Initial treatment response to transarterial chemoembolization as a predictive factor for Child-Pugh class deterioration prior to refractoriness in hepatocellular carcinoma.
Repeated transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC) eventually leads to either deteriorated hepatic reserve or TACE refractoriness. Switching to molecular targeted agents after TACE requires preservation of hepatic reserve. This study aimed to investigate the predictive factors associated with early deterioration of hepatic reserve by repeated TACE prior to refractoriness. Ninety-three patients with intermediate-stage HCC who underwent TACE as the first-line treatment and had a Child-Pugh class A hepatic reserve were retrospectively analyzed. The time to Child-Pugh class deterioration (TTCPD), defined as the duration from initial TACE to the diagnosis of Child-Pugh class B or C prior to TACE refractoriness, was assessed. Patients who progressed to TACE refractoriness prior to Child-Pugh class deterioration were censored at TACE refractoriness. The radiological response to initial TACE was assessed as responders and non-responders in 59 (63.4%) and 34 (36.6%) patients, respectively. The median TTCPD was 40.6 months in all patients. The hepatic reserve in 31 (33.3%) patients deteriorated to Child-Pugh class B or C prior to TACE refractoriness. In the multivariate analysis, non-response to initial TACE, albumin-bilirubin grade 2, and non-selective TACE were identified as independent predictors associated with a shortened TTCPD. The TTCPD was significantly shorter in the non-responders than in the responders to initial TACE (median, 19.6 vs. 55.9 months; P < 0.001). Failure to respond to initial TACE was a predictive factor for early deterioration of hepatic reserve prior to TACE refractoriness in intermediate-stage HCC patients with repeated TACE.


Taurine-like immunoreactivity in octopaminergic neurones of the cockroach, Periplaneta americana (L.).
Taurine (2-aminoethanesulphonic acid) is reported to interact with the octopaminergic system. The distribution of taurine-like immunoreactivity (-LIR) in relation to octopamine-like immunoreactive dorsal unpaired median (DUM) neurones was investigated with the aim of revealing possible colocalization of these two neuromediators. The specificity of the anti-taurine serum used was demonstrated by dot blot immunoassay and by use of preabsorption controls. There was no crossreactivity with octopamine. The specificity of the octopamine antiserum employed has been described elsewhere. Taurine-LIR could be demonstrated in large dorso-median cells in the suboesophageal and the mesothoracic ganglion as well as in the abdominal ganglia. In addition taurine-LIR is distributed in numerous other regions of the ganglia. A comparison of the immunostaining for taurine and octopamine indicates that several of the taurine-like immunoreactive (-LI) neurones are probably members of the octopamine-immunoreactive DUM cell population. These taurine-LI neurones resemble octopamine-LI DUM cells in soma position and size as well as in the projections of their primary neurites. Colocalization of octopamine-LIR and taurine-LIR within the same neuronal element could be shown by alternate immunostaining of consecutive sections. It is probable that all octopamine-LI DUM neurones also exhibit taurine-LIR, and the possible physiological significance of this coexistence is discussed.


Pilot study: elevated circulating levels of the proinflammatory cytokine macrophage migration inhibitory factor in patients with chronic spinal cord injury.
To test the hypothesis that the proinflammatory cytokine macrophage migration inhibitory factor (MIF) is elevated in the circulation of patients with chronic spinal cord injury (SCI) relative to uninjured subjects, and secondarily to identify additional immune mediators that are elevated in subjects with chronic SCI. Prospective, observational pilot study. Outpatient clinic of a department of physical medicine and rehabilitation and research institute in an academic medical center. Individuals with chronic (>1y from initial injury) SCI (n=22) and age- and sex-matched uninjured subjects (n=19). Not applicable. Plasma levels of MIF, as determined by a commercially available multiplex suspension immunoassay. The relationship between MIF levels and clinical/demographic variables was also examined. As a secondary outcome, we evaluated other cytokines, chemokines, and growth factors. Plasma MIF levels were significantly higher in subjects with chronic SCI than in control subjects (P<.001). Elevated MIF levels were not correlated significantly with any one clinical or demographic characteristic. Subjects with SCI also exhibited significantly higher plasma levels of monokine induced by interferon-gamma/chemokine C-X-C motif ligand 9 (P<.03), macrophage colony stimulating factor (P<.035), interleukin-3 (P<.044), and stem cell growth factor beta (SCGF-β) (P<.016). Among subjects with SCI, the levels of SCGF-β increased with the time from initial injury. These data confirm the hypothesis that MIF is elevated in subjects with chronic SCI and identify additional novel immune mediators that are also elevated in these subjects. This study suggests the importance of examining the potential functional roles of MIF and other immune factors in subjects with chronic SCI.


In vitro quality of cold and delayed cold-stored platelet concentrates from interim platelet units during storage for 21 days.
Based on previous success using apheresis platelets, we wanted to investigate the in vitro quality and platelet function in continuously cold-stored and delayed cold-stored platelet concentrates (PCs) from interim platelet units (IPUs) produced by the Reveos system. We used a pool-and-split design to prepare 18 identical pairs of PCs. One unit was stored unagitated and refrigerated after production on day 1 (cold-stored). The other unit was stored agitated at room temperature until day 5 and then refrigerated (delayed cold-stored). Samples were taken after pool-and-split on day 1 and on days 5, 7, 14 and 21. Swirling was observed and haematology parameters, metabolism, blood gas, platelet activation and platelet aggregation were analysed for each sample point. All PCs complied with European recommendations (EDQM 20th edition). Both groups had mean platelet content >200 × 109 /unit on day 21. The pH remained above 6.4 for all sample points. Glucose concentration was detectable in every cold-stored unit on day 21 and in every delayed cold-stored unit on day 14. The cold-stored group showed a higher activation level before stimulation as measured by flow cytometry. The activation levels were similar in the two groups after stimulation. Both groups had the ability to form aggregates after cold storage and until day 21. Our findings suggest that PCs from IPUs are suitable for cold storage from day 1 until day 21 and delayed cold storage from day 5 until day 14.


Brain and lower body protection during aortic arch surgery.
Deep hypothermic circulatory arrest (DHCA) at ≤20°C for aortic arch surgery has been widely used for decades, with or without cerebral perfusion (CP), antegrade (antegrade cerebral perfusion [ACP]), or retrograde. In recent years nadir temperature progressively increased to 26°C-28°C (moderately hypothermic circulatory arrest [MHCA]), adding ACP. Aim of this multicentric study is to evaluate early results of aortic arch surgery and if DHCA with 10 min of cold reperfusion at the same nadir temperature of the CA before rewarming (delayed rewarming [DR]) can provide a neuroprotection and a lower body protection similar to that provided by MHCA + ACP. A total of 210 patients were included in the study. DHCA + DR was used in 59 patients and MHCA + ACP in 151. Primary endpoints were death, neurologic event (NE), temporary (TNE), or permanent (permanent neurologic deficit [PND]), and need of renal replacement therapy (RRT). Operative mortality occurred in 14 patients (6.7%), NEs in 17 (8.1%), and PNDs in 10 (4.8%). A total of 23 patients (10.9%) needed RRT. Death + PND occurred in 21 patients (10%) and composite endpoint in 35 (19.2%). Intergroup weighed logistic regression analysis showed similar prevalence of deaths, NDs, and death + PND, but need of RRT (odds ratio [OR]: 7.39, confidence interval [CI]: 1.37-79.1) and composite endpoint (OR: 8.97, CI: 1.95-35.3) were significantly lower in DHCA + DR group compared with MHCA + ACP group. The results of our study demonstrate that DHCA + DR has the same prevalence of operative mortality, NE and association of death+PND than MHCA + ACP. However, the data suggests that DHCA + DR when compared with MHCA + ACP provides better renal protection and reduced prevalence of composite endpoint.


[Changes of endometrial macrophages and nature kill cells during luteal phase and early pregnancy].
To investigate the effect of endometrial microenvironment on pregnancy. The number of macrophage and nature kill (NK) cells in decidua and endometrium were determined in 19 cases of early pregnancy and 11 non-pregnant women respectively by cytometric analysis. The percentages of macrophages (leukocyte antigen molecules CD14 positive) and NK cells (CD56 positive) were significantly increased in decidua of first trimester as compared with those in luteal endometrium (P < 0.01). The number of CD(56)(+)CD(16)(-) subset of NK cells increased significantly during early pregnancy. While the number of CD(56)(+)CD(16)(+) subset did not change. The endometrial macrophages and NK cells may be involved in the mechanism of the fetal protective immune reaction during pregnancy.


Sigmoid colon perforation in a SARS-CoV-2 positive neonate: a uniqueness report and a brief review.
Despite the relative prevalence of small bowel and proximal colon perforation in the neonatal period, recto-sigmoid perforation is extremely rare. Full-term neonates experience intestinal perforation less frequently than premature infants. Here we report a neonate with sigmoid perforation and simultaneous Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. A 2550 g female neonate born at 38-weeks' gestation from a coronavirus disease-2019 (COVID-19) infected mother by cesarean section. Despite a good Apgar score in the first and fifth minutes, she was admitted to the neonatal intensive care unit with grunting and mild respiratory distress. She underwent antibiotics and oxygen by head box resulting in an Oxygen Saturation rate of 94%. The patients' respiratory distress decreased during the second day, resulting once breastfeeding without tolerance. While she passed meconium in the first 2 days, she developed abdominal distention on day 3. The nasopharyngeal SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) was performed with positive results. Surgical consultation was requested and a thoraco-abdominal X-Ray was performed at this stage, which suspected to be a gastrointestinal perforation. Due to clinical deterioration and persistent abdominal distention, a contrast study was performed with water-soluble contrast, which confirmed intestinal perforation. However, the surgical exploration revealed perforation of the sigmoid colon at the posterior segment. The patient underwent antibiotic therapy, abdominal lavage, and colostomy, immediately. She was discharged in good condition approximately 14-days later. To our knowledge, this is the first report of sigmoid colon perforation in a term neonate following COVID-19.


Evaluation of breast tumour cell contamination in the bone marrow and leukapheresis collections by RT-PCR for cytokeratin-19 mRNA.
There is considerable interest in an autologous transplantation (AT) programme for patients with high-risk breast cancer; however, the issue of the incidence of occult bone marrow (BM) micrometastasis at diagnosis, and the cancer contamination of peripheral blood stem cell (PBSC) collections used for haematological rescue, is still debated. The presence of BM micrometastasis was evaluated in bilateral BM biopsies obtained at diagnosis of 33 patients with stage II/IIIA breast cancer using: (i) a 'nested' reverse transcriptase-polymerase chain reaction (RT-PCR) assay for cytokeratin 19 (K19) mRNA, (ii) histology, and (iii) immunohistochemistry (IHC) analysis with a panel of three monoclonal antibodies. The RT-PCR assay only was used to determine contamination of PBSC collections obtained after priming with recombinant human granulocyte-colony stimulating factor (rhG-CSF). K19 transcripts in one or both BM samples were detected in 48% of patients at diagnosis, with an overall 85% concordance with the results of IHC analysis. On the other hand, 56% of PCR- and IHC-positive BM samples were diagnosed as 'normal' on histological analysis. 57% of patients showed K19 mRNA in at least one PBSC collection; the possibility to have contaminated PBSC collections was significantly higher in patients with K19 positivity in BM at diagnosis. In four patients who had shown K19 positivity in BM and in PBSC collections, immunoselected CD34+ cells used for haematological rescue were K19-negative. There was a trend towards longer relapse free survival (RFS) in patients transplanted with K19-negative PBSC collections as compared to the others. In conclusion, a substantial proportion of patients with high-risk non-metastatic breast cancer present occult BM micrometastasis at diagnosis and also show cancer contamination of PBSC collections used for AT. These might represent a category of patients with poorer prognosis after AT, and possible candidates for more intensive and/or alternative therapeutic regimens, including AT with purged PBSCs.


Abnormalities of cardiac repolarization in Williams syndrome.
Williams syndrome (WS) affects 1 in 8,000 live births and has a high risk of sudden death. No previous studies have evaluated corrected QT (QTc) prolongation in WS. Retrospective review of all patients with WS evaluated at our institution from January 1, 1980 to December 31, 2007 was performed. WS was diagnosed by a medical geneticist and/or by fluorescence in situ hybridization. Patients with ≥1 electrocardiogram (ECG) with sinus rhythm and measurable intervals were included. Normal control ECGs were identified from a large clinical database. Corrected JT (JTc) interval was calculated when QRS and QTc intervals were prolonged. QTc interval ≥460 ms and JTc interval >340 ms were defined as prolonged. Prevalence comparisons were made using Fisher's exact test. Statistical probability of <0.05 was considered significant. Of 270 patients identified, 188 had ECGs for review. Complete data were present in 499 of 517 ECGs (patients' mean age 10.3 ± 9.9 years); 1,522 normal ECGs of age-similar patients composed the control group. QTc prolongation prevalences were 2.0% in controls and 13.6% in WS (p <0.0001); in those, JTc prolongation prevalences were 1.8% in controls and 11.7% in WS (p <0.0001). Four patients died during follow-up; 2 had QTc prolongation and 1 died during noncardiac surgery. Another patient with QTc prolongation sustained cardiac arrest during a procedure. In conclusion, cardiac repolarization is prolonged in WS. Presence of prolonged cardiac repolarization may contribute to the high incidence of periprocedural mortality in these patients. All patients with WS should be screened for cardiac repolarization abnormalities, especially before surgery.


Trends in time to cancer diagnosis around the period of changing national guidance on referral of symptomatic patients: A serial cross-sectional study using UK electronic healthcare records from 2006-17.
UK primary-care referral guidance describes the signs, symptoms, and test results ("features") of undiagnosed cancer. Guidance revision in 2015 liberalised investigation by introducing more low-risk features. We studied adults with cancer whose features were in the 2005 guidance ("Old-NICE") or were introduced in the revision ("New-NICE"). We compared time to diagnosis between the groups, and its trend over 2006-2017. Clinical Practice Research Datalink records were analysed for adults with incident myeloma, breast, bladder, colorectal, lung, oesophageal, ovarian, pancreatic, prostate, stomach or uterine cancers in 1/1/2006-31/12/2017. Cancer-specific features in the year before diagnosis were used to create New-NICE and Old-NICE groups. Diagnostic interval was time between the index feature and diagnosis. Semiparametric varying-coefficient analyses compared diagnostic intervals between New-NICE and Old-NICE groups over 1/1/2006-31/12/2017. Over all cancers (N = 83,935), median (interquartile range) Old-NICE diagnostic interval rose over 2006-2017, from 51 (20-132) to 64 (30-148) days, with increases in breast (15 vs 25 days), lung (103 vs 135 days), ovarian (65·5 vs 100 days), prostate (80 vs 93 days) and stomach (72·5 vs 102 days) cancers. Median New-NICE values were consistently longer (99, 40-212 in 2006 vs 103, 42-236 days in 2017) than Old-NICE values over all cancers. After guidance revision, New-NICE diagnostic intervals became shorter than Old-NICE values for colorectal cancer. Despite improvements for colorectal cancer, scope remains to reduce diagnostic intervals for most cancers. Liberalised investigation requires protecting and enhancing cancer-diagnostic services to avoid their becoming a rate-limiting step in the diagnostic pathway.


Prenatal care comparisons among privately insured, uninsured, and Medicaid-enrolled women.
Women without health insurance and those covered by Medicaid have been shown to obtain prenatal care later in pregnancy and make fewer visits for care than do women with private insurance. Factors that keep women from obtaining care include inadequate maternity care resources, difficulty in securing financial coverage, and the psychosocial issues of pregnancy. This study identified and compared prenatal care use patterns, insurance coverage changes, and psychosocial factors among 149 women in Minneapolis, MN, with private health insurance, Medicaid, and no health insurance. Little information has been available on the insurance status of women at the start of pregnancy and the paths subsequently taken to obtain financial coverage for prenatal care.


Correction: Band-gap tailoring and visible-light-driven photocatalytic performance of porous (GaN)1-x(ZnO)x solid solution.
Correction for 'Band-gap tailoring and visible-light-driven photocatalytic performance of porous (GaN)1-x(ZnO)x solid solution' by Aimin Wu et al., Dalton Trans., 2017, 46, 2643-2652.


Cyclins in meiosis: lost in translation.
In a recent issue of Cell, Carlile and Amon examine the regulation of four budding yeast B-type cyclins, crucial for regulating and distinguishing meoisis I and meoisis II divisions, and find a surprising diversity of behaviors and modes of regulation. In particular, Clb3 is regulated by a striking translational repression specific to meoisis I.


Histomorphological evaluation of atherosclerotic lesions in patients with peripheral artery occlusive disease.
Peripheral arterial occlusive disease (PAOD) is mainly caused by atherosclerosis of the vessel wall. These pathological changes are classified into different stages and are well described for carotid and coronary vessels, but not for PAOD. The aim of our study was to analyze plaque morphology of femoral arteries in patients with intermittent claudication and critical limb ischemia. In this retrospective study 85 atherosclerotic plaques (common and superficial femoral artery) of 71 patients with a clinical symptomatic PAOD were analyzed, by histology (01/2009-07/2010). Atherosclerotic lesions were classified according to Stary (type I-VIII). For further characterization, plaques were evaluated for the presence of collagen, elastin, calcifications, smooth muscle cells, macrophages, leucocytes, and cellularity. The majority (91%) of atherosclerotic lesions were of advanced types according to Stary (V-VII). Atherosclerotic lesion type VI was associated with significant higher amount of inflammatory cells in comparison to all other atherosclerotic plaque types (CD45: p<0.001; CD68: p=0.013). In addition, atherosclerotic plaques with a pronounced neovascularization contained a higher amount of CD45 (p=0.015; rho=0.273) and CD68 (p=0.016; rho=0.275) positive cells. Atherosclerotic lesions of femoral arteries show similar morphological changes as coronary or carotid arteries. But inflammatory cells had a higher impact on plaque progression and destabilization than any other factor.


Does antiaggregant administration lead to early diagnosis in proximal colon cancer?
Cancers of the proximal colon are often diagnosed in advanced stages with iron deficiency anemia and nonspecific symptoms. Aspirin and clopidogrel are commonly used antiaggregant agents for various clinical conditions. The aim of this study was to investigate the effects of antiaggregant medication on the early diagnosis of proximal colon cancer. Cases of colon cancer patients who had received curative surgical procedures between January 1, 2013 and July 31, 2016 were retrospectively reviewed. The clinical and pathological results of patients who had used antiaggregant drugs were compared to those who had not. During the studied period, 246 colorectal cancer patients underwent curative surgical procedures. Of the 67 patients with proximal colon cancer who were included in the study, 27 (40.3%) had taken antiaggregant medication. The mean age of the antiaggregant group was 67.1 years (range: 34-88 years), while it was 58.3 years (range: 34-83 years) for the non-antiaggregant group; the difference between the 2 groups was statistically significant (p=0.03). A pathological evaluation revealed that 74.1% of the antiaggregant group was in the early stages (Stage I/II: 7/13), while 42.5% of the non-antiaggregant group was in the early stages (Stage I/II: 2/15); the difference was statistically significant (p=0.011). Antiaggregant medication has a positive effect on diagnosing proximal colon cancer at early stages. Patients using aspirin or clopidogrel should undergo a complete colonoscopic evaluation in the presence of gastrointestinal tract bleeding or newly developed anemia.


An ecological classification of European Drosophila species.
The associations shown between species of Drosophila collected in three European countries are analysed using a clustering method. The resulting dendrograms are combined to give a plan of associations shown by all three surveys. These general groupings are interpreted in the light of what is known about Drosophila breeding sites.One ecological group, the fungal breeding species are examined in detail and their pattern of geographical associations investigated. The three most abundant species in collections, D. transversa, D. phalerata and D. cameraria appear to replace one another in a north-south direction in western Europe. It is suggested that ecologically marginal areas may be defined using the frequency of a species within its ecological group.


Youth in India ready for sex education? Emerging evidence from national surveys.
Sex education/family life education (FLE) has been one of the highly controversial issues in Indian society. Due to increasing incidences of HIV/AIDS, RTIs/STIs and teenage pregnancies, there is a rising need to impart sex education. However, introducing sex education at school level always received mixed response from various segments of Indian society. We attempt to understand the expectations and experiences of youth regarding family life education in India by analysing the data from District Level Household and Facility Survey (DLHS-3: 2007-08) and Youth Study in India (2006-07). We used descriptive methods to analyse the extent of access to FLE and socio demographic patterning among Indian youth. We found substantial gap between the proportion of youth who perceived sex education to be important and those who actually received it, revealing considerable unmet need for FLE. Youth who received FLE were relatively more aware about reproductive health issues than their counterparts. Majority among Indian youth, irrespective of their age and sex, favoured introduction of FLE at school level, preferably from standard 8(th) onwards. The challenge now is to develop a culturally-sensitive FLE curriculum acceptable to all sections of society.


Resumption of Anticoagulation After Intracranial Hemorrhage.
Anticoagulation is a vital therapy in a number of different disease processes, and is strongly recommended for the prevention of stroke in patients with atrial fibrillation and/or with mechanical prosthetic heart valves. Studies involving patients on oral anticoagulants (OACs) have revealed that ICH can occur eight times more frequently in this population, with an annual estimated incidence of 0.25 to 1.1%. The decision of whether and when to resume anticoagulation following intracranial hemorrhage is challenging and requires an assessment of associated risks and benefits. Clinical data, imaging, and risk factors for both ischemic and hemorrhagic complications may aid in decision-making. Baseline functional status, life expectancy, compliance with therapy, and family support also impact decision analyses. Currently available data suggest that anticoagulation could be safely restarted in select groups of OAC-ICH patients within 4 weeks of intracranial hemorrhage; however, high-quality randomized, clinical trials are needed.


Bradykinin stimulates prostaglandin E2 production and cyclooxygenase activity in equine nonglandular and glandular gastric mucosa in vitro.
There are few data available regarding regulation of prostaglandin (PG) generation by equine gastric mucosae and the role of the cyclooxygenase (COX) isoforms in their production. To: 1) characterise and quantify PGE2 output in vitro; 2) examine the sensitivity of PGE2 production to exogenous bradykinin (BK) exposure; 3) determine the contribution of the COX-1 and COX-2 pathways to basal and BK-stimulated PGE2 production; and 4) measure if BK influences electrogenic ion transport in equine gastric mucosae in vitro. Full thickness gastric sheets were obtained from horses at post mortem, stripped of muscle layers and mounted in Ussing chambers. Tissues were exposed to bradykinin (BK, 0.1 micromol/l) either alone, or following pretreatment with a selective COX-2 inhibitor (NS-398, 1 micromol/l) or a nonselective COX inhibitor (piroxicam, 1 micromol/l), or were untreated. BK administration increased PGE2 output from the basolateral but not the apical faces of both tissue types. Piroxicam, but not NS-398, reduced basolateral PGE2 release below control levels in both tissue types. Both piroxicam and NS-398 pretreatment inhibited BK-stimulated PGE2 release. In separate experiments, BK was without effect upon electrophysiological parameters of tissues mounted in Ussing chambers. PGE2 is produced by the nonglandular and glandular equine gastric mucosae in vitro. Significantly more PGE2 is released basolaterally than apically. BK stimulated the production of PGE2 from the basolateral side of both tissue types. These findings suggest that COX-1 is a significant pathway for basal PGE2 production from the basolateral faces of both nonglandular and glandular equine gastric mucosae in vitro.


Maternal and perinatal outcome of eclampsia over a decade at a tertiary hospital in Kuwait.
To determine maternal and perinatal outcome of eclampsia patients over a decade. Analysis of case records of all eclampsia cases from January 2005 to December 2014. There were 30 cases of eclampsia. The most significant risk factors for developing pre-eclampsia are unbooked cases (97%), nulliparity, young age, marriage ≤4 months, history of pre-eclampsia in previous pregnancy, remarriage, preexisting diabetes mellitus, interval between pregnancies ≥10 years, positive family history. The incidence of eclampsia was 0.05%, antepartum eclampsia 15 (50%), intrapartum 6 (20%) and postpartum 9 (30%) with no maternal deaths, and 1 perinatal death. Perinatal mortality was 33.3/1000. 22 (73%) patients received magnesium sulphate (MgSO4) and 8 patients (27%) received Diazepam, of which 1 had recurrence of convulsions. All 15 antepartum cases were delivered by cesarean section as were 2 intrapartum. 13 (43%) of women delivered vaginally. Only 6 (20%) patients were of low socio-economic status and were primary school educated. Severe maternal complications occurred in 8 (27%), with abruptio placentae being the most common 3 (38%). Incidence of eclampsia was low, with no maternal deaths. MgSO4 was found to be highly effective. Lack of antenatal care is a major risk factor.


Environmental pathways of exposure to DDT for children living in a malarious area of Chiapas, Mexico.
Considering that DDT was used for control of malaria vectors in Mexico, and taking into account that the information regarding children in areas exposed to DDT is scarce, we started a research program for the assessment of health effects in children living in DDT sprayed areas. In this first report, we present information about pathways of exposure in two communities with a different history of exposure to DDT. Environmental pathways such as outdoor soils, indoor soils and household dust were assessed comparing a community highly exposed to DDT (HEC) and a community less exposed to DDT (LEC). Also in these communities, a cross-sectional study of 60 children (30 in each community) aged 6--12 years was conducted. Tests included a questionnaire and the measurement of whole blood DDT and DDE. Results show that in children living in the HEC, DDT and DDE mean blood levels were higher (15.9+/-8.2 and 58.2+/-29.2 microg/L) than in the LEC (1.9+/-3.6 and 9.2+/-5.7 microg/L) (P<0.01). Concentrations of DDT, DDE and DDD in indoor soil were higher in the HEC (10.3+/-10; 4.9+/-5.8; and 4.4+/-9.1mg/kg) than in the LEC (0.3+/-0.3; 0.04+/-0.06; and 0.03+/-0.04 mg/kg) (P<0.001). Similar results were obtained for outdoor soils; in the HEC, levels for DDT, DDE and DDD were 3.1+/-3.0; 1.0+/-0.8; and 0.3+/-0.2mg/kg; whereas levels in the LEC were 0.16+/-0.2; 0.02+/-0.03; and 0.02+/-0.03 mg/kg (P<0.001). High concentrations of DDT, DDE, and DDD were obtained in samples of indoor dust collected from the walls in the HEC (17.5+/-10.0; 5.5+/-6.2; and 9.8+/-16.8 mg/kg); levels in the LEC were lower (0.6+/-0.9; 0.07+/-0.1; and 0.05+/-0.07 mg/kg) (P<0.001). We did not find any correlation between blood levels of DDE and total DDT with environmental concentrations but there levels increased in LEC and HEC as the frequency of fish consumption increased (P<0.01).


Understanding differences between high and low volume hospitals for radical prostatectomy.
We evaluated the impact of the specialized medical and ancillary services available at low vs. high volume prostatectomy centers on prolonged length of stay (LOS) outcomes after radical prostatectomy. Using the Nationwide Inpatient Sample, we identified patients who underwent prostatectomy (n = 9,266) for prostate cancer in 2003 using ICD-9 codes. Hospital characteristics were ascertained using the American Hospital Association file. Differences in health services availability according to hospital prostatectomy volume were estimated using logistic regression. Logistic models were fitted to measure the effect of available health services on a prolonged LOS (>90 percentile for sample was 5 days). Among patients undergoing radical prostatectomy in 2003, 19.0% and 5.4% of patients had a prolonged LOS at low and high volume hospitals, respectively (unadjusted OR 4.2, 95% CI 2.5-6.9). After adjusting for differences in patients and availability of select health services, those treated at low volume centers were 3.3 times more likely to have a prolonged hospitalization compared with those treated at high volume hospitals (95% CI 1.9-5.6). Adjusting for hospital differences attenuated the volume effect by 14.8%. There are substantial differences in the health care environment according to radical prostatectomy volume. Generally, high volume hospitals offer a much wider array of health care services specific to both post-prostatectomy and general medical care.


Phylogeny and taxonomy of three new Ctenomyces (Arthrodermataceae, Onygenales) species from China.
Twelve Ctenomyces (Arthrodermataceae, Onygenales) strains were obtained and identified during a survey of keratinophilic fungi in soils from China. We used molecular identification combined with morphological evidence to delimit species, circumscribing five species in the genus. Three new species are herein described: C.albus sp. nov., C.obovatus sp. nov. and C.peltricolor sp. nov. We also described, illustrated and compared the novel species with related species in the morphology.


Passive leg raising during cardiopulmonary resuscitation in out-of-hospital cardiac arrest--does it improve circulation and outcome?
Passive leg raising (PLR), to augment the artificial circulation, was deleted from cardiopulmonary resuscitation (CPR) guidelines in 1992. Increases in end-tidal carbon dioxide (P(ET)CO(2)) during CPR have been associated with increased pulmonary blood flow reflecting cardiac output. Measurements of P(ET)CO(2) after PLR might therefore increase our understanding of its potential value in CPR. We also observed the alteration in P(ET)CO(2) in relation to the return of spontaneous circulation (ROSC) and no ROSC. The P(ET)CO(2) was measured, subsequent to intubation, in 126 patients suffering an out-of-hospital cardiac arrest (OHCA), during 15 min or until ROSC. Forty-four patients were selected by the study protocol to PLR 35 cm; 21 patients received manual chest compressions and 23 mechanical compressions. The PLR was initiated during uninterrupted CPR, 5 min from the start of P(ET)CO(2) measurements. During PLR, an increase in P(ET)CO(2) was found in all 44 patients within 15 s (p=0.003), 45 s (p=0.002) and 75 s (p=0.0001). Survival to hospital discharge was 7% among patients with PLR and 1% among those without PLR (p=0.12). Among patients experiencing ROSC (60 of 126), we found a marked increase in P(ET)CO(2) 1 min before the detection of a palpable pulse. Since PLR during CPR appears to increase P(ET)CO(2) after OHCA, larger studies are needed to evaluate its potential effects on survival. Further, the measurement of P(ET)CO(2) could help to minimise the hands-off periods and pulse checks.


Impaired function of alpha-2 adrenoceptors in smooth muscle of mesenteric arteries from spontaneously hypertensive rats.
The alpha2-adrenoceptor function in mesenteric arteries of spontaneously hypertensive rats (SHR) was investigated by comparing membrane potential changes in response to adrenergic agonists in preparations from female SHR, Wistar-Kyoto (WKY) and normotensive Wistar rats (NWR). Resting membrane potential was found to be less negative in mesenteric arteries from SHR than in those from NWR and WKY. Apamin induced a decrease in the membrane potential of mesenteric artery rings without endothelium from NWR and WKY, but had no effects in those from SHR. Both UK 14,304 and adrenaline, in the presence of prazosin, induced a hyperpolarization that was significantly lower in de-endothelialized mesenteric rings from SHR than in those from NWR and WKY. In mesenteric rings with endothelium, however, similar hyperpolarization was observed in the three strains. In NWR mesenteric rings with endothelium the hyperpolarization induced by activation of alpha2-adrenoceptors was abolished by apamin, whereas in intact SHR mesenteric rings this hyperpolarization was slightly reduced by apamin and more efficiently reduced by Nomega-nitro-L-arginine. It is concluded that the activity of potassium channels coupled to alpha2-adrenoceptors is altered in the smooth muscle cells of SHR mesenteric arteries, contributing to their less negative membrane potential. On the other hand, the endothelial alpha2-receptors are functioning in mesenteric vessels from SHR and their stimulation induces a hyperpolarization mainly through the release of nitric oxide.


The effects of accumulated muscle fatigue on the mechanomyographic waveform: implications for injury prediction.
Muscle fatigue has been identified as a risk factor for spontaneous muscle injuries in sport. However, few studies have investigated the accumulated effects of muscle fatigue on human muscle contractile properties. This study aimed to determine whether repeated bouts of exercise inducing acute fatigue leads to longer-term fatigue-related changes in muscle contractile properties. Maximum voluntary contraction (MVC), electromyographic (EMG) and mechanomyographic (MMG) measures were recorded in the biceps brachii of 11 participants for 13 days, before and after a maximally fatiguing exercise protocol. The exercise protocol involved participants repetitively lifting a weight (concentric contractions only) equal to 40 % MVC, until failure. A significant (p < 0.05) acute pre- to post-exercise decline of biceps brachii MVC and median power frequency (MPF) was observed each day, whilst no difference existed between pre-exercise MVC or MPF values on subsequent days (days 2-13). However, decreases in number of lift repetitions and in pre-exercise MMG values of muscle belly displacement, contraction velocity and half-relaxation velocity were observed through to day 13. Whilst MVC and MPF measures resolved by the following day's test session, MMG measures indicated an ongoing decrement in muscle performance through days 2-13 consistent with the decline in lift repetitions observed. These results suggest that MMG may be more sensitive in detecting accumulated muscle fatigue than the 'gold standard' measures of MVC/MPF. Considering that muscle fatigue leads to injury, the on-going monitoring of MMG derived contractile properties of muscles in athletes may aid in the prediction of fatigued-induced muscle injury.


HDlive imaging of the face of fetuses with autosomal trisomies.
Our objective is to present our experience of facial dysmorphism reconstructed employing conventional three-dimensional (3D) ultrasound and HDlive in fetuses with autosomal trisomies. Seven fetuses with autosomal trisomies (one case of trisomy 13, three of trisomy 18, and three of trisomy 21) at 16-38 weeks' gestation were studied using 3D ultrasound and HDlive. In one case of trisomy 21 at 29 weeks and 5 days, upward slanting eyes, a flattened nose, low-set ears, and the corners of the mouth turned down were noted employing HDlive. In the other two cases of trisomy 21, both techniques showed the same facial findings. In one case of trisomy 18 at 27 weeks and 6 days, a small head accompanied by a prominent back portion of the head, low-set ears, a small jaw, upturned nose, narrow eyelid folds, and widely spaced eyes were identified using HDlive. In the other two cases of trisomy 18, HDlive showed more detailed features of the fetal face compared to conventional 3D ultrasound. In the single case of trisomy 13 at 31 weeks and 1 day, cleft lip and close-set eyes were recognized with both 3D ultrasound and HDlive. HDlive can provide clearer facial images than conventional 3D ultrasound. In particular, HDlive is superior to conventional 3D ultrasound for the depiction of eye fissures because of its shadowing effect. HDlive may be a useful diagnostic modality for the antenatal evaluation of subtle fetal facial dysmorphism.


Using Oncology Nursing Society Cancer Chemotherapy Guidelines as a basis for continuing education in rural hospitals.
To describe a workshop developed to teach nurses caring for patients with cancer in a southern, rural area how to administer chemotherapy in an inpatient or homecare setting. The Oncology Nursing Society (ONS) Cancer Chemotherapy Guidelines and published articles and books. An oncology clinical nurse specialist teaching at a local university developed and presented 10 hours of didactic content and a 6-hour clinical practicum. The workshop was conducted in association with a community hospital, which offered oncology care to patients with cancer in the community. All nurses who successfully completed the workshop demonstrated improved ability in caring for patients with cancer and in administering chemotherapy. The ONS Cancer Chemotherapy Guidelines provided an excellent outline for the development of an initial course on the science of chemotherapy and management of related symptoms. Many nurses work in rural areas where they are expected to provide competent nursing care to a variety of specialized patient populations, yet they have limited access to educational opportunities. A workshop format is feasible and can provide the education necessary for nurses who care for patients with cancer.


Tourniquet and tranexamic acid use in total knee arthroplasty.
There is no consensus on how tourniquet and tranexamic acid (TXA) use in total knee arthroplasty (TKA) affect blood transfusion rates and total blood loss. We compared outcome measures and transfusion rates after TKA, with and without the use of tourniquet and TXA. A retrospective study of 477 consecutive patients undergoing primary TKA between 2008 and 2013 was performed. There were 243 in the tourniquet-assisted (TA) and 234 in the tourniquet-unassisted (TU) group. Operative times, hemoglobin levels, blood transfusion rates, complications, and length of stay were assessed. Subanalysis was performed on those patients receiving and not receiving TXA within the TU group. Mean operative duration was 66.4 minutes in the TA group and 87.5 minutes in the TU group (P < .0001). Mean postoperative drop in hemoglobin was greater in TU group (3.1 g/dL vs 2.8 g/dL, P = .002). The transfusion rate was 9.5% in TA compared with 11.5% in TU patients (P = .46) with comparable mean units transfused (2.6 vs 2.2, P = .30). There was no difference in wound infection (P = .82) and total complication rates (P = .27) between groups. Those patients given TXA had a lower hemoglobin drop (2.6 g/dL vs 3.3 g/dL, P = .04) with similar transfusion (13.3% vs 11%, P = .61) and complication (P = .95) rates. TU TKA had a greater operative duration and postoperative drop in hemoglobin than TA TKA. However, transfusion rates were similar between groups. TXA use reduced the operative decrease in hemoglobin with no effect on complication or transfusion rates. Level III, retrospective cohort study.


[Clinical aspects and surgical therapy of cerebral metastases].
Authors describe clinical presentation, signs and symptoms and diagnostic procedures in case of metastatic brain tumors. Incidence and different pathological aspects are considered. Surgical treatment is discussed in its limits and indications. Surgical management of intracranial metastasis is palliative but it leads to pathological diagnosis, permits clinical improvement and adjuvant therapies.


Expanding the repertoire of small molecule transcriptional activation domains.
Molecules that can reconstitute the function of transcriptional activators hold enormous potential as therapeutic agents and as mechanistic probes. Previously we described an isoxazolidine bearing functional groups similar to natural transcriptional activators that up-regulates transcription 80-fold at 1 microM in cell culture. In this study, we analyze analogs of this molecule to define key characteristics of small molecules that function as transcriptional activation domains in cells. Conformational rigidity is an important contributor to function as is an overall amphipathic substitution pattern. Using these criteria, we identified additional molecular scaffolds with excellent (approximately 60-fold) activity as transcriptional activation domains. These results point the way for the creation of new generations of small molecules with this function.


Cytotoxic effect of lomefloxacin in culture of human epidermal melanocytes.
Lomefloxacin is a potent bactericidal antibiotic. The use of this drug in treatment of various infections is accompanied by serious adverse effects on pigmented tissues. The exact mechanisms of lomefloxacin side effects have not been well established yet. The aim of this study was to characterize the interaction between lomefloxacin and melanin, and to examine how this interaction affects the cell viability and melanization in melanocytes. Normal human epidermal melanocytes and the model DOPA-melanin were used. The binding parameters of lomefloxacin-melanin complexes as well as the antibiotic effect on cell viability and melanization in pigmented cells were investigated using a spectrophotometric method. Our results indicate that lomefloxacin forms stable complexes with melanin. The analysis of drug binding to melanin has shown that at least two classes of independent binding sites are involved in formation of these complexes. The WST-1 assay was used to detect the antibiotic cytotoxic effect. The value of ED50 for lomefloxacin was about 0.75 mmol/l. It has been shown that lomefloxacin causes inhibition of tyrosinase activity, and reduces melanin content in human skin melanocytes in a dose-dependent manner. The ability of the analyzed fluoroquinolone to form complexes with melanin, and the demonstrated inhibitory effect on a melanization process in melanocytes in vitro may explain a potential role of melanin biopolymer in the mechanisms of undesirable side effects of lomefloxacin in vivo resulting from its accumulation in pigmented tissues.


A potential spontaneous rat model of X-linked congenital stationary night blindness.
To describe a possible spontaneous rat model of X-linked congenital stationary night blindness (CSNB). Experimental animals were generated by mating the affected animal to normal rats, and from interbreeding littermates. To define the inheritance pattern, full-field electroretinograms (ERGs) were recorded from all progeny. During the course of other experiments, an affected male rat was identified by a reduced amplitude ERG b-wave. When this rat was mated to normal Sprague-Dawley rats, all of the F1 progeny had normal ERG waveforms. When F1 offspring were interbred, 51% of the male offspring had b-wave reductions while all female offspring had normal ERG waveforms. When F1 females were backcrossed to the original affected male, b-wave reductions were noted in both male and female offspring; overall, 46.8% of the backcross progeny exhibited a b-wave reduction. In affected animals, the b-wave was selectively affected as the a-wave appeared to retain normal amplitude and kinetics at 1-4 months old. Cone ERGs were significantly reduced in amplitude and somewhat delayed. Similar ERG results were also obtained under the same stimulus conditions from human patients with complete CSNB (CSNB1). The inheritance pattern is consistent with an X-linked recessive trait. The electrophysiological results suggest that this mutant rat line may provide another model for CSNB1.


Dietary predictors of young children's exposure to current-use pesticides using urinary biomonitoring.
Few data exist on the association between dietary habits and urinary biomarker concentrations of pesticides in children. The objective was to examined the association between the weekly intake frequency of 65 food items and urinary biomarkers of exposure to chlorpyrifos (3,5,6-trichloro-2-pyridinol [TCP]), permethrin (3-phenoxybenzoic acid [3-PBA]), and 2,4-dichlorophenoxyacetic acid [2,4-D] in 135 preschool-aged children. TCP and 3-PBA are nonspecific biomarkers as they are also urinary metabolites of other pesticides. TCP, 3-PBA, and 2,4-D were detected in 99%, 64%, and 92% of the urine samples, respectively. Mean urinary TCP concentrations were statistically significantly higher in children consuming fresh apples (9.40±15.5 ng/mL versus 5.76±3.57 ng/mL, p=0.040) and fruit juices (8.41±11.5 ng/mL versus 4.11±2.77 ng/mL, p=0.020) ≥3 times a week compared to <3 times a week. For 3-PBA, mean urinary metabolite concentrations were statistically significantly greater in children consuming chicken/turkey meats (0.79±0.81 versus 0.41±0.39, p=0.013) ≥3 times a week compared to <3 times a week. No association occurred between the consumption of any food item and children's mean urinary 2,4-D concentrations by intake group. In conclusion, frequent consumption of fresh apples and fruit juices or chicken/turkey meats were significant dietary predictors of urinary levels of TCP or 3-PBA, respectively.


Patterning methods for polymers in cell and tissue engineering.
Polymers provide a versatile platform for mimicking various aspects of physiological extracellular matrix properties such as chemical composition, rigidity, and topography for use in cell and tissue engineering applications. In this review, we provide a brief overview of patterning methods of various polymers with a particular focus on biocompatibility and processability. The materials highlighted here are widely used polymers including thermally curable polydimethyl siloxane, ultraviolet-curable polyurethane acrylate and polyethylene glycol, thermo-sensitive poly(N-isopropylacrylamide) and thermoplastic and conductive polymers. We also discuss how micro- and nanofabricated polymeric substrates of tunable elastic modulus can be used to engineer cell and tissue structure and function. Such synergistic effect of topography and rigidity of polymers may be able to contribute to constructing more physiologically relevant microenvironment.


Fine structure of the cerebellum of "staggerer-reeler", a double mutant of mice affected by staggerer and reeler conditions. II. Purkinje cell anomalies.
Purkinje cells in double mutant were very similar to those in staggerer both at days 7 and 15, and could not be distinguished from staggerer Purkinje cells by morphological criteria. They were small and immature looking, and their nuclei were invariably eccentric in position both at days 7 and 15. The typical funnel stage was not observed at any time. Somatic spines and their synapses were extermely rare at day 7 when they are abundant in the normal, but they were present at day 15 with typical synapses with climbing fibers. Dendritic spines were also present at day 15 although extremely infrequent, and they showed synapses both with parallel and climbing fibers. More often, however, parallel and climbing fibers were found in synapsis with the smooth surgace of these dentrites. These observations were in close agreement with those of staggerer Purkinje cells. The persistence of staggerer Purkinje cell soma anomalies in double mutant was interpreted as indicating that these anomalies are specific effects of the staggerer gene, being relatively free from environmental influences.


Dimensionality Reduction Based Optimization Algorithm for Sparse 3-D Image Reconstruction in Diffuse Optical Tomography.
Diffuse optical tomography (DOT) is a relatively low cost and portable imaging modality for reconstruction of optical properties in a highly scattering medium, such as human tissue. The inverse problem in DOT is highly ill-posed, making reconstruction of high-quality image a critical challenge. Because of the nature of sparsity in DOT, sparsity regularization has been utilized to achieve high-quality DOT reconstruction. However, conventional approaches using sparse optimization are computationally expensive and have no selection criteria to optimize the regularization parameter. In this paper, a novel algorithm, Dimensionality Reduction based Optimization for DOT (DRO-DOT), is proposed. It reduces the dimensionality of the inverse DOT problem by reducing the number of unknowns in two steps and thereby makes the overall process fast. First, it constructs a low resolution voxel basis based on the sensing-matrix properties to find an image support. Second, it reconstructs the sparse image inside this support. To compensate for the reduced sensitivity with increasing depth, depth compensation is incorporated in DRO-DOT. An efficient method to optimally select the regularization parameter is proposed for obtaining a high-quality DOT image. DRO-DOT is also able to reconstruct high-resolution images even with a limited number of optodes in a spatially limited imaging set-up.


Advances in the treatment of oxygenation disturbances.
The treatment of oxygen transport parameters centers on improving any aspect of oxygen delivery that is threatened. The most important improvements center on improving cardiac output and oxygen carrying capacity, primarily through improving hemoglobin levels, and to a smaller extent, PaO2/SaO2 values. This article reviewed the highlights for improving the key components of oxygen transport while providing examples to aid clinical application.


Is early laparoscopic appendectomy feasible in children with acute appendicitis presenting with an appendiceal mass? A prospective study.
The management of an appendiceal mass remains controversial with 2 schools of thought; early surgical intervention vs nonoperative management with or without interval appendectomy. The aim is to determine the role and safety of early laparoscopic appendectomy (LA) in children with acute appendicitis presenting with an appendiceal mass. This is a prospective study of 88 consecutive pediatric patients who underwent attempted LA for suspected acute appendicitis at KK Women's and Children's Hospital, Singapore, between May and October 2003. A total of 88 patients with a mean age of 10 +/- 3 years (range, 3-16 years) underwent LA for an appendiceal mass (n = 22), simple appendicitis (n = 36), other complicated (gangrenous or perforated) appendicitis (n = 23), and a normal appendix (n = 7). There were 7 conversions to open appendicectomy, 3 of which occurred in patients with an appendiceal mass. There were no perioperative or postoperative mortalities. Morbidity occurred in only one patient who underwent LA for perforated appendicitis. He had prolonged sepsis that resolved after 2 weeks of intravenous antibiotics. None of the patients with an appendiceal mass developed complications. Patients who underwent early LA for an appendiceal mass had a statistically significant (P < .05) longer operating time (median, 103 minutes; interquartile range, 90-151 minutes, vs median, 87 minutes; interquartile range, 71-112 minutes), prolonged time to ambulation (median, 2.0 days; interquartile range, 2-2.5 days, vs median, 1.0 days; interquartile, 1-2 days), increased time to resumption of diet (median, 4 days; interquartile, 3-5 days, vs median, 2 days; interquartile, 2-3 days), and longer postoperative stay (median, 6.0 days; interquartile, 5.5-6.5 days, vs median, 4.0 days; interquartile, 3-5.5 days) compared with patients presenting with appendicitis without mass formation. However, there was no statistical difference in these parameters when LA for an appendiceal mass was compared with LA for other complicated appendicitis (perforated and gangrenous). Although early LA for an appendiceal mass is a technically demanding procedure, it can be performed safely in children with minimal morbidity and mortality. In an era where patients' demand for "key-hole" surgery is rising, early LA is a safe and viable option in the management of children with an appendiceal mass. It also offers the advantage of avoiding misdiagnoses and the need for a second hospitalization.


Participants' perspectives on perceived usefulness of digital and in-person diabetes prevention programs: A qualitative study to inform decisions related to program participation.
Given the effectiveness of both in-person and digital diabetes prevention programs (DPPs), participants have an opportunity to select a delivery mode based on their needs and preferences. The objective of this study was to understand and compare participants' experiences with digital and in-person DPPs to identify factors that affected how useful participants perceived these two program delivery modes. Semi-structured interviews with participants who were enrolled in DPPs as either a digital (n = 23) or in-person (n = 20) program within one health care system were conducted. Data were analyzed following the template method using the qualitative software NVivo 12. Findings from the interviews indicated that creating accountability for weight loss was crucial for all program participants. In the digital program, weight and food tracking played a central role in creating accountability, while in the in-person program, group interactions fostered accountability. The digital program was perceived to encourage self-monitoring, oftentimes resulting in participants' reflection on their habits. The in-person program provided a platform for group support and mutual encouragement. Participants perceived both programs as similarly useful. Yet program characteristics such as the ability to engage with other participants in-person or to seamlessly track weight on a daily basis appealed to different participants. It may be beneficial to align participants' preferences with programs' characteristics and strengths.


Crown lengthening in mandibular molars: a 5-year retrospective radiographic analysis.
Crown lengthening procedures are a significant part of the periodontist's armamentarium. In order to recreate the clinical space lost to caries or trauma necessary for prosthetic restoration, osseous surgery is often required. If the procedure is not carefully planned, it may result in furcation involvement of multirooted teeth. Twenty-six subjects with 26 mandibular molar teeth requiring crown lengthening procedures prior to prosthetic crown placement were evaluated. Nineteen subjects with 24 prosthetic crowns on lower molars which had not undergone crown lengthening were included as control teeth. Bite-wing radiographs prior to surgery (for the test group) or placement of the crown (control group) and 5 years after completion of the prosthesis were compared and analyzed. Of the 26 test teeth, 10 teeth (38.5%) were found to have radiographic evidence of furcation involvement, whereas none of the control teeth developed furcation invasions. A critical distance from the furcation (CDF) of 4 mm was established as a landmark under which, if surgery was performed on mandibular molars, chances of furcation involvement in the future were very high.


Association between environmental exposure to cadmium and risk of suspected non-alcoholic fatty liver disease.
We evaluated the associations between blood Cadmium (Cd) concentrations and risk of suspected NAFLD using nationally representative data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2013, 2016 and 2017. This cross-sectional study included 12,099 adults for the serum alanine aminotransferase (ALT) and hepatic steatosis index (HSI) analyses and 2,904 adults for the serum gamma-glutamyl transferase (GGT) and fatty liver index (FLI) analyses, without significant alcohol consumption. Blood Cd concentrations were measured by graphite furnace atomic absorption spectrometry. Data were analyzed using survey logistic regression models. Odds ratios (ORs) of suspected NAFLD increased significantly per unit of natural log-transformed blood Cd concentration (OR [95% (CI)], for ALT, overall: 1.50 [1.34, 1.68], men: 1.64 [1.40, 2.10] and women: 1.29 [1.08, 1.47]; for GGT, overall: 1.77 [1.33, 2.35], men: 2.28 [1.53, 3.41] and women: 1.27 [0.82, 1.97]; for FLI, overall: 1.84 [1.32, 2.57], men: 1.91 [1.24, 2.94] and women: 1.58 [0.87, 2.86]; for HSI, overall: 1.19 [1.07, 1.32], men: 1.17 [1.01, 1.37] and women: 1.14 [0.99, 1.32]). The blood Cd concentrations associated with risk of suspected NAFLD were lower than those previously reported (for ALT, > 0.64 μg/L, for GGT, > 1.41 μg/L, for FLI, > 0.96 μg/L, and for HSI, > 1.41 μg/L). This study suggests that the reference level of blood Cd should probably be lower than the previously recommended value to prevent adverse health effects due to Cd exposure.


Glycosylation pattern of platelet glycoprotein IIb and IIIa in type IIa hypercholesterolemia.
The microheterogeneity and polymorphism of platelet membrane glycoproteins IIb and IIIa from hypercholesterolemic type IIA patients and from normolipidemic controls were compared by isoelectric focusing followed by immunological detection. Their size and the extent of glycosylation were investigated by polyacrylamide gel electrophoresis and carbohydrate affinity stain. No qualitative or quantitative differences could be detected, either within each test group or between the two groups. This finding rules out the hypothesis that altered molecular forms of the glycoproteins forming the fibrinogen receptor might be involved in the pathogenesis of platelet hyperaggregability in hypercholesterolemic patients.


Spinal epidural hematoma as a stroke mimic.
Spinal epidural hematoma is a rare but important disease as it can be a stroke mimic. Our aim was to investigate the clinical characteristics of patients with an activated stroke code and spinal epidural hematoma. Patients with an activated stroke code were examined retrospectively. Patients with spinal epidural hematoma were evaluated with further neurological examinations and neuroimaging. Of 2866 patients with an activated stroke code, spinal epidural hematoma was detected in 5 (0.2%, 63-79 years, 2 men). In all 5 cases, hematoma was located in the unilateral dorsal region of the spinal canal and spread to 5-9 vertebral segments at the C1-T3 level. None of the patients had a medical history of head or neck injury, coagulopathy, or use of anti-thrombotic agents. All of the patients had occipital, neck, and/or back pain, and their hemiparesis occurred simultaneously or within 1 h after the onset of pain. Hyperalgesia ipsilateral to the hematoma was observed in 1 patient, hypoalgesia contralateral to the hematoma was observed in 1, and quadriparesis and bilateral hypoalgesia were observed in 1. The hematomas spontaneously decreased in size in 4 patients, and cervical laminectomy was performed in the other patient. In the 1860 patients with an activated stroke code and spontaneous eye opening, the sensitivity of pain as a predictor of spinal epidural hematoma was 100%, with a specificity of 88.7%, and positive predictive value of 2.3%. Patients with spinal epidural hematoma could present with clinical characteristics mimicking ischemic stroke. Spinal epidural hematoma should be differentiated in patients treated under stroke code activation.


Phylogenetic relationships of Cryptococcus neoformans and some related basidiomycetous yeasts determined from partial large subunit rRNA sequences.
The genus Cryptococcus was found to be heterogeneous on the basis of partial rRNA sequences. The human-pathogenic species C. neoformans, comprising 4 serotypes and having Filobasidiella neoformans and F. bacillispora as teleomorphs, was found at a relatively large distance from Filobasidium. Serotypes B and C had identical sequences, while in A and D they were different, with D closer to B and C than to A. Filobasidiella depauperata, which lacks a yeast-like anamorph, clustered with F. neoformans. The genus Filobasidium was clearly separated from Filobasidiella and clustered with C. albidus, C. kuetzingii, C. gastricus, C. lupi, C. vishniaciae, C. bhutanensis, C. aerius, C. terreus and C. ater. The latter may represent the anamorph of Filobasidium elegans. The orange to red species of Cryptococcus, as well as C. aquaticus and C. yarrowii, were found completely unrelated with these taxa, C. macerans being affiliated to Cystofilobasidium capitatum. The genus Trichosporon was found relatively homogeneous; it includes C. humicola, C. curvatus and the filamentous species Hyalodendron lignicola. Cryptococcus flavus and C. dimennae probably belong to the Tremellales, though distances between these species are large. The positions of C. laurentii and C. luteolus remains to be determined.


Effect of cortisone or triiodothyronine administration to pregnant rats on lysosomal hydrolases in fetal forebrain and cerebellum.
Triiodothyronine injected daily to pregnant rats for the last week of gestation (50 microgram/100 g b.wt) increased the specific activities of 5 acid glycosidases in the fetal forebrain and cerebellum. Cortisone (50 mg/100 g b.wt) administered in the same period had no effect on cerebellum acid hydrolases, but decreased their activity in the forebrain.


Effects of ethanol in vitro on rat intestinal brush-border membranes.
Ethanol, at concentrations found in the intestinal lumen after moderate drinking, has been shown to inhibit carrier-mediated intestinal transport processes. This inhibition could occur by direct interaction with membrane transporters, dissipation of the energy producing Na+ electrochemical gradient and/or nonspecific alteration of membrane integrity. The latter alteration may be reflected by changes in membrane fluidity, chemical composition or vesicular size. These possibilities were examined with studies in purified brush border membrane vesicles of rat intestine. Ethanol inhibited concentrative Na+-dependent D-glucose uptake in a dose-dependent manner. In contrast, ethanol did not inhibit concentrative D-glucose uptake under conditions of D-glucose trans-stimulation in the absence of a Na+ electrochemical gradient. Ethanol also inhibited initial, concentrative Na+-dependent taurocholic acid uptake, as well as equilibrium uptake. That ethanol exerted a dual effect on transport by increasing membrane conductance for Na+ while decreasing intravesicular space was supported by direct studies of Na+ uptake. Morphometric analysis confirmed that ethanol-treated membranes had a decreased intravesicular size when compared to untreated membranes. Finally, membrane fluidity measured by EPR showed that ethanol had a significant fluidizing effect without producing qualitative changes in membrane proteins, as determined by SDS gel electrophoresis. These results suggest that ethanol inhibits carrier-mediated transport by dissipation of the Na+ electrochemical gradient and alteration of membrane integrity rather than by direct interaction with membrane transporter.


Cloning and characterization of the gene encoding murine insulin-like growth factor-binding protein-2, mIGFBP-2.
We present a characterization of the single-copy gene, mIGFBP-2, encoding the murine insulin-like growth factor-binding protein-2 (mIGFBP-2). It consists of four exons with sizes of 470 +/- 2, 227, 141 and > 475 nucleotides (nt). The first intron spans 23 kb of genomic sequence, and the complete gene extends to more than 28 kb. Two kb of the 5'-flanking region were sequenced. This region has no TATA or CAAT boxes but is G+G-rich and contains several potential regulatory sequence motifs. A total of five GC boxes, which may serve as potential binding sites for a transcription factor, Sp1, are present immediately upstream of the transcription start point (tsp). By primer extension, we identified a single tsp at nt position -85 +/- 2. The murine IGFBP-2 locus was mapped to the proximal region of mouse chromosome 1, to a region of conserved synteny with human chromosome 2q. A comparison of the deduced amino acid sequences of mouse, rat and human IGFBP-2 reveals a high degree of homology between all three species.


Resemblances of parents and twins in sports participation and heart rate.
A model to analyze resemblances of twins and parents using LISREL is outlined and applied to sports participation and heart-rate data. Sports participation and heart rate were measured in 44 monozygotic and 46 dizygotic adolescent twin pairs and in their parents. Genetic factors influence variation in both sports behavior and heart rate, while there is no evidence for transmission from parental environment to offspring environment. For sports participation the data support a model in which there is a high positive correlation between environments of spouses and between environments of female twins. This correlation is absent for male twins and negative for opposite sex twins. For heart rate, a positive correlation between environmental influences was observed for all twins; there is no evidence for assortative mating. The proposed model can also handle data sets where parents and twins have been measured on more than one variable. This is illustrated by an application to the observed association of sports participation and heart rate.


Electrophysiological evaluation of the patient with acute spinal cord injury.
This article reviews basic principles, equipment and techniques, and clinical applications of electrophysiologic monitoring in patients with spinal cord injuries. Four groups of electrophysiologic measurements are considered: Somatosensory evoked potentials (SEPs); motor evoked potentials (MEPs); electromyography (EMG) and nerve conduction studies; and late responses, including H reflex, M response, and F wave. Reports of SEP recordings in spinal cord injury, as drawn from the literature, are tabulated in detail.


Asymmetric switch-costs and ERPs reveal facial identity dominance over expression.
Previous studies on face processing have revealed an asymmetric overlap between identity and expression, as identity is processed irrespective of expression while expression processing partly depends on identity. To investigate whether this relative interaction is caused by dominance of identity over expression, participants performed familiarity and expression judgments during task switching. This paradigm reveals task-set dominance with a paradoxical asymmetric switch-cost (i.e., greater difference between switch and repeat trials when switching toward the dominant task). Event-related potentials (ERPs) were recorded to find the neural signature of the asymmetric cost. As expected, greater switch-cost was shown in the familiarity task with respect to response times, indicating its dominance over the expression task. Moreover, a left-sided ERP correlate of this effect was observed at the level of the frontal N2 component, interpreted as an index of modulations in endogenous executive control. Altogether, these results confirm the overlap between identity and expression during face processing and further indicate their relative dominance.


Liquid chromatographic assay of urinary free cortisol.
Cortisol in concentrated sulfuric acid forms two major fluorescing compounds which are separated by chromatography on a reversed-phase column. Based on this reaction, urine free cortisol, after double extraction was assayed by high-performance liquid chromatography with fluorescent detection. The method is sensitive, rapid, and free from interferences. The values by this method are 30% lower than radioimmunoassay. In addition to Cushing's syndrome, patients with acute pancreatitis had elevated levels of urinary free cortisol which parallel urinary amylase levels while patients with myocardial infarction had normal levels. Urinary free cortisol showed diurnal variation with elevated values early in the morning.


Seroprevalence of anti-HTLV I/II and anti-HIV-1 antibodies in a sample population in the Marche Region, Italy.
A total of 1292 sera, provided by different USLs (Local Health Centers) in the Marche Region (Italy), was tested by ELISA and Western Blot for the detection of anti-HTLV I/II ad HIV-1 antibodies. It was decided not to follow any particular criterion when collecting the sera, so no protocol of admission was established in advance. Of the 1292 sera tested, 12 were found antibody positive to HTLV I/II, 18 to HIV-1 and 4 to both viruses. Of the seropositives, for HTLV I/II and HIV-1, respectively, 2 and 3 were prisoners; 2 and 4 were IVDAs, 3 and 7 were hematological patients, 3 and 2 were hospitalized subjects (not for hematological disorders), and 2 and 2 were positives belonging to a healthy population group. These data suggest that the viruses may also be spreading among groups other than the high-risk ones (homosexuals, IVDAs, prisoners, blood-transfusion recipients, promiscuous heterosexuals).


Dynamic of expression and localization of cannabinoid-degrading enzymes FAAH and MGLL in relation to CB1 during meiotic maturation of human oocytes.
The endogenous cannabinoid system has been characterized in some female reproductive organs but little is known about the expression and localization pattern of cannabinoid-degrading enzymes in relation to the CB1 cannabinoid receptor in human oocytes. In this study, we focus on the investigation of the presence and differential distribution of fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGLL) in relation to CB1 during the maturation of human oocytes. We used a total of 290 human oocytes not suitable for in vitro fertilization/intracytoplasmic sperm injection (ICSI): germinal-vesicle (GV) and metaphase-I (MI) stages and metaphase-II (MII) oocytes that had not developed into an embryo after ICSI. Cannabinoid-degrading enzymes and the cannabinoid CB1 receptor were present in human oocytes. Specifically, FAAH was detected in the periphery of the oocyte from the GV to MI stage and co-localized with CB1. Later, by the MII stage, FAAH was spread within the oocyte, whereas MGLL immunostaining was homogeneous across the oocyte at all stages of maturation and only overlapped with CB1 at the GV stage. This coordinated redistribution of cannabinoid system proteins suggests a role for this system in the maturation of the female gamete.


Anamnestic data in allergic rhinitis.
In a study of 770 patients with allergic rhinitis, anamnestic data were collected by means of a questionnaire. 484 (63%) of the patients were women and 286 (37%) men. 45.5% of the patients had perennial symptoms, 33.5% had seasonal symptoms only, and 21% had predominantly seasonal but also some perennial symptoms. More than 50% of the patients belonged to the age group 21-40 years. The seasonal group included significantly more young patients than the perennial group. More than 50% of the parents and about 45% of the siblings had some atopic disorder. About 20% of the rhinitis patients had a concomitant allergic disorder. Sneezing was the commonest complaint in both rhinitis groups, but it was significantly more frequent in patients with seasonal rhinitis. Nasal blockage, again, was significantly commoner in perennial rhinitis. More than half of the patients reported severest symptoms in the morning. 282 patients had some domestic animal or pet, and 34% of these developed symptoms when close to an animal. Hypersensitivity to animals was significantly more frequent in patients who had domestic animals or pets than in those who did not. There was a clear correlation in perennial allergic rhinitis between the duration of rhinitis and deterioration of the sense of smell.


[Patients' autonomy and right to the information: from the recognition of rights, to the loss of confidence. Reflections on the new regulation about patients' rights at the end of life].
This paper analyses the evolution of physician-patient relationship in the last decades, and the way in which the law influences in it through the regulation of the patient's rights. It underlines the importance of defend patient's autonomy, and, at the same time, alerts to the risks of the widespread of the defensive healthcare.


In Vivo Ear Sponge Lymphangiogenesis Assay.
Lymphangiogenesis, the formation of lymphatic vessels from preexisting ones, is an important process in wound-healing physiology. Deregulation of lymphangiogenesis and lymphatic vascular remodeling have been implicated in a range of inflammatory conditions, such as lymphedema, lymphadenopathy, tumor growth, and cancer metastasis. Any attempt in understanding various parameters of the lymphangiogenic process and developing desirable therapeutic targets requires recapitulating these conditions in in vivo models. One pitfall with some experimental models is the absence of immune response, an important regulatory factor for lymphangiogenesis. We overcome this issue by using immune competent mice. In this chapter, by using Angiopoietin-2 (Ang2), a protein that belongs to the Ang/Tie signaling pathway, we describe the ear sponge assay with important adaptations, highlighting a reproducible and quantitative tool for assessment of in vivo lymphangiogenesis.


Fish size and habitat depth relationships in headwater streams.
Surveys of 262 pools in 3 small streams in eastern Tennessee demonstrated a strong positive relationship between pool depth and the size of the largest fish within a pool (P<0.001). Similarly, the largest colonizers of newly-created deep pools were larger than the colonizers of shallow pools. We explored the role of predation risk in contributing to the "bigger fish - deeper habitat" pattern, which has been noted by others, by conducting five manipulative field experiments in two streams. Three experiments used stoneroller minnows (Campostoma anomalum); one used creek chubs (Semotilus atromaculatus); and one used striped shiners (Notropis chrysocephalus). The stoneroller experiments showed that survival of fish approximately 100 mm in total length (TL) was much lower in shallow pools (10 cm deep) than in deep (40 cm maximum) pools (19% versus 80% survival over 12 d in one experiment) and added cover markedly increased stoneroller survival in shallow pools (from 49% to 96% in an 11-d experiment). The creek chub experiment showed that, as for stonerollers, pool depth markedly influenced survival: the chubs survived an average of 4.9 d in shallow pools and >10.8 d in deep pools. In the striped shiner experiment in shallow artificial streamside troughs, no individuals 75-100 mm TL survived as long as 13 d, where-as smaller (20-25 mm) fish had 100% survival over 13 d. The results of the experiments show that predation risk from wading/diving animals (e.g., herons and raccoons) is much higher for larger fishes in shallow water than for these fishes in deeper water or for smaller fish in shallow water. We discuss the role of predation risk from two sources (piscivorous fish, which are more effective in deeper habitats, and diving/wading predators, which are more effective in shallow habitats) in contributing to the bigger fish - deeper habitat pattern in streams.


[Surgical treatment of gastroesophageal reflux in the child using Dor's anterior partial fundoplication procedure. Report of 37 cases].
A retrospective study of 37 children with gastroesophageal reflux, treated by Dor's anterior partial fundoplication procedure, objects a good clinical result in a rate of 95%. The late radiologic examinations confirm a good result in 84%, without gastroesophageal reflux or fundoplication alteration, with a mean follow-up of 6 years. The late efficiency of the partial fundoplication is assured by a safe fixation of the abdominal oesophagus and the partial fundoplication to the diaphragnatic crus.


Chronic Subdural Medical Management.
Chronic subdural hematomas (cSDHs) that are asymptomatic or have minimal symptoms have become more prevalent, with an increased rate of detection with neuroimaging in the setting of an aging population and increasing use of anticoagulants. These cSDHs have been known to spontaneously resolve, and subsequent efforts have been made to study the role of nonoperative initial medical management strategies in these patients. Current and potential strategies for the medical management of cSDH are discussed.


Chemoprophylaxis of pulmonary tuberculosis. Current recommendations and controversies.
The recommendation for chemoprophylaxis for all persons under 21 years of age with a positive tuberculin reaction is accepted by nearly all authorities. Doubt exists concerning the treatment of those over 21 unless special risk factors are present. The key to safe isoniazid prophylaxis lies in emphasizing the side effects of hepatitis and in urging patients to report any untoward symptom. The alternative to prophylaxis must be close surveillance by means of periodic chest roentgenograms.


Fd : FNR Electron Transfer Complexes: Evolutionary Refinement of Structural Interactions.
During the evolution of higher-plant root and leaf-type-specific Fd : FNR complexes from an original cyanobacterial type progenitor, rearrangement of molecular interaction has altered the relative orientation of prosthetic groups and there have been changes in complex induced conformational change. Selection has presumably worked on mutation of residues responsible for interaction between the two proteins, favoring optimized electron flow in a specific direction, and efficient dissociation following specific oxidation of leaf Fd and reduction of root Fd. Major changes appear to be: loss in both leaf and root complexes of a cyanobacterial mechanism that ensures Fd dissociation from the complex following change in Fd redox state, development of a structural rearrangement of Fd on binding to leaf FNR that results in a negative shift in Fd redox potential favorable to photosynthetic electron flow, creation of a vacant space in the root Fd:FNR complex that may allow access to the redox centers of other enzymes to ensure efficient channeling of heterotrophic reductant into bioassimilation. Further structural analysis is essential to establish how root type FNR distinguishes between Fd isoforms, and discover how residues not directly involved in intermolecular interactions may affect complex formation.


Optimized autoantibody profiling on protein arrays.
Profiling the autoantibody (AAb) repertoire in serum has been routinely used for many years for the diagnosis of autoimmune diseases, including rheumatoid arthritis, scleroderma, and lupus. In recent years, AAb profiling of cancers has become a prominent field in oncology research. Protein arrays enable high-throughput screening of clinical samples, characterising the serum profile using low volumes of samples. This chapter describes the use of a protein array comprising 37,200 redundant proteins (containing over 10,000 non-redundant human recombinant proteins) for identification of the proteins bound by the antibodies in human sera using a test set of serum samples. The proteins identified have the potential to be candidate biomarkers. These recombinant proteins are expressed, purified, and robotically spotted on microarrays or chips to facilitate the screening of additional serum samples with the aim of identifying a candidate biomarker or panel of potential biomarkers for applications in disease diagnosis, stage, progression, or response to therapy.


Palytoxin detection and quantification using the fluorescence polarization technique.
Palytoxin (PLT) is a highly toxic nonpeptidic marine natural product, with a complex chemical structure. Its mechanism of action targets Na,K-ATPase. Fluorescence polarization (FP) is a spectroscopic technique that can be used to determine molecular interactions. It is based on exciting a fluorescent molecule with plane-polarized light and measuring the polarization degree of the emitted light. In this study, FP was used to develop a detection method based on the interaction between the Na,K-ATPase and the PLT. The Na,K-ATPase was labeled with a reactive succinimidyl esther of carboxyfluorescein, and the FP of protein-dye conjugate was measured when the amount of PLT in the medium was modified. The assay protocol was first developed using ouabain as a binding molecule. The final result was a straight line that correlates FP units and PLT concentration. Within this line the PLT equivalents in a natural sample can be quantified. A selective cleaning procedure to mussel samples and dinoflagellates cultures was also developed to avoid the matrix effect. The LOQ (limit of quantification) of the method is 10nM and the LOD (limit of detection) is 2 nM. This new PLT detection method is easier, faster, and more reliable than the other methods described to date.


A radiological diary of gallstone migration in a patient with acute pancreatitis.
This case report is interesting in radiologically showing migration of stones from the gallbladder via the biliary tree and into the gastrointestinal tract.


Surgical treatment of arthrogryposis of the elbow.
The purpose of this study was to analyze our results of surgical treatment of arthrogryposis of the elbow and to compare our tendon transfer results using range of motion (ROM) criteria versus functional use criteria. Eighteen tendon transfers for elbow flexion in 14 children with arthrogryposis with an average follow-up period of 4 years (range, 1-14 years) and 6 elbow capsulotomies with triceps lengthening in 6 children with arthrogryposis with an average follow-up period of 5 years (range, 2-9 years) were evaluated. Each child was assessed by a questionnaire regarding functional use of the upper extremity, physical examination of ROM and strength, and a videotaped activities of daily living evaluation. Tendon transfer results were classified and compared using 2 methods of evaluation: postoperative strength and ROM and effective functional use of the tendon transfer to perform activities of daily living. The 6 elbow capsulotomies improved from an average preoperative arc of 17 degrees of motion (average extension, -2 degrees; average flexion, 19 degrees) to an average final follow-up arc of 67 degrees (average extension, -25 degrees; average flexion, 92 degrees). The 18 tendon transfers evaluated by strength and ROM criteria showed 9 triceps to biceps transfers in 9 arms (7 good, 1 fair, and 1 poor), 5 pectoralis to biceps transfers in 4 arms (1 good, 3 fair, and 1 poor), and 4 latissimus dorsi to biceps transfers in 3 arms (2 good and 2 fair). Evaluation by functional use criteria gave the same result in 13 transfers and downgraded the result in 5; the downgraded results were due to resultant flexion contracture or limited functional use because the transfer was in the nondominant arm. Based on this review, optimal surgical candidates for tendon transfer are children older than 4 years, who have full passive ROM of the elbow in the dominant arm, and at least grade 4 strength of the muscle to be transferred.


Association between mortality risk and the number, location, and sequence of subsequent fractures in the elderly.
The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk. It is unclear whether subsequent fractures or a certain location and sequence of subsequent fractures are associated with mortality risk in the elderly. We aimed to investigate the relationship between subsequent fractures and mortality risk. Using the Korean National Health Insurance Research Database, we analyzed the cohort data of 24,756 patients aged > 60 years who sustained fractures between 2002 and 2013. Cox regression was used to assess the mortality risk associated with the number, locations, and sequences of subsequent fractures. Mortality hazard ratios (HRs) for women and men were shown to be associated with the number of subsequent fractures (one, 1.63 (95% confidence interval [CI], 1.48-1.80) and 1.42 (95% CI, 1.28-1.58); two, 1.75 (95% CI, 1.47-2.08) and 2.03 (95% CI, 1.69-2.43); three or more, 2.46(95% CI, 1.92-3.15) and 1.92 (95% CI, 1.34-2.74), respectively). For women, the mortality risk was high when hip (HR, 2.49; 95% CI, 1.80-3.44) or vertebral (HR, 1.40; 95% CI, 1.03-1.90) fracture occurred as a second fracture. Compared with a single hip fracture, there was a high mortality risk in the group with hip fracture after the first vertebral fracture (HR, 2.90; 95% CI, 1.86-4.54), followed by vertebral fracture after the first hip fracture (HR, 1.90; 95% CI, 1.12-3.22). The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk.


Indication of aortocoronary by-pass for coronary arterial obstruction due to Kawasaki disease.
Six patients with coronary arterial lesions due to Kawasaki disease underwent aortocoronary by-pass grafting at our institute. Before surgery, all of them had been closely monitored for some years by means of selective coronary arteriography, thallium myocardial imaging, electrocardiography (treadmill and/or Holter), and two-dimensional echo cardiography. Based on this experience, we propose the following guidelines as an indication for aortocoronary by-pass in such patients. First, the following three conditions should be satisfied: 1) The progress of coronary arterial lesions has been documented by serial selective coronary arteriography; 2) redistribution to the perfusion defect has been detected on the delayed image in myocardial imaging; 3) no coronary arterial lesions distal to the graft site have been detected by coronary angiography. When these three conditions are satisfied, at least one of the following conditions must apply: 1) Localized stenosis in the left main trunk has progressed to critical stenosis; 2) there is occlusion of two or more vessels; 3) collateral vessels connecting to the peripheral portion of an occluded coronary artery arise from the peripheral part of a vessel with progressive localized stenosis; 4) progressive localized stenosis or critical stenosis has developed in the left anterior descending artery, in addition to significant stenosis in the right coronary artery.


Microalgae as tools for bio-circular-green economy: Zero-waste approaches for sustainable production and biorefineries of microalgal biomass.
Microalgae are promising organisms that are rapidly gaining much attention due to their numerous advantages and applications, especially in biorefineries for various bioenergy and biochemicals. This review focuses on the microalgae contributions to Bio-Circular-Green (BCG) economy, in which zero-waste approaches for sustainable production and biorefineries of microalgal biomass are introduced and their possible integration is discussed. Firstly, overviews of wastewater upcycling and greenhouse gas capture by microalgae are given. Then, a variety of valuable products from microalgal biomass, e.g., pigments, vitamins, proteins/peptides, carbohydrates, lipids, polyunsaturated fatty acids, and exopolysaccharides, are summarized to emphasize their biorefinery potential. Techno-economic and environmental analyses have been used to evaluate sustainability of microalgal biomass production systems. Finally, key issues, future perspectives, and challenges for zero-waste microalgal biorefineries, e.g., cost-effective techniques and innovative integrations with other viable processes, are discussed. These strategies not only make microalgae-based industries commercially feasible and sustainable but also reduce environmental impacts.


Survival in frontotemporal dementia.
To establish survival in patients with pathologically confirmed frontotemporal dementia (FTD) and to determine whether clinical or pathologic subtype affects prognosis. The authors reviewed the presenting clinical features of 61 patients with dementia and pathologically confirmed FTD studied in Sydney (n = 31) and Cambridge (n = 30) over a 10-year period. Data were available on time of symptom onset, diagnosis, institutionalization, and death. Cases were classified pathologically as tau-positive and tau-negative. Of the 61 patients with FTD, 26 presented with frontal variant (fvFTD), 9 with semantic dementia, 8 with progressive nonfluent aphasia (PNFA), 9 with associated motor neuron disease (FTD-MND), and 9 with corticobasal degeneration features. There was no difference between the groups in age at symptom onset (overall mean 58.5 +/- 7.8 years), but at diagnosis the PNFA (68.3 +/- 2.7) group was significantly older than the fvFTD (59.9 +/- 7.4) and FTD-MND (57.7 +/- 7.9) groups. The median survival from symptom onset and from diagnosis was 6 +/- 1.1 years (95% CI) for fvFTD and 3 +/- 0.4 years for FTD-MND. Survival across subgroups was equivalent except for the FTD-MND group, which had significantly shorter survival. Cases with tau-positive pathology had an older age at onset and a significantly better prognosis: median survival 9.0 +/- 0.9 years vs 5.0 +/- 1.1 years. FTD is a malignant disorder with limited life expectancy. FTD-MND has the shortest duration both before and after diagnosis. Tau-positivity is associated with a more slowly progressive form of FTD.


Identification of the novel HLA-A*02:981 allele by sequencing-based typing.
One nucleotide replacement at position 728 of HLA-A*02:07:01 results in a novel allele, HLA-A*02:981.


Clinical decision thresholds for surfactant administration in preterm infants: a systematic review and network meta-analysis.
The ideal threshold at which surfactant administration in preterm neonates with respiratory distress syndrome (RDS) is most beneficial is contentious. The aim of this systematic review was to determine the optimal clinical criteria to guide surfactant administration in preterm neonates with RDS. The systematic review was registered in PROSPERO (CRD42022309433). Medline, Embase, CENTRAL and CINAHL were searched from inception till 16th May 2023. Only randomized controlled trials (RCTs) were included. A Bayesian random effects network meta-analysis (NMA) evaluating 33 interventions was performed. The primary outcome was requirement of invasive mechanical ventilation (IMV) within 7 days of life. 58 RCTs were included. In preterm neonates ≤30 weeks after adjusting for the confounding factor of modality of surfactant administration, an arterial alveolar oxygen tension ratio (aAO2) <0.36 (FiO2: 37-55%) was ranked the best threshold for decreasing the risk of IMV, very low certainty. Further, surfactant administration at an FiO2 40-45% possibly decreased mortality compared to rescue treatment when respiratory failure was diagnosed, certainty very low. The reasonable inference that could be drawn from these findings is that surfactant administration may be considered in preterm neonates of ≤30 weeks' with RDS requiring an FiO2 ≥ 40%. There was insufficient evidence for the comparison of FiO2 thresholds: 30% vs. 40%. The evidence was sparse for surfactant administration guided by lung ultrasound. For the sub-group >30 weeks, nebulized surfactant administration at an FiO2 < 30% possibly increased the risk of IMV compared to Intubate-Surfactant-Extubate at FiO2 < 30% and 40%, and less invasive surfactant administration at FiO2 40%, certainty very low. Surfactant administration may be considered in preterm neonates of ≤30 weeks' with RDS if the FiO2 requirement is ≥40%. Future trials are required comparing lower FiO2 thresholds of 30% vs. 40% and that guided by lung ultrasound. None.


Increased β2-adrenergic vasorelaxation at the early phase of endotoxemic shock in rats.
The early management of the cardiovascular dysfunction of septic shock is critical as it is associated with a poor outcome. Although the use of catecholamines is a common therapy in this syndrome, no data are available on the involvement of β-adrenoceptor (β-AR) subtypes and only few studies report an alteration of β-adrenergic-induced vasodilation in septic shock. The purpose of the study was to evaluate vascular β1, β2 and β3-AR expression and function in an endotoxemic rat model. Endotoxemia was induced in rats by intravenous injection of lipopolysaccharide (LPS). β1, β2 and β3-AR mRNA expression was evaluated by RT-PCR in aorta and vascular β1, β2 and β3-AR responses were determined on conducting (aorta) and/or resistance (mesenteric and renal) arteries by constructing relaxation curves in response to different β-AR agonists. The maximal effect of isoproterenol decreased by 31 to 61% in the three vascular beds of LPS-treated rats compared to controls. In aortas from LPS-treated rats, β1 and β3-AR mRNA expression was decreased and associated to a reduced β1 and β3-induced vasodilation. Conversely, albeit β2-AR mRNA was unchanged, the maximal β2-AR-induced vasodilation increased by 49% in aortas from LPS-treated rats compared to controls. This increase was not affected by endothelium removal but was abolished in the presence of a β2-AR antagonist or an adenylate cyclase inhibitor. In endotoxemia, β2-AR vasodilation was increased by a potential recruitment of β2-AR located on smooth muscle cells. This study suggests that vascular β2-AR should be a putative new therapeutic target in septic shock.


Power profiling and the power-duration relationship in cycling: a narrative review.
Emerging trends in technological innovations, data analysis and practical applications have facilitated the measurement of cycling power output in the field, leading to improvements in training prescription, performance testing and race analysis. This review aimed to critically reflect on power profiling strategies in association with the power-duration relationship in cycling, to provide an updated view for applied researchers and practitioners. The authors elaborate on measuring power output followed by an outline of the methodological approaches to power profiling. Moreover, the deriving a power-duration relationship section presents existing concepts of power-duration models alongside exercise intensity domains. Combining laboratory and field testing discusses how traditional laboratory and field testing can be combined to inform and individualize the power profiling approach. Deriving the parameters of power-duration modelling suggests how these measures can be obtained from laboratory and field testing, including criteria for ensuring a high ecological validity (e.g. rider specialization, race demands). It is recommended that field testing should always be conducted in accordance with pre-established guidelines from the existing literature (e.g. set number of prediction trials, inter-trial recovery, road gradient and data analysis). It is also recommended to avoid single effort prediction trials, such as functional threshold power. Power-duration parameter estimates can be derived from the 2 parameter linear or non-linear critical power model: P(t) = W'/t + CP (W'-work capacity above CP; t-time). Structured field testing should be included to obtain an accurate fingerprint of a cyclist's power profile.