Viability of spermatozoa in the human ejaculate after vasectomy.
Ejaculates produced by 82 men between 6 and 19 days after removal of approximately 5 cm of vas deferens were assessed specifically for motility of residual spermatozoa. Several of 23 ejaculates produced 6 to 8 days after vasectomy still contained spermatozoa of the quality and number likely to produce pregnancy. By 13 to 15 days, however, all or the great majority of residual spermatozoa were dead, and in only 1 of 50 men were there numbers of motile spermatozoa possibly compatible with fertility. The results seem to justify more extensive surveys to confirm the absolute or biologic limits of the viability of spermatozoa in the terminal portion of the human male reproductive tract, anticipated here to be 16 to 18 days, as a suggested basis for a standard postvasectomy protocol. Second, these data support the choice of the 3rd postoperative week as the earliest rational moment to confirm the absence of motile spermatozoa, or in their presence to suspect an incomplete block.


The influence of osmotic treatment assisted by ultrasound on the physico-chemical characteristics of blueberries (Vaccinium myrtillus L.).
The aim of the study was to analyse the effect of osmotic treatment assisted by ultrasound on the physico-chemical properties of blueberries from Suceava county, Romania. Ultrasound treatment was conducted at the frequency of 25 kHz (using different values of amplitude - 20, 60 and 100%, respectively) in 61.5% sucrose solution at 30, 40 and 50 °C for 20, 40 and 60 min. The Box-Behnken design was used to investigate the influence of independent variables (time, temperature and amplitude) on the osmotic dehydration. The results showed that for physico-chemical characteristics (mass transfer parameters; moisture content; total content of anthocyanins, flavonoids and polyphenols; DPPH assay scavenging activity) that optimal conditions were obtained at 30 °C for 40 min at a 100% amplitude. Ultrasound treatment stimulated changes in the main characteristics, especially of colour leading to a higher lightness (L*), decreasing AsA-POD and water activity. The results indicated that the higher the values of independent variables are, the more representative is the correlation between them.


[Modified-coblation assisted UPPP in treatment of severe obstructive sleep apnea-hypopnea syndrome].
To explore a new way to modify the UPPP and to assess the operative efficacy of modified-coblation assisted UPPP (M-CAUP) on patients with severe obstructive sleep apnea-hypopnea syndrome (OSAHS). A retrospective analysis was made on surgical therapeutic effect of M-CAUP performed in our hospital. 87 adult inpatients with severe OSAHS were involved in the study whose preoperative AHI were beyond 30/h and LSaO2 were under or equal to 85%. All those had the primary level obstruction within the retropalatal region as determined by PSG and airway pressure fluctuation monitoring (ApneaGraph 200, MRA-Medical Ltd, Gloucestershire UK) . The surgical approach of M-CAUP: (1) bilateral tonsillectomy by using Arthrocare EVac 70 T&A Wand. (2) dissection of velum palatinum space by using Arthrocare EVac 70 T&A Wand, ablation of fat tissue to removed it from the space, avoiding injure levator palatini muscle and tensor palatini muscle and preserving musculus uvula, maintaining the normal structure of oropharynx. (3) ablation of channel of soft palate by using Arthrocare EVac 55 T&A Wand to reduce the volume of soft palate moderately. (4) plasty: suturing the tonsilar fossa to close the space, interrupted suture two sides of palatine arch and uvula. All patients were followed up for six to eighteen months postoperatively and received PSG. After M-CAUP, the pharyngeal cavity was enlarged while the basic structure of oropharynx was maintained and no nasopharyngeal refluxing occurred. The subjective symptoms were also improved evidently after operation. After operation, the AHI and Epworth sleepiness scale (ESS) decreased while LSaO2 increased. The reduction of AHI and ESS had statistical significance (P < 0.01), and the rise of LSaO2 also had statistical significance (P < 0.01). The total effective ratio of the operation was 89.7%. Despite of various treatment, the operative efficacy of conventional UPPP was almost not ideal on severe OSAHS due to complex pathogeny. It was proved that M-CAUP was an effective surgical treatment of severe OSAHS with less blood loss. The operation was minimally invasive and maintained the normal functions of palatopharynx in principle. It could be applied in clinical practice.


Topical propranolol improves epistaxis in patients with hereditary hemorrhagic telangiectasia - a preliminary report.
Severe epistaxis is often difficult to control in patients with hereditary hemorrhagic telangiectasia (HHT). Propranolol has been shown to have antiangiogenic properties in vitro and in vivo and is commonly used to treat hemangiomas. We present our experience with topical nasal propranolol for the treatment of moderate to severe epistaxis in patients with HHT. Retrospective case series. Six patients with HHT were treated with 0.5 cm3 of 1.5% propranolol gel, applied to each nostril twice daily for at least 12 weeks. Outcome measures were epistaxis severity score (ESS), hemoglobin level, and number of blood transfusions prior to and while on treatment. Local and systemic side effects were recorded. The mean duration of treatment was 30 ± 5.6 weeks. A significant improvement in the ESS was found in all patients, with a mean decrease from 6.4 ± 2.1 at treatment onset to 3.5 ± 1.7 at 12 weeks (p = 0.028). Hemoglobin level increased significantly from 8.4 ± 3.1 to 11.0 ± 1.8 g/dL at 12 weeks (p = 0.043). The mean number of blood transfusions decreased from 4.5 ± 4.9 before treatment to 2.5 ± 2.9 at 12 weeks and 0.3 ± 0.8 at 24 weeks, but the difference did not reach statistical significance (p = 0.109 for both). No significant side effects of treatment were recorded. These preliminary results suggest that topical propranolol may be effective for the treatment of epistaxis in patients with HHT. A prospective controlled trial is required to confirm our findings.


Heavy metal adsorbents prepared from the modification of cellulose: a review.
A number of industries currently produce varying concentrations of heavy metal laden waste streams with significant consequences for any receiving environmental compartment. In recent years, increasing emphasis has been placed on environmental impact minimisation and resulting from this the range and capability of natural and prepared materials capable of heavy metal removal has seen steady development. In particular considerable work has been carried out on the use of both natural materials and their modifications. These natural materials, in many instances are relatively cheap, abundant in supply and have significant potential for modification and ultimately enhancement of their adsorption capabilities. This review paper reviews the current state of research on the use of the naturally occurring material cellulose, its modified forms and their efficacy as adsorbents for the removal of heavy metals from waste streams. Adsorbents based on direct modification of cellulose are evaluated initially and subsequently modifications resulting from the grafting of selected monomers to the cellulose backbone with subsequent functionalisation are assessed. The heavy metal adsorption capacities for these modified cellulose materials were found to be significant and levels of uptake were comparable, in many instances, to both other naturally occurring adsorbent materials and commercial ion exchange type resins. Many of the modified cellulose adsorbents proved regenerable and re-usable over a number of adsorption/desorption cycles allowing recovery of the adsorbed heavy metal in a more concentrated form.


Impact of neuropathic pain on quality of life in adults with sickle cell disease: observational study.
Knowledge on the characteristics of neuropathic pain in people with sickle cell disease (SCD) may help to provide more effective treatment procedures. To describe the characteristics of neuropathic pain in patients with sickle cell disease and identify the impact on their quality of life. A cross-sectional study (CAAE 57274516.8.0000.5544) was conducted at a reference center in Salvador, Bahia, Brazil. The instruments used were the Brief Pain Inventory (BPI), the Douleur Neuropatique Questionnaire (DN-4), the Anxiety and Depression Hospital scale (ADH) and the abbreviated version of the World Health Organization of Quality of Life questionnaire (WHOQOL-brief). The Mann-Whitney test was used to evaluate the association between the scores (5% alpha). A total of 100 adults with SCD participated in the study, 69.7% of whom had neuropathic pain. Anxiety was present in 99% of the sample and depression, in 100%. Patients with neuropathic pain had worse scores in all domains of quality of life (p < 0.05), but no association was found with pain intensity. Neuropathic pain was more frequent than nociceptive pain in adults with SCD and generated worse scores in all domains of quality of life. Anxiety and depression were present in patients with both types of pain.


Significance of soluble CD40 ligand, adiponectin and reactive oxygen metabolites in aging.
We analyzed the association between platelet activation, adiponectin, insulin resistance and oxidative stress in aging. In addition, we included American football (AB) players to investigate whether this association is modulated by exercise. Eighty-six old age patients (> or = 65 years old) hospitalized at the nursing institution and 62 AB players were recruited as study subjects. Reactive oxygen metabolites (ROM), soluble CD40 ligand (sCD40L) and adiponectin were estimated with these patients. In comparison to old age, plasma adiponectin levels in AB players were significantly low. In addition, the adiponectin values of elder group (> 80 years) in old age were significantly increased higher than those for younger group (< or = 80 years). There were no differences of sCD40L in two groups. Levels of ROM in AB players were also significantly lower than that in old age. However, the ROM values of younger group in old age were significantly increased higher than those for elder group. The sCD40L also exhibited the same results. There were no significant differences in ROM and adiponectin levels between the high homeostasis model assessment-insulin resistance (HOMA-IR) (> 2.0) and the low HOMA-IR (< or = 2.0). In contrast, in the old age, the sCD40L and ROM levels in the high HOMA-IR group were significantly higher than those in the low HOMA-IR group. In addition, the adiponectin level in the high HOMA-IR group was significantly lower than that in the low HOMA-IR group. Our results suggest that platelet activation, adiponectin and oxidative stress are the very important factors for aging, and the maintenance of exercise could prevent the occurrence of metabolic syndrome or insulin resistance.


Sensitivity of Anguilliformes leptocephali to metamorphosis stimulated by thyroid hormone depends on larval size and metamorphic stage.
Metamorphosis of teleosts including Anguilliformes is well known to be induced by thyroid hormone (TH), although the underlying mechanism is not fully understood. In this study, we investigated the experimental conditions needed to induce normal metamorphosis in artificially spawned Japanese eel (Anguilla japonica), including initial larval size, TH concentration, and timing of TH immersion. Around 37 mm TL was found to be the minimum size of larvae that underwent successful metamorphosis induced by l-thyroxine (T4); notably, smaller larvae did not show increased expression of TH receptors in response to T4, suggesting that small leptocephali are not sufficiently responsive to TH. Furthermore, successful completion of metamorphosis depended on sensitivity to TH, which changed with metamorphic stage; for example, prolonged exposure to higher TH concentrations led to morphological defects. Collectively, these results reveal that the induction of metamorphosis by TH is dependent on larval size, and that the concentration of TH must be adjusted in line with metamorphic stage to achieve successful progression of metamorphosis. Our findings will contribute to improving production technology in the aquaculture of Japanese eels by facilitating the earlier induction of metamorphosis in artificial leptocephali.


Factors Impacting Discharge Destination Following Head and Neck Microvascular Reconstruction.
Determine which variables impact postoperative discharge destination following head and neck microvascular free flap reconstruction. Retrospective review of prospectively collected databases. Consecutive patients undergoing head and neck microvascular free flap reconstruction between January 2010 and December 2019 (n = 1972) were included. Preoperative, operative and postoperative variables were correlated with discharge destination (home, skilled nursing facility [SNF], rehabilitation facility, death). The mean age of patients discharged home was lower (60 SD ± 13, n = 1450) compared to those discharged to an SNF (68 SD ± 14, n = 168) or a rehabilitation facility (71 SD ± 14, n = 200; p < 0.0001). Operative duration greater than 10 h correlated with a higher percentage of patients being discharged to a rehabilitation or SNF (25% vs. 15%; p < 0.001). Patients were less likely to be discharged home if they had a known history of cardiac disease (71% vs. 82%; p < 0.0001). Patients were less likely to be discharged home if they experienced alcohol withdrawal (67% vs. 80%; p = 0.006), thromboembolism (59% vs. 80%; p = 0.001), a pulmonary complication (46% vs. 81%; p < 0.0001), a cardiac complication (46% vs. 80%; p < 0.0001), or a cerebral vascular event (25% vs. 80%; p < 0.0001). There was no correlation between discharge destination and occurrence of postoperative wound infection, salivary fistula, partial tissue necrosis or free flap failure. Thirty-day readmission rates were similar when stratified by discharge destination. There was no correlation with the anatomic site, free flap donor selection, or free flap survival and discharge destination. Patient age, operative duration and occurrence of a medical complication postoperatively did correlate with discharge destination. 4 Laryngoscope, 133:95-104, 2023.


Increased 2-hydroxylation of estrogen is associated with lower body fat and increased lean body mass in postmenopausal women.
Menopause is associated with changes in bone, muscle and fat mass. The importance of postmenopausal estrogen metabolism in bone health has been established. However, its relationship to body composition in postmenopausal women remains undetermined. The objective of this study is to determine the association between estrogen metabolism and body composition in postmenopausal women. This is a cross sectional study of 97 postmenopausal Caucasian women, 49-80 y.o., ≥1 year from the last normal menstrual period or those who have had oophorectomy. Inactive [2-hydroxyestrone (2OHE(1))] and active [16α-hydroxyestrone (16α-OHE(1))] urinary metabolites of estrogen were measured by ELISA. The whole and regional body composition was measured by DXA. We have found that both 2OHE(1), and 2OHE(1)/16α-OHE(1) ratio were negatively correlated with % total fat, and % truncal fat but positively correlated with % total lean mass. Comparing the fat and lean parameters of body composition according to tertiles of 2OHE(1) and 2OHE(1)/16αOHE(1) ratio showed that subjects in the lowest tertiles, had the highest % total fat, and % truncal fat and the lowest % total lean mass. Multiple regression analysis also showed 2OHE(1) and calcium intake as statistically significant predictors of all body composition parameters. In conclusion, in postmenopausal women, an increase in the metabolism of estrogen towards the inactive metabolites is associated with lower body fat and higher lean mass than those with predominance of the metabolism towards the active metabolites.


The effects of tick-borne fever on some functions of polymorphonuclear cells of sheep.
Peripheral leucocytes obtained from sheep experimentally infected with tick-borne fever had a significantly reduced capacity to phagocytose and kill Staphylococcus aureus in vitro. Infected neutrophils were also less able to attach to glass surfaces than normal neutrophils. The period of reduced phagocytic activity coincided with the period of parasitaemia and severe neutropenia.


Influence of stress simulation parameters on the fracture strength of all-ceramic fixed-partial dentures.
This in vitro study tested the influence of diverse stress simulation parameters on the fracture strength of all-ceramic three-unit fixed partial dentures (FPDs). All-ceramic FPDs made of Empress 2 (Ivoclar-Vivadent, FL) were exposed to thermal cycling and mechanical loading (TCML) with varying loading parameters such as chewing force (amount, frequency), thermal loading, lateral jaw motion, abutment material, artificial periodontium or antagonistic denture. To investigate the influence of the abutment material, human teeth, polymer abutments and alloy abutments were used. Two different TCML devices with pneumatic or weight loading were compared. FPDs without aging were used as a control. Combined thermal and mechanical loading significantly reduced the FPD fracture resistance from 1832N to 410N. Duplication of chewing frequency, phase load increase or additional lateral movement did not effect the results. Increasing chewing force, artificial periodontium, and antagonist or abutment material reduced the fracture resistance of the tested FPDs. Different devices with weight or pneumatic loading had no significant influence on the loading capacity of the FPDs. Artificial aging should be performed combining thermal cycling with mechanical loading. Simulation of the artificial periodontium, human antagonists and abutments should be included to achieve a significant aging.


Social and racial inequalities in diabetes and cancer in the United States.
Cancer and diabetes are among the leading causes of morbidity and mortality worldwide. Several studies have reported diabetes as a risk factor for developing cancer, a relationship that may be explained by associated factors shared with both diseases such as age, sex, body weight, smoking, and alcohol consumption. Social factors referred to as social determinants of health (SDOH) were shown to be associated with the risk of developing cancer and diabetes. Despite that diabetes and social factors were identified as significant determinants of cancer, no studies examined their combined effect on the risk of developing cancer. In this study, we aim at filling this gap in the literature by triangulating the association between diabetes, indices of SDOH, and the risk of developing cancer. We have conducted a quantitative study using data from the Behavioral Risk Factor Surveillance System (BRFSS), whereby information was collected nationally from residents in the United States (US) with respect to their health-related risk behaviors, chronic health conditions, and the use of preventive services. Data analysis using weighted regressions was conducted on 389,158 study participants. Our findings indicated that diabetes is a risk factor that increases the likelihood of cancer by 13% (OR 1.13; 95%CI: 1.05-1.21). People of White race had higher odds for cancer compared to African Americans (OR 0.44; 95%CI: 0.39-0.49), Asians (OR 0.27; 95%CI: 0.20-0.38), and other races (OR 0.56; 95%CI: 0.46-0.69). The indices of SDOH that were positively associated with having cancer encompassed unemployment (OR 1.78; 95%CI: 1.59-1.99), retirement (OR 1.54; 95%CI: 1.43-1.67), higher income levels with ORs ranging between 1.16-1.38, college education (OR 1.10; 95%CI: 1.02-1.18), college graduates (OR 1.31; 95%CI: 1.21-1.40), and healthcare coverage (OR 1.44; 95%CI: 1.22-1.71). On the other hand, the indices of SDOH that were protective against having cancer were comprised of renting a home (OR 0.86; 95%CI: 0.79-0.93) and never married (OR 0.73; 95%CI: 0.65-0.81). This study offers a novel social dimension for the association between diabetes and cancer that could guide setting strategies for addressing social inequities in disease prevention and access to healthcare.


Downregulation of KLF8 expression by shRNA induces inhibition of cell proliferation in CAL27 human oral cancer cells.
KLF8 is a member of KLF transcription factors which play an important tolr in oncogenesis. It is barely expressed in normal human epithelial cells but highly overexpressed in several types of human cancer cell lines. In the present study, we investigate the role of KLF8 in oral cancer and the effects of KLF8 knockdown via lentivirus mediated siRNA infection in human adenosquamos carcinoma CAL 27 cells. We developed a vector-based siRNA expression system that can induce RNAi in CAL 27 oral cancer cells. Downregulation of KLF8 was confirmed by evaluating GFP expressions, RT-PCR and western blot analysis. Finally, the effects of KLF8 downregulation were analyzed by MTT assay and colony formation assays. The expression levels of KLF8 mRNA and proteins are reduced in CAL 27 cells that transfected with 21-nt siRNA against KLF8. Lentivirus-mediated silencing of KLF8 reduces cell proliferation and colonies number, thereby indicating the role of KLF8 in cell proliferation and tumorigenesis. These results strongly suggest that KLF8 is essential for growth of CAL 27 cancer cells. A better understanding of KLF8 function and processing may provide novel insights into the clinical therapy of oral cancer.


[Health-related quality of life in patients with amyotrophic lateral sclerosis].
Progressive deterioration in patients with amyotrophic lateral sclerosis (ALS) has a major impact on their health-related quality of life (HRQOL). The objectives of this study are to evaluate HRQOL in a sample of patients diagnosed with ALS and estimate the predictive capability of a set of sociodemographic variables for the different scales covered by a general health survey. A total of 63 patients diagnosed with ALS were assessed using a sociodemographic questionnaire and the SF-36 general health survey. The sociodemographic variables studied were sex, age, presence of a caregiver, employment status, and time from diagnosis of disease. The SF-36 survey shows positive correlations between the different scales composing it, which proves its reliability. The mean scores obtained for each of the SF-36 scales were higher in men than in women, although the only statistically significant difference was for the Physical Role scale. The lowest age range (less than 56 years) presented the highest mean scores for most of these dimensions. Most of the variance in the test is explained by the variable 'presence of caregiver'. The SF-36 health survey has been confirmed as a valid and useful tool for evaluating HRQOL in ALS patients, and it discriminates between patients in different states of health according to their level of dependency.


EEG findings during basilar migraine attacks in children.
We present clinical and EEG findings in 4 children with basilar migraine (BM) (three female and one male, age 11 to 13.5 years). All patients had an EEG during the acute attack and a follow-up EEG within 4 to 18 days. In two patients the EEG, done within 4 h of the onset of symptoms (initial stage), showed diffuse polymorphic subdelta-delta activity. In two other children the EEG, performed 16 h after the onset of symptoms, showed delta-theta activity predominant over the occipital regions. Resolution of these abnormalities during follow-up was observed in all patients. We wish to stress the danger of misinterpretation of the slow wave activity in the EEG of patients with BM attacks. Together with the clinical findings and their evolution, EEG results should not be interpreted as a sign of a structural brain-stem lesion, such as infarction or inflammation.


Effect of total lymphoid irradiation on functional status in chronic multiple sclerosis: importance of lymphopenia early after treatment--the pros.
To determine whether immunosuppression by total lymphoid irradiation (TLI) slowed deterioration of chronic progressive multiple sclerosis (MS), functional impairment score and blood lymphocyte counts were compared at 6-month intervals through 4 years following treatment of MS patients by either TLI (n = 27) or sham irradiation (n = 21). At each interval, 20 to 30% fewer TLI-treated patients had deteriorated (p less than 0.05 at 6, 12, and 18 months), and the difference in mean functional impairment score between groups became progressively greater (p less than 0.01 at 42 and 48 months). Benefit accrued principally to the 17 TLI-treated patients with absolute blood lymphocyte counts less than 900/mm3 3 months after treatment, whose mean functional impairment score remained within 0.6 units of baseline (p = NS), whereas the ten TLI patients with higher post-treatment lymphocyte counts had progressive deterioration (p less than 0.05 to p less than 0.001 versus TLI-treated patients with lower lymphocyte counts at all intervals except 30 months) and had deteriorated by more than 5 functional scale units by 42 and 48 months. Side effects were minor and complications rare in TLI-treated patients, but one TLI-treated patient developed staphylococcal sepsis. Thus, TLI slows deterioration of chronic progressive MS, with what appears to be enduring benefit through 4 years compartmented to patients with greater induced lymphopenia. Modification of lymphoid irradiation regimens to increase the proportion of MS patients who achieve a favorable degree of lymphopenia and to avert functional hyposplenism may further improve the benefit/risk ratio.


Absorbed fractions for dose calculations of neuroreceptor PET studies.
A simple Monte Carlo program was constructed for the purpose of calculating absorbed fractions of relevance to neurologic positron-emission-tomography studies. The caudate, putamen, and cerebellum regions of the brain were mathematically modeled to serve as source regions for the absorbed-fraction calculations for positron-annihilation photons. The target organs were the caudate, putamen, cerebellum, brain, spine portion in the head, skull, and head. Absorbed fractions were also calculated for a uniform ring source which encircled the head phantom.


Considerable differences between methods for plasma D-dimer in the diagnosis of venous thrombosis: increased positive prediction using elevated discriminatory limits.
Four analytical methods for plasma D-dimer have been compared in a group of 82 consecutive patients with suspected venous thrombosis, 22 of whom subsequently received a positive clinical diagnosis. Differences in diagnostic power between methods were observed. In three of the four methods tested, the use of elevated discriminatory limits (rather than conventional 95-percentile upper reference limits) resulted in stronger positive predictive values for thromboembolism. We suggest that this approach may result in better diagnostic performance of the D-dimer method.


Effects of buyang huanwu decoction on ventricular remodeling and differential protein profile in a rat model of myocardial infarction.
Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from "Correction on Errors in Medical Classics" in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18 g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF.


Acid hydrolases in blister fluid. 7. Influence of dimethyl sulphoxide and heat.
Increased acid hydrolase activity has been demonstrated in suction blister fluid 1.5 h after the application of established lysosomal labilizing agents. Both the pattern of enzyme activity and the magnitude of the increases were similar to those following cutaneous inflammation. These data confirm our previous observations that acid hydrolases do indeed play a role in cutaneous inflammation, but their release is not the initial event in this process.


The fate of flowers and fruits of Cornus sanguinea L. in three contrasting Mediterranean habitats.
In the Mediterranean region of southern France, the fate of flowers and fruits of Cornus sanguinea, a deciduous shrub, was studied in three contrasting habitats: (1) an abandoned olive grove, (2) the edge and (3) the interior of a deciduous forest. Abundance of flowering and fruiting of C. sanguinea differed widely between the three habitats. The fate of the flowers, on the other hand, did not differ significantly between habitats. Taking all three habitats together, 77% of the flowers aborted, 23% initiated fruits, 6% developed mature fruits, and 3% produced ripe fruits that were eaten by birds. Likewise, there were for the most part no significant differences in the fate of immature and mature fruits between the habitats. On average, 58% of the immature fruits were abscised undamaged, 24% matured, 10% were damaged by insects and 8% dried up. Of the mature fruits, on average, 51% were eaten by birds, 23% damaged by insects, 20% dried up and 6% fell to the ground undamaged. Independent of habitat conditions, C. sanguinea seems to regulate the quantity of its seed crop primarily by limiting the number of flowers and secondarily by aborting surplus immature fruits, and the number of flowers is mainly controled by resource availability and genetic factors. In the case of C. sanguinea, both the fruit/flower ratio and the proportion of flowers producing mature fruits that are eaten by birds remain constant over a wide range of environmental conditions.


Myeloperoxidase deficiency in mice exacerbates lung inflammation induced by nonviable Candida albicans.
This study aimed to evaluate the effect of myeloperoxidase (MPO) deficiency on lung inflammation induced by nonviable Candida albicans (nCA). Mice were inoculated intranasally with nCA, and accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid was analyzed by flow cytometry. The levels of macrophage inflammatory protein 2 (MIP-2), keratinocyte-derived chemokine (KC), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in the lung were measured by ELISA. Production of MIP-2 and KC from neutrophils and macrophages was quantified in vitro. MIP-2 mRNA expression in the neutrophils was analyzed by real-time reverse transcription-PCR, and the extent of phosphorylation of ERK1/2 and Syk in the neutrophils was analyzed by Western blotting. The MPO(-/-) mice that received nCA showed more severe pneumonia than wild-type mice. Within 12 h of nCA administration, MPO(-/-) mice had significantly higher numbers of alveolar neutrophils and increased production of MIP-2 and KC relative to the responses seen in wild-type mice. Neutralization of MIP-2 and KC in vivo significantly reduced neutrophil infiltration. In vitro, production of MIP-2, but not that of KC, was enhanced in the nCA-stimulated neutrophils from MPO(-/-) mice, concomitant with up-regulation of Syk and ERK1/2. At 1 and 3 days after nCA administration, MPO(-/-) mice had significantly higher lung concentrations of TNF-α and IL-1β than wild-type mice. Pulmonary administration of nCA produced an altered inflammatory response in MPO(-/-) mice relative to wild-type mice. Enhanced MIP-2 production by MPO(-/-) neutrophils may at least partly contribute to exacerbated inflammation in mutant mice.


Predictive value of the complement factors B and H for women with gestational diabetes mellitus who are at risk of preeclampsia.
We aimed to define the relationships between the serum concentrations of complement factors B and H in mid-pregnancy and the risk of preeclampsia (PE) in patients with gestational diabetes mellitus (GDM). We performed a prospective nested case-control study of 503 patients with GDM who attended Peking University Third Hospital between March 2018 and December 2018. 456 patients were followed until delivery and blood samples were collected between gestational weeks 24 and 28. Thirty patients developed PE, 12 developed gestational hypertension (GH), and 42 matched cases were selected as a control group. The incidence of PE was 5.96 %. The serum concentrations of triacylglycerol (TG), FB, and FH of women with GDM who developed PE (GDM-PE group) in mid-pregnancy were significantly higher than those of the GDM group [TG: 3.60 (2.94-4.63) vs 2.54 (2.14-3.01) mmol/L, p < 0.001; FB: 346 (314-378) vs 284 (263-323) mg/L, p < 0.001; FH: 417 ± 45 vs 379 ± 47 mg/L, p = 0.003]. Multivariate regression analysis showed that high serum concentrations of TG and FB in mid-pregnancy were related to the risk of patients with GDM developing PE [TG: odds ratio (OR) 2.035 (95 % confidence interval (CI) 1.032-4.013); FB: OR 1.018 (95 % CI 1.001-1.035)]. The area under the curve (AUC) of FB for the prediction of PE was 0.821 (95 % CI 0.722-0.921) and that for a combination of TG, FB, and FH was 0.857 (95 % CI 0.770-0.944). High serum FB concentration during mid-pregnancy is a potential predictor of the risk of PE in patients with GDM, and the combination of FB, FH, and TG increased this predictive value.


A new assay and cellular localization for an inducible glucuronyltransferase in the embryonic chick liver.
A direct, radioisotopic assay is described for the uridine diphosphate glucuronic acid (UDPGA): p-aminophenol glucuronyltransferase. The assay uses solid phase p-aminophenol-Sephadex as the glucuronyl acceptor and UDP-[14C]GA as the glucuronyl donor. After incubation with the enzyme, the derivatized Sephadex beads are washed in SDS-urea or with high salt concentrations to remove all labeled material except for that covalently attached to the beads. Sonicated livers from chick embryos exposed to phenobarbital for at least 5 days transfer more than ten times the glucuronic acid to derivatized beads than do uninduced livers of the same developmental age. Glucuronyl-transferase activity can be detected on intact, living cells after 5 days of phenobarbital induction, whereas sonicate activity is detectable within 3 days of induction. Suspensions of living cells can show 25% the activity found in the same suspension after all the cells are lysed by sonication.


Niche-specific gene expression in a parasitic nematode; increased expression of immunomodulators in Teladorsagia circumcincta larvae derived from host mucosa.
Metazoan parasites have to survive in many different niches in order to complete their life-cycles. In the absence of reliable methods to manipulate parasite genomes and/or proteomes, identification of the molecules critical for parasite survival within these niches has largely depended on comparative transcriptomic and proteomic analyses of different developmental stages of the parasite; however, changes may reflect differences associated with transition between developmental stages rather than specific adaptations to a particular niche. In this study, we compared the transcriptome of two fourth-stage larval populations of the nematode parasite, Teladorsagia circumcincta, which were of the same developmental stage but differed in their location within the abomasum, being either mucosal-dwelling (MD) or lumen-dwelling (LD). Using RNAseq, we identified 57 transcripts which were significantly differentially expressed between MD and LD larvae. Of these transcripts, the majority (54/57) were up-regulated in MD larvae, one of which encoded for an ShKT-domain containing protein, Tck6, capable of modulating ovine T cell cytokine responses. Other differentially expressed transcripts included homologues of ASP-like proteins, proteases, or excretory-secretory proteins of unknown function. Our study demonstrates the utility of niche- rather than stage-specific analysis of parasite transcriptomes to identify parasite molecules of potential importance for survival within the host.


[The relationship between microalbuminuria and plasma high sensitivity C reactive protein].
To investigate the relationship between microalbuminuria (MA) and plasma high sensitivity C reactive protein (hsCRP). The plasma hsCRP level and urine albumin level of 746 Chinese people were detected with ELISA and analyzed, respectively. The hsCRP level of MA group increased significantly compared with the control group (2.23 +/- 3.35 mg/L vs 1.68 +/- 2.58 mg/L, P < 0.05), the incidence of MA increased significantly when the plasma hsCRP level was beyond 0.77 mg/L (P < 0.05); logistic analysis showed that the occurrence of MA was associated with the plasma hsCRP level (OR = 1.153, P < 0.05). Increased plasma hsCRP was probably involved in the occurrence of MA, suggesting that inflammation may deteriorate endothelial dysfunction.


K⁺ and Rb⁺ Affinities of the Na,K-ATPase α₁ and α₂ Isozymes: An Application of ICP-MS for Quantification of Na⁺ Pump Kinetics in Myofibers.
The potassium affinities of Na,K-ATPase isozymes are important determinants of their physiological roles in skeletal muscle. This study measured the apparent K⁺ and Rb⁺ affinities of the Na,K-ATPase α₁ and α₂ isozymes in intact, dissociated myofibers obtained from WT and genetically altered mice (α₁S/Sα₂R/R and skα₂-/-). It also validates a new method to quantify cations in intact, dissociated myofibers, using inductively coupled plasma mass spectrometry (ICP-MS). Our findings were that: (1) The extracellular substrate sites of Na,K-ATPase bind Rb⁺ and K⁺ with comparable apparent affinities; however; turnover rate is reduced when Rb⁺ is the transported ion; (2) The rate of Rb⁺ uptake by the Na,K-ATPase is not constant but declines with a half-time of approximately 1.5 min; (3) The apparent K⁺ affinity of the α₂ isozymes for K⁺ is significantly lower than α₁. When measured in intact fibers of WT and α₁S/Sα₂R/R mice in the presence of 10 µM ouabain; the K1/2,K of α₁ and α₂ isozymes are 1.3 and 4 mM, respectively. Collectively, these results validate the single fiber model for studies of Na,K-ATPase transport and kinetic constants, and they imply the existence of mechanisms that dynamically limit pump activity during periods of active transport.


Critical issues in the study of the acute effects of solvent exposure.
The acute effects of exposure to solvent vapour can be studied under highly controlled conditions in laboratory experiments on volunteers or in quasi-experimental field studies on occupationally exposed workers. Although these two types of investigations can provide valuable information on the neurotoxicity of solvents, their accomplishment encounters theoretical and practical difficulties. In the present paper the independent, the extraneous and the dependent variables of these studies are described, and both the research strategy and the methodology of these types of investigations are presented and discussed.


Real-time monitoring of mesenchymal stem cell responses to biomaterial surfaces and to a model drug by using quartz crystal microbalance.
In this study, the mesenchymal stem cell (MSC) responses to biomaterial surfaces and to an anti-microtubule drug (vinblastine) were detected by using the quartz crystal microbalance (QCM). Gold electrodes with different coatings were subjected to MSCs under flow conditions; thus, crystal frequency decreased due to the adhesion of MSCs on the crystal. For evaluation of cell-drug interactions, vinblastine was introduced to MSCs attached onto the surfaces. The changes in frequency indicated the binding of drug to cell microtubules. The present study demonstrates the suitability of QCM as an invaluable tool for the real-time monitoring of cell-surface and cell-drug interactions.


Multiple Endocrine Neoplasia: Genetics and Clinical Management.
Early diagnosis of multiple endocrine neoplasia (MEN) syndromes is critical for optimal clinical outcomes; before the MEN syndromes can be diagnosed, they must be suspected. Genetic testing for germline alterations in both the MEN type 1 (MEN1) gene and RET proto-oncogene is crucial to identifying those at risk in affected kindreds and directing timely surveillance and surgical therapy to those at greatest risk of potentially life-threatening neoplasia. Pancreatic, thymic, and bronchial neuroendocrine tumors are the leading cause of death in patients with MEN1 and should be aggressively considered by at least biannual computed tomography imaging.


Neuroscience: Hedonic worms gorge on high-energy foods.
Cannabinoids can enhance the preference for calorific foods through hedonic feeding behaviors. A new study identifies and characterizes these indulgent behaviors in the nematode Caenorhabditis elegans, providing insights into the mechanisms of their regulation.


A Magnetic Adsorbent for the Removal of Cationic Dyes from Wastewater.
In this article, a study was presented on the adsorption activity of a new nanocomposite particle Fe₃O₄@1, which was synthesized by combining [Cu(HL)₂]₂H₂[P₂Mo₅O23]·10H₂O (1) (HL = 2-acetylpyridine semicarbazone) and Fe₃O₄ nanoparticles. Transmission electron microscopy and X-ray powder diffraction analyses revealed that Fe₃O₄@1 possessed high crystallinity with an average particle size of 19.1 nm. The adsorption activity of the as-prepared Fe₃O₄@1 was investigated by photometrically monitoring the removal of methylene blue, rhodamine B, safranine T, gentian violet, fuchsin basic, and methyl orange from aqueous solutions. Significantly, we could easily separate Fe₃O₄@1 from the reaction media by applying an external magnet. Furthermore, the recycling performance was observed using methylene blue, revealing the recyclability and high stability of Fe₃O₄@1. It was shown that Fe₃O₄@1 is a promising candidate material for adsorbing cationic dyes in aqueous media.


Politics of rural health care: recruitment and retention of physicians.
The shortage of physicians in underserviced areas has been defined, and the causative recruitment and retention factors have been identified. The CMA report provides a framework for understanding these factors. Many can be modified, but this requires cooperation between physicians, communities, hospitals, medical schools, medical associations and governments. The development of a rural-practice master plan in each province would facilitate this process.


EMG median frequency changes in the neck-shoulder stabilizers of symptomatic office workers when challenged by different physical stressors.
The problem of work-related neck and upper limb disorders among computer users has been reported extensively in the literature, and commonly cited risk factors include static posture, speed and force of keyboard operation. The present study examined changes in median frequency (MF) of the neck-shoulder muscles in symptomatic and asymptomatic office workers when they were exposed to these three physical stressors. A quasi-experimental Case-Control design was used to examine MF changes in two groups of female office workers when they were subjected to controlled doses of computer work involving prolonged static posture, increased typing speed and increased typing force. The MF of four major neck-shoulder muscles were examined bilaterally and compared between groups. The MF changes over time-at-task did not clearly illustrate any muscle fatigue mechanism. However, Case Group consistently showed trends for higher MF than the Control Group, and this pattern was observed in response to all three physical stressors. The consistent group differences in MF suggest different muscle recruitment strategies between symptomatic and asymptomatic office workers. These results implied that symptomatic individuals had altered motor control, which may have important implications in understanding the etiology of work-related musculoskeletal disorders.


Ultrastructural alterations and retention of the C-propeptide of type II collagen in human chondrocytes exposed in vitro to brefeldin A.
Normal human chondrocytes grown in vitro were exposed to 10 micrograms/ml Brefeldin A (BFA) for 24 h, 1 microgram/ml for 4 h, or 0.1 microgram/ml for 4 h and evaluated for ultrastructural alterations. BFA in the amount of 0.1 microgram/ml resulted in vacuolization, disappearance of the Golgi, and moderate increases in rough endoplasmic reticulum (rER) vesicles. After 1 microgram/ml BFA exposure large interconnected cisternae were identified. BFA treatment of 10 micrograms/ml was associated with large dilated ER cisternae which contained material of variable electron densities. Immunocytochemical localization showed markedly increased type II procollagen intracellular retention in BFA-treated cells. High dose BFA-treated cells showed ultrastructural similarities to those seen in the skeletal dysplasia hypochondrogenesis. Results presented here show that in vitro culture of normal human chondrocytes results in retention of the C-propeptide of type II collagen and marked alterations in cytoplasmic ultrastructure.


Role of subcutaneous drains in obese patients undergoing elective cholecystectomy: a cohort study.
Prophylactic drainage of wounds is aimed to reduce the wound complications and thereby morbidity. Obese patients are at more risk. The objective of the present study was to determine whether subcutaneous drainage can reduce such complications in elective abdominal surgery (cholecystectomy) in obese patients. Randomized, prospective and comparative study. Two hundred and fifty obese patients with body mass index (BMI) >32 and subcutaneous fat thickness of >3 cm undergoing elective Cholecystectomy were allocated into two groups, viz. study (n=125) and control (n=125). Incision technique was standardized for all the patients. Patients with sepsis, spillage and comorbid conditions were excluded from the study. Overall seroma formation occurred in 11 (8.80%) patients in the study group and 42 (33.60%) patients in the control group (p<0.05), the likelihood of seroma formation without drains was 6.5 times and 9.3 times more in patients with subcutaneous fat thickness of 3-3.9 cm and 4-5 cm, respectively. 71.43% of patients in the control group and 54.55% patients in the study group who developed seroma presented in the first week of surgery. Prophylactic use of subcutaneous drains in obese patients undergoing cholecystectomy was found to reduce the seroma formation significantly.


The effectiveness of a collaborative infertility counseling (CIC) on pregnancy outcome in women undergoing in vitro fertilization: a randomized trial.
The optimal objective of infertility treatments is to increase pregnancy rate. The aim of this study was to assess the effectiveness of a collaborative counseling program on pregnancy rate in women undergoing in vitro treatment. This was a parallel group randomized trial on a sample of 60 women attending to an infertility research center affiliated to Mashhad University of Medical Sciences for fertility treatment. Women were randomly assigned to an intervention or a control group. Then, a five-session program offered to the intervention group while the control group received nothing expect the usual care. The primary outcome for the study was positive pregnancy test at the end of study. Statistical analyses including independent samples t-test were performed to explore the data. The outcome analysis showed that there were no significant differences in pregnancy rate between the intervention and the control groups (P = 0.298). Also, there were no significant differences in follicle and embryo numbers between two groups. However, a significant difference was observed between two groups in terms of oocyte numbers where the intervention group had more oocyte (P = 0.014). Overall the findings indicated that the collaborative infertility counseling did not improve treatment success in infertile women undergoing in vitro fertilization. IRCT201110267915N1. Registered 2014.07.25-Retrospectively registered ( http://en.irct.ir/trial/8359 ).


[Significance of Clostridium septicum as a cause of gas edema].
Gas gangrene caused by Clostridium septicum is relatively rare. In this paper 15 cases are described observed within the last 5 years. In 3 cases the gas gangrene was acquired exogenously. The other cases were endogenous infections. 9 of these cases were associated with colon carcinoma. C. septicum gas gangrene has a high lethality rate: 11 of the 15 patients died from the infection.


Mouse models of cancer: does the strain matter?
Mouse models are indispensible tools for understanding the molecular basis of cancer. However, despite the invaluable data provided regarding tumour biology, owing to inbreeding, current mouse models fail to accurately model human populations. Polymorphism is the essential characteristic that makes each of us unique humans, with different disease susceptibility, presentation and progression. Therefore, as we move closer towards designing clinical treatment that is based on an individual's unique biological makeup, it is imperative that we understand how inherited variability influences cancer phenotypes, how it can confound experiments and how it can be exploited to reveal new truths about cancer biology.


Sorption, desorption and degradation of neonicotinoids in four agricultural soils and their effects on soil microorganisms.
In this study, the sorption, desorption and degradation of three neonicotinoids, imidacloprid (IMI), clothianidin (CLO) and thiacloprid (THI), and their effects on microorganisms in four different agricultural soils were systematically evaluated. The sorption of neonicotinoids on the soils was generally low with distribution coefficients (Kd) up to 16.2L/kg at Ce of 0.05mg/L following the order THI>IMI≈CLO, and the sorption were mainly influenced by the soil organic carbon content. The percentage degradation rates of the pesticides in different soils ranged from 25.4% to 80.9%, all following the order THI>IMI≈CLO. All the three neonicotinoids degraded much faster under non-sterilized conditions than sterilized conditions, indicating considerable contribution of biodegradation. The total degradation or biodegradation of neonicotinoids was the fastest in the soil with the highest organic carbon content, and the neonicotinoids' bioavailability was not the primary influencing factor due to their weak sorption. The chemical degradation was mainly affected by pH and cation exchange capacity. The degradation of neonicotinoids occurred mainly via nitrate reduction, cyano hydrolysis and chloropyridinyl dechlorination. High-throughput sequencing data showed that the microbial community structure and abundance changed greatly in neonicotinoid-spiked soils as compared to the control, which might influence their degradation pathways. Some microbe families associated with the biodegradation of neoniconoids were found, which were all belonging to Proteobacteria and Actinobacteria. The degradation of neoniconoids influenced the soil nitrifying process. The present study provides valuable information for comprehensively understanding the fate of neonicotinoids in soils.


Malnutrition increases NO production and induces changes in inflammatory and oxidative status in the distal colon of lactating rats.
Epidemiological studies have indicated the lack of breast feeding as a risk factor associated with later development of inflammatory bowel disease. Nevertheless, the repercussion of little feeding during suckling on large intestine inflammatory response and anti-oxidant resources has not yet been completely understood. This study hypothesized that unfavorable lactation is able to induce oxidative stress and release of inflammatory mediators modifying the integrity of the colon epithelium in weanling rats. Wistar rats were reared under different early nutritional conditions according to litter size in two groups: N6 (6 pups/dam) and N15 (15 pups/dam) until the 25th postnatal day. The distal colon was removed and processed for biochemical, morphometric, and immunohistochemical analyzes. Lipoperoxidation, nitric oxide (NO), reduced (GSH) and oxidized (GSSG) glutathione, tumor necrosis factor-alpha (TNF-α), interleukins-1β, 4 and 10 (IL-1β; IL-4; IL-10) levels, and total superoxide dismutase (tSOD), and catalase (CAT) activities were assessed. Morphometric analysis was carried out using paraffin sections and wholemount myenteric plexus preparations. Increased lipoperoxidation, NO, TNF-α and IL-1b levels, reduced tSOD and increased CAT activities were found in the N15 compared to N6 group. No intergroup difference was detected for IL-10, while lower levels of IL-4, GSH and GSSG and lower neuronal size and density were induced by undernutrition. Reduced feeding during suckling changed the inflammatory response and oxidative status in the colon of weanling rats. These data suggest potential mechanisms by which malnutrition early in life may increase the vulnerability of the large intestine to insults.


Layered materials as a platform for quantum technologies.
Layered materials are taking centre stage in the ever-increasing research effort to develop material platforms for quantum technologies. We are at the dawn of the era of layered quantum materials. Their optical, electronic, magnetic, thermal and mechanical properties make them attractive for most aspects of this global pursuit. Layered materials have already shown potential as scalable components, including quantum light sources, photon detectors and nanoscale sensors, and have enabled research of new phases of matter within the broader field of quantum simulations. In this Review we discuss opportunities and challenges faced by layered materials within the landscape of material platforms for quantum technologies. In particular, we focus on applications that rely on light-matter interfaces.


Acceptance of intradermal inactivated influenza vaccines among hospital staff following 2 seasonal vaccination campaigns.
After a Canadian hospital's official influenza vaccination campaign concluded in the 2011-2012 and 2012-2013 influenza seasons, study nurses provided additional vaccination mobile cart hours and the added choice of an intradermal injection. An additional 2.1% of staff in the first and 1.4% in the second season were vaccinated during the study with 90-99% preferring the intradermal injection or having no preference. All 13 staff who attempted self-injection with the intradermal vaccine in 2012-2013 were successful on their first attempt. Offering alternatives to intramuscular vaccines may increase rates of vaccination.


Sex related differences in muscle health and metabolism in chronic obstructive pulmonary disease.
Sex differences in muscle function and mass, dyspnea, and clinical outcomes have been observed in patients with Chronic Obstructive Pulmonary Disease (COPD) despite a similar level of airflow obstruction. Protein and amino acid metabolism is altered in COPD, however, it remains unclear whether a difference in metabolic signature exists between males and females with COPD that may explain the observed differences in muscle health and clinical outcomes. In 234 moderate to severe COPD patients (males/females: 113/121) and 182 healthy controls (males/females: 77/105), we assessed, besides presence of comorbidities and clinical features, muscle function by handgrip and leg dynamometry, and body composition by dual-energy x-ray absorptiometry. In the postabsorptive state, a mixture of 18 stable isotopes of amino acids was administered by pulse and arterialized blood was sampled for 2 h. Amino acid concentrations and enrichments were analyzed by LC-MS/MS to calculate whole body (net) protein breakdown (WBnetPB) and whole body production (WBP) rates (μmol/hour) of the amino acids playing a known role in muscle health. Statistics was done by ANCOVA to examine the effects of sex, COPD, and sex-by-COPD interaction with as covariates age and lean mass. Significance was set as p < 0.05. Lung function was comparable between males and females with COPD. Being a female and presence of COPD were independently associated with lower appendicular lean mass, muscle strength, and WBnetPB (p < 0.05). Being a male was associated with higher visceral adipose tissue, C-reactive protein (CRP) (p < 0.05), and higher prevalence of heart failure and obstructive sleep apnea. Sex-by-COPD interactions were found indicating lower fat mass (p = 0.0005) and WBPs of phenylalanine (measure of whole body protein turnover) and essential amino acids (p < 0.05), particularly in COPD females. Higher visceral adipose tissue (p = 0.025), CRP (p < 0.0001), and WBP of tau-methylhistidine (p = 0.010) (reflecting enhanced myofibrillar protein breakdown) were observed in COPD males. Presence of sex specific changes in protein and amino acid metabolism and cardiometabolic health in COPD need to be considered when designing treatment regimens to restore muscle health in males and females with COPD. www. gov, NCT01787682, NCT01624792, NCT02157844, NCT02065141, NCT02770092, NCT02780219, NCT03327181, NCT03796455, NCT01173354, NCT01154400.


Pseudoaneurysm inside of a true aneurysm.
Left ventricular pseudoaneurysms and true aneurysms are two possible complications of myocardial infarction. However, while pseudoaneuryms require urgent surgical resection, true aneuryms can often be managed medically, making imperative an accurate diagnosis.The authors describe a case of a delayed rupture of a true aneurysm that was contained and gave rise to a pseudoaneurysm inside of a true aneurysm. The echocardiography allowed the differential diagnosis for a timely surgical intervention which resulted in the patient's full recovery.


Analysis of the methylation patterns of the p16 INK4A, p15 INK4B, and APC genes in gastric adenocarcinoma patients from a Brazilian population.
Gastric cancer is a major public health problem in Pará state, where studies suggest complex genetic and epigenetic profiles of the population, indicating the need for the identification of molecular markers for this tumor type. In the present study, the methylation patterns of three genes [p16 (INK4A), p15 (INK4B), and adenomatous polyposis coli (APC)] were assessed in patients with gastric adenocarcinoma from Pará state in order to identify possible molecular markers of gastric carcinogenesis. DNA samples from tumoral and non-tumoral gastric tissues were modified with sodium bisulfite. A fragment of the promoter region of each gene was amplified and sequenced, and samples with more than 20 % of methylated CpG sites were considered hypermethylated. The correlation between the methylation pattern of the selected genes and the MTHFR C677T polymorphism, as well as the relationship between APC and CDH1 methylation, were evaluated. The results suggest that APC hypermethylation is an age-specific marker of gastric carcinogenesis, and the concordance of this event with CDH1 hypermethylation suggests that the Wnt pathway has an important role in gastric carcinogenesis. While the hypermethylation pattern of p15 (INK4B) seems to be an earlier event in this type of tumor, the hypomethylated status of this gene seems to be correlated to the C677T MTHFR TT genotype. On the other hand, the observed pattern of p16 (INK4A) hypermethylation suggests that this event is a good marker for the gastric cancer pathway in the Pará state population.


Heterothallism in Cordyceps takaomontana.
Perithecium formation of an entomopathogenic fungus Cordyceps takaomontana was promoted by treating the mycelia with cell wall-degrading enzymes and PEG 4000. Perithecia were formed in the mixed culture of both mating-type strains MAT1 and MAT2, and not in the culture of MAT1 or MAT2 alone. The MAT1 strains did not possess a mating-type gene MAT1-1-3, but could produce perithecia. These results strongly suggested that C. takaomontana is heterothallic, and does not need MAT1-1-3 for the perithecium formation. MAT1-1-3 was also not found in another entomopathogenic fungus Cordyceps militaris. On the other hand, phytopathogenic fungi Balansia sp., Claviceps purpurea and Epichloë typhina possessed MAT1-1-3. The structures of mating-type locus MAT1-1 of these phytopathogenic fungi in the family Clavicipitaceae were similar to that of a phytopathogenic fungus Gibberella fujikuroi in the family Nectriaceae, which is closely related to Clavicipitaceae. These results suggested that phytopathogen might be more ancestral group than entomopathogen in Clavicipitaceae, and that MAT1-1-3 might be lost in the course of the host shift from plants to insects.


Continuous popliteal sciatic nerve block for outpatient foot surgery--a randomized, controlled trial.
A major problem in outpatient foot surgery is severe postoperative pain that is not sufficiently treated by peroral analgesics. Sixty-three patients underwent foot surgery under spinal anesthesia. Immediately on conclusion of the operation, sciatic and saphenous nerve blocks were performed. The sciatic nerve was blocked in the popliteal fossa with 30 ml of ropivacaine 5 mg ml(-1) and a perineural catheter was passed through the cannula. The patients were randomized to receive either ropivacaine 2 mg ml(-1) (n=30) or saline (n=30) in the catheter through a disposable elastomeric pump with a fixed infusion rate of 5 ml h(-1) for 55 h. Analgesia was excellent until 23 h 44 min (14 h 34 min) in the treatment group and 18 h 16 min (7 h) in the placebo group [mean (SD), P=0.07]. Thereafter, pain was significantly less in the treatment group on the first and second postoperative days (P=0.001). Sleep disturbances because of the pain in the foot were experienced by 25% of the treatment group on the first night at home and by 50% of the control group (P=0.29). There were no differences between the groups in their need for rescue opioid medication. None of the patients had any major problem with the catheter or pump, and none had any toxic effect referable to the technique. This randomized, double-blind study shows that continuous blockade of the sciatic nerve in the popliteal fossa reduces postoperative pain and has no untoward effects in a patient group known to experience severe pain after ambulatory surgery.


Endometrioid carcinoma of prostate.
A prostatic tumor that was excised from a sixty-two-year-old man was found histologically to resemble papillary endometrial carcinoma. A specimen of this prostatic endometrioid carcinoma tested positive for prostate-specific antigen and focally positive for mucin, confirming the prostatic epithelial origin of the tumor. A review of the literature indicates that tumors of this type are best approached as a standard acinar adenocarcinoma of the prostate.


A possible role for natural killer cells in providing protection against Plasmodium berghei in early stages of infection.
Beige mutant mice, which are deficient in natural killer (NK) cells, exhibited a significantly higher parasitaemia than the parental C57BL/6 strain between days 4 and 10 after infection with Plasmodium berghei. Within 8-12 days after infection 70% of beige mice were dead but no deaths occurred in the parental strain until day 16. The median survival time of the beige mice (10 days) was significantly lower than that of the parental strain (22 days). It appears that NK cells may be protective in the early stages of malarial infection.


Relational and therapeutic aspects of children with late onset of a terminal disease.
The authors studied the patterns by which children and adolescents with spinal amyotrophy face their disease and the psychological difficulties involved. Five case histories regarding forms II and III of spinal amyotrophy are discussed in detail. Intense and recurrent anguish about death and the image of a narcissistically injured self were found to be present in all patients. We believe that these are the emotional elements that are most important in influencing the development of the child's relations with his own mental objects. This should be taken into account in any type of approach to the treatment of patients with this disease.


Sex difference in cerebral atherosclerotic stenosis in Chinese asymptomatic subjects.
Sex difference in cerebral atherosclerosis has been noted in previous studies, but the precise characteristics remain incompletely elucidated. This study aims to identify the sex difference in patients with asymptomatic cerebrovascular stenosis. The image and clinical data of 1305 consecutive patients who had head and neck computed tomography angiography (CTA) were collected. Fifty hundred and seventy-three patients (287 males) with asymptomatic atherosclerotic stenosis in cerebral arteries were finally included. The stenosis number, distribution, severity and their changes with age were analyzed and compared between males and females. Simple linear regression was used to assess the change in lesions with age. A total of 2097 stenoses were identified in 573 patients, males had more stenoses than females (3 [2, 5] vs 3 [2, 4], p=0.015). The number of stenoses in extracranial arteries was much higher in males (p = 0.001). Females had higher percentage of stenosis in anterior (89.6% vs 85.9%, p = 0.012) and intracranial arteries (63.3% vs 57.1%, p = 0.004) than males. Males had higher percentage of moderate-severe stenosis (5.1% vs 3.2%, p = 0.026). Age (OR = 1.67; 95% CI 1.24-2.25; p < 0.001) and hypertension (OR = 2.53; 95% CI 1.24-5.15; p = 0.01) were associated with moderate-severe stenosis. In patients over 50 years old, the number of stenoses increased by 1.03 per 10 years (p < 0.001), with 0.72 more stenoses in males (p = 0.003). Cerebral atherosclerotic stenosis was different between sexes regarding the distribution, severity and the change pattern with age, which underline the sex specific management in patients with cerebral atherosclerosis.


Evaluation of stability and sensitivity of cell fluorescent labels when used for cell migration.
The directed migration of mammalian cells is a foundation of development and growth. A variety of processes such as tissue development, wound healing, pathogen recognition/destruction as well as cancer metastasis are the result of regulated or dysregulated cell migration. While the ability to measure a cell's propensity to migrate has clinical relevance in several settings, no universal protocol has been established to measure cell migration. A variety of techniques are currently used to measure migration including manual counting, flow cytometry or Coulter counting, microfluidic devices, computerized spectroscopic methods, or the use of various tracking dyes interfaced with fluorescent or non-fluorescent plate readers. In order to expedite the measurement of migration, we compared several common cytoplasmic and lipophilic cell tracking dyes to determine the best dye for determining migration of rare population of cells. CellVue® Burgundy was found to be superior over calcein AM, Cell Tracker Green CMFDA (chloromethyl fluorescein diacetate), Vybrant CFDA (carboxy fluorescein diacetate succinimidyl ester) in its retention within cells, superior to CellVue® NIR 815, PKH67, and CM DiI with regard to signal to noise ratio, and superior to PKH26 with regard to instrument versatility.


Establishment of a novel volume-loaded heterotopic heart transplantation model in rats.
Non-volume-loaded (NL) donor hearts in the heterotopic heart transplantation model in rats undergo atrophy and thrombus formation in graft cavities after transplantation. The present study aimed to establish a novel model with volume-loaded donor hearts. We used Sprague-Dawley rats as donors and recipients. We established an NL model by anastomosing the donor ascending aorta and pulmonary artery end-to-side to the recipient abdominal aorta and inferior vena cava, respectively, and ligating the superior and inferior vena cava on the donor right atrium. The method of the volume-loaded (VL) model was the same as described above, except we performed an anastomosis of the donor left atrium to the recipient abdominal aorta to allow volume loading of the donor's left ventricle. We assessed the characteristics of the grafts by the surgical success rate, echocardiography, and histologic evaluation between the two models. Echocardiography showed that donor left ventricle in VL models was volume loaded and had normal systolic and diastolic function compared with the NL models. The mean weight of NL hearts was significantly less than that of VL hearts. Morphologic observation revealed that thrombus formation in donor heart cavities in NL model was significantly higher than that in the VL model. The area of cardiomyocytes per high-power field in the NL model was significantly lower than that in the VL model. We provide a novel VL heterotopic heart transplantation model in rats, in which hemodynamic performance of grafts is close to the normal cardiac physiologic situation; thus, the novel model will be more suitable for clinical research.


Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response.
Ultrahypofractionationed radiation therapy for prostate cancer is increasingly studied and adopted. The American Association of Physicists in Medicine Working Group on Biological Effects of Hypofractionated Radiotherapy therefore aimed to review studies examining toxicity and quality of life after stereotactic body radiation therapy (SBRT) for prostate cancer and model its effect. We performed a systematic PubMed search of prostate SBRT studies published between 2001 and 2018. Those that analyzed factors associated with late urinary, bowel, or sexual toxicity and/or quality of life were included and reviewed. Normal tissue complication probability modelling was performed on studies that contained detailed dose/volume and outcome data. We found 13 studies that examined urinary effects, 6 that examined bowel effects, and 4 that examined sexual effects. Most studies included patients with low-intermediate risk prostate cancer treated to 35-40 Gy. Most patients were treated with 5 fractions, with several centers using 4 fractions. Endpoints were heterogeneous and included both physician-scored toxicity and patient-reported quality of life. Most toxicities were mild-moderate (eg, grade 1-2) with a very low overall incidence of severe toxicity (eg, grade 3 or higher, usually <3%). Side effects were associated with both dosimetric and non-dosimetric factors. Prostate SBRT appears to be overall well tolerated, with determinants of toxicity that include dosimetric factors and patient factors. Suggested dose constraints include bladder V(Rx Dose)Gy <5-10 cc, urethra Dmax <38-42 Gy, and rectum Dmax <35-38 Gy, though current data do not offer firm guidance on tolerance doses. Several areas for future research are suggested.


Prostaglandin protection of rat colonic mucosa from damage induced by ethanol.
The effects of pretreatment with 16,16-dimethyl prostaglandin E2 (dmPGE2) on ethanol-induced colonic damage were studied in the rat. Colonic damage was assessed macroscopically, histologically, and using cytoplasmic (lactate dehydrogenase) and lysosomal (acid phosphatase) enzyme markers of cell disruption. Intrarectal administration of 30% ethanol produced grossly visible regions of hyperemia and hemorrhage. Histologically, the ethanol injury was characterized by complete destruction of the surface epithelium and necrosis extending throughout most of the mucosal layer. When incubated in vitro after challenge with ethanol in vivo, the colons released significantly more acid phosphatase and lactate dehydrogenase than did controls. Intrarectal pretreatment with dmPGE2 caused a dose-dependent reduction in ethanol-induced damage, as measured by all three parameters. A significant (P less than 0.05) reduction of macroscopically visible damage was observed with 0.2 micrograms/kg dmPGE2, while at higher doses (20 micrograms/kg) the histological signs of damage, including that to the colonic epithelium, were reduced or completely prevented. This dose of dmPGE2 also reduced (P less than 0.01) the release of the enzyme-markers to control levels. The possibility that this protection was mediated by increased colonic fluid secretion was studied. Pretreatment with dmPGE2 had no effect on net colonic fluid secretion (measured using the nonabsorbable marker [3H]inulin) or on the absorption of ethanol by the colon. This study demonstrates that intrarectal administration of dmPGE2 can protect the colonic mucosa from damage induced by direct application of a potent topical irritant. With the highest dose of dmPGE2 tested (20 micrograms/kg), protection of the colonic epithelium from ethanol injury was observed.


Competitive, uncompetitive, and mixed inhibitors of the alkaline phosphatase activity associated with the isolated brush border membrane of the tapeworm Hymenolepis diminuta.
Several compounds were tested as inhibitors of the alkaline phosphatase (AlkPase) activity associated with the isolated brush border membrane of the tapeworm, Hymenolepis diminuta. Molybdate, arsenate, arsenite and beta-glycerophosphate (BGP) were competitive inhibitors of the hydrolysis of p-nitrophenyl phosphate, while levamisole and clorsulon were uncompetitive and mixed inhibitors, respectively. Molybdate was also a competitive inhibitor of the hydrolysis of BGP and 5'-adenosine monophosphate, and levamisole was an uncompetitive inhibitor of BGP hydrolysis. The apparent inhibitor constants (Ki') for molybdate and levamisole were virtually identical regardless of the substrate, and these data support the hypothesis that the AlkPase activity is represented by a single membrane-bound enzyme with low substrate specificity. Quinacrine, Hg2+, and ethylenediaminetetraacetate were also potent inhibitors of the AlkPase activity, but the mechanisms by which these latter three inhibitors function were not clear.


Real-time diagnosis and Gleason grading of prostate core needle biopsies using nonlinear microscopy.
Rapid histologic assessment of fresh prostate biopsies may reduce patient anxiety, aid in biopsy sampling, and enable specimen triaging for molecular/genomic analyses and research that could benefit from fresh tissue analysis. Nonlinear microscopy (NLM) is a fluorescence microscopy technique that can produce high-resolution images of freshly excised tissue resembling formalin-fixed paraffin-embedded (FFPE) H&E. NLM enables evaluation of tissue up to ~100 µm below the surface, analogous to serial sectioning, but without requiring microtome sectioning. One hundred and seventy biopsies were collected from 63 patients who underwent in-bore MRI or MRI/ultrasound fusion biopsy procedures. Biopsies were stained in acridine orange and sulforhodamine 101, a nuclear and cytoplasmic/stromal fluorescent dye, for 45 s. Genitourinary pathologists evaluated the biopsies using NLM by translating the biopsies in real time to areas of interest and NLM images were recorded. After NLM evaluation, the biopsies were processed for standard FFPE H&E and similarities and differences between NLM and FFPE H&E were investigated. Accuracies of NLM diagnoses and Gleason scores were calculated using FFPE histology as the gold standard. Pathologists achieved a 92.4% sensitivity (85.0-96.9%, 95% confidence intervals) and 100.0% specificity (94.3-100.0%) for detecting carcinoma compared to FFPE histology. The agreement between the Grade Group determined by NLM versus FFPE histology had an unweighted Cohen's Kappa of 0.588. The average NLM evaluation time was 2.10 min per biopsy (3.08 min for the first 20 patients, decreasing to 1.54 min in subsequent patients). Further studies with larger patient populations, larger number of pathologists, and multiple institutions are warranted. NLM is a promising method for future rapid evaluation of prostate needle core biopsies.


Respiratory uptake kinetics of neutral hydrophobic organic chemicals in a marine benthic fish, Pseudopleuronectes yokohamae.
We investigated the respiratory uptake kinetics of polychlorinated biphenyls (PCBs), organohalogen pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs), and 2,2',4,4'-tetrabrominated diphenyl ether (BDE #47) in a marine benthic fish, Pseudopleuronectes yokohamae. The respiratory uptake efficiencies (EW) of the chemicals, of which there have been no reports for the majority of persistent organic pollutants (POPs), were obtained by measuring the respiratory uptake rate constants (k1) and the oxygen consumption rates of fish. Fish were exposed to water in which these chemicals were dissolved at environmentally relevant concentrations for 28 d, followed by 168 d of depuration in clean seawater. The k1 and EW values for 99 compounds were obtained, and they ranged from 2000 to 42000 L kg-lipid(-1) d(-1) and from 0.060 to 1.3, respectively. The EW values of the chemicals, except for PAHs, tended to increase with increasing values of the log octanol-water partition coefficients (KOW) of the chemicals up to a log KOW of 5. For log KOW in the range 3-5, the EW values in this study were much lower than those in a published study (about one-third). As a result of analysis by a two-phase resistance model, the resistance of transport rates to the lipid phase in this study was lower than was the case in the published study. These findings indicate that the EW predicted by the published study for log KOW in the range 3-5 may differ among fish species and water temperature, and further study is needed.


Somatic cell genetics and the study of cholesterol metabolism.
The regulation of cholesterol biosynthesis by extracellular cholesterol occurs both in whole animal tissue and in permanent somatic cell lines in culture. Permanent mammalian cells lines, under optimized growth conditions, are easily manipulated both biochemically and genetically. The Chinese hamster ovary cell line (CHO-K1) is the most widely used cell line for genetic studies. CHO-K1 is a pseudo-diploid mammalian cell exhibiting a short doubling time and a relatively high plating efficiency. Somatic cell mutants can be generated through mutagenesis and also by drug adaptation. Following mutagenesis, auxotrophs may be isolated either by selection or by screening. Most selection procedures for mutants of cholesterol metabolism must be done in serum depleted of cholesterol which requires the endogenous biosynthetic pathway to be intact. Mutants failing to produce cholesterol do not replicate their DNA and exhibit reduced concentrations of cholesterol in their membranes. BUdR and polyene antibiotics have both been used to select against the wild-type cells which incorporate these compounds and are killed, allowing the survival of the mutant cells. Both mevalonate and cholesterol auxotrophs have been isolated with the BUdR technique and have proven useful for elucidation of the early steps in cholesterol biosynthesis, particularly for the ratelimiting enzyme HMG-CoA reductase. Somatic cell fusion of a mutant and wild-type cell followed by chromosomal segregation, routinely used to map human genes, has also been used to map the human gene for HMG-CoA synthase. Such hybrids also provide valuable information on the dominance or recessivity of a specific lesion. DNA-mediated gene transfer into somatic cell mutants allows the selection of DNA sequences which complement the mutation, and is also useful for analysis of regions of regulatory significance. Mutants, resistant to the regulatory effects of oxygenated sterols, can be isolated following mutagenesis. Mutants of this type vary the lipid content of their membranes in response to cholesterol concentration in the medium. All such mutants tested exhibit a pleiotropic regulatory effect on more than one enzyme in the cholesterol biosynthetic pathway. Adaptation to drugs such as compactin and mevinolin, which inhibit HMG-CoA reductase, have been used to produce mutants which overexpress enzymes in the pathway. These amplified cells are useful sources of specific mRNAs for construction of cDNA libraries and gene isolation. Structure-function relationships of membrane sterols can be studied in cholesterol auxotrophs where changes in acyl-chain ordering can be manipulated by exogenous sterols in the medium.


Studies on the positive inotropic effect of dopamine in the guinea-pig heart.
The positive inotropic effect of dopamine has been studied in isolated ventricular strips of guinea-pig heart. The concentration-inotropic response curve for dopamine was significantly shifted to the right by pretreatment with reserpine. In preparations obtained from animals pretreated with reserpine (2.5 mg/kg, 24 h prior to the experiment) the dose-response curve was not significantly affected by haloperidol, a dopamine vascular receptor antagonist (10(-6)-3X10(-6) M). The inotropic effect of dopamine was antagonized by practolol (3X10(-7)-10(-6) M), but not by phentolamine (3X10(-6)-10(-5) M); moreover the alpha-adrenoceptor blocking drug (10(-5) M) did not affect the curve for dopamine in the presence of practolol (3X10(-7) M). In preparations in which fast sodium channels were blocked by K+ -rich medium, slow electrical responses (calcium-mediated action potentials) as well as contractions were induced by high concentrations of dopamine (10(-4)-3X10(-4) M); again these responses were unaffected by phentolamine or haloperidol, but were blocked by practolol. It was concluded that in the guinea-pig ventricular muscle dopamine induced a positive inotropic effect through both indirect and direct action, and that the latter is due to the activation of beta-adrenoceptors.


Pro-inflammatory responses of human bronchial epithelial cells to acute nitrogen dioxide exposure.
Nitrogen dioxide (NO2) is an environmental oxidant, known to be associated with lung epithelial injury. In the present study, cellular pro-inflammatory responses following exposure to a brief high concentration of NO2 (45 ppm) were assessed, using normal human bronchial epithelial (NHBE) cells as an in vitro model of inhalation injury. Generation and release of pro-inflammatory mediators such as nitric oxide (NO), IL-8, TNF-alpha, IFN-gamma and IL-1beta were assessed at different time intervals following NO2 exposure. Effects of a pre-existing inflammatory condition was tested by treating the NHBE cells with different inflammatory cytokines such as IFN-gamma, IL-8, TNF-alpha, IL-1beta, either alone or in combination, before exposing them to NO2. Immunofluorescence studies confirmed oxidant-induced formation of 3-nitrotyrosine in the NO2-exposed cells. A marked increase in the levels of nitrite (as an index of NO) and IL-8 were observed in the NO2-exposed cells, which were further enhanced in the presence of the cytokines. Effects of various NO inhibitors combined, with immunofluorescence and Western blotting data, indicated partial contribution of the nitric oxide synthases (NOSs) toward the observed increase in nitrite levels. Furthermore, a significant increase in IL-1beta and TNF-alpha generation was observed in the NO2-exposed cells. Although NO2 exposure alone did induce slight cytotoxicity (<12%), but presence of inflammatory cytokines such as TNF-alpha and IFN-gamma resulted in an increased cell death (28-36%). These results suggest a synergistic role of inflammatory mediators, particularly of NO and IL-8, in NO2-mediated early cellular changes. Our results also demonstrate an increased sensitivity of the cytokine-treated NHBE cells toward NO2, which may have significant functional implications in vivo.


Pressure response of Raman spectra of water and its implication to the change in hydrogen bond interaction.
In situ Raman spectroscopic measurements of water in the region of OH vibration were conducted up to 0.4 GPa at 23 and 52 degrees C. The frequencies of the decomposed OH stretching bands initially decreased with increasing pressure, reached a minimum at 0.15 GPa and increased up to 0.3 GPa and then decreased, which corresponds to the variations of the strength of hydrogen bonding. This variation was observed at 23 degrees C, but not at 52 degrees C, which suggests a change in pressure dependence on the hydrogen bond interaction between these two temperatures. Based on the equilibration model between hydrogen-bonded and nonhydrogen-bonded molecules, the present experimental results indicate that the pressure variation of the viscosity depends on the ratio of hydrogen-bonded molecules, rather than the strength of hydrogen bonding between molecules.


Molecular basis for coordinating secondary metabolite production by bacterial and plant signaling molecules.
The production of secondary metabolites is a major mechanism used by beneficial rhizobacteria to antagonize plant pathogens. These bacteria have evolved to coordinate the production of different secondary metabolites due to the heavy metabolic burden imposed by secondary metabolism. However, for most secondary metabolites produced by bacteria, it is not known how their biosynthesis is coordinated. Here, we showed that PhlH from the rhizobacterium Pseudomonas fluorescens is a TetR-family regulator coordinating the expression of enzymes related to the biosynthesis of several secondary metabolites, including 2,4-diacetylphloroglucinol (2,4-DAPG), mupirocin, and pyoverdine. We present structures of PhlH in both its apo form and 2,4-DAPG-bound form and elucidate its ligand-recognizing and allosteric switching mechanisms. Moreover, we found that dissociation of 2,4-DAPG from the ligand-binding domain of PhlH was sufficient to allosterically trigger a pendulum-like movement of the DNA-binding domains within the PhlH dimer, leading to a closed-to-open conformational transition. Finally, molecular dynamics simulations confirmed that two distinct conformational states were stabilized by specific hydrogen bonding interactions and that disruption of these hydrogen bonds had profound effects on the conformational transition. Our findings not only reveal a well-conserved route of allosteric signal transduction in TetR-family regulators but also provide novel mechanistic insights into bacterial metabolic coregulation.


Penile and scrotal Paget's disease: 130 Chinese patients with long-term follow-up.
To report a retrospective series of 130 Chinese patients with penoscrotal extramammary Paget's diseases (EMPD), with a long-term follow-up, and thus improve the diagnosis and therapy of this disease. The history, clinical presentation, pathology, treatment, and prognosis of 130 patients were analysed. All cases were confirmed by skin biopsy, and then the patients had local wide resection to remove the involved skin and subcutaneous tissue. The large defective wound was reconstructed using a split-thickness skin graft or local flap. Forty-five patients were evaluated by frozen-section biopsy of the margins during surgery, five of whom had positive margins and then had an extended resection immediately. Most of these patients had local skin or adjacent scrotal flaps to cover their skin defects. Of the 130 patients, 81 had a mean (range) follow-up of 3.2 (0.5-10) years after surgery. Five of nine patients with positive margins and three (4%) of 72 with negative margins had tumour recurrence. Five patients died from metastatic disease. Penoscrotal EMPD needs be differentiated from other chronic dermatitis. A 3 cm surgical margin should be sufficient and frozen-section pathological examinations are necessary for some complicated conditions. Skin grafts or local flaps are good for large skin defects.


Objectives and Design of BLEEDS: A Cohort Study to Identify New Risk Factors and Predictors for Major Bleeding during Treatment with Vitamin K Antagonists.
Risk scores for patients who are at high risk for major bleeding complications during treatment with vitamin K antagonists (VKAs) do not perform that well. BLEEDS was initiated to search for new biomarkers that predict bleeding in these patients. To describe the outline and objectives of BLEEDS and to examine whether the study population is generalizable to other VKA treated populations. A cohort was created consisting of all patients starting VKA treatment at three Dutch anticoagulation clinics between January-2012 and July-2014. We stored leftover plasma and DNA following analysis of the INR. Of 16,706 eligible patients, 16,570 (99%) were included in BLEEDS and plasma was stored from 13,779 patients (83%). Patients had a mean age of 70 years (SD 14), 8713 were male (53%). The most common VKA indications were atrial fibrillation (10,876 patients, 66%) and venous thrombosis (3920 patients, 24%). 326 Major bleeds occurred during 17,613 years of follow-up (incidence rate 1.85/100 person years, 95%CI 1.66-2.06). The risk for major bleeding was highest in the initial three months of VKA treatment and increased when the international normalized ratio increased. These results and characteristics are in concordance with results from other VKA treated populations. BLEEDS is generalizable to other VKA treated populations and will permit innovative and unbiased research of biomarkers that may predict major bleeding during VKA treatment.


Effects of hypoxia/ischemia on catabolic mediators of cartilage in a human chondrocyte, SW1353.
Cells from a human chondrocyte cell line were studied in 1% oxygen and/or a lower glucose concentration (5.5 mM), compared to the routine culture conditions of normoxia and high glucose. HIF-1α, IL-1β, IL-6, IL-8, COX-2, TNFα, LIF, MMP-3, MMP-13, and reactive oxygen species (ROS) were evaluated, respectively. Effects of hypoxia inducing expression of HIF-1α were statistically significant at 72 h (p<0.05). Increased production of ROS by hypoxia was also observed with passage of time (p<0.05). The effects of hypoxia on HIF-1α and IL-1β were potentiated by 5.5 mM glucose, especially after 48 h (p<0.05). IL-8 production was significantly induced in 1% O(2), with 5.5 mM glucose (p<0.01). IL-8 mRNA expression and production in response to IL-1β were potentiated by hypoxia/ischemia (p<0.05, p<0.01, respectively). Up-regulation of IL-1β, ROS, and IL-8 by hypoxia/ischemia in human chondrocytes may occur in correlation with HIF-1α. IL-8 response to IL-1β may be potentiated synergically by hypoxia/ischemia, as an effector of hypoxia/ischemia. The results may suggest aggressive biology of the ordinary cartilage hypoxia/ischemia in the context of arthro-degeneration.


An overview of penetrating ocular trauma with retained intraocular foreign body.
Penetrating trauma is one of the common causes of ocular morbidity world wide. Violation of the globe integrity, also known as a ruptured globe is an ocular emergency that universally threatens vision. Prompt recognition and management is prudent. Here we report a case of a 26-year-old-female, university teacher, who presented with pain and sudden loss of vision in the left eye of 2 h duration subsequent to a test tube blast in the chemical laboratory. Examinations revealed a ruptured globe with vitreous haemorrhage and an intraocular glass foreign body in the left eye. Primary repair was done with good post operative visual recovery. We report this case to emphasize that protective measures should be taken to prevent such eye traumas.


Transduction of PACAP38 protects primary cortical neurons from neurotoxic injury.
Neurotrophic factors such as pituitary adenylate cyclase activating polypeptide (PACAP38) are promising therapeutics for neurodegenerative diseases. However, delivery of trophic factors into brain neurons remains a challenge. The objective of this study is to determine whether adeno-associated virus (AAV) can mediate PACAP38 gene delivery into neurons in vitro and if transduction of AAV/PACAP38 into cortical neurons protects cells against neurotoxic insult. Primary cortical neuronal cultures are transduced with rAAV/PACAP38/GFP and cell survival against the nitric oxide releasing neurotoxin sodium nitroprusside (SNP) determined. GFP expression, a surrogate marker for successful transduction, is detected using fluorescent microscopy. The results show expression of GFP transgene and AAV capsid proteins in neurons. PACAP38 transduction significantly increases cell survival of neurons exposed to SNP. These results support the feasibility of using AAV-mediated delivery of PACAP38 to enhance neuronal survival and suggest that AAV-delivered PACAP38 maybe a therapeutic strategy for neurodegenerative diseases.


Temporal and geographic dynamics of bovine viral diarrhea virus in American countries.
Bovine viral diarrhea virus (BVDV) is a worldwide distributed pathogen of livestock classified into three species, BVDV-1 (Pestivirus A), BVDV-2 (Pestivirus B), and HoBi-like pestivirus (HoBiPeV; Pestivirus H). Despite being considered endemic in several regions of the Americas, the spatiotemporal distribution of BVDV is scarcely known. This study aimed to reconstruct the population dynamics of BVDV in American countries. The analyses performed with the partial 5´UTR gene showed that BVDV-1 and -2 would have started their diversification in the 1670s and 1790s in the United States, whereas HoBiPeV probably emerged in the 1980s in Brazil. No evident geographic clustering was observed in the Bayesian trees, which may indicate that multiple introductions events would have occurred following the first introduction. This study provides new insights into BVDV dynamics, although further analyses including sequences from other American countries and continents will help to expand the knowledge of BVDV evolution and transmission.


Management of refractory chylothorax in the neonatal intensive care unit: A 22-year experience.
The aim was to assess the therapeutic strategy of patients with chylothorax in a neonatal intensive care unit. Twenty-eight infants with chylothorax were included in this study. Their clinical characteristics and outcomes were reviewed retrospectively. The male-to-female ratio was 1:1. The mean gestational age and birthweight were 35.1 ± 3.5 weeks and 2,692 ± 791 g, respectively. Eighteen patients were diagnosed with congenital chylothorax; chylothorax occurred postoperatively in 10 patients. Chromosomal anomalies were diagnosed in 8 patients. Six patients received surgical therapy, such as pleurodesis, thoracic duct ligation, or lymphaticovenous anastomosis. Two patients required surgery due to resistance to pleurodesis. In surgically managed patients, the daily maximum amount of pleural effusion (mL)/bodyweight (kg) ratio was significantly larger than in non-surgically managed patients: 229.0 ± 180.5 versus 59.7 ± 49.2 mL/kg. In the receiver operating characteristic analysis of the daily maximum amount of pleural effusion/bodyweight ratio, the area under the curve was 0.889 when the cut-off value was 101 mL/kg, and the sensitivity was 0.8333 and the specificity was 0.8095 (P = 0.0059). Pleurodesis using OK432 could become a surgical first-line therapy for chylothorax even for neonates. It was important to initiate pleurodesis for refractory chylothorax at an earlier stage. A daily chylous effusion/bodyweight ratio of >101 mL/kg was a good predictor and seemed to be a useful parameter for prompt surgical intervention.


Muscarinic cholinergic receptors in the normal and neurogenic human bladder.
Bladder dysfunction secondary to neurologic conditions occurs in all age groups and is associated with significant morbidity. The role of neuroreceptors in the development of detrusor dysfunction has not been studied previously. Control bladder tissue specimens were obtained from eight children with ureterovesical reflux undergoing ureteral reimplantation and 14 adults with bladder carcinoma undergoing cystectomy. Neurogenic bladder specimens were obtained from 10 children with myelomeningocele and five adults with neurogenic bladder dysfunction undergoing augmentation cystoplasty. Saturation experiments using 3H-N-methylscopolamine (3H-NMS) were performed in these control and neurogenic bladder homogenates. The mean equilibrium dissociation constants in the neurogenic and control bladders were 0.41 nM and 0.55 nM, respectively. The mean density of muscarinic cholinergic (MCh) receptor binding sites in the neurogenic and control bladders was 0.34 fmol/mg wet wt. and 0.65 fmol/mg. wet wt., respectively. Competitive binding experiments with 3H-NMS and various unlabelled MCh antagonists indicated that the pharmacology of MCh binding sites was similar in neurogenic and control bladders. Age was not significantly correlated with MCh receptor density in the control and neurogenic bladders. Muscarinic cholinergic binding sites are homogeneous in neurogenic and control bladders. The lower density of MCh receptors in the neurogenic bladders may represent down regulation of MCh receptors or a replacement of smooth muscle by fibrosis.