (MGC80-3). The major differences among these HAPN preparations were their size and specific surface area, with the L200 showing a smaller size and higher specific surface area. Although all HAPNs inhibited cell proliferation and induced apoptosis of cancer cells, L200 exhibited the greatest toxicity. All types of HAPNs were internalized through energy-dependent pathways, but the L200 nanoparticles were more efficiently uptaken by MGC80-3 cells. Inhibitor studies with dynasore and methyl-β-cyclodextrin suggested that caveolae-mediated endocytosis and, to a much lesser extent, clathrin-mediated endocytosis, were involved in cellular uptake of the various preparations, whereas the inhibition of endocytosis was more obvious for L200. Using fluorescein isothiocyanate-labeled HAPNs and laser-scanning confocal microscopy, we found that all forms of nanoparticles were present in the cytoplasm, and some L200 HAPNs were even found within nuclei. Treatment with all HAPN preparations led to the increase in the intracellular calcium level with the highest level detected for L200.


Life-threatening pediatric dextromethorphan polistirex overdose.
Dextromethorphan polistirex is an extended-release formulation of dextromethorphan hydrobromide, marketed as Delsym® (Reckitt; Parsippany, NJ), with a duration of action roughly two to three times that of the standard formulation. The polistirex binder is responsible for the prolonged duration of action by slowing the release of active ingredient; the liberated dextromethorphan has unchanged pharmacokinetics and clinical effects. A 23-month-old male presented following a 900 mg (71.4 mg/kg) dextromethorphan polistirex ingestion 90 min prior. On arrival, he was unresponsive, tachycardic, and hypertensive with mydriasis, roving eye movements, rotary nystagmus, and opisthotonos. Approximately 90 min after arrival, he required intubation for airway protection. The blood dextromethorphan concentration from 75 min after arrival was 110 ng/mL (10-40 ng/ml therapeutic). He was extubated approximately 13 h after arrival and discharged that day. Most pediatric dextromethorphan overdoses produce mild symptoms that are not considered to be life-threatening. Life threatening overdoses are rare. The toxic dextromethorphan dose and blood concentration as well as the toxicokinetics of the polistirex formulation are not well defined. Our case suggests that a blood dextromethorphan concentration exceeding 100 ng/mL can be toxic in this age group, however further study is needed.


Diuretics and calcium metabolism.
In this review the normal renal tubular handling of calcium is briefly described. A detailed examination follows of the sites and modes of action of furosemide and thiazide diuretics on renal calcium handling and overall calcium metabolism. The clinical applications of these effects are also considered. Finally, the use of diuretics with different tubular sites of action on calcium transport as probes to study disorders of calcium excretion is discussed.


Gene Therapy for the Treatment of Neurological Disorders: Central Nervous System Neoplasms.
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults with a median survival of 16.2-21.2 months post diagnosis (Stupp et al., N Engl J Med 352(10): 987-996, 2005). Because of its location, complete surgical resection is impossible; additionally because GBM is also resistant to chemotherapeutic and radiotherapy approaches, development of novel therapies is urgently needed. In this chapter we describe the development of preclinical animal models and a conditionally cytotoxic and immune-stimulatory gene therapy strategy that successfully causes tumor regression in several rodent GBM models.


Tail-flick test. I: Impact of a suprathreshold exposure to radiant heat on pain reactivity in rats.
Radiant heat applied to the tail elicits a vigorous tail-flick response in rats. This tail-flick reflex is frequently used to measure pain reactivity. Prior research has shown that a suprathreshold exposure to the radiant heat used to elicit this reflex causes a reduction in tail-flick latencies in pentobarbital anesthetized rats. Experiment 1 replicated this observation and showed that the effect is not due to a change in tail temperature. Experiment 2 showed that reduced latencies (hyperalgesia) are not observed if the spinal cord is transected prior to testing. Experiment 3 revealed that pentobarbital anesthesia is required to observe thermal-induced hyperalgesia, for this effect is not observed in awake subjects. Experiments 4 and 5 extended this observation by showing that awake rats also fail to exhibit hyperalgesia if others measures of pain reactivity are employed (shock-induced vocalization and motor reactivity). Implications of the results are discussed.


[Bone histology and 25-OH vitamin D plasma levels in alcoholics without cirrhosis (author's transl)].
Bone mineralization is impaired in alcoholic non cirrhotics admitted to hospital for withdrawal. The defect is more marked in women than in men. Low 25-OH vitamin D plasma values may be observed in these patients and seem to be related to malnutrition. The degree of bone demineralization is not statistically correlated to 25-OH vitamin D plasma level.


Encapsulated titanium dioxide nanoparticle-Escherichia coli hybrid system improves light driven hydrogen production under aerobic condition.
Utilizing light energy for hydrogen production by combining nano-bio inspired photosynthetic system has received remarkable attention in renewable energy production. In this study, we applied a sodium alginate encapsulation strategy to our previously developed nano-bio hybrid system for photocatalytic hydrogen production under aerobic condition by combining the inorganic semiconductor titanium dioxide (TiO2), electron mediator methylviologen (MV2+), along with E. coli (hydrogenases) in an encapsulated system under the given light intensity of 2000 W m-2 and its hydrogen production efficiency was studied. Under aerobic condition the encapsulated hybrid system produced hydrogen (2.4 mmol H2/ mmol glucose) 3-fold higher than the unencapsulated hybrid system (0.8 mmol H2/ mmol glucose), suggesting that encapsulation is essential to protect oxygen sensitive hydrogenase under aerobic condition. The encapsulated hybrid system was also feasible under direct sunlight for hydrogen production. Overall, this study could serve as a new strategy for biological hydrogen production under aerobic condition.


alpha-Thalassemia and beta-thalassemia in a Turkish family.
A Turkish family is described in which three children have a clinical picture similar to that of thalassemia major, with typical red cell morphology and indices, and with about 10% Hb Bart's but without measurable amounts of Hb H. Hematological evaluation of six members of this family that included in vitro hemoglobin synthesis suggests that beta-(or delta beta-) thalassemia, beta-silent thalassemia, and mild and severe alpha-thalassemia genes are present in different combinations. The data indicate that beta/alpha chain ratios in patients with more than one type of thalassemia should be evaluated in relationship to values obtained for several relatives even though some of the thalassemia determinants may be silent in the parents.


Recruitment of coregulator G9a by Runx2 for selective enhancement or suppression of transcription.
Runx2, best known for its role in regulating osteoblast-specific gene expression, also plays an increasingly recognized role in prostate and breast cancer metastasis. Using the C4-2B/Rx2(dox) prostate cancer cell line that conditionally expressed Runx2 in response to doxycycline treatment, we identified and characterized G9a, a histone methyltransferase, as a novel regulator for Runx2 activity. G9a function was locus-dependent. Whereas depletion of G9a reduced expression of many Runx2 target genes, including MMP9, CSF2, SDF1, and CST7, expression of others, such as MMP13 and PIP, was enhanced. Physical association between G9a and Runx2 was indicated by co-immunoprecipitation, GST-pulldown, immunofluorescence, and fluorescence recovery after photobleaching (FRAP) assays. Since G9a makes repressive histone methylation marks and is primarily known as a corepressor, we further investigated the mechanism by which G9a functioned as a positive regulator for Runx2 target genes. Transient reporter assays indicated that the histone methyltransferase activity of G9a was not required for transcriptional activation by Runx2. Chromatin immunoprecipitation assays for Runx2 and G9a showed that G9a was recruited to endogenous Runx2 binding sites. We conclude that a subset of cancer-related Runx2 target genes require recruitment of G9a for their expression, but do not depend on its histone methyltransferase activity.


Outbreak report of SARS-CoV-2 infection by airborne transmission: Epidemiologic and molecular evidence.
It has been shown that the transmission of SARS-CoV-2 occurs mainly by air, and the risk of infection is greater in closed spaces. To describe the epidemiology, virology and molecular characterization of a COVID-19 outbreak at a closed vaccination point during the third wave of SARS-CoV-2 in Colombia. Diagnostic tests, interviews, sampling, cell cultures and viral sequencing were carried out, the latter being molecular characterization and lineage identification. Seven workers were positive for SARS-CoV-2; among these, 3 samples were analyzed, plus an additional sample belonging to the mother of the presumed index case; all samples were identified with lineage B.1.625, with a maximum of 2 nucleotides difference between them. Variant B.1.625 was identified as the cause of the COVID-19 outbreak, and a co-worker was also identified as the index case. Unexpectedly, attending a vaccination day became a risk factor for acquiring the infection.


Esophageal stasis in achalasia patients without symptoms after treatment does not predict symptom recurrence.
After achalasia treatment, a subset of patients has poor esophageal emptying without having symptoms. There is no consensus on whether to pre-emptively treat these patients. We hypothesized that, if left untreated, these patients will experience earlier symptom recurrence than patients without stasis. 99 treated achalasia patients who were in clinical remission (Eckardt ≤3) at 3 months after treatment were divided into two groups, based on presence or absence of esophageal stasis on a timed barium esophagogram performed after 3 months. Two years after initial treatment, patients with stasis after treatment still had a wider esophagus (3 cm; IQR: 2.2-3.8) and more stasis (3.5 cm; IQR: 1.9-5.6) than patients without stasis (1.8 cm wide and 0 cm stasis; both P<.001). In patients with stasis, the esophageal diameter had increased from 2.5 to 3.0 cm within 2 years of follow-up. The symptoms, need for and time to retreatment were comparable between the two groups. Quality of life and reflux symptoms were also comparable between the two groups. Although patients with stasis initially had a wider esophagus and 2 years after treatment also had a higher degree of stasis and a more dilated esophagus, compared to patients without stasis, they did not have a higher chance of requiring retreatment. We conclude that stasis in symptom-free achalasia patients after treatment does not predict treatment failure within 2 years and can therefore not serve as a sole reason for retreatment.


Mutational analyses of the nonconserved sequences in the Bunyamwera Orthobunyavirus S segment untranslated regions.
Bunyamwera virus (BUNV) is the prototype of the genus Orthobunyavirus and the family Bunyaviridae. BUNV has a tripartite genome of negative-sense RNA composed of small (S), medium (M), and large (L) segments. Partially complementary untranslated regions (UTRs) flank the coding region of each segment. The terminal 11 nucleotides of these UTRs are conserved between the three segments and throughout the genus, while the internal regions are unique to each segment and largely nonconserved between different viruses. To investigate the functions of the UTR sequences, we constructed a series of BUNV S segment cDNA clones with deletions in the 3' and/or 5' UTR and then attempted to rescue these segments into recombinant viruses. We found that the genomic 5' UTR was much more sensitive to mutation than the 3' UTR and, in general, sequences proximal to the termini were more important than those flanking the coding region. Northern blot analyses of infected-cell RNA showed that the internal, nonconserved sequences of the S segment 3' UTR play a role in the regulation of transcription and replication and the balance between these two processes. In contrast, deletions in the 5' UTR caused attenuation of the recombinant virus but did not specifically affect levels of S segment RNAs or the encoded nucleocapsid protein. Thus, the internal regions of both UTRs are functional: most of the 5' UTR is essential to viral growth, and, while nonessential, the internal 3' UTR is important to the regulation of viral RNA synthesis.


Relationship between serum angiotensin-converting enzyme activity and plasma plasminogen activator inhibitor activity in patients with recent myocardial infarction.
An elevated level of angiotensin-converting enzyme (ACE) has been demonstrated to increase the risk of myocardial infarction. Plasminogen activator inhibitor (PAI) is the most important physiological inhibitor of tissue plasminogen activator in plasma. An elevated level of PAI has been reported to be associated with decreased fibrinolytic capacity and to constitute a marker of the risk for recurrent coronary thrombosis. We measured the serum ACE activity and plasma PAI activity in 34 patients with recent myocardial infarction, and evaluated the correlation between these two values by linear regression analysis. We also administered captopril (37.5 mg/day) to 17 of these patients and placebo to the other 17 patients at random, and compared the changes in PAI activity and ACE activity in these two groups over a 1-month period. There was a significant correlation between the serum ACE activity and the plasma PAI activity at baseline in the patients (r = 0.498, P < 0.01). The captopril-treated patients showed significantly reduced PAI activity (P < 0.01), and a concomitant decrease in ACE activity. These results suggest that elevated ACE activity is associated with impaired fibrinolysis and that treatment with an ACE inhibitor improves the fibrinolytic function in patients with recent myocardial infarction. The results also suggest that the renin-angiotensin system plays a role in the increased risk of ischemic cardiovascular events when it is activated, and in the reduction of risk of recurrent myocardial infarction by ACE inhibition.


Differentiation of the intracytoplasmic membrane of Rhodopseudomonas palustris induced by variations of oxygen partial pressure or light intensity.
The photosynthetic apparatus of Rhodopseudomonas palustris contains, in addition to reaction center bacteriochlorophyll (Bchl) two spectral forms of light harvesting (LH) Bchl, i.e. LH Bchl I, characterized by an infrared absorption maximum at 880 nm (890 nm at 77 degrees K) and LH Bchl II absorbing at 805 and 855 nm (805 and 870 nm at 77 degrees K). LH Bchl I seems to be associated with a single protein species of an apparent mol. wt. of 13 000 whereas LH Bchl II is apparently associated with two proteins of mol. wts. of 9000 and 11 000. Cells in anaerobic cultures adapt to changes of light intensity 1. by variation of the size of the photosynthetic unit, i.e. the molar ratio of LH Bchl II to reaction center Bchl, 2. by variation of the number of photosynthetic units per unit of membrane area, 3. by regulation of the size of the intracytoplasmic membrane system. During adaptation of changes of oxygen partial pressure cells are able to synthesize reaction center Bchl, LH Bchl and intracytoplasmic membranes at different rates. The synthesis of reaction center Bchl and LH Bchl I are, however, coordinated with each other, while the synthesis of LH Bchl II and reaction center Bchl proceed independently.


Integrated green algal technology for bioremediation and biofuel.
Sustainable non-food energy biomass and cost-effective ways to produce renewable energy technologies from this biomass are continuously emerging. Algae are capable of producing lipids and hydrocarbons quickly and their photosynthetic abilities make them a promising candidate for an alternative energy source. In addition, their favorable carbon life cycle and a renewed focus on rural economic development are attractive factors. In this review the focus is mainly on the integrated approach of algae culture for bioremediation and oil-based biofuel production with mention of possible other value-added benefits of using algae for those purposes.