Endurance-dependent urinary extracellular vesicle signature: shape, metabolic miRNAs, and purine content distinguish triathletes from inactive people.
Extracellular vesicles (EVs) enriched with bioactive molecules have gained considerable attention in nanotechnology because they are critical to intercellular communication while maintaining low immunological impact. Among biological matrices, urine has emerged as a noninvasive source of extracellular-contained liquid biopsy, currently of interest as a readout for physiological adaptations. Therefore, we aimed to evaluate chronic adaptations of endurance sport practice in terms of urinary EV parameters and evaluated by food consumption assessment. Two balanced groups of 13 inactive controls vs. triathlon athletes were enrolled; their urinary EVs were obtained by differential ultracentrifugation and analyzed by dynamic light scattering and transmission electron and atomic force microscopy. The cargo was analyzed by means of purine and miRNA content through HPLC-UV and qRT-PCR. Specific urinary EV signatures differentiated inactive versus endurance-trained in terms of peculiar shape. Particularly, a spheroid shape, smaller size, and lower roughness characterize EVs from triathletes. Metabolic and regulatory miRNAs often associated with skeletal muscle (i.e., miR378a-5p, miR27a-3p, miR133a, and miR206) also accounted for a differential signature. These miRNAs and guanosine in urinary EVs can be used as a readout for metabolic status along with the shape and roughness of EVs, novel informative parameters that are rarely considered. The network models allow scholars to entangle nutritional and exercise factors related to EVs' miRNA and purine content to depict metabolic signatures. All in all, multiplex biophysical and molecular analyses of urinary EVs may serve as promising prospects for research in exercise physiology.


Transthoracic high frequency (7.5 MHz) echocardiographic assessment of coronary vascular reserve and its relation to left ventricular mass.
Transthoracic high frequency (7.5 MHz) ultrasonography can visualize the distal left anterior descending coronary artery. Thirty-seven patients were studied before and after administration of 0.4 mg sublingual nitroglycerin to determine whether this technique could quantitatively record changes in coronary artery diameter after intervention. Left anterior descending coronary artery diameter increased from 2.2 to 2.8 mm (p less than 0.05). The vasodilator response of this artery was compared with left ventricular mass index in normal subjects, patients with congestive cardiomyopathy and those with end-stage renal disease and left ventricular hypertrophy. Left anterior descending artery diameter increased 55% in normal subjects, 27% in patients with dilated cardiomyopathy and 10% in those with end-stage renal disease with left ventricular hypertrophy. These results demonstrate that high frequency ultrasound can detect nitroglycerin-induced changes in left anterior descending artery diameter. The percent increase is related to the diameter before nitroglycerin administration, which is related to the underlying diagnosis and left ventricular mass index.


Multiple spinal arteriovenous fistulas: A case-based review.
The occurrence of multiple spinal dural arteriovenous fistulas (AVFs) is rare. The majority of cases reported are synchronous and the lesions are mainly found at different spinal levels. Metachronous AVFs have been defined as lesions that manifest in a temporal sequence after treatment of a first AVF. In this report, we present two distinct cases of multiple spinal AVFs. Also, we review the main features of the cases previously reported, with emphasis on the proposed theories for the origin of multiple AVFs. In patients with failure to improve after treatment of a spinal DAVF, a whole-spine angiographic examination is mandatory, not only to ascertain the complete closure of the treated fistula, but also to look for a possible second lesion at a different spinal level.


Targeted delivery of 5-fluorouracil, miR-532-3p, and si-KRAS to the colorectal tumor using layer-by-layer liposomes.
Co-delivery of siRNA or miRNA with chemotherapeutic drugs into tumor sites is an attractive synergetic strategy for treating colorectal cancer (CRC) due to their complementary mechanisms. In the current work, a liposome nanoparticle (Huang et al., Cancer Metastasis Rev., 2018, 37, 173-187) coated by cationic chitosan (CS) using a controlled layer-by-layer (LbL) process was designed to deliver simultaneous si-KRAS, miRNA-532-3p, and 5-Fluorouracil (5-FU) into CRC cells. The LbL NPs exhibited a spherical structure with an average size of 165.9 nm and effectively protected si-KRAS and miRNA-532-3p against degradation by serum and nucleases. Interestingly, the LbL NPs were successfully entered into cells and efficiently promoted cytotoxicity and suppressed cancer cell migration and invasion. In vivo, the LbL NPs reduced tumor growth in SW480-tumor-bearing mice models. In conclusion, these results suggested that the LbL NPs co-loaded with 5-FU and miR-532-3p/si-KRAS might provide a promising potential strategy for inhibiting the malignant phenotypes of CRC cells.


Impact of BMI and the metabolic syndrome on the risk of diabetes in middle-aged men.
The existence of an obese subgroup with a healthy metabolic profile and low diabetes risk has been proposed; yet long-term data are lacking. We aimed to investigate associations between combinations of BMI categories and metabolic syndrome and risk of type 2 diabetes in middle-aged men. At age 50, cardiovascular risk factors were assessed in 1,675 participants without diabetes in the community-based Uppsala Longitudinal Study of Adult Men (ULSAM) study. According to BMI/metabolic syndrome status, they were categorized as normal weight (BMI <25 kg/m²) without metabolic syndrome (National Cholesterol Education Program criteria, n = 853), normal weight with metabolic syndrome (n = 60), overweight (BMI 25-30 kg/m²) without metabolic syndrome (n = 557), overweight with metabolic syndrome (n = 117), obese (BMI >30 kg/m²) without metabolic syndrome (n = 28), and obese with metabolic syndrome (n = 60). We investigated the associations between BMI/metabolic syndrome categories at baseline and diabetes incidence. After 20 years, 160 participants had developed diabetes. In logistic regression models adjusting for age, smoking, and physical activity, increased risks for diabetes were observed in the normal weight with metabolic syndrome (odds ratio 3.28 [95% CI] 1.38-7.81; P = 0.007), overweight without metabolic syndrome (3.49 [2.26-5.42]; P < 0.001), overweight with metabolic syndrome (7.77 [4.44-13.62]; P < 0.001), obese without metabolic syndrome (11.72 [4.88-28.16]; P < 0.001), and obese with metabolic syndrome (10.06 [5.19-19.51]; P < 0.001) categories compared with the normal weight without metabolic syndrome category. Overweight or obese men without metabolic syndrome were at increased risk for diabetes. Our data provide further evidence that overweight and obesity in the absence of the metabolic syndrome should not be considered a harmless condition.


A Protective Role of Coenzyme Q10 in Ethambutol-Induced Retinal Ganglion Cell Toxicity: A Randomised Controlled Trial in Mice.
Ethambutol is a widely used drug to treat tuberculosis that may cause visual disturbance including ethambutol toxic optic neuropathy (ETON). The disease disrupts bodily tissues' energy production, including the retinal ganglion cells (RGC). Many have proposed treatment with coenzyme Q10 (coQ10) due to its antioxidant and facilitative effects that can improve mitochondrial electron transport. The present study hence assessed whether coQ10 could protect against ETON through a parallel triple-blinded randomised controlled trial in 18 mice using computer-generated tables for treatment allocation. All of the mice received 25 mg/kg ethambutol daily, while only nine in the treated group also received 100 mg/kg coQ10. After 30 days, blinded pathologists counted RGC numbers in enucleated and dyed orbital tissue. The treated group had significantly denser RGCs at 47.2 (standard deviation [SD] 10.6) cells per 500 µm microscope field vs 33.5 (SD 6.3) in the control group (t = 3.34, p = .004). CoQ10 therefore protected RGCs from ETON. Clinical trials of coQ10 in human subjects treated with ethambutol should be considered.


Experimental and Theoretical Study of the Kinetics of the CH3 + HBr → CH4 + Br Reaction and the Temperature Dependence of the Activation Energy of CH4 + Br → CH3 + HBr.
The rate coefficient of the reaction of CH3 with HBr was measured and calculated in the temperature range 225-960 K. The results of the measurements performed in a flow apparatus with mass spectrometric detection agree very well with the quasiclassical trajectory calculations performed on a previously developed potential energy surface. The experimental rate coefficients are described well with a double-exponential fit, k1(exp) = [1.44 × 10-12 exp(219/T) + 6.18 × 10-11 exp(-3730/T)] cm3 molecule-1 s-1. The individual rate coefficients below 500 K accord with the available experimental data as does the slightly negative activation energy in this temperature range, -1.82 kJ/mol. At higher temperatures, the activation energy was found to switch sign and it rises up to about an order of magnitude larger positive value than that below 500 K, and the rate coefficient is about 50% larger at 960 K than that around room temperature. The rate coefficients calculated with the quasiclassical trajectory method display the same tendencies and are within about 8% of the experimental data between 960 and 300 K and within 25% below that temperature. The significant variation of the magnitude of the activation energy can be reconciled with the tabulated heats of formation only if the activation energy of the reverse CH4 + Br reaction also significantly increases with the temperature.


Guillain-Barré syndrome diagnosed as central cervical spinal cord injury after hyperextension injury.
The clinical features of Guillain-Barré syndrome (GBS) are progressive, fairly symmetric muscle weakness, and patients present a few days to a week after onset of symptoms. A 63-y-old man strongly hit his forehead, and next day felt paresthesia in both upper limbs, with difficulty in walking. Spinal cord injury (SCI) was suspected; the cervical cord was severely compressed at the C4 level. He was diagnosed with central cervical SCI and transferred to a community hospital. Three days after the injury, oxygenation worsened, and the patient was transferred to our hospital for laminoplasty. After admission, we noticed bilateral ptosis-an atypical finding for SCI. Under analgesic sedation, he could only move his fingertips. Severe respiratory muscle weakness and absence of reflexes were observed. Moreover, albuminocytologic dissociation and decreased motor nerve conduction were observed, and GBS was suspected. Intravenous immunoglobulin was administered; thereby, the muscle weakness gradually improved, and the patient returned to work. Muscle weakness usually starts in the legs in GBS; however, in 10% of patients, it starts in the arms. In our patient, the symptoms started with paresthesia, followed by severe respiratory muscle weakness in a short period. Furthermore, intubation made history-taking and neurological examination difficult. The degree of inflammation in the acute GBS phase correlates with the severity of nerve injury. Therefore, early diagnosis and treatment of GBS is important. We should perform detailed history-taking and consider GBS as a differential diagnosis, especially when neurological examination cannot be performed at the emergency department.


Metformin functionalized dendritic fibrous nanosilica (KCC-1-nPr-Met) as an innovative and green nanocatalyst for the efficient synthesis of tetrahydro-4H-chromene derivatives.
An innovative nanocatalyst (KCC-1-nPr-Met) has been prepared from the covalent attachment of metformin on the channels and the pores of n-propyl amine functionalized dendritic fibrous nanosilica (DFNS) and used towards efficient, green, and high yield synthesis of tetrahydro-4H-chromenes derivatives by one-pot three-component reaction of aromatic aldehydes, malononitrile, and dimedone in H2 O-EtOH at room temperature. The designed nanocatalyst has been characterized by energy dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FT-IR), and adsorption/desorption analysis (BET) techniques. Also, field emission scanning electron microscopy (FE-SEM) was used to study the morphology of prepared nanocatalyst. The engineered nanocatalyst with uniform fibrous spheres has dendritic structure, high pore volume (0.35 cm3 /g), and great surface area (178 m2 /g). Hence, the specific dendritic structure of the prepared nanocatalyst not only improve the diffusion ability of the reactants and products, but also, increase the availability of dynamic sites in the pores and channels of the catalyst. According to the obtained results, a unique strategy was proposed towards the synthesis of important biologically active scaffolds in the presence of nontoxic and environmental friendly nanocatalyst and media. Milder reaction conditions (room temperature), shorter reaction times (5-30 minutes), excellent yields (92%-98%) of the products with higher purity, very simple workup procedure, and using of EtOH: H2 O as a green solvent are the advantages of the presented work.


An investigation of the effects of metformin on ovarian ischemia-reperfusion injury in rats.
Damage to the ovaries or tissue torsion can significantly reduce the ovarian reserve and thus cause severe gynecological and hormonal deficiencies. The discovery of new agents is always needed in the treatment of this condition. Metformin (MET) has been shown to be beneficial in attenuating ovarian ischemia-reperfusion injury. Fifty-six female Sprague Dawley rats were divided into seven groups. Group 1 represented the control group (C), Group 2, the ischemia group (I), and Group 3, the ischemia/reperfusion group (I/R). Group 4, the ischemia (I)+250 group, and Group 5, the ischemia (I)+500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Group 6, the ischemia/reperfusion (I/R)+250 group, and Group 7, the ischemia/reperfusion (I/R)+500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Tissue malondialdehyde (MDA), glutathione (GSH), and tumor necrosis factor-alpha (TNF-α) levels in ovarian tissue increased following I/R, while estradiol (E2) levels decreased. Moreover, infiltration and diffuse edematous areas were observed in addition to diffuse vascular congestion and hemorrhage findings. Caspase-3 and nuclear factor kappa B (NF-κβ) expression levels also increased. MDA and TNF-α concentrations decreased in the MET treatment groups, while GSH and E2 levels increased. The findings showed that I/R causes ovarian damage through the induction of oxidative stress, inflammation, and apoptosis. However, MET application was effective in preventing damage in ovarian tissue by reducing levels of reactive oxygen species, proinflammatory cytokines, caspase-3 and NF-κβ.


[Comparison of the effectiveness of artemether and quinine for treatment of severe malaria in children, Bangui, Central African Republic].
The management of severe malaria is a major challenge in the health care services in sub-Saharan Africa. This study aimed to assess the efficacy and safety of artemether and quinine in severe malaria at Complexe pédiatrique of Bangui, Central African Republic. A total of 212 children among 1125 hospital admissions (18.8%), and aged 6 to 59 months were randomly treated with artemether and quinine. Anemia (58.5%) and seizures (33.5%) were the major syndromes observed. On the third day of follow up, a regression of clinical signs and parasite clearance were observed in 98.1% of children treated with artemether and 97.1% of children treated with quinine. The death rate was 2.3% due to anemic and neurological forms. These findings show that the artemether and quinine have similar efficacy. Hence, associated with adequate intensive health care, the use of these antimalarial drugs can significantly reduce mortality from severe malaria in the Central African Republic.


Prognostic Impact of Pre- and Post-Procedural Renal Dysfunction on Late All-Cause Mortality Outcome Following Transcatheter Edge-to-Edge Repair of the Mitral Valve: A Systematic Review and Meta-Analysis.
Impaired renal function, a well-recognized complication of severe heart failure is associated with adverse outcomes following cardiovascular interventions. There are conflicting data reported about its impact on late all-cause mortality following transcatheter edge-to-edge mitral valve repair (TEER) with MitraClip (MC) implantation. To evaluate the impact of pre- and post- procedural renal dysfunction on late (≥12 months) all-cause mortality following TEER with MC. Electronic databases PubMed, Embase, and Web of Science were systematically reviewed from inception to February 2021 for studies evaluating MC outcomes, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A random-effects model meta-analysis was performed and heterogeneity of the included studies was assessed using I-squared test. Out of 2606 articles, 15 studies with 19,545 patients were included. Pre-procedural renal dysfunction i.e. chronic kidney disease (CKD) was independently associated with higher late all-cause mortality (Hazard ratio [HR] 1.57, 95% CI 1.25-1.97, I2 = 57%) after TEER with MC. A similar association was observed irrespective of CKD severity (HR 1.62 95% CI 1.21-2.16, I2 = 0% and HR 2.86, 95% CI 1.87-4.39, I2 = 26% for CKD stage 3 and ≥ stage 4 respectively). In addition, the development of post-procedural renal dysfunction was independently associated with higher late all-cause mortality (HR = 2.32, 95% CI 1.71-3.15, I2 = 42%) after TEER with MC. Pre- and post-procedural renal dysfunction is a strong independent predictor of late all-cause mortality following TEER with MC and this should be considered during periprocedural planning for these patients.


A retrospective study of arterial stiffness and subsequent clinical outcomes in cancer patients undergoing percutaneous coronary intervention.
Increasing attention is being paid to the relationship between cancer and cardiovascular diseases. In this study, we examined arterial stenosis and stiffness in patients with malignant diseases requiring percutaneous coronary intervention. This was a retrospective, single-center, observational study. Participants (n = 1003) were divided into a malignant group, with current or past malignant disease, and a nonmalignant group. The ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) were evaluated. The endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, and revascularization within 1 year. We observed significantly impaired ABI and baPWV in the malignant group. A total of 148 patients had a cardiovascular event. Kaplan-Meier analysis showed a significantly higher probability of cardiovascular events in the malignant group (P = 0.012). The combination of malignancy with ABI/baPWV identified subgroups with significantly different probabilities of cardiovascular events. Multivariate Cox hazard analysis identified malignancy as an independent predictor of cardiovascular events (hazard ratio, 1.54; 95% confidence interval, 1.06-2.26; P = 0.025) with an increased hazard ratio by adding the status of low ABI/high baPWV to malignancy (hazard ratio, 2.36; 95% confidence interval, 1.35-4.12; P = 0.003). We found significantly higher follow-up baPWV values in the malignancy group (P = 0.016). Atherosclerosis is advanced and accelerated in patients with malignancy, and these patients had significantly higher rates of adverse cardiovascular events, and their risk might be stratified by ABI and baPWV. University Hospital Medical Information Network-CTR (http://www.umin.ac.jp/ctr/). Kumamoto University Malignancy and Atherosclerosis study (UMIN000028652). Opt-out materials are available at the following website: http://www.kumadai-junnai.com/home/wp-content/uploads/akusei.pdf.


'Wind turbine syndrome': fact or fiction?
Symptoms, including tinnitus, ear pain and vertigo, have been reported following exposure to wind turbine noise. This review addresses the effects of infrasound and low frequency noise and questions the existence of 'wind turbine syndrome'. This review is based on a search for articles published within the last 10 years, conducted using the PubMed database and Google Scholar search engine, which included in their title or abstract the terms 'wind turbine', 'infrasound' or 'low frequency noise'. There is evidence that infrasound has a physiological effect on the ear. Until this effect is fully understood, it is impossible to conclude that wind turbine noise does not cause any of the symptoms described. However, many believe that these symptoms are related largely to the stress caused by unwanted noise exposure. There is some evidence of symptoms in patients exposed to wind turbine noise. The effects of infrasound require further investigation.


Transcranial direct current stimulation associated with physical-therapy in acute stroke patients - A randomized, triple blind, sham-controlled study.
Transcranial Direct Current Stimulation has been increasing in popularity in the last few years. Despite vast amounts of articles on the use of tDCS on stroke patients, very little has been done during the acute phase. Measure the effects of tDCS on functional and sensory outcomes throughout the first year post onset of stroke. 50 acute stroke patients were randomized and placed into either the treatment or sham group. Anodal tDCS was applied (2 mA, 20 min) 5 times a week during the first month post stroke. Patients were evaluated with the Wolf Motor Function Test, the Semmes Weinstein Monofilament Test, the Upper Extremity section (UEFM), the Lower Extremity section (LEFM) and the Somatosensory section of the Fugl Meyer Test, the Tardieu Spasticity Scale, the Stroke Impact Scale (SIS), the Hospital Anxiety and Depression Scale (HADS) and the Barthel Index. Evaluations were held at 48 h post stroke, week 1, 2, 3, 4, 3 months, 6 months and 1 year. There were statistically and clinically significant improvements after tDCS in all functional motor outcomes, and somatosensory functions. Differences between both groups for the main outcome (WMFT time) were 51% (p = 0.04) at one month, and 57% (p = 0.02) at one year. tDCS seems to be an effective adjuvant to conventional rehabilitation techniques. If applied in the acute stages of stroke, functional recovery is not only accelerated, but improved, and results are maintained up to one-year post stroke.


[Epidermal growth factor with insulin used for stimulation of exogenous colony formation in the spleen of mice irradiated with lethal doses of X-rays].
Epidermal growth factor (12 ng per 1 g of body mass) and insulin (0.004 units per 1 g of body mass) were introduced into X-ray irradiated (1.8, 2.12, 2.7 Cr) mice. Four hours later bone marrow was extracted from femurs to be introduced into syngenic lethally irradiated recipients. On the 11th day after transplantation the number of exogenic spleen colonies was computed. The epidermal growth factor, in combination with insulin, stimulates in the organism the restoration of hemopoietic colony-forming cells after radiation injury.


The effect of orthognathic surgery on occlusal force.
To investigate the effect of orthognathic surgery on occlusal force, such force was measured during maximum effort, chewing, and swallowing in 70 patients who had superior repositioning of the maxilla and/or mandibular advancement or setback. Larger changes in occlusal force than could be accounted for by the altered geometry were observed in all groups. Of 15 patients who had only superior repositioning of the maxilla, ten had greater than 20% increase in occlusal force, three had little change, and two showed a greater than 20% decrease. When the mandible was advanced, 11 of 34 patients had greater than 20% increase in maximum biting force, 11 had little or no change, and 12 had greater than 20% decrease. When the mandible was set back, six of the 21 patients had greater than 20% increase, nine had little or no change, and six had greater than 20% decrease. It appears that considerable change in bit force, which is not primarily related to jaw geometry, occurs after orthognathic surgery.


Neuraminidase fluorescence test for the differentiation of Trypanosoma cruzi and Trypanosoma rangeli.
The cell free supernatants of 13 stocks of Trypanosoma rangeli/T. rangeli-like, 50 stocks of T. cruzi/T. cruzi-like and 3 stocks of T. conorhini grown in culture were examined by using the 2-(4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid) test. It could be demonstrated that only the supernatants of the T. rangeli/T. rangeli-like stocks showed a white-yellow fluorescence under UV light. In contrast, the cell free supernatants of the T. cruzi/T. cruzi-like and T. conorhini stocks showed an ash-grey colour under UV light undistinguishable from that of the control reactions. The 4-MUAc test could be a method of choice for the routine detection of T. rangeli/T. rangeli-like flagellates in culture.


Influence of some traditional medicinal plants of Senegal on prostaglandin biosynthesis.
Aqueous extracts of Combretum micranthum G. Don, Euphorbia hirta L., Guiera senegalensis Lam. and Melaleuca leucadendron L. were investigated for their influence on prostaglandin biosynthesis (PG I2, PG E2, PG D2). Only the extract of Euphorbia hirta strongly reduced the release of prostaglandins I2, E2, and D2. Additionally Euphorbia hirta extracts exerted an inhibitory effect on platelet aggregation and depressed the formation of carrageenin induced rat paw oedema. The chemical nature of the active principle of Euphorbia hirta could be characterized as (a) compound(s) of medium polarity in the molecular weight range of 1000 to 3000 Da.


Dimeric antioxidant and cytotoxic triterpenoid saponins from Terminalia ivorensis A. Chev.
Three saponins, including two dimeric triterpenoid glucosides possessing an unusual skeleton, ivorenosides A and B, and a monomeric triterpenoid saponin (ivorenoside C), together with the known sericoside, were isolated from the bark of Terminalia ivorensis. Their structures were established on the basis of 1D and 2D NMR data, chemical methods and tandem MS-MS spectrometry as a dimer of β-D-glucopyranosyl-18,19-seco-2α,3β,19,19,24-pentahydroxyolean-12-en-28-oate and β-D-glucopyranosyl-2α,3β,19α,24-tetrahydroxyolean-12-en-28-oate (ivorenoside A, 1), a dimer of β-D-glucopyranosyl-18,19-seco-24-carboxyl-2α,3β,19,19-tetrahydroxyolean-12-en-28-oate and β-D-glucopyranosyl-2α,3β,19α,24-tetrahydroxyolean-12-en-28-oate (ivorenoside B, 2) and β-D-glucopyranosyl-2α,3β,19β,24-tetrahydroxyolean-11-oxo-olean-12-en-28-oate (ivorenoside C, 3). Ivorenosides A and B are the first examples in nature of dimeric triterpenoid saponins with a 18,19-seco E ring of one of the two units. These isolated compounds were evaluated for their antioxidant properties and further for their cytotoxic activity against four human cancer cell lines. Ivorenoside B and C exhibited scavenging activity against DPPH and ABTS(+) radicals with IC(50) values comparable with that of the standard drug Trolox and ivorenoside A showed antiproliferative activity against MDA-MB-231 and HCT116 human cancer cell lines with IC(50) values of 3.96 and 3.43 μM, respectively.


Progesterone receptor activity and relapse-free survival in patients with primary breast cancer: the role of adjuvant chemotherapy.
The prognostic significance of progesterone receptor activity (PgR) with regard to the estimated relapse-free survival (RFS) was studied in 350 one-center patients with primary breast cancer. All receptor assays were performed in one laboratory; PgR levels greater than 10 fmol/mg protein were considered positive. Univariate as well as multivariate statistical analyses were used to examine the prognostic significance of several variables. Eighty-nine of the 350 patients received adjuvant CMF chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil). The median observation period was 69 months (range 12-125 months). In the group of 261 patients who did not receive adjuvant CMF, the PgR-status lacked prognostic significance; only the lymph node status significantly affected the RFS (p less than 0.00001). In contrast, in the CMF-treated group of patients, the PgR-status was the most powerful predictor of recurrence (p less than 0.001). Premenopausal CMF-treated patients with PgR+ tumors had a significantly longer RFS than those with PgR- tumors (p less than 0.02). The present data urge the need for a reappraisal of the prognostic significance of PgR and of the mechanism of action of adjuvant chemotherapy in primary breast cancer.


Antibody response using six different serological assays in a completely PCR-tested community after a coronavirus disease 2019 outbreak-the CoNAN study.
Due to a substantial proportion of asymptomatic and mild courses, many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remain unreported. Therefore, assessment of seroprevalence may detect the real burden of disease. We aimed to determine and characterize the rate of SARS-CoV-2 infections and the resulting seroprevalence in a defined population. The primary objective of the study was to assess SARS-CoV-2 antibody seroprevalence using six different IgG-detecting immunoassays. Secondary objectives of the study were: (a) to determine potential risk factors for symptomatic versus asymptomatic coronavirus disease 2019 courses, and (b) to investigate the rate of virus RNA-persistence. CoNAN is a population-based cohort study performed in the community Neustadt am Rennsteig, Germany, which was quarantined from 22 March to 5 April after six SARS-CoV-2 cases were detected in the village's population. The SARS-CoV-2 outbreak comprised 51 cases and 3 deaths. The CoNAN study was performed from 13 May to 22 May 2020, 6 weeks after a SARS-CoV-2 outbreak. We enrolled a total of 626 participants (71% of the community population) for PCR and antibody testing in the study. All actual SARS-CoV-2 PCR tests were negative. Fifty-two out of 620 (8.4%) participants had antibodies against SARS-CoV-2 in at least two different assays. There were 38 participants with previously PCR-confirmed SARS-CoV-2 infection. Of those, only 19 (50%) displayed anti-SARS-CoV-2 antibodies. We also show that antibody-positive participants with symptoms compatible with a respiratory tract infection had significantly higher antibody levels then asymptomatic participants (EU-assay: median 2.9 versus 7.2 IgG-index, p 0.002; DS-assay: median 45.2 versus 143 AU/mL, p 0.002). Persisting viral replication was not detected. Our data question the relevance and reliability of IgG antibody testing to detect past SARS-CoV-2 infections 6 weeks after an outbreak. We conclude that assessing immunity for SARS-CoV-2 infection should not rely on antibody tests alone.


Role of the two activating domains of the oestrogen receptor in the cell-type and promoter-context dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen.
Various oestrogen responsive reporter genes and vectors expressing truncated or chimeric human oestrogen receptors (hER) containing either of the two independent hER transcriptional activation functions (TAF-1 and TAF-2) have been transfected into HeLa cells, chicken embryo fibroblast (CEF) or yeast cells to investigate the agonistic activity of the anti-oestrogen 4-hydroxytamoxifen (OHT). We demonstrate that the agonistic effect of OHT on the whole hER is due to the cell-type and promoter-context dependent activity of TAF-1. In similar experiments, we show that the anti-oestrogen, ICI 164,384, does not exhibit any oestrogenic activity and, therefore, acts always as a pure antagonist, even though it does not inhibit the activity of the isolated TAF-1. We also confirm that the wild type human oestrogen receptor has no ligand independent transcriptional activity. The implications of our results for the variable antagonist/agonist activity of anti-oestrogens in vivo are discussed.


Synthesis of LIAZAL, a retinoic acid metabolism blocking agent (RAMBA) with potential clinical applications in oncology and dermatology.
The synthesis of LIAZAL (compound 9, R085246) is described. LIAZAL inhibits all-trans-retinoic acid metabolism and thereby exerts retinoid-like effects in vivo.


Using real-time alerts for clinical trials: Identifying potential study subjects.
Clinical trials are widely accepted as a necessary step in evaluating the safety and efficacy of new pharmaceutical products. In order for a sufficiently powered study, a clinical trial depends on the effective and unbiased recruitment of eligible patients. Trials involving seasonal diseases like influenza pose additional challenges. This is a feasibility study of a mobile real-time alerting system to systematically identify potential study subjects for a randomized controlled trial evaluating the safety and efficacy of early intervention with interferon alfacon-1 for patients hospitalized for influenza virus infection. The alerting system was setup in a 471-bed acute care teaching hospital, enabled with computerized physician order entry (CPOE) and a rules-based alerting system. Patients were identified from the entire hospital using two alerts types: pharmacy prescription records for antiviral drugs, and positive influenza laboratory results. Email alerts were generated and sent to BlackBerry(®) devices carried by the study personnel for a 6 month period. The alerts were archived automatically on a secure server and were exported for analysis in Microsoft Access. Over a period of 21 weeks, 779 total alerts were received. The study team was alerted to 241 patients, of whom 85 were potential study subjects. The alert system identified all but one of the patients independently identified by infection control. Real-time identification of potential study subjects is possible with the integration of computerized physician order entry and BlackBerry(®) technology. It is a viable method for the systematic identification of patients throughout a hospital, particularly for trials investigating time-sensitive disease progression.


Treatment of acute cluster headache with 20 mg sumatriptan nasal spray--an open pilot study.
We investigated the efficacy and tolerability of 20 mg sumatriptan nasal spray in the acute treatment of cluster headache attacks in an open-label study. 10 patients met the criteria of the International Headache Society (IHS) for episodic or chronic cluster headache and were enrolled in our study. The primary efficacy measure was "pain free" 30 minutes after treatment. Secondary end-points included "headache response" (defined as headache improvement from "very severe", "severe" or moderate" pain to "mild" or "no" pain) 15, 30, 45 and 60 minutes after treatment. We also assessed the participant's overall treatment satisfaction at the end of the study. Sumatriptan nasal spray was applied in 154 "moderate" to "very severe" cluster headache attacks. 30 minutes after nasal spray application, 50% of attacks were completely aborted and 58% of attacks responded to treatment. The overall efficacy of sumatriptan nasal spray was considered "excellent" in two, "good" in four, "reasonable" in two and "poor" in two patients. Eight patients indicated their intention to treat further attacks with intranasal sumatriptan. Seven patients were interviewed after a follow-up period of six months. Four patients continued to treat all cluster headache attacks with the intranasal sumatriptan formula, two patients had switched to subcutaneous sumatriptan and one patient was in remission since the end of the study. We conclude that 20 mg sumatriptan nasal spray might be an alternative therapy for the treatment of cluster headache attacks, but double-blind studies are needed to further evaluate its efficacy.


Laparoscopic retrieval of a migrating intrapelvic pin: case report and review of the literature.
Migration of orthopedic implants is a well documented phenomenon. Prompt recognition and immediate retrieval may prevent significant and potentially fatal sequelae. The following report describes a unique case in which laparoscopic techniques were successfully used to recover a migrating intrapelvic pin.


Antenatal predictors of neonatal outcome in fetal growth restriction with absent end-diastolic flow in the umbilical artery.
Absent end-diastolic blood flow in the umbilical artery identifies growth-restricted fetuses at high risk of perinatal mortality and severe morbidity. We explored antenatal variables predictive of perinatal mortality or severe neonatal morbidity in such fetuses. We accessed a cohort of 39 singleton, non-malformed, growth-restricted fetuses with absent end-diastolic blood flow at less than 34 weeks between January 1995 and December 2004. The ratio of umbilical artery pulsatility index to middle cerebral artery pulsatility index was calculated to assess redistribution of the fetal arterial circulation. Prenatal and neonatal variables were compared between subjects with versus those without perinatal mortality or severe morbidity using unpaired Student t test or Fisher exact test. Statistical analysis included stepwise logistic regression and receiver operating characteristic curve analysis. P < .05 was considered significant. Stepwise logistic regression analysis demonstrated that the last umbilical artery/middle cerebral artery ratio (P = .02) and estimated fetal weight before delivery (P = .02) were independent predictors of adverse neonatal outcome, with an umbilical artery/middle cerebral artery ratio 1.9 or greater having a sensitivity of 75% and a 13% false-positive rate. Umbilical artery/middle cerebral artery ratio alone accounted for 54% of the variability in outcome. Among preterm growth-restricted fetuses with absent end-diastolic blood flow in the umbilical artery, the umbilical artery/middle cerebral artery ratio is the best predictor of neonatal mortality or severe morbidity.


"Single-use peripheral" vs "conventional" reaming in total hip arthroplasty: how to respect native centre of rotation and acetabular offset? A CT study.
The respect of native hip offset represents a mainstay for satisfying results in total hip arthroplasty (THA). Historically, a great interest has been focused on restoration of femoral offset, while only in recent years, acetabular offset (AO) has been considered. The purpose of the current study was to compare the "single-use peripheral" reaming technique with the "conventional" one for the maintenance of the native COR of the hip and AO in patients undergoing to primary THA. Eighty patients affected from primary hip osteoarthritis were prospectively enrolled in the study and were divided in two groups (Group A "single-use peripheral" and Group B "conventional" reaming technique). Pre- and post-operatively, AO, acetabular floor distance (AFd) and acetabular version (AV) were assessed through a CT scan. A comparison between groups for the radiological parameters, surgical time and complications was performed. The demographic data were similar in both groups. The complications rate and the AV did not differ statistically between groups. Group A presented a statistically significant shorter surgical time and lower variation between pre- and post-operative AO and AFd. Statistical significance was defined as p < 0.05. The "single-use peripheral" reaming technique demonstrated to be more reliable in reproducing the native COR and AO of patients undergoing to primary THA than the "conventional" one. The operative time was significantly reduced, and it may lead to a reduction in the infection risk even though it was not observed in the current study. Further research could be useful to validate such findings and to assess clinical impact and long-term survival of the implant.


Chronic Antipsychotic Treatment in the Rat - Effects on Brain Interleukin-8 and Kynurenic Acid.
Schizophrenia is associated with activation of the brain immune system as reflected by increased brain levels of kynurenic acid (KYNA) and proinflammatory cytokines. Although antipsychotic drugs have been used for decades in the treatment of the disease, potential effects of these drugs on brain immune signaling are not fully known. The aim of the present study is to investigate the effects of chronic treatment with antipsychotic drugs on brain levels of cytokines and KYNA. Rats were treated daily by intraperitoneally administered haloperidol (1.5 mg/kg, n = 6), olanzapine (2 mg/kg, n = 6), and clozapine (20 mg/kg, n = 6) or saline (n = 6) for 30 days. Clozapine, but not haloperidol or olanzapine-treated rats displayed significantly lower cerebrospinal fluid (CSF) levels of interleukin-8 compared to controls. Whole brain levels of KYNA were not changed in any group. Our data suggest that the superior therapeutic effect of clozapine may be a result of its presently shown immunosuppressive action. Further, our data do not support the possibility that elevated brain KYNA found in patients with schizophrenia is a result of antipsychotic treatment.


A comparative life cycle assessment of different pyrolysis-pretreatment pathways of wood biomass for levoglucosan production.
In order to identify the most environmental-friendly pretreatment for pyrolsis of wood residue to levoglucosan (LG), for the first time a comparative life cycle assessment (LCA) was carried out for hot water treatment (HWT), torrefaction, acid pretreatment (AP) and salt pretreatment (SP) pathways. Since LG production can facilitate both resource recovery (RR) and wood residue handling (WRH), two different functional units (FUs), i.e., 1 kg LG production and 1 kg wood residue handling were considered. AP was found to generate the least global warming potential of 134.60 kg CO2-eq and human carcinogenic toxicity of 0.59 kg 1,4-dichlorobenzene-eq. for RR perspective. However, for WRH perspective, HWT was found to be the best pretreatment (6.39 kg CO2-eq; 0.03 kg 1,4-dichlorobenzene-eq.). Sensitivity analysis revealed that a reduction in electricity consumption by 15% could reduce the overall impacts by 14.00-14.82 %. This study also highlights the impact of goal and FU selection on LCA.


Molecular evolution of snake venom toxins.
Phylogenetic trees were constructed for 62 venom toxins of snakes of Proteroglyphae suborder using matrix method. The resulting tree from Minimum Spanning Tree-Cluster Analysis technique had the lowest "percent deviation" (8.55). The taxonomic relationship of these toxins agrees very well with zoological opinions. However, the appearance of the tree did not directly provide a plausible evolutionary model for the toxins. A model was derived from nodal ancestral sequence calculations, comparisons between intra- and intergenerical rates of amino acid change, and generally held ideas about protein evolution. According to the model, short neurotoxin is the ancient form of snake venom toxins. The courses of evolution leading to the present intraspecific homologous toxins are explained by gene duplication and allelomorphism.


Latanoprost rescues retinal neuro-glial cells from apoptosis by inhibiting caspase-3, which is mediated by p44/p42 mitogen-activated protein kinase.
The purpose of this study was to investigate whether latanoprost, a prostaglandin F2alpha analogue, has a direct anti-apoptotic effect both in retinal neuro-glial cells in culture and in diabetic retina. R28 cells, immortalized retinal neuroglial progenitor cells, were induced apoptosis by 24h serum deprivation. Serum withdrawal made up to 15% of R28 cells pyknotic and activated caspase-3 immunoreactive, and latanoprost acid suppressed apoptosis with dose dependency at an optimum concentration of 1.0 microM (P<0.001). UO126, a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase (MEK) 1 and 2 inhibitor reversed this effect. Streptozotocin induced one- or three-month diabetic rats received balanced-salt-solution (BSS) in the left eye and latanoprost eye drops in the right for 5 days. Retinal wholemount was subjected to terminal dUTP nick end labeling (TUNEL) staining, whereas eyeballs were enucleated for cleaved caspase-3 immunofluorescence. Retinal homogenates were probed for phospho- or total p44/p42 MAPK and Akt. One- and three-month diabetic retina had 30.2+/-15.3 and 23.6+/-9.0 TUNEL positive cells per 0.5 cm(2), respectively, whereas control retina had few TUNEL positive cells. Latanoprost instillation significantly reduced these cells (10.0+/-3.1 and 11.3+/-3.1 cells per 0.5 cm(2) for 1M and 3M, respectively, P<0.01), whereas BSS did not. Latanoprost also significantly reduced cleaved caspase-3 immunoreactive cells in ganglion cell and inner nuclear layers (P<0.05). Latanoprost increased phosphorylated to total protein ratio of p44/p42 MAPK (P<0.05), but not of Akt. Taken together, the present findings suggest that latanoprost rescues retinal neurons and/or glial cells from apoptosis, which is probably mediated by p44/p42 MAPK through caspase-3 inhibition.


Identification of phenotypes at risk of transition from diastolic hypertension to isolated systolic hypertension.
Little is known about the potential progression of hypertensive patients towards isolated systolic hypertension (ISH) and about the phenotypes associated with the development of this condition. Aim of this study was to detect predictors of evolution towards ISH in patients with initial systolic-diastolic hypertension. We selected 7801 hypertensive patients free of prevalent cardiovascular (CV) diseases or severe chronic kidney disease and with at least 6-month follow-up from the Campania Salute Network. During 55±44 months of follow-up, incidence of ISH was 21%. Patients with ISH at the follow-up were significantly older (P<0.0001), had longer duration of hypertension, higher prevalence of diabetes and were more likely to be women (all P<0.0001). They exhibited higher baseline left ventricular mass index (LVMi), arterial stiffness (pulse pressure/stroke index), relative wall thickness (RWT) and carotid intima-media thickness (IMT; all P<0.001). Independent predictors of incident ISH were older age (odds ratio (OR)=1.14/5 years), female gender (OR=1.30), higher baseline systolic blood pressure (OR=1.03/5 mm Hg), lower diastolic blood pressure (OR=0.89/5 mm Hg), longer duration of hypertension (OR=1.08/5 months), higher LVMi (OR=1.02/5 g m(-2.7)), arterial stiffness (OR=2.01), RWT (OR=1.02), IMT (OR=1.19 mm(-1); all P<0.0001), independently of antihypertensive treatment, obesity, diabetes and fasting glucose (P>0.05). Our findings suggest that ISH is a sign of aggravation of the atherosclerotic disease already evident by the target organ damage. Great efforts should be paid to prevent this evolution and prompt aggressive therapy for arterial hypertension should be issued before the onset of target organ damage, to reduce global CV risk.


Flare changes after intravitreal injection of ocriplasmin in symptomatic vitreomacular traction syndrome.
To evaluate the changes in anterior chamber flare after a single intravitreal injection of ocriplasmin (125 μg), in patients with symptomatic vitreomacular traction syndrome (VMT). An institutional review board-approved single-center not randomized prospective study. Fifteen eyes of fifteen patients (9 women, 6 men) underwent intravitreal injection with ocriplasmin for symptomatic VMT (width of attachment ≤ 1500 μm). Anterior segment flare was measured with a laser flare meter (Kowa) before intravitreal injection and 1 day, 1 week, 1 month after injection. The changes in flare were analyzed; the resolution of VMT was evaluated with spectral-domain OCT. The mean anterior chamber flare was 10.5 ± 1.9 photons per millisecond (photons/ms) before the injection. After 1 day it increased to 13.6 ± 2.7 photons/ms (p = 0.027) and after 1 week to 14.4 ± 2.5 photons/ms (p = 0.005); after 1 month it decreased to 12.3 ± 2.3 photons/ms (p = 0.123). At 1 day and 1 week after injection, mean anterior chamber flare of fellow eyes was significantly lower than study eyes, while at 1 month this difference was not significant (12.3 ± 2.3 vs. 10.5 ± 1.8 photons/ms, p = 0.124, for study and fellow eyes). There was no statistically significant difference in the changes in flare between women and men or between phakic (N = 10) and pseudophakic (N = 5) eyes. No eye demonstrated intraretinal damage at any time-point. Also, 9 eyes showed resolution of VMT while 6 eyes demonstrated persistence of VMT. Our study shows that intravitreal injection of ocriplasmin can be a safe and effective approach to treat symptomatic VMT syndrome in selected patients.


Detection of cell-cell interactions via photocatalytic cell tagging.
The growing appreciation of immune cell-cell interactions within disease environments has led to extensive efforts to develop immunotherapies. However, characterizing complex cell-cell interfaces in high resolution remains challenging. Thus, technologies leveraging therapeutic-based modalities to profile intercellular environments offer opportunities to study cell-cell interactions with molecular-level insight. We introduce photocatalytic cell tagging (PhoTag) for interrogating cell-cell interactions using single-domain antibodies (VHHs) conjugated to photoactivatable flavin-based cofactors. Following irradiation with visible light, the flavin photocatalyst generates phenoxy radical tags for targeted labeling. Using this technology, we demonstrate selective synaptic labeling across the PD-1/PD-L1 axis in antigen-presenting cell-T cell systems. In combination with multiomics single-cell sequencing, we monitored interactions between peripheral blood mononuclear cells and Raji PD-L1 B cells, revealing differences in transient interactions with specific T cell subtypes. The utility of PhoTag in capturing cell-cell interactions will enable detailed profiling of intercellular communication across different biological systems.


Angiosarcoma of the spleen clinically presenting as metastatic ovarian cancer. A case report and review of the literature.
Primary angiosarcomas of the spleen are rare and almost always fatal. With no more than 200 cases reported in the literature worldwide, no specific risk factors are strongly associated with the disease. The mean age of patients at presentation is 59 years and the major clinical findings include abdominal pain, splenic rupture, and splenomegaly. Grossly, this neoplasm appears as hemorrhagic and/or cystic nodules, with a low-density signal seen on computed tomographic scans. Histologically, the tumor is characterized by neoplastic proliferation with diffuse or focal areas of a vasoformative component with cavernous and arborizing channels. The vascular spaces are lined by endothelial cells with variable degree of atypia. The differential diagnosis includes a variety of benign and malignant vascular proliferations (littoral cell angioma and Kaposi's sarcoma) as well as metastatic tumors. The worst prognostic factor is splenic rupture with early metastasis. The liver is the most common site. We report a case of the 43-year-old woman with a long-standing history of recurrent ovarian carcinoma treated with surgery and multiple courses of radiation therapy and chemotherapy who clinically appeared to have a metastatic ovarian cancer to the spleen and treated with partial resection of stomach and splenectomy. However, histopathologic examination of the specimen showed the tumor to be of a primary angiosarcoma. We believe that the lengthy exposure to radiation may have played a role in the histopathogenesis of this neoplasm in this patient.


Lower extremity rotational deformities and patellofemoral alignment parameters in patients with anterior knee pain.
Anterior knee pain is a common musculoskeletal condition amongst young adult population. Lower extremity structural factors, such as increased femoral anteversion and lateral tibial torsion, may contribute to patellofemoral malalignment and anterior knee pain. The aim of this study was to evaluate the lower extremity structural factors and related patellofemoral alignment parameters that play a role in the aetiology of anterior knee pain. This study involved three groups: patients with unilateral symptomatic knees (n = 35), asymptomatic contralateral knees in the same patients and a control group (n = 40). All subjects were physically examined, and Q-angles were measured. The lower extremities of all subjects were imaged by a very low-dose CT scan, and the symptomatic knees of patients were compared with their asymptomatic contralateral knees and with the healthy knees of controls regarding femoral anteversion, tibial torsion, sulcus angle, patellar tilt angle and lateral patellar displacement. Regarding the Q-angle, femoral anteversion and lateral tibial torsion, no significant differences were found between the symptomatic and asymptomatic knees, whereas significant differences were found between the symptomatic knees and controls. The symptomatic group demonstrated significantly greater sulcus angle only in 30° of knee flexion than did the controls. Patients with unilateral anterior knee pain may have similar morphology at their contralateral asymptomatic lower extremity, and different morphology compared with healthy controls. Lower extremity rotational deformities may increase the risk of anterior knee pain; however, these deformities alone are not sufficient to cause knee pain, and may be predisposing factor rather than a direct aetiology. Diagnostic study, Level III.


Effect of platelet-rich fibrin on epidural fibrosis and comparison to ADCON® Gel and hyaluronic acid.
In this experimental study, PRF (Platelet Rich Fibrin), HA (Hyaluronic Acid) gel and ADCON® Gel were compared in terms of preventing epidural fibrosis. Twenty-eight Sprague-Dawley rats (mean weight, 400-450 g) were divided into 4 groups. L3-L4 laminectomy was performed in each group. Following laminectomy, Adcon® Gel, HA gel and PRF were applied onto the surgery site locally in Group 1, 2 and 3, respectively. Group 4 was maintained as control without any local application. After five weeks, L3-L4 vertebrae were removed totally and taken to histopathological evaluation for epidural fibrosis, acute inflammatory cell density, chronic inflammatory cell density, hemorrhage, angiogenesis and new bone formation. Acute inflammation cell density, angiogenesis, and new bone formation levels were comparable among the study groups (p > 0.05). However, new bone formation was higher in the PRF group. Epidural fibrosis and chronic inflammatory cell density were significantly lower in the PRF group (p < 0.05). We concluded that PRF contributed to hemostasis and prevented epidural fibrosis.


Preterm birth and neonatal mortality in a rural Bangladeshi cohort: implications for health programs.
To estimate the burden of prematurity, determine gestational age (GA)-specific neonatal mortality rates and provide recommendations for country programs. Prospective data on pregnancy, childbirth, GA and newborn mortality collected by trained community health workers from 10 585 mother-newborn pairs in a community-based study. A total of 19.4% of newborn infants were preterm; 13.5% were late preterm (born between 34 and 36 weeks of gestation), 3.3% were moderate preterm (born at 32 to 33 weeks) and 2.6% were extremely preterm (born at 28 to 31 weeks of gestation). Preterm babies experienced 46% of all neonatal deaths; 40% of preterm deaths were in late preterm, 20% in moderate preterm and 40% in very preterm infants. The population attributable fraction of neonatal mortality in premature babies was 0.16 for very preterm, 0.07 for moderately preterm and 0.10 for late preterm. In settings where the majority of births and newborn deaths occur at home and successful referral is a challenge, moderate and late preterm babies may be an important target group for home-based or first-level facility-based management.


Lactation Outcomes After Participation in a Tailored Prenatal Nutrition Consultation Among Women With Infants With Congenital Anomalies.
To describe lactation outcomes among of a cohort of mother-infant dyads in which the women had an individualized prenatal nutrition consultation intervention. Descriptive cohort study. A free-standing children's hospital with a center for fetal diagnosis and treatment and a specialized maternity unit. A total of 160 women who had prenatal nutrition consultations in 2014 to 2017 and gave birth to infants with known congenital anomalies and required intensive care after birth. We surveyed women regarding their lactation outcomes after the Breastfeeding Report Card metrics of the Centers for Disease Control and Prevention and obtained permission to abstract demographic and clinical information from the setting's electronic health record. We analyzed data with standard descriptive statistics. Among the cohort, 86.9% (n = 139) of participants intended to provide human milk or combination feeding in the prenatal period. A total of 128 (92.1%) infants were first exposed to human milk enterally. At the time of discharge, 92.1% (n = 128) of the infants received human milk. The breastfeeding outcomes of the cohort significantly surpassed national data: initiation (98.1% vs. 84.1% national), breastfeeding at 3 months (89.4%), exclusive breastfeeding at 3 months (60% vs. 46.9% national), breastfeeding at 6 months (76.9% vs. 58.3% national), exclusive breastfeeding at 6 months (45% vs. 25.6% national), breastfeeding at 12 months (50.6% vs. 35.3% national), and breastfeeding beyond 12 months (34.4%). Lactation outcomes among women who had prenatal nutrition consultations far surpassed national data, and this intervention has implications for family-centered prenatal care, informed decision making, and improved breastfeeding outcomes in the hospital setting and postdischarge.


Sequential changes in rat femoral artery blood flow and tissue degeneration after exposure to high-intensity focused ultrasound.
The purpose of this study was to investigate the sequential changes in rat artery blood flow and tissue degeneration after exposure to high-intensity focused ultrasound (HIFU) in vivo. HIFU was applied through the skin to the femoral artery of Sprague-Dawley rats. The peak intensities used were 530, 1080, 2750, and 4300 W/cm(2). After exposure, we measured the peak systolic velocity (PSV) in the artery every 1 min until the velocity stabilized. The vessel was resected and examined histologically 7 days after exposure. PSV was not significantly affected by HIFU exposure at 530 W/cm(2). PSV increased immediately after HIFU exposure at intensities of 1080 and 2750 W/cm(2). PSV after HIFU exposure at 1080 W/cm(2) fell to the control level within minutes; however, PSV increased immediately after HIFU exposure at 2750 W/cm(2) and then decreased slowly but remained at a higher level than the control for 15 min. On HIFU exposure at 4300 W/cm(2), the target artery was completely occluded. Histological studies 7 days after HIFU exposure demonstrated that exposure at 530 and 1080 W/cm(2) induced vacuolar degeneration in the tunica media of the femoral artery in rats; exposure to HIFU at 2750 and 4300 W/cm(2) resulted in strong necrotic degeneration in the tunica media. These histological changes were more marked than those found immediately after HIFU exposure. Organized thrombus formation was observed only for HIFU exposure at 4300 W/cm(2). Sequential changes in arterial blood flow after HIFU exposure vary with the intensity, and the histological changes in arterial tissue progress over time. These phenomena should be considered when HIFU is clinically applied to achieve arterial occlusion.


Characterising school-age health and function in rural Zimbabwe using the SAHARAN toolbox.
We developed the School-Age Health, Activity, Resilience, Anthropometry and Neurocognitive (SAHARAN) toolbox to address the shortage of school-age assessment tools that combine growth, physical and cognitive function. Here we present i) development, acceptability and feasibility of the SAHARAN toolbox; ii) characteristics of a pilot cohort; and iii) associations between the domains measured in the cohort. Growth was measured with anthropometry, knee-heel length and skinfold thicknesses. Bioimpedance analysis measured lean mass index and phase angle. Cognition was assessed using the mental processing index, derived from the Kaufman Assessment Battery for Children version 2, a fine motor finger-tapping task, and School Achievement Test (SAT). Physical function combined grip strength, broad jump and the 20m shuttle-run test to produce a total physical score. A caregiver questionnaire was performed in parallel. The SAHARAN toolbox was feasible to implement in rural Zimbabwe, and highly acceptable to children and caregivers following some minor modifications. Eighty children with mean (SD) age 7.6 (0.2) years had mean height-for-age (HAZ) and weight-for-age Z-scores (WAZ) of -0.63 (0.81) and -0.55 (0.85), respectively. Lean mass index and total skinfold thicknesses were related to WAZ and BMI Z-score, but not to HAZ. Total physical score was associated with unit rises in HAZ (1.29, 95% CI 0.75, 1.82, p<0.001), and lean mass index (0.50, 95% CI 0.16, 0.83, p = 0.004), but not skinfold thicknesses. The SAT was associated with unit increases in the mental processing index and child socioemotional score. The caregiver questionnaire identified high levels of adversity and food insecurity. The SAHARAN toolbox provided a feasible and acceptable holistic assessment of child growth and function in mid-childhood. We found clear associations between growth, height-adjusted lean mass and physical function, but not cognitive function. The SAHARAN toolbox could be deployed to characterise school-age growth, development and function elsewhere in sub-Saharan Africa.


Exploring the mechanism of TCM formulae in the treatment of different types of coronary heart disease by network pharmacology and machining learning.
Traditional Chinese medicine (TCM) has long been used in the clinical treatment of coronary heart disease (CHD). TCM is characterized by syndrome-based medication, which is, using different TCM formulae for different syndromes. However, the underlying mode of action remains unclear. In this work, we utilized network pharmacology and machine learning to explore the mechanism of eight classic TCM formulae in the treatment of different types of CHD. First, by integrating multiple databases, a total of 669 potential bioactive compounds and 581 targets of the eight formulae were screened. Then, the effectiveness of these formulae on CHD was evaluated using two network-based indicators. The results showed that each formula's targets were significantly correlated with CHD associated genes and overlapped with the targets of 9 classes of drugs for cardio vascular diseases (CVD) to some degree. Next, from 5 different levels, i.e., herb, symptom, compound, target, and pathway level, we systematically compared the eight formulae using network clustering and hierarchical clustering. We found that all the formulae could be grouped into five clusters and the clustering results were approximately consistent at different levels. All the formulae were involved in 7 pathways closely related to CHD and may exhibit the common effect of relieving angina. Formulae in the same group collectively regulated some unique pathways and suggest further specific indications. For example, the three formulae used for Qi stagnation and blood stasis, Qi deficiency and blood stasis, and Qi-Yin deficiency syndromes acted on two special pathways (TNF signaling pathway, NF-kappa B signaling pathway) and may exert anti-inflammatory and immune-enhancing effects; the two formulae for Yin deficiency of heart and kidney, and Yang deficiency of heart and kidney syndromes regulated two special pathways (PPAR signaling pathway, thyroid hormone signaling pathway) in endocrine system and could improve renal function. Subsequently, we designed a rank algorithm, which integrated network topology with biological function, to identify important targets of these formulae. The results were consistent with the multi-level clustering results. At last, our literature mining validated about 20 % putative targets, as well as clustering results and effects of the formulae by experimental evidences. This study explained the medication patterns and scientific significance of TCM formulae on different types of CHD from perspective of systems biology. It may facilitate the understanding of different types of CHD described by traditional Chinese medicine from the perspectives of modern biology.


MIC and serum bactericidal activity of clindamycin against methicillin-resistant and -sensitive staphylococci.
Six volunteers were given 600 mg clindamycin intravenously to investigate the serum bactericidal activity (SBA) against 50 methicillin susceptible (MSSA) and 50 methicillin resistant Staphylococcus aureus (MRSA) strains. Minimal inhibitory concentrations (MIC) against MSSA, MRSA and 50 methicillin resistant strains of Staphylococcus epidermidis (MRSE), of which 50% were slime-producing, were determined. SBA of clindamycin against MSSA and MRSA was equally high (mean reciprocal SBA titer against MSSA vs MRSA 1 h after application was 13.0 vs 13.45), although MICs against MRSA were markedly higher than against MSSA (MIC 90 of MRSA vs MSSA: 0.06 vs > 32 mg/l). There was no difference in MICs between slime- and non-slime-producing MRSE.


Clinical effects and mechanism of action of sumatriptan in migraine.
Sumatriptan is a novel, highly effective drug against migraine and cluster headache attacks. It shows a remarkably selective pharmacological profile in animals. Determination of its mechanism of action in human should further the understanding of the pathophysiology of migraine and cluster headache. We, therefore, review current knowledge on the clinical and pharmacological effects of sumatriptan. Important pharmacological actions of sumatriptan are (i) poor penetration of the blood-brain barrier suggesting a peripheral point of action; (ii) 5-HT1-like/5-HT1d receptor-mediated vasoconstriction of large cerebral arteries and dural vessels; and (iii) blockade of neurogenic dural inflammation via 5-HT1d autoreceptor-mediated inhibition of vasoactive neuropeptides within the trigeminovascular system. Future research will tell which mechanism is involved in the pathophysiology of migraine and cluster headache.


Dipyridamole decreases glomerular filtration in the sodium-depleted dog. Evidence for mediation by intrarenal adenosine.
To determine the renal effects of inhibiting the uptake and subsequent metabolism of endogenous adenosine, dipyridamole, a nucleoside transport inhibitor, was infused intrarenally into anesthetized dogs. Dipyridamole (24 micrograms/kg per min) inhibited the cellular extraction of [14C]adenosine (72 +/- 3% vs. 9 +/- 3%) and elevated the excretion of endogenous adenosine (0.60 +/- 0.08 to 1.70 +/- 0.21 nmol/min, P less than 0.05). The action of exogenous adenosine to decrease glomerular filtration rate is known to be enhanced by sodium depletion, and is minimal or absent in sodium-loaded animals. To ascertain whether dietary sodium intake alters the renal effects of elevated endogenous adenosine, dipyridamole was infused into sodium-depleted and sodium-loaded dogs. In the sodium-depleted dogs (n = 9), dipyridamole infusion decreased the glomerular filtration rate by 59 +/- 7% (20 +/- 1 to 8 +/- 2 ml/min, P less than 0.05) which returned to control levels within 30 minutes after stopping infusion of dipyridamole. Renal vascular resistance was unchanged during dipyridamole infusion. In the sodium-loaded dogs (n = 5), dipyridamole had no effect on glomerular filtration rate (22 +/- 4 vs. 25 +/- 3 ml/min) or renal vascular resistance. In a separate series of sodium-depleted dogs (n = 8), the dipyridamole-induced decrease in glomerular filtration rate was completely reversed or inhibited by theophylline, an adenosine receptor antagonist. These experiments demonstrate that inhibition of cellular uptake of adenosine elevates adenosine levels, that dipyridamole decreases glomerular filtration rate in sodium-depleted but not sodium-loaded dogs, and that the decrease in glomerular filtration rate is inhibited by theophylline. We conclude that the decrease in glomerular filtration rate during dipyridamole administration is mediated by increased endogenous adenosine.


The mtDNA fragments within exosomes might be novel diagnostic biomarkers of non-small cell lung cancer.
A portion of circulating mtDNAs is encapsulated in exosomes, but their contribution to cancers is rarely studied. We aim to investigate the diagnostic potential of exosomal mtDNA content for non-small cell lung cancer (NSCLC). Exosomes were isolated from plasma and identified by western blot, scanning electron microscopy, and particle size analysis. The plasma and plasma exosomal mtDNA fragment levels (mtDNA79, mtDNA230, and MTATP8) in healthy, pneumonia, benign lung tumors, and NSCLC were quantified by qPCR. Statistical analyses were performed to compare the levels of mtDNA fragments in different subgroups. ROC analyses were used to evaluate mtDNA fragments' diagnostic sensitivity and specificity. We found that plasma mtDNAs were partially present in exosomes. Both plasma and exosomal mtDNA fragments (mtDNA79, mtDNA230, and MTATP8) were increased in NSCLC, particularly more malignant NSCLC. Compared to plasma mtDNAs and traditional tumor markers, exosomal mtDNAs are more closely associated with aggressive features of NSCLC, like bigger tumor sizes, advanced stages, lymph node metastasis, and distant metastasis, showing higher sensitivity and specificity to diagnose NSCLC. Changed contents of plasma and plasma exosomal mtDNAs show great potential to diagnose NSCLC, and exosomal mtDNAs might be promising biomarkers for more aggressive NSCLC.


Oxygen Demand, Uptake, and Deficits in Elite Cross-Country Skiers during a 15-km Race.
This study aimed to quantify the repeated oxygen deficits attained during intermittent endurance exercise by measuring oxygen consumption (V˙O2) and oxygen demand (V˙O2) throughout a simulated roller ski race. Eight male elite cross-country skiers (V˙O2peak, 77.4 ± 4.4 mL·kg⋅min) raced a 13.5-km roller ski time trial on a World Cup course. On two additional days, athletes completed (i) six submaximal loads (~5 min) and ~4-min maximal trial to establish athlete-specific estimates of skiing economy, V˙O2peak, and maximal ΣO2 (MAOD); and (ii) a simulation of the time trial on a roller skiing treadmill. During the simulation, external work rate (Pprop) and skiing speed (v) were adjusted to match the Pprop and v measured during the time trial, and pulmonary V˙O2 was measured breath by breath. V˙O2 and ΣO2 were calculated using an athlete-specific model for skiing economy throughout the treadmill simulation. During the treadmill simulation, V˙O2 was on average 0.77 V˙O2peak, and active V˙O2 (i.e., excluding the time in simulated downhill) was on average 1.01 V˙O2peak. The athletes repeatedly attained substantial oxygen deficits in individual uphill sections of the treadmill simulation, but the deficits were typically small compared with their MAOD (average 14%, range ~0%-50%). However, the ΣO2 summed over all periods of active propulsion was on average 3.8 MAOD. Athletes repeatedly attain substantial oxygen deficits in the uphill segments of a distance cross-country ski race. Furthermore, the total accumulated oxygen deficit of all these segments is several times higher than the athletes' MAOD. This suggests that the rapid recovery of the energy stores represented by the oxygen deficit is necessary during downhill sections, and that this might be an important determinant of distance skiing performance.


Housing and harm reduction: what is the role of harm reduction in addressing homelessness?
Homelessness and drug use often overlap and the harms of substance use are exacerbated by homelessness. Responding to the twin problems of homelessness and substance use is an important aspect of strategies to end homelessness. The introduction and development of ten year plans to end homelessness in North America heralds a new era of systemic responses to homelessness. Central to many of these plans is the adoption of 'Housing First' as a policy response. Housing First focuses directly on housing people regardless of current patterns of substance use. As such, harm reduction is a key principle of Housing First. In this paper, we examine Housing First as an example of the integration of housing and harm reduction and then put forth a community level policy framework to further promote the integration of harm reduction as part of a response to homelessness. Drawing on Rhodes' risk environment framework and current evidence of Housing First and harm reduction, we describe four key policy areas for action: (1) social inclusion policies; (2) adequate and appropriate supply of housing; (3) on demand harm reduction services and supports and (4) systemic and organizational infrastructure. We conclude by identifying areas for future research.


Physical structure of constitutional isomers influences antiproliferation activity of thiosemicarbazone-alkylthiocarbamate copper complexes.
A series of hybrid thiosemicarbazone-alkylthiocarbamate copper complexes with similar electronic environments but distinct physical structures have been prepared, characterized, and evaluated for antiproliferation activity. The complexes include the constitutional isomers (1-phenylpropane-1-imine-(O-ethylthiocarbamato)-2-one-(N-methylthiosemicarbazonato))copper(II) (CuL1) and (1-phenylpropane-1-one-(N-methylthiosemicarbazonato)-2-imine-(O-ethylthiocarbamato))copper(II) (CuL2) along with (1-propane-1-imine-(O-ethylthiocarbamato)-2-one-(N-methylthiosemicarbazonato))copper(II) (CuL3). Complexes CuL1 and CuL2 differ in the positions of the pendent thiosemicarbazone (TSC) and alkylthiocarbamate (ATC) moieties on the 1-phenylpropane backbone. Complex CuL3 employs a propane backbone with the TSC in the 2-position as in CuL1. The isomer pair CuL1 and CuL2 have equivalent electronic environments with indistinguishable CuII/I potentials (E1/2 = -0.86 V vs. ferrocenium/ferrocene) and electron paramagnetic resonance (EPR) spectra (g∥ = 2.26, g⊥ = 2.08). The electronic structure of CuL3 has a similar E1/2 of -0.84 V and identical EPR parameters to CuL1, 2. Single crystal X-ray diffraction studies confirm a consistent donor environment with no substantial variation in the CuN or CuS bond distances and angles between the complexes. The antiproliferation activities of the CuL1-3 were evaluated against the lung adenocarcinoma cell line (A549) and nonmalignant lung fibroblast cell line (IMR-90) using the MTT assay. CuL1 had the highest A549 activity (A549EC50 = 0.065 μM) and selectivity (IMR-90EC50/A549EC50 = 20). The constitutional isomer CuL2 displayed decreased A549 activity (0.18 μM) and selectivity (10.6). The complex CuL3 displayed activity (0.009 μM) similar to CuL1 but with a lack of selectivity (1.0). Cellular copper loading determined by ICP-MS was consistent with the activity and selectivity trends. The complexes CuL1-3 did not induce reactive oxygen species (ROS) generation.


Colour dependence of the early receptor potential and late receptor potential in scallop distal photoreceptor.
1. Intracellular voltage and current responses to short (blue) and long (red) wave-length lights were measured in the distal hyperpolarizing photoreceptor (;off receptor') of the isolated and perfused scallop (Pecten irradians) retina.2. The early receptor potential (e.r.p.) was isolated by holding membrane potential at the reversal potential for the late receptor potential (l.r.p.) or by working at temperatures (< 5.0 degrees C) that abolished the l.r.p.3. The e.r.p., measured using intense flashes of white light, consisted of a positive phase followed by a negative phase, but was converted to a monophasic, negative-going wave following pre-adaptation with red light and to a monophasic, positive-going wave following pre-adaptation with blue light.4. The spectral sensitivity curve for the negative e.r.p. was maximum at 500 nm, whereas the spectral sensitivity curve for the positive e.r.p. was maximum at 575 nm.5. The positive or negative e.r.p.s approached their maximum amplitude exponentially when tested with red or blue flashes of increasing intensity. The results suggest that the positive (or negative) e.r.p. is proportional to the number of photopigment molecules photo-isomerized.6. The photosensitivity maximum of rhodopsin calculated at 500 nm, using the exponential constant and the spectral sensitivity data, was estimated to be 2.1 x 10(-16) cm(2) photon(-1), whereas the photosensitivity maximum of metarhodopsin calculated at 575 nm was estimated to be 2.6 x 10(-16) cm(2) photon(-1).7. In cells pre-adapted with white light, stimulation with blue light caused a hyperpolarizing l.r.p. which was followed by a prolonged hyperpolarizing after-potential (p.h.a.). Stimulation with red light under similar conditions caused an initial hyperpolarization which was followed by a small depolarization during the stimulus, but no after-potential.8. The duration of the p.h.a. was increased by pre-adaptation with a red light, which caused the maximum net transfer of metarhodopsin to rhodopsin; however, its decay was always complete in 5 min or less.9. The photo-isomerization of metarhodopsin by red light suppressed the p.h.a. and caused an after-depolarizing response that decayed in less than 1 min.10. The spectral sensitivity curve for the induction of the p.h.a. was maximum at 500 nm and corresponded to the spectral sensitivity for the negative e.r.p. and for the l.r.p. studied in the dark-adapted retina, whereas the spectral sensitivity curve for the suppression of the p.h.a. and for the induction of the after-depolarization was maximum at 575 nm and corresponded to the spectral sensitivity for the positive e.r.p.11. In photoreceptors clamped to the resting potential in normal ASW, the photo-isomerization of rhodopsin, in the absence of light absorption by metarhodopsin, activated a persistent outward current that had the same time course of decay as the p.h.a. The photo-isomerization of metarhodopsin suppressed the persistent outward current and activated an inward current whose decay took longer than the decay of the after-depolarizing response.12. In the absence of external Ca(2+) and Na(+) ions, the persistent outward current produced by light absorption by rhodopsin, and the inward current produced by light absorption by metarhodopsin, both reversed at the K(+) equilibrium potential. The results show that the induction of the prolonged hyperpolarizing after-potential and the after-depolarizing response involve only the movement of K(+) ions through the same light-dependent K(+) channels that determine the hyperpolarizing l.r.p. of the distal cells.


Scavenger receptor SRA attenuates TLR4-induced microglia activation in intracerebral hemorrhage.
Scavenger receptor A (SRA) has been shown to participate in the pattern recognition of pathogen infection. However, its role in intracerebral hemorrhage has not been well defined. In this study, we detected SRA and TLR4 expression and inflammatory response of microglia treated with erythrocyte lysate in vitro, and observed the cerebral water content and neurological deficit of ICH mice in vivo. We found that SRA deficiency leads to greater sensitivity to erythrocyte lysate-induced inflammatory response. SRA down-regulated inflammatory response expression in microglia by suppressing TLR4-induced activation. Collectively, we have identified the molecular linkage between SRA and the TLR4 signaling pathways in ICH. And our results reveal that SRA has important clinical implications for TLR-targeted immunotherapeutical strategy in ICH.


Design and validation of a low-cost open-source impedance based quartz crystal microbalance for electrochemical research.
The quartz crystal microbalance (QCM) measurement technique is utilized in a broad variety of scientific fields and applications, where surface and interfacial processes are relevant. However, the costs of purchasing QCMs is typically high, which has limited its employment in education as well as by scientists in developing countries. In this article, we present an open-source QCM, built on the OpenQCM project, and using an impedance-based measurement technique (QCM-I), which can be built for <200 euro. Our QCM allows for simultaneous monitoring of the frequency change and dissipation, such that both soft and rigid materials can be characterized. In addition, our QCM measurements can be combined with simultaneous electrochemical measurement techniques (EQCM-I). We demonstrate the validity of our system by characterizing the electrodeposition of a rigid metallic film (Cu) and by the electropolymerization of aniline. Finally, we discuss potential improvements to our system.


Challenges in the Diagnosis and Treatment of Homozygous Familial Hypercholesterolemia.
Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic disorder characterized by an absence or impairment of low-density lipoprotein receptor (LDLR) function resulting in significantly elevated low-density lipoprotein cholesterol (LDL-C) levels. The cholesterol exposure burden beginning in utero greatly increases the risk for atherosclerotic cardiovascular disease (ASCVD) and premature death. The genetic heterogeneity of HoFH results in a wide range of LDL-C levels among both untreated and treated patients. Diagnosis of HoFH should, therefore, be based on a comprehensive evaluation of clinical criteria and not exclusively LDL-C levels. As treatment goals, the European Atherosclerosis Society and International FH Foundation suggest target LDL-C levels of <100 mg/dL (<2.5 mmol/L) in adults or <70 mg/dL (<1.8 mmol/L) in adults with clinical coronary artery disease or diabetes. The National Lipid Association (NLA) recommends that LDL-C levels be reduced to <100 mg/dL (<2.5 mmol/L) or by at least ≥50 % from pretreatment levels. Conventional therapy combinations that lower atherogenic lipoproteins levels in the blood, such as statins, ezetimibe, bile acid sequestrants and niacin, as well as lipoprotein apheresis, are usually unable to reduce LDL-C levels to recommended targets. Two recently approved agents that reduce lipoprotein synthesis and secretion by the liver are lomitapide, a microsomal triglyceride transfer protein inhibitor, and mipomersen, an apolipoprotein B antisense oligonucleotide. The newly approved inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), evolocumab, also shows promise for the management of FH. Because of the extremely high risk for ASCVD, HoFH patients should be identified early.


The three isoforms of hepcidin in human serum and their processing determined by liquid chromatography-tandem mass spectrometry (LC-tandem MS).
Hepcidin, the iron regulatory hormone, has three isoforms; -20, -22 and -25. While hepcidin-25 has been studied extensively, the physiological significance of other isoforms remains poorly understood. Using a quantitative method based on liquid chromatography-tandem mass spectrometry (LC-tandem MS) developed by our group, we quantified hepcidin isoforms in human serum to elucidate their characteristics, and investigated the role of hepatocytes in isoform processing. Hepcidin isoforms in serum obtained from 40 healthy volunteers were quantified. Synthetic hepcidin peptides were added to healthy serum, and to HepG2 culture media, and hepcidin isoform concentrations determined. All three hepcidin isoforms were detected in human serum; however, hepcidin-25 concentrations were highest. The three hepcidin isoforms showed a strong positive correlation with each other and with serum ferritin. Additionally, while hepcidin-20 was strongly correlated with serum creatinine, the other isoforms were not. Hepcidin-20 and -25 levels were also increased in chronic kidney disease (CKD) serum. Hepcidin-22 rapidly degraded into hepcidin-20, whereas hepcidin-25 remained relatively stable. Finally, hepcidin-22 degradation into hepcidin-20 was accelerated in the presence of HepG2. This method has enabled us to reveal fundamental characteristics of the three hepcidin isoforms in serum and may be a powerful tool for quantifying hepcidin isoform expression and processing.


Direct Vision, Transfascial (DVT) Approach to Submuscular Reservoir Placement in Patients Undergoing Multicomponent Penile Implant Surgery Following Prior Pelvic Surgery or Radiation Therapy.
Submuscular reservoir placement has fulfilled a critical need for patients desiring multicomponent penile implants following pelvic surgery and radiation therapy. Passage of the reservoir through the inguinal canal into the submuscular space is often challenging and carries the risk of the reservoir being placed unknowingly outside of the targeted space. To evaluate the safety and accuracy of a direct vision, transfascial (DVT) approach to submuscular reservoir placement. We retrospectively reviewed outcomes for consecutive patients undergoing DVT submuscular reservoir placement abstracted from a large IRB-approved database at our institution. Postimplant cross-sectional imaging performed on many of these patients was used to ascertain the final location of the reservoir. Outcome measures included the perioperative and intermediate-term safety and complications of the procedure. Postimplant imaging ascertained the accuracy in providing patients with a submuscular reservoir. There were 107 DVT submuscular reservoirs placed in 100 consecutive patients. No intraoperative complications occurred, there were no postoperative rectus hematomas, and there were 4 (3.7%) postoperative infections. With a mean follow up of 17.5 +/- 20.5 months there was one reservoir herniation, one patient had autoinflation, and one patient required repositioning of a high riding pump. There were 4 mechanical malfunctions requiring revision at a median of 74 months (range: 69-108 months.) following implant placement. Of the 43 patients who underwent imaging: 34 (79%) reservoirs were accurately positioned, 5 (12%) were in the lateral abdominal wall, 1(2%) was in the retroperitoneum, and 3 (7%) were intraperitoneal. Intraperitoneal reservoirs occurred exclusively in postcystectomy patients. The DVT approach is technically safe, although a slightly higher than expected infection risk was noted. It provides accurate reservoir placement for the majority of imaged patients. Postcystectomy patients have a risk of insidious intraperitoneal reservoir placement. Preoperative counseling should mention this and postimplant imaging may be considered for some of these patients. Imaging may also helpful prior to future revision surgery in order to identify and remove insidious intraperitoneal reservoirs. We investigated 100 patients, almost half underwent cross sectional imaging. Weaknesses include the retrospective nature of this single-institutional study, which may not have similar outcomes at other centers. DVT submuscular reservoir placement is safe following pelvic surgery and radiation therapy. Despite careful and deliberate surgical technique imaging found that approximately 20% of reservoirs are not in their expected location. Intraperitoneal reservoirs are of concern, particularly in postcystectomy patients. Kava BR, Levine A, Hauser N, et al. Direct Vision, Transfascial (DVT) Approach to Submuscular Reservoir Placement in Patients Undergoing Multicomponent Penile Implant Surgery Following Prior Pelvic Surgery or Radiation Therapy. J Sex Med 2022;19:394-400.


Intranasal volume increases with age: Computed tomography volumetric analysis in adults.
It is theorized that intranasal cavity volumes change throughout the aging process, possibly secondary to hormonal changes and atrophy of the sinonasal mucosa. Our objective is to compare intranasal volumes from different age groups to test the hypothesis that intranasal cavity volume increases with age. Case series. An analysis of computed tomography (CT) scans performed for reasons other than sinonasal complaints. Intranasal volumes of three groups (age 20-30 years, 40-50 years, and 70 years and above) were calculated using Vitrea software. The total intranasal volume was measured from the nasal vestibule anteriorly, the nasopharynx posteriorly, the olfactory cleft superiorly, and the nasal floor inferiorly. The total volume included the sum of the right and left sides. Sixty-two CT scans were analyzed. There was a progressive, relatively linear, increase in intranasal volume with increasing age: 20 to 30 years = 15.73 mL, 40 to 50 years = 17.30 mL, and 70 years and above = 18.38 mL. Mean intranasal volume for males was 19.07 mL, and for females was 15.23 mL. Analysis of variance demonstrated significant group differences in mean intranasal volume for age (P = .003) and gender (P < .001), with moderate-to-large effect size of 0.206 and 0.289 (partial η(2) ), respectively. Post hoc testing revealed a significant difference between the 20 to 30-year and >70-year age groups (P = .006). There was no significant difference in intranasal volume dependent upon body mass index. Intranasal volume increases with age and is larger in males. Specific etiologies responsible for increased intranasal cavity volume with age are actively being evaluated. 4 Laryngoscope, 126:2212-2215, 2016.


Bromate and trace metal levels in bread loaves from outlets within Ile-Ife Metropolis, Southwestern Nigeria.
Bread loaves randomly sampled from nine outlets and bakeries within Ile-Ife were analysed to determine their safety levels for human consumption with respect to bromate and trace metal contents. Bromate determination was carried out via spectrophotometric method while trace metals in the digested bread samples were profiled using Flame Atomic Absorption Spectrophotometer. Bromate levels in the analyzed bread samples ranged from 2.051 ± 0.011 μg/g to 66.224 ± 0.014 μg/g while the trace metal levels were of the order: 0.03-0.10 μg/g Co = 0.03-0.10 μg/g Pb < 0.23-0.46 μg/g Cu < 2.23-6.63 μg/g Zn < 25.83-75.53 μg/g Mn. This study revealed that many bread bakers around Ile-Ife had not fully complied with the bromate-free rule stipulated by NAFDAC contrary to the "bromate free" inscribed on the labels of the bread. The bread samples contained both essential and toxic trace metals to levels that could threaten the health of consumers over prolonged regular consumption.


Influence of renal function on the pharmacokinetics of lomefloxacin compared with other fluoroquinolones.
Fluoroquinolones have similar chemical structures but wide differences in their pharmacokinetic profiles. Disparity in fluoroquinolone elimination is most evident in patients with various degrees of renal insufficiency. Ofloxacin is almost exclusively eliminated by the kidney, whereas pefloxacin is predominantly cleared by the liver. The fluoroquinolones eliminated by both renal and nonrenal routes (hepatic and transintestinal) include norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin. The primary renal mechanism of elimination for norfloxacin, ciprofloxacin, enoxacin, fleroxacin, temafloxacin, and lomefloxacin is glomerular filtration and tubular secretion. Both total clearance and renal clearance significantly correlate with creatinine clearance for these fluoroquinolones, and creatinine clearance is a useful clinical marker on which to base dosage adjustments. For some fluoroquinolones, dosage adjustments are recommended when creatinine clearances fall below 30-40 mL/min. This is especially evident for lomefloxacin, temafloxacin, norfloxacin, ciprofloxacin, enoxacin, and fleroxacin. There is very little removal of fluoroquinolones from the plasma during hemodialysis due to their extensive tissue distribution.


Differential diagnosis of common acute toxicologic versus nontoxicologic illness.
This table outlines common toxicologic versus nontoxicologic rule outs based on clinical abnormalities seen in an acutely ill animal. The purpose is to provide an initial guideline for considering toxicologic versus nontoxicologic rule outs when a patient is presented to a practicing veterinarian. Major clinical abnormalities followed by common toxicologic rule outs and non-toxicologic rule outs have been listed so that practicing veterinarians can narrow down an etiology quickly. Based on history, physical examination findings, and blood work changes, once a reasonable etiology has been narrowed down or established, the reader is encouraged to review a more detailed discussion on management of the particular poisoning or disease listed in this or other references.


Effects of intrathecal administration of thyrotropin releasing hormone and its analogue, DN1417, on plasma glucose and catecholamine levels in conscious rats.
Effects of intrathecal (i.t.) administration of TRH and the TRH analogue, DN1417, on plasma catecholamines and glucose levels were studied in conscious male rats. The i.t. administration of TRH (0.6 and 3 nmol) at the T8-10 vertebral level resulted in a dose-related increase in epinephrine (E), norepinephrine (NE), and glucose levels, which was suppressed by prior administration of the ganglionic blocker, hexamethonium (1.5 mg/100 g b. wt.). I.t. administration of TRH (3 nmol) caused small increases in plasma E and glucose at the C7-T1 vertebral level, but it did not change plasma E, NE and glucose levels at the sacral level. DN1417 (3 nmol) administered i.t. at the T8-10 or C7-T1 vertebral level had a more potent and long-lasting effect in stimulating the release of E than TRH. These findings suggest that TRH may act on sympathetic preganglionic neurons at the T7-10 spinal levels and stimulate the release of catecholamines from the adrenal medulla.


Age-related gadolinium-enhancement of MRI brain lesions in multiple sclerosis.
There is evidence that inflammatory processes in multiple sclerosis (MS) are age-dependent. In this study we evaluated the impact of aging on gadolinium (Gd) enhancement of brain magnetic resonance imaging (MRI) lesions in MS patients. Pre- and post-contrast MRI scans, acquired using a standardized procedure by the same MRI scanner, at least 1 month far from clinical relapse or steroid treatment, were examined in 200 disease-modifying treatment free MS patients. Seventy-three patients (36.5%) showed at least one enhancing lesion. Age at MRI examination (p=0.0001), disease duration (p=0.002) and EDSS score were significantly (p=0.02) lower, whereas relapse rate in the preceding 2 years was higher (p=0.003) in patients with enhancing lesions than in patients with unenhancing scans. Multivariate logistic analysis showed that current age was the variable better predicting Gd enhancement (p=0.004). The odds ratios were 0.95 (CI: 0.92-0.98) for each year of patient's age and 0.64 (CI: 0.48-0.87) for each age decade. The main changes in enhancement risk occurred after 35 years of age. Multivariate Poisson regression model showed that relapse rate in the preceding 2 years (p<0.0001) and current age (p=0.0003) were the best predictors of the number of enhancing lesions. This information can be used to increase the statistical power of clinical trials using Gd-enhancing lesions as an outcome measure.


[Studies on the chemical constituents of a fungus producing perylenequinones].
To study the chemical constituents in the mycelia of Hypomyces sp.. Silica gel column chromatography was employed for the isolation and purification. Chemical and spectral methods were used to determine the structures of the isolated compounds. Two compounds were isolated and identified as: hypomycin C (I) and hypomycin D (II). Compounds I and II are new compounds.


Neochordae implantation versus leaflet resection in mitral valve posterior leaflet prolapse and dilated left ventricle: a propensity score matching comparison with long-term follow-up.
Uncorrected severe mitral regurgitation (MR) due to posterior prolapse leads to left ventricular dilatation. At this stage, mitral valve repair becomes mandatory to avoid permanent myocardial injury. However, which technique among neochoardae implantation and leaflet resection provides the best results in this scenario remains unknown. We selected 332 patients with left ventricular dilatation and severe degenerative MR due to posterior leaflet (PL) prolapse who underwent neochoardae implantation (85 patients) or PL resection (247 patients) at our institution between 2008 and 2020. A propensity score matching analysis was carried on to decrease the differences at baseline. Matching yielded 85 neochordae implantations and 85 PL resections. At 10 years, freedom from cardiac death and freedom from mitral valve reoperation were 92.6 ± 6.1% vs 97.8 ± 2.1% and 97.7 ± 2.2% vs 95 ± 3% in the neochordae group and in the PL resection group, respectively. The MR ≥2+ recurrence rate was 23.9 ± 10% in the neochordae group and 20.8 ± 5.8% in the PL resection group (P = 0.834) at 10 years. At the last follow-up, the neochordae group showed a higher reduction of left ventricular end-diastolic diameter (44 vs 48 mm; P = 0.001) and a better ejection fraction (60% vs 55%; P < 0.001) compared to PL resection group. In this subgroup of patients, both neochordae implantation and leaflet resection provide excellent durability of the repair in the long term. Neochordae implantation might have a better effect on dilated left ventricle.