Fluid technologies: The Bush Pump, the LifeStraw and microworlds of humanitarian design.
Over the past decade, many ingenious, small-scale gadgets have appeared in response to problems of disaster and extreme poverty. Focusing on the LifeStraw, a water filtration device invented by the company Vestergaard Frandsen, I situate this wave of humanitarian design relative to Marianne de Laet and Annemarie Mol's classic article on the Zimbabwe Bush Pump. The LifeStraw shares the Bush Pump's principle of technical minimalism, as well as its ethical desire to improve the lives of communities. Unlike the pump, however, the straw defines itself through rather than against market logic, accepting the premise that one can 'do well while doing good'. Moreover, it does not share the assumed framework of de Laet and Mol's Zimbabwean socio-technical landscape: a postcolonial state happily en route to national self-definition. Nonetheless, it clearly embodies moral affect, if in the idiom of humanitarian concern rather than development. My aim is to open up three interrelated lines of inquiry for discussion. First, I consider aspects of a postcolonial condition at the micro-level of immediate needs, including assumptions about nation-state politics and markets. Second, I emphasize science and technology in the form of infrastructure, the material frontline of norms. Third, I return reflexively to love, and the complicated allure of engagement in academic work.


Inhibitory TMS over Visual Area V5/MT Disrupts Visual Speech Recognition.
During face-to-face communication, the perception and recognition of facial movements can facilitate individuals' understanding of what is said. Facial movements are a form of complex biological motion. Separate neural pathways are thought to processing (1) simple, nonbiological motion with an obligatory waypoint in the motion-sensitive visual middle temporal area (V5/MT); and (2) complex biological motion. Here, we present findings that challenge this dichotomy. Neuronavigated offline transcranial magnetic stimulation (TMS) over V5/MT on 24 participants (17 females and 7 males) led to increased response times in the recognition of simple, nonbiological motion as well as visual speech recognition compared with TMS over the vertex, an active control region. TMS of area V5/MT also reduced practice effects on response times, that are typically observed in both visual speech and motion recognition tasks over time. Our findings provide the first indication that area V5/MT causally influences the recognition of visual speech.SIGNIFICANCE STATEMENT In everyday face-to-face communication, speech comprehension is often facilitated by viewing a speaker's facial movements. Several brain areas contribute to the recognition of visual speech. One area of interest is the motion-sensitive visual medial temporal area (V5/MT), which has been associated with the perception of simple, nonbiological motion such as moving dots, as well as more complex, biological motion such as visual speech. Here, we demonstrate using noninvasive brain stimulation that area V5/MT is causally relevant in recognizing visual speech. This finding provides new insights into the neural mechanisms that support the perception of human communication signals, which will help guide future research in typically developed individuals and populations with communication difficulties.


High national rates of high-dose dopamine agonist prescribing for restless legs syndrome.
Long-term dopamine agonist (DA) use in restless legs syndrome (RLS) is associated with augmentation, a dose-related symptom worsening leading to further dose escalation to manage RLS. This study investigated rates and factors of high-dose DA prescribing in US RLS patients. This retrospective analysis examined data from a US longitudinal prescriptions database (October 2017-September 2018). Patients diagnosed with RLS (ICD-10 G255.81) without Parkinson's disease who were prescribed ropinirole, pramipexole, and/or rotigotine were included. Daily DA dosage was categorized: LOW/MID (US Food and Drug Administration [FDA]-approved/guideline or slightly above FDA-approved [pramipexole]); HIGH (101%-149%); VERY HIGH (>150%). Patient counts were converted to US national estimates. Logistic regression of patient counts evaluated factors associated with HIGH/VERY HIGH DA dosing. Of 670,404 RLS patients (131,289,331 therapy days), 58.8% were prescribed DA therapy. Overall, 19.1% of RLS patients were prescribed DAs above maximum FDA-approved/guideline daily doses-over half of these were >150% maximum recommended doses; 67.6% of HIGH/VERY HIGH-dose prescriptions were pramipexole (OR [95% CI] pramipexole vs ropinirole, 5.8 [5.7 to 6.0]). The highest 1% of DA prescriptions were ≥10× the FDA-recommended maximum daily dose. Rates of HIGH/VERY HIGH DA dosing increased with patient age. Twice as many neurologists (31.1%) prescribed HIGH/VERY HIGH doses vs other specialties (OR [95% CI], 2.1 [1.2 to 2.0]). Approximately 20% of DA-treated RLS patients were prescribed doses above the approved and guideline daily maximum. Pramipexole, Neurology as specialty, and patient age were independently associated with HIGH/VERY HIGH DA dosing. Increased education is warranted regarding risks of high-dose DA exposure in RLS.


Individualized Family-Centered Developmental Care: An Essential Model to Address the Unique Needs of Infants With Congenital Heart Disease.
Infants born with critical congenital heart disease (cCHD) who require surgical intervention in the newborn period are often hospitalized in a cardiac intensive care unit (CICU). Cardiac surgery and the CICU environment are traumatic to infants and their families. Infants are exposed to overwhelming stress, which can result in increased pain, physiologic instability, behavioral disorganization, disrupted attachment, and altered brain development. Individualized Family-centered Developmental Care (IFDC) is a model that can address the unique needs and developmental challenges of infants with cCHD. The purpose of this article is to (1) clearly describe the uniqueness of the infant with cCHD, including the medical, neurological, and parental challenges, and (2) propose methods to apply IFDC to support recovery of infants with cCHD in the CICU. The experiences in the CICU shape the developing brain and alter recovery and healing, thus adversely impacting development. Individualized Family-centered Developmental Care is a promising model of care that nurses can integrate into the CICU to promote neuroprotection and development. Nurses can effectively integrate IFDC into the CICU by understanding the unique characteristics of infants with cCHD and applying IFDC interventions that include both maturity and recovery perspectives. The incorporation of IFDC interventions is essential for the infant with cCHD and should be a standard of care. Applying IFDC with a recovery perspective in all aspects of caregiving will provide opportunities for individualization of care and parent engagement, allowing infants in the CICU to recover from surgery while supporting both short- and long-term neurodevelopment.


Dose-dependent alcohol-induced alterations in chromatin structure persist beyond the window of exposure and correlate with fetal alcohol syndrome birth defects.
In recent years, we have come to recognize that a multitude of in utero exposures have the capacity to induce the development of congenital and metabolic defects. As most of these encounters manifest their effects beyond the window of exposure, deciphering the mechanisms of teratogenesis is incredibly difficult. For many agents, altered epigenetic programming has become suspect in transmitting the lasting signature of exposure leading to dysgenesis. However, while several chemicals can perturb chromatin structure acutely, for many agents (particularly alcohol) it remains unclear if these modifications represent transient responses to exposure or heritable lesions leading to pathology. Here, we report that mice encountering an acute exposure to alcohol on gestational Day-7 exhibit significant alterations in chromatin structure (histone 3 lysine 9 dimethylation, lysine 9 acetylation, and lysine 27 trimethylation) at Day-17, and that these changes strongly correlate with the development of craniofacial and central nervous system defects. Using a neural cortical stem cell model, we find that the epigenetic changes arising as a consequence of alcohol exposure are heavily dependent on the gene under investigation, the dose of alcohol encountered, and that the signatures arising acutely differ significantly from those observed after a 4-day recovery period. Importantly, the changes observed post-recovery are consistent with those modeled in vivo, and associate with alterations in transcripts encoding multiple homeobox genes directing neurogenesis. Unexpectedly, we do not observe a correlation between alcohol-induced changes in chromatin structure and alterations in transcription. Interestingly, the majority of epigenetic changes observed occur in marks associated with repressive chromatin structure, and we identify correlative disruptions in transcripts encoding Dnmt1, Eed, Ehmt2 (G9a), EzH2, Kdm1a, Kdm4c, Setdb1, Sod3, Tet1 and Uhrf1. These observations suggest that the immediate and long-term impacts of alcohol exposure on chromatin structure are distinct, and hint at the existence of a possible coordinated epigenetic response to ethanol during development. Collectively, our results indicate that alcohol-induced modifications to chromatin structure persist beyond the window of exposure, and likely contribute to the development of fetal alcohol syndrome-associated congenital abnormalities.


Multicultural identity and gay men in the era of AIDS.
In establishing integrated identities, gay men face psychosocial challenges that differ from those of most heterosexuals, although heterosexual males of minority cultures may confront similar developmental tasks. In the 1990s, the need for gay men to integrate bicultural identity and the "coming-out" process is further complicated by the stigma of AIDS. This paper aims to enhance clinicians' understanding of the multiple influences of culture and subculture, the AIDS epidemic, and racial and ethnic factors on the healthy development of gay males.


[Effect of bisoprolol, a beta 1-selective beta-blocker, on lipid and glucose metabolism and quality of life in elderly patients with essential hypertension].
The present study investigated the effect of bisoprolol, a beta 1-selective beta-blocker without intrinsic sympathomimetic activity (ISA), on lipid and glucose metabolism and quality of life (QOL) in elderly patients with essential hypertention. Bisoprolol at doses of 5-10 mg was administered once daily for 12 weeks to 60 non-elderly and 21 elderly outpatients with mild to moderate essential hypertension. In both groups bisoprolol significantly decreased both systolic and diastolic blood pressures and significantly reduced pulse rates to the same extent. The levels of serum cholesterol, HDL-cholesterol and triglyceride, and the response of plasma glucose and insulin to 75 g oral glucose load, were not changed in either group by the bisoprolol treatment. Bisoprolol significantly improved QOL in both groups. Bradycardia, a side effect attributable to bisoprolol, was noted in only one patient in the elderly group. These results suggest that bisoprolol is a safe and useful antihypertensive drug in elderly and non-elderly patients with essential hypertension.


Study on early intervention with ACE inhibitor in myocardical infarction and short term outcome.
The present study was carried out on 100 patients with acute myocardial infarction (AMI) being treated with angiotensin converting enzyme (ACE) inhibitor and another 80 patients with conventional treatment but without ACE inhibitor during the period from May 1, 1995 to August 7, 1996 in Medical College, Calcutta. Clinical and other laboratory investigations including echocardiographic parameters were noted and recorded meticulously within 24-48 hours after AMI and repeated at 4th week. The present study based on non-invasive methods other than haemodynamic methods has shown that the echocardiographic assessment of left ventricular functional parameters after 4 weeks of ACE inhibitor therapy (n = 100) were better in treated group in comparison to control group without ACE inhibitor (n = 80) and the difference was statistically significant at 99% level of confidence. Overall mortality was 4% in ACE inhibitor group and 8.75% in the control group. This short term study with early intervention with ACE inhibitor within 48 hours of AMI has shown statistically significant evidence of beneficial effect of ACE inhibitor in improving the ventricular functional parameters and also reducing short term mortality from cardiac cause within 4 weeks compared to the group not receiving ACE inhibitors.


Evidence in support of self-declaration as a sampling method for the formation of sub-population DNA databases.
Well constructed sub-population databases are fundamental to the application of DNA-based forensic statistics. The size of such databases can affect the ability to examine adequately statistical or population genetic features, and the integrity of both the DNA profile and associated ethnicity information is also of importance. Use of short tandem repeat (STR) DNA profiling technology and the thoughtful construction of the governing legislation has seen large databases of DNA profiles collated for the four major sub-populations of New Zealand. Examination of the data illustrates the suitability of self-declaration as a means of categorizing samples on the basis of ethnicity.


Effects of High-intensity Warm-ups on Running Performance.
The objective of this study was to determine the effects of high-intensity warm-ups (WUs) on performance, physiological, neuromuscular and biomechanical parameters. Three randomized cross-over 105%vVO2max time limit trials (TLimT) were performed by 11 well-trained runners following three different WU protocols. These included two experimental high-intensity variants and one control WU variant: (i) 9x20-sec level strides (105%vVO2max; 1% gradient) with 60 s of recovery (level); (ii) 6x6-sec uphill strides (105%vVO2max; 5% gradient), with the same recovery (uphill) and (iii) 7 min at 60%vVO2max as control condition (control). The uphill and level WUs resulted in a greater performance during TLimT (160.0±6.62 s and 152.64±10.88 s, respectively) compared to control WUs (144.82±6.60 s). All WU conditions reduced the energy cost (EC) of running, respiratory exchange ratio, and step frequency (SF) after the experimental and control phases of WU, while blood lactate (BLC) increased in uphill and level WUs and decreased in control WUs. Changes in kinematic variables were found without differences between WU conditions during TLimT. BLC rose at conclusion of TLimT without differences between WU conditions. Both high-intensity WUs show a longer TLimT. EC is deteriorated after the high-intensity WU exercise due to a change of substrate utilization, increase of BLC and SF. A long transient phase (18 min) is necessary to avoid impairing the performance.


Challenges and Considerations Related to Studying Dementia in Blacks/African Americans.
Blacks/African Americans have been reported to be ∼2-4 times more likely to develop clinical Alzheimer's disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses. Here we provide a selected historical background, discuss challenges, present opportunities, and suggest considerations for studying health outcomes among racial/ethnic groups. We encourage neuroscientists to consider shifting away from using biologic determination to interpret data, and work instead toward a paradigm of incorporating both biological and socio-environmental factors known to affect health outcomes with the goal of understanding and improving dementia treatments for Blacks/African Americans and other underserved populations.


Intra-arterial blood pressure monitoring in the neonate.
The advent of intra-arterial pressure monitoring has had a significant impact on the nursing care given in the neonatal intensive care unit. The nurse working in these units must become technically competent in monitoring techniques as well as clinically acute to physiologic measurements and their significance. These skills can be incorporated into planning and providing effective, individualized patient care. Continuous intra-arterial pressure monitoring is an invaluable clinical tool when caring for critically ill neonates. With care, an intra-arterial monitoring system can be easily prepared. This procedure requires minimal nursing time for care and maintenance and is a very safe procedure if appropriate nursing precautions are followed.


Structural Evolution of Metastable Protein Aggregates in the Presence of Trivalent Salt Studied by (V)SANS and SAXS.
We present a study of the structural evolution of protein aggregates formed in solutions of a globular protein, β-lactoglobulin (BLG), in the presence of YCl3. These aggregates are often observed before crystallization starts and they are metastable with respect to the crystalline phase. Here we focus on the characterization of the hierarchical structure of this intermediate phase and its temperature dependent structure evolution using a combination of (very) small angle neutron and X-ray scattering (VSANS, SANS, and SAXS). Results show that the hierarchical structure ranges from nanometer scale protein monomer, dimer and compact protein clusters to micrometer scale fractal protein aggregates. Upon cooling, the overall hierarchical structure is preserved, but the evolution of the internal structure within the aggregates is clearly visible: the monomer-monomer correlation peak reduces its intensity and disappears completely at lower temperatures, whereas the cluster-cluster correlation is enhanced. At a larger length scale, the fractal dimension of protein aggregates increases. The kinetics of the structure change during a temperature ramp was further investigated using time-resolved SAXS. The time dependent SAXS profiles show clear isosbestic points and the kinetics of the structural evolution can be well described using a two-state model. These dynamic properties of protein aggregates on a broad length scale may be essential for being the precursors of nucleation.


The Pharmacokinetics of Inhaled Drugs.
The pharmacokinetic (PK) profile of a drug after inhalation may differ quite markedly from that seen after dosing by other routes of administration. Drugs may be administered to the lung to elicit a local action or as a portal for systemic delivery of the drug to its site of action elsewhere in the body. Some knowledge of PK is important for both locally- and systemically-acting drugs. For a systemically-acting drug, the plasma concentration-time profile shares some similarities with drug given by the oral or intravenous routes, since the plasma concentrations (after the distribution phase) will be in equilibrium with concentrations at the site of action. For a locally-acting drug, however, the plasma concentrations reflect its fate after it has been absorbed and removed from the airways, and not what is available to its site of action in the lung. Consequently, those typical PK parameters which are determined from plasma concentration measurements, e.g., area under the curve (AUC), Cmax, tmax and post-peak t1/2 may provide information on the deposition and absorption of drugs from the lung; however, the information from these parameters becomes more complicated to decipher for those drugs which are locally-acting in the lung. Additionally, the plasma concentration profile for both locally- and systemically-acting drugs will not only reflect drug absorbed from the lung but also that absorbed from the gastrointestinal (GI) tract from the portion of the dose which is swallowed. This absorption from the GI tract adds a further complication to the interpretation of plasma concentrations, particularly for locally-acting drugs. The influence of physiological and pathological factors needs to be considered in the absorption of some inhaled drugs. The absorption of some hydrophilic drugs is influenced by the inspiratory maneuver used during initial inhalation of the drug, and at later times after deposition. Similarly, the effects of smoking have been shown to increase lung permeability and increase the absorption of certain hydrophilic drugs. The effects of different disease states of the lung have less defined influences on absorption into the systemic circulation.


Disparity of Gut Microbiota Composition Among Elite Athletes and Young Adults With Different Physical Activity Independent of Dietary Status: A Matching Study.
This study aimed to investigate the disparity of gut microbiota among elite athletes and young adults with different physical activity independent of dietary status. In Hangzhou, China, an age and sex matching study was conducted between April and May 2021. A total of 66 Chinese young adults were recruited in this study and divided into an elite athlete group, physically active group, and physically inactive group. Fecal samples were collected to assess gut microbiota composition. Dietary status was measured using a food-frequency questionnaire. Comparisons in gut microbiota and blood biomarkers among three groups were analyzed by using the analysis of covariance. The findings depicted a tendency to form clusters for beta diversity among three groups, while no significant difference was observed in both alpha and beta diversity. In the multiple analysis model, by adjusting dietary status, a significantly higher abundance of Clostridiaceae (p = 0.029) and Megamonas_rupellensis (p = 0.087) was observed in elite athletes compared to that in general young adults. Furthermore, inflammation-related bacteria such as Bilophila (p = 0.011) and Faecalicoccus (p = 0.050) were enriched in physically inactive young adults compared to two other groups. Pearson's correlation analysis showed a positive association between Bilophila and circulating white body cell count (r = 0.332, p = 0.006) and its subtypes including neutrophils (r = 0.273, p = 0.027), and lymphocytes (r = 0.327, p = 0.007). Megamonas_rupellensis has been shown associated positively with serum lymphocytes levels (r = 0.268, p = 0.03). Although no significant differences were observed, the elite athletes tended to have lower levels of blood biomarkers of immunity within a normal range, which may reflect a better immune function. This matching study indicated that physically inactive young adults are more likely to have a lower immune function and a higher abundance of pro-inflammatory gut bacteria than elite athletes and physically active young adults. Dietary status should be considered as an important factor that may affect the association of physical activity with immune function and gut microbiota.


Long-term clinical and radiological outcomes of endoscopic ultrasound-guided radiofrequency ablation of benign insulinomas.
In recent years, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as an alternative nonsurgical treatment for pancreatic neuroendocrine tumours. The aim of our study was to assess the long-term follow-up of patients treated with EUS-RFA for a sporadic insulinoma in our centre in terms of efficacy, safety and risk of recurrence. We retrospectively analysed the data of 11 patients with an insulinoma treated by EUS-RFA in our tertiary centre between June 2018 and April 2022. Clinical and biological, as well as imaging, follow-up was planned at 3, 6, 12 months and then annually. In our series, there were nine women and two men with a median age of 65 years. All tumours were sporadic, with a mean size of 11 mm. The procedure allowed an immediate and complete symptomatic and biological remission in all patients without notable complications. Complete radiological resolution of the tumour after ablation was observed in seven patients, and persistence of an asymptomatic tumour residue was observed in four patients. During the mean follow-up period of 26 months, two patients presented a significant but asymptomatic increase of the tumour residue; a second EUS-RFA session was performed in one patient and the other patient is being closely monitored. EUS-RFA treatment of benign insulinomas provides a long-term complete clinical resolution of hypoglycaemia. A long-term follow-up is essential if residual tumour persists after initial EUS-RFA treatment.


[Palliative care during chemotherapy for advanced colon cancers].
The median survival time following chemotherapy for unresectable metastatic colorectal cancer (mCRC) is approximately 2 years. Although palliative care during the chemotherapy period is very important, it has not been reported in detail. Information on the palliative care of 110 patients with Stage IV mCRC, who were treated from September 2007 to March 2011, was retrospectively examined. Following an explanation of their recurrence or metastases of mCRC, all the patients received mental care from nurses or psychiatrists. They also needed care to prevent the side effects of chemotherapy. Some patients experienced pain associated with tumor growth. Thus, they required NSAIDs or opioids to reduce the cancer-related pain. After they could not be taken chemotherapy, 87.5% of these patients consulted medical social workers to discuss where they would live. The patients required palliative care depending on the duration of chemotherapy for mCRC. Thus, we believe that palliative care is an important part of treatment for advanced cancer.


[Aorto-left ventricular tunnel with origin in the left sinus of Valsalva: a rare cause of congenital aortic insufficiency].
Aortico-left-ventricular tunnel is a rare congenital cardiac lesion that often results in severe aortic insufficiency in infancy. Normally, the defect appears immediately above the right coronary sinus of Valsalva and consists of a tunnel-like connection between the aortic root and the left ventricle. The differential diagnosis to coronary artery fistulae and ruptured aneurysms of the sinus of Valsalva is often difficult. We describe a patient with an aortico-left-ventricular tunnel originating from the left aortic sinus. Similar findings have been described in only three case reports. Additionally, in our case there was a stenosis in the midportion of the tunnel which was connected to an intraseptal aneurysm communicating with the left ventricular chamber via a "septal" defect. The infant underwent successful surgical correction of this malformation at 1 year and 5 months of age.


Future Directions in Peer Relations Research.
Peer relationships among youth have been examined as predictors of mental health outcomes for at least fifty years, revealing dozens of discrete peer constructs that each are associated with adjustment in childhood, adolescence, and later in adulthood. Future research may benefit by examining a range of new outcomes and psychological processes that have been discussed recently in related literatures. This paper reviews recent research on interpersonal determinants of physical health outcomes, and opportunities for greater examination of 1) peer influence processes toward health risk behaviors; 2) neural correlates of peer adversity; 3) adverse peer experiences that may affect physiological markers of stress response; and 4) immune system markers of peer adversity. Additional future directions include the study of differences in the forms and functions of peer interactions within the digital age.


Autoantibodies against glucose-regulated protein 78 as serological diagnostic biomarkers in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a type of cancer with a very poor prognosis. Although α-fetoprotein (AFP) is the most effective marker available to detect HCC, the sensitivity and specificity are not optimal. Therefore, there is a need for the development of more sensitive and specific methods that can supplement AFP in the early detection of this cancer. In this study, autoantibody responses to glucose-regulated protein 78 (GRP78) were evaluated by enzyme-linked immunosorbent assay (ELISA), western blotting and indirect immunofluorescence assay in sera from patients with HCC, liver cirrhosis (LC) and chronic hepatitis (CH), as well as from normal human individuals. Immunohistochemistry (IHC) with tissue array slides was also preformed to analyze protein expression profiles of GRP78 in HCC and control tissues. The prevalence of autoantibodies against GRP78 was 35.5% (27/76) in HCC, which was significantly higher than that in LC, CH and normal human sera (NHS; P<0.01). The average titer of autoantibodies against GRP78 in HCC sera was higher compared to that in LC, CH and NHS(P<0.01). When both autoantibodies against GRP78 and AFP were used simultaneously as diagnostic markers, sensitivity reached 71.4%. Our data indicate that anti-GRP78 autoantibodies may be potential diagnostic markers for HCC, especially in conjunction with AFP.


Mitochondria-Anchored Molecular Thermometer Quantitatively Monitoring Cellular Inflammations.
Temperature in mitochondria can be a critical indicator of cell metabolism. Given the highly dynamic and inhomogeneous nature of mitochondria, it remains a big challenge to quantitatively monitor the local temperature changes during different cellular processes. To implement this task, we extend our strategy on mitochondria-anchored thermometers from "on-off" probe Mito-TEM to a ratiometric probe Mito-TEM 2.0 based on the Förster resonance energy transfer mechanism. Mito-TEM 2.0 exhibits not only a sensitive response to temperature through the ratiometric changes of dual emissions but also the specific immobilization in mitochondria via covalent bonds. Both characters support accurate and reliable detection of local temperature for a long time, even in malfunctioning mitochondria. By applying Mito-TEM 2.0 in fluorescence ratiometric imaging of cells and zebrafishes, we make a breakthrough in the quantitative visualization of mitochondrial temperature rises in different inflammation states.


[Comparison of dorso-lateral and dorso-ventral stabilization procedures in the treatment of vertebral fractures].
The radiological and clinical outcome of surgical treated thoracolumbal fractures were followed up after 6.7 years. The study encompassed 97 patients. The degrees of the bony deformation and the local kyphosis were measured on the lateral view X-ray at 4 different time points: post trauma, after the operation, before implant removal and at the follow up examination. The clinical outcome was evaluated by the Oswestry score. 74 fractures were treated with a fixateur intern and a dorsal fusion by apposition of autologous bone postero-laterally. 23 fractures were fused in a combined dorso-ventral manner by intervertebral fusion with tricortical autologous bone. The lateral X-rays showed a loss of correction up to 48 % in the dorsal fused group and 10 % loss of correction in the combined group. The local kyphosis increased up to 84 % in the dorsal operated group due to degeneration of the injured disk. The clinical Oswestry score showed no significant difference in both groups. The additional ventral surgery should be evaluated carefully.


Pharmacodynamic effects of a novel prokinetic 5-HT receptor agonist, ATI-7505, in humans.
ATI-7505, an investigational 5-HT(4) receptor agonist, was designed to have similar activity as cisapride without the cardiac adverse effects, i.e. without QT prolongation. In addition, ATI-7505 is not metabolized by CYP450. The aim of the study was to assess the effect of ATI-7505 on gastrointestinal (GI) and colonic transit in healthy humans. A randomized, parallel-group, double-blind, placebo-controlled study evaluated effects of 9-day treatment with ATI-7505 (3, 10 or 20 mg t.i.d.) on scintigraphic GI and colonic transit in healthy volunteers (12 per group). Primary endpoints were gastric-emptying (GE) T(1/2), colonic geometric centre (GC) at 24 h and ascending colon (AC) emptying T(1/2). Daily stool diaries were kept. Analysis of covariance assessed overall treatment group differences, followed by post hoc unadjusted pairwise comparisons. There were borderline overall treatment effects (decrease) on GE T(1/2) (P = 0.154); the 20 mg t.i.d. of ATI-7505-accelerated GE vs placebo (P = 0.038). ATI-7505 increased colonic transit (GC24, P = 0.031) with fastest transit at 10 mg t.i.d. vs placebo (P = 0.065). ATI-7505 accelerated AC emptying T(1/2) (overall P = 0.075) with 10 mg dose vs placebo (P = 0.042). There was looser stool (Bristol stool form scale, overall P = 0.056) with the 10 and 20 mg t.i.d. doses. No safety issues were identified. ATI-7505 accelerates overall colonic transit and tends to accelerate GE and AC emptying and loosen stool consistency.


Candida glabrata sepsis associated with chorioamnionitis in an IVF twin pregnancy: Should we deliver?
We report a case of in vitro fertilization (IVF)-acquired Candida glabrata chorioamnionitis successfully treated through systemic maternal antifungal treatment prior to delivery. To the best of our knowledge, this is the first case of its kind in the literature. C. glabrata chorioamnionitis in pregnancy is rare, but the current literature suggests a very high fetal fatality in such cases. It is known to have an association with cervical stitch, amniocentesis, chorionic villous sampling, and assisted reproductive techniques such as IVF. Given the increasing global use of artificial reproductive techniques, it is important to raise awareness of this condition and highlight its potential complications. Early recognition of possible fetal infection could enable early initiation of systemic antifungal treatment. It would be prudent to consider early delivery once fetal maturity is achieved despite normal fetal monitoring.


Signal quality of home polygraphy in children and adolescents.
The aims of the study were to examine the signal quality (SQ) of home polygraphy (PG) in children and adolescents and to compare automatic and manual scoring of the PGs. Clinical Trials Registration: NCT04964830. Participants and caregivers were instructed to set up the equipment and perform home PGs themselves. The PGs were analysed according to SQ and their interpretability and differences in automatic vs. manual scoring regarding apnoea-hypopnoea index (AHI), apnoea index (AI), hypopnoea index (HI) and oxygen desaturation index (ODI) were examined. 54 healthy children aged 9-14 years participated in the study. 86% of the PGs were interpretable with mean SQ of 79.1% (CI 95%: 73.5%; 84.8%). Significant differences between the automatic and manual scoring were found for AHI, AI, HI and ODI (p < 0.0001). Home PGs of children and adolescents are feasible to be performed with good SQ. Significantly higher markers of sleep-disordered breathing were achieved in the automatic scoring in comparison with the manual scoring.


Aging with hemophilia: implications for social work practice.
Individuals with hemophilia and other congenital bleeding disorders are surviving beyond any life expectancy previously predicted and now face conditions associated with "normal" aging. Hemophilia along with co-morbid conditions of HIV and Hepatitis C complicate treatment for heart disease, cancer, kidney disease, and other age-related diseases. Lack of understanding of the condition, its treatment, and its costs hampers care, particularly when patients are treated outside of specialty clinics. This article provides an overview of bleeding disorders with a special focus on aging considerations. The role of social work in specialized hemophilia treatment centers is described and suggestions made to other social workers who may encounter this population in their practice. Finally, the need for policy and advocacy strategies is also addressed.


Community-based organizations' perspective on health information outreach: a panel discussion.
A panel was convened to elicit guidance for librarians in initiating and implementing community-based health information outreach. Participants included a panel of individuals from communities or community organizations who represented the types of groups with which librarians or information specialists need to interact and an audience who represented health sciences libraries, public libraries, academic institutions, government agencies, funding agencies, and community-based organizations and could contribute to a discussion on community-based health information outreach. The panel was presented with a hypothetical community setting and asked to respond to a series of questions: What do librarians need to learn about the community before they make their visits? What methods of outreach have been successful in your work? How would you implement and sustain a health information program in your community? How would health information interventions reduce racial and ethnic disparities in health? The panel helped to frame many of the issues that may confront librarians as they initiate information-related programs in communities. There is clear consensus on the need for librarians to make the effort to reach out into the community, to make the contacts, to seek to understand the community, to talk with leaders, and to respect the community as they promote and teach the use of health information resources. It was confirmed that librarians and libraries have an important role in diminishing health disparities by improving access to health information.


Regioselective aromatic C-H silylation of five-membered heteroarenes with fluorodisilanes catalyzed by iridium(I) complexes.
The aromatic C-H silylation of five-membered heteroarenes with 1,2-di-tert-butyl-1,1,2,2-tetrafluorodisilane regioselectively proceeded at 120 degrees C in octane in the presence of a catalytic amount of iridium(I) complexes generated from 1/2[Ir(OMe)(COD)]2 and 2-tert-butyl-1,10-phenanthroline.


Effect of immunological castration management strategy on lipid oxidation and sensory characteristics of bacon stored under simulated food service conditions.
The objectives of this study were to determine the effect of 1) immunological castration (Improvest, a gonadotropin releasing factor analog-diphtheria toxoid conjugate) management strategy (age at slaughter and time of slaughter after second dose) and 2) sex on lipid oxidation and sensory characteristics of bacon stored under simulated food service conditions. For Objective 1, immunological castration management strategies included 24-wk-old immunologically castrated (IC) barrows 4, 6, 8, or 10 wk after the second Improvest dose (ASD); 26-wk-old IC barrows 6 wk ASD; and 28-wk-old IC barrows 8 wk ASD ( = 63). Objective 2 ( = 97) included IC barrows, physically castrated (PC) barrows, and gilts slaughtered at 24, 26, and 28 wks of age. Bellies from 2 slaughter dates were manufactured into bacon under commercial conditions. Bacon slices were laid out on parchment paper, packaged in oxygen-permeable poly-vinyl-lined boxes, and frozen (-33°C) for 1, 4, 8, or 12 wk to simulate food service conditions. At the end of each storage period, bacon was evaluated for lipid oxidation, moisture and lipid content, and sensory characteristics. Data from both objectives were analyzed using the MIXED procedure in SAS with belly as the experimental unit. For both objectives, as storage time increased, lipid oxidation of bacon increased ( < 0.01), regardless of management strategy or sex. Also, there was no sex or management strategy × week of frozen storage interaction for any traits evaluated ( ≥ 0.25). For Objective 1, lipid content of bacon from IC barrows increased as time of slaughter ASD increased ( < 0.05), regardless of age at slaughter. Additionally, there were no differences in sensory attributes of bacon across management strategies. For the evaluation of sex effects in Objective 2, lipid oxidation was greater ( < 0.05) in IC barrows compared with PC barrows but was not different than gilts ( > 0.05). After 12 wk of frozen storage, lipid oxidation values for IC barrows, PC barrows, and gilts were still below 0.5 mg malondialdehyde/kg of meat, the threshold at which trained panelists may deem a food to be rancid. In conclusion, bacon shelf life characteristics were not altered by the immunological castration management strategy and bacon from IC barrows was similar to bacon from gilts. Therefore, bacon from IC barrows would result in shelf life and sensory quality similar to PC barrows and gilts.


Employment Status and Participation in Cardiac Rehabilitation: DOES ENCOURAGING EARLIER ENROLLMENT IMPROVE ATTENDANCE?
For patients hospitalized for a cardiac event, an earlier appointment to outpatient cardiac rehabilitation (CR) increases participation. However, it is unknown what effect hastening CR enrollment might have among employed patients planning to return to work (RTW). Using 2 complementary data sets from Henry Ford Hospital (HFH) and Mayo Clinic, we assessed when employed patients eligible for CR anticipated a RTW, the impact of an earlier appointment on CR enrollment, and the effect of employment status on the number of CR sessions attended. Patients at HFH attended CR at either 8 or 42 days (through randomization), whereas Mayo Clinic patients attended 10 days after hospital discharge per standard routines. Among 148 patients at HFH, 65 (44%) were employed and planned to RTW. Of these, 67% desired to RTW within 1 to 2 weeks, whereas 28% anticipated an RTW within 1 to 3 days. Home financial strain predicted nonparticipation in CR (P < .001) and was associated with an earlier planned RTW. Among 1030 patients at Mayo Clinic, 393 (38%) were employed. Employed (vs nonemployed) patients enrolled in CR 3.3 days sooner (P < .001), but attended 1.6 fewer CR sessions (P = .04). In employed patients from both health systems, an earlier (vs later) appointment to CR did not result in additional exercise sessions of CR. Employed patients plan to RTW quickly, in part because of home finances. They also enroll earlier into CR than nonemployed patients. Despite these findings, earlier appointments do not seem to favorably impact overall CR participation.


In order to lower the antinutritional activity of serine protease inhibitors, we need to understand their role in seed development.
Proteases, including serine proteases, are involved in the entire life cycle of plants. Proteases are controlled by protease inhibitors (PI) to limit any uncontrolled or harmful protease activity. The role of PIs in biotic and abiotic stress tolerance is well documented, however their role in various other plant processes has not been fully elucidated. Seed development is one such area that lack detailed work on the function of PIs despite the fact that this is a key process in the life cycle of the plant. Serine protease inhibitors (SPI) such as the Bowman-Birk inhibitors and Kunitz-type inhibitors, are abundant in legume seeds and act as antinutrients in humans and animals. Their role in seed development is not fully understood and present an interesting research target. Whether lowering the levels and activity of PIs, in order to lower the anti-nutrient levels in seed will affect the development of viable seed, remains an important question. Studies on the function of SPI in seed development are therefore required. In this Perspective paper, we provide an overview on the current knowledge of seed storage proteins, their degradation as well as on the serine protease-SPI system in seeds and what is known about the consequences when this system is modified. We discuss areas that require investigation. This includes the identification of seed specific SPIs; screening of germplasms, to identify plants with low seed inhibitor content, establishing serine protease-SPI ratios and lastly a focus on molecular techniques that can be used to modify seed SPI activity.


Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility.
The ovulatory process is tightly regulated by endocrine as well as paracrine factors. In the periovulatory period, extensive remodeling of the follicle wall occurs to allow the extrusion of the oocyte and accompanying cumulus granulosa cells. Growth differentiation factor-9 (GDF-9) and bone morphogenetic protein-15 (BMP-15) are secreted members of the TGFbeta superfamily that are expressed beginning in the oocyte of small primary follicles and through ovulation. Besides its critical role as a growth and differentiation factor during early folliculogenesis, GDF-9 also acts as a paracrine factor to regulate several key events in preovulatory follicles. By analyzing GDF-9-regulated expression profiles using gene chip technology, we identified TNF-induced protein 6 (Tnfip6) and pentraxin 3 (Ptx3 or PTX3) as novel factors induced by GDF-9 in granulosa cells of preovulatory follicles. Whereas Tnfip6 is induced in all granulosa cells by the LH surge, Ptx3 expression in the ovary is specifically observed after the LH surge in the cumulus granulosa cells adjacent to the oocyte. PTX3 is a member of the pentraxin family of secreted proteins, induced in several tissues by inflammatory signals. To define PTX3 function during ovulation, we generated knockout mice lacking the Ptx3 gene. Homozygous null (Ptx3(-/-)) mice develop normally and do not show any gross abnormalities. Whereas Ptx3(-/-) males are fertile, Ptx3(-/-) females are subfertile due to defects in the integrity of the cumulus cell-oocyte complex that are reminiscent of Bmp15(-/-)Gdf9(+/-) double mutant and BMP type IB receptor mutant mice. These studies demonstrate that PTX3 plays important roles in cumulus cell-oocyte interaction in the periovulatory period as a downstream protein in the GDF-9 signal transduction cascade.


Modelling and Optimization of Polycaprolactone Ultrafine-Fibres Electrospinning Process Using Response Surface Methodology.
Electrospun fibres have gained broad interest in biomedical applications, including tissue engineering scaffolds, due to their potential in mimicking extracellular matrix and producing structures favourable for cell and tissue growth. The development of scaffolds often involves multivariate production parameters and multiple output characteristics to define product quality. In this study on electrospinning of polycaprolactone (PCL), response surface methodology (RSM) was applied to investigate the determining parameters and find optimal settings to achieve the desired properties of fibrous scaffold for acetabular labrum implant. The results showed that solution concentration influenced fibre diameter, while elastic modulus was determined by solution concentration, flow rate, temperature, collector rotation speed, and interaction between concentration and temperature. Relationships between these variables and outputs were modelled, followed by an optimization procedure. Using the optimized setting (solution concentration of 10% w/v, flow rate of 4.5 mL/h, temperature of 45 °C, and collector rotation speed of 1500 RPM), a target elastic modulus of 25 MPa could be achieved at a minimum possible fibre diameter (1.39 ± 0.20 µm). This work demonstrated that multivariate factors of production parameters and multiple responses can be investigated, modelled, and optimized using RSM.


Co-infection of hepatitis B and hepatitis C virus in human immunodeficiency virus-infected patients in New York City, United States.
To study the prevalence and risk factors associated with triple infection with human immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) in an urban clinic population. Retrospective chart review of 5639 patients followed at St. Luke's-Roosevelt Hospital HIV Clinic (Center for Comprehensive Care) in New York City, USA from January 1999 to May 2007. The following demographic characteristics were analyzed: age, sex, race and HIV risk factors. A multiple logistic regression analysis was performed to evaluate the influence of demographic factors on acquisition of these viruses. HIV/HBV, HIV/HCV and HIV/HBV/HCV infections were detected in 252/5639 (4.47%), 1411/5639 (25.02%) and 89/5639 (1.58%) patients, respectively. HIV/HBV co-infections were associated with male gender (OR 1.711; P = 0.005), black race (OR 2.091; P < 0.001), men having sex with men (MSM) (OR 1.747; P = 0.001), intravenous drug use (IDU) (OR 0.114; P < 0.001), IDU and heterosexual activity (OR 0.247; P = 0.018), or unknown (OR 1.984; P = 0.004). HIV/HCV co-infections were associated with male gender (OR 1.241; P = 0.011), black race (OR 0.788; P = 0.036), MSM (OR 0.565; P < 0.001), IDU (OR 8.956; P < 0.001), IDU and heterosexual activity (OR 9.106; P < 0.001), IDU and MSM (OR 9.179; P < 0.001), or transfusion (OR 3.224; P < 0.001). HIV/HBV/HCV co-infections were associated with male gender (OR 2.156; P = 0.015), IDU (OR 6.345; P < 0.001), IDU and heterosexual activity (OR 9.731; P < 0.001), IDU and MSM (OR 9.228; P < 0.001), or unknown (OR 4.219; P = 0.007). Our study demonstrates that co-infection with HBV/HCV/HIV is significantly associated with IDU. These results highlight the need to intensify education and optimal models of integrated care, particularly for populations with IDU, to reduce the risk of viral transmission.


Bimanual tactual discrimination in aging alcoholics.
Somesthesis and perceptual laterality were studied in normal aging and in aging alcoholic populations. The bimanual (dichhaptic) stimulation technique that was employed required participants to recognize and identify items traced onto the palms of both hands simultaneously, thereby eliciting competition for analysis by the two cerebral hemispheres. Performance of five groups of participants was compared (younger and older alcoholics and age-matched normal controls, and alcoholic Korsakoff patients); within each of the groups, the ability to identify verbal stimuli (letters) was compared with nonverbal stimuli (lines differing in orientation) for the right and the left hands separately. The results suggest that tactile discrimination accuracy for nonverbal information is disrupted by aging, but that alcoholism per se does not have this effect. The combined effects of alcohol abuse and aging were seen only on the tactual tasks that required identification of verbal items. Lateralization measures based upon performance by the two hands separately did not differentiate among the groups.


Role of the microRNA-29 family in fibrotic skin diseases.
Fibrotic skin diseases are characterized by the accumulation of collagen. The hallmarks of fibrotic skin diseases are unbalanced fibroblast proliferation and differentiation, extracellular matrix production and transforming growth factor-β signalling. Numerous studies have investigated the possibility that microRNAs (miRNAs or miRs) are involved in the pathogenesis of certain fibrotic diseases, including skin, heart, lung and liver diseases. miRNAs are a class of small non-coding RNAs, which modify gene expression by binding to target messenger RNA (mRNA) and blocking the translation or inducing the degradation of target mRNA. The biological relevance of miRNAs has been investigated in physiological and pathological conditions, and there is increasing evidence that the miR-29 family is associated with fibrotic diseases. The aim of the present review is to provide an up-to-date summary of current knowledge on the latest developments associated with the miR-29 family and fibrotic skin diseases.


A Novel Intuitively Controlled Articulating Instrument for Reoperative Foregut Surgery: A Case Report.
The field of laparoscopic surgery has continued to grow exponentially over the years, prompting new innovative technologies. Despite substantial advancements, standard laparoscopic tools have undergone little design changes and fail to optimize mobility in limited spaces. Advancements in robotics have attempted to address this, allowing for increasing degrees of freedom and articulation of instruments. Even so, this system has proven to be cumbersome with questionable cost-effectiveness. In this study, we present the first use of a solely mechanical intuitively controlled articulating laparoscopic needle driver. The ability to naturally articulate allowed for ease during suturing and knot tying during the critical portions of the operation. The FlexDex surgical instrument demonstrates promise in the field of foregut surgery in addition to other areas of minimally invasive specialties.


[OPTIMIZATION OF DIAGNOSTICS OF EXUDATIVE PLEURITIS OF UNKNOWN ORIGIN].
The article describes 143 cases of exudative pleuritis of unknown origin in patients who were diagnosed and treated with any minimally invasive surgical procedures: pleural puncture (PP), video-assisted thoracoscopy (VATS) with biopsy of the pleura. A different diagnostic methods (cytological, microbiological, histological) used in various diagnostic surgical procedures are analyzed in detail and calculated diagnostic sensitivity, specificity, and accuracy of each method. Based on the analysis of cytological, histological and microbiological studies in the performance of VATS concluded relatively high, comparable with the method of open pleural biopsy, diagnostic efficiency, the sensitivity of this method in the scheme of the diagnostic algorithm of EP of unknown origin.


Impact of Oxycodone HCl Extended-release Formulary Restrictions on Extended-release Opioid Market Share, Healthcare Resource Utilization and Costs in Commercial and Medicare Plans.
Background: Previous research demonstrated that utilization management (UM) such as prior authorization (PA) or non-formulary (NF) restrictions may reduce pharmacy costs when designed and applied appropriately to certain drug classes. However, such access barriers may also have unintended consequences. Few studies systemically analyzed the impact of major UM strategies to extended-release (ER) opioids on different types of health plans. Objective: This study evaluated, from payer perspective, the impact of formulary restrictions (PA, NF, or step therapy [ST]) for branded oxycodone HCl extended release (OER) on market share, and healthcare resource utilization/costs in ER opioids patients for multiple types of health plans in the United States. Methods: This retrospective, longitudinal case-control study analyzed prescription and outpatient medical claims data (2012 to 2015) for adult ER opioid patients from US plans (commercial,/Medicare, national/regional) that instituted OER PA, NF, or ST. Patients from each restricted plan (cases) were matched to patients in an unrestricted plan (controls) on key patient characteristics. ER opioid market share and healthcare resource utilization/costs for both cases and controls were evaluated for the 6-month period before and after the formulary restriction dates. A difference-in-differences (DiD) approach was utilized to evaluate change in the total per patient per month (PPPM) healthcare utilization and costs. Results: The study comprised 1622 (national commercial PA), 2020 (regional commercial PA), 34 703 (national commercial ST), and 4372 (national Medicare NF) cases and equivalent number of controls. OER market share decreased after the formulary restrictions, with the national Medicare NF plan showing the greatest decrease (9.2%). DiD analyses indicated that PPPM office visit change in the PA and NF plans were non-significant (decreased by 0.1 and 0.2, P>0.05), but significant in the ST plan (increased by 0.1, P=0.0001). For most plans, no significant total monthly cost change was observed; PPPM costs decreased by $48.74 and $59.87 in ST and regional PA plans and increased by $37.90 in national NF plans (all P>0.05). Conclusions: This study observed that despite reducing the market share of OER, OER formulary restrictions had negligible impact on overall ER opioid utilization, and did not result in substantial pharmacy/medical cost savings.


mRNA Expression Profile of SFKs and Involvement of SFKs in the Regulation of LPS-Induced Erk1/2 Signaling in PBMCs of Active BD Patients.
Behcet's Disease (BD) is a multisystemic inflammatory disorder affecting large vessels, lungs joints, gastrointestinal and neurological systems. The pathogenesis of BD remains poorly understood. Identifying the key signaling pathway is crucial for a complete understanding of the pathogenesis of BD. The aim of this study was to determine mRNA expression level of Src family kinases (SFKs) members and their involvement in lipopolysaccharide (LPS)-induced mitogen-activated protein kinases (MAPKs) regulation in peripheral blood mononuclear cells (PBMCs) of active BD patients. Twenty- five active BD patients and twenty-five healthy controls were included in the study. PBMCs were isolated from total blood by density gradient centrifugation. The mRNA expression levels of SFKs members were measured by real-time quantitative PCR (RT-qPCR). The effect of SFKs activity on LPS-induced activation MAPKs (Erk1/2, p38 and JNK) was examined by Western blot. The mRNA expression levels of Hck, Src, Lyn, Yes and Fyn were found to be slightly decreased in active BD patients compared to the control subjects, but a slight change in mRNA level of SFKs members did not impact on protein levels and protein activity. LPS-induced Erk1/2 phosphorylation was significantly increased in the absence of SFKs activity in active BD patients. However, inhibition of SFKs activity had no effect on LPS-induced phosphorylation of p38 and JNK in both controls and active BD patients. SFKs downregulate LPS-induced Erk1/2 phosphorylation in PBMCs of active BD patients.


Impact of Walking Cadence Prescription to Reach the Global Physical Activity Recommendations in Older Adults.
Walking cadence is a new monitoring strategy used to increase bouts of time at moderate intensity. Inactive older adults were instructed to walk 150 min per week at no specified intensity during phase one. In phase two, the intervention group (N = 23) received instructions on how to reach moderate intensity, using a pedometer and an individualized walking cadence, while the control group (N = 22) did not. The main outcomes were time at moderate intensity and moderate intensity in 10-min bouts. During phase two only the intervention group increased time at moderate intensity and moderate intensity in 10-min bouts compared with phase one and compared with the control group (p ≤ .01). Older adults can increase time walked at moderate intensity in 10-min bouts weekly by using individually prescribed walking cadence, a pedometer to track intensity, and practicing walking at this cadence.


Menthol facilitates the skin analgesic effect of tetracaine gel.
The aim of this study is to observe the effect of menthol on the percutaneous penetration and skin analgesic action of tetracaine gel (T-gel). Anesthetic gels containing 4% tetracaine in carbomer vehicle with and without menthol were prepared. The menthol penetration-enhanced gel conferred significantly higher diffusion of tetracaine across full-thickness mouse skin than non-penetration-enhanced gel, in a dose-dependent manner. The inter-cellular spaces of the stratum corneum in skin treated with menthol penetration-enhanced gel became extended as compared with those in non-penetration-enhanced gel. This may suggest that menthol's action was related to the changes of the epidermis ultra structures. An enlarged inter-cellular space, per se, would allow a better passage to tetracaine. To determine the efficacy of menthol penetration-enhanced tetracaine gel in the management of pain, a double-blind, placebo-controlled, randomized controlled trial (RCT) design was used. The mean verbal pain scores (VPS) were significantly lower in volunteers treated with penetration-enhanced tetracaine gel than those in volunteers receiving non-penetration-enhanced tetracaine gel or placebo. Menthol improved the analgesic efficacy of the tetracaine 4% gel in part through enhanced percutaneous permeation.


Comparison of avian and human influenza A viruses reveals a mutational bias on the viral genomes.
In the last few years, the genomic sequence data for thousands of influenza A virus strains, including the 1918 pandemic strain, and hundreds of isolates of the avian influenza virus H5N1, which is causing an increasing number of human fatalities, have become publicly available. This large quantity of sequence data allows us to do comparative genomics with the human and avian versions of the virus. We find that the nucleotide compositions of influenza A viruses infecting the two hosts are sufficiently different that we can determine the host at almost 100% accuracy. This assignment works at the segment level, which allows us to construct the reassortment history of individual segments within each strain. We suggest that the different nucleotide compositions can be explained by a host-dependent mutation bias. To support this idea, we estimate the fixation rates for the different polymerase segments and the ratios of synonymous to nonsynonymous changes. Additionally, we provide evidence supporting the hypothesis that the H1N1 influenza virus entered the human population just prior to the 1918 outbreak, with an earliest bound of 1910.


[Risk factors for unfavorable birth weight in areas surrounding Guadalajara, Mexico].
This study seeks to identify the incidence of unfavorable birth weight (UBW) -< 3000 grams, the factors associated with this condition, and the probability that a child has an UBW in the presence or absence of identified risk factors, in Tlaquepaque and Tonal , outlying areas of Greater Metropolitan Guadalajara, Mexico. A sample of live-born infants in 1991, children of mothers covered by the Mexican Institute of Social Security were selected from the study area; through multistage probabilistic sampling, random selection was made of Family Medical Units within the study areas, and of physicians' offices within those selected units; finally, all the liveborn infants in 1991 from these selected physicians' offices were studied: a total of 141 newborns were studied Mothers of the newborns chosen were interviewed; a questionnaire with different biomedical, socioeconomic, and demographic items was applied by social workers specially trained for the purpose. Logistic regression models were used lo estimate odds ratios (OR), with 95% confidence intervals (CI). The probability that a child would have UBW in the presence or absence of identified risk factors were also calculated. The results show that 22% of the infants studied were born weighing less than 3000 grams; four risk factors were statistically associated with UBW: mother's age of 35 or older (OR=18.47, CL 1.86-83.54); mother worked outside the home (OR= 3.14, C1:1.15-8.59); mother's pre-pregnancy low weight (OR= 5.04, CL1.04-24.47); and late detection of pregnancy (OR=2.64, CI: 1.02-6.84). In the presence of all the risk factors identified, there is a very high probability (0.97) that a child be born with birthweight less than 3000 g, and in the absence of these factors the probability is reduced substantially (0.04). The findings indicate the magnitude of the problem studied, but also the possibility of health services acting in a timely fashion, since the identified risk factors make it possible lo predict, with relative certainty, the birth of a child weighing less than 3000 g.


DnaJ/hsp40 chaperone domain of SV40 large T antigen promotes efficient viral DNA replication.
The amino-terminal domain of SV40 large tumor antigen (TAg) is required for efficient viral DNA replication. However, the biochemical activity associated with this domain has remained obscure. We show here that the amino-terminal domain of TAg shares functional homology with the J-domain of DnaJ/hsp40 molecular chaperones. DnaJ proteins function as cofactors by regulating the activity of a member of the 70-kD heat shock protein family. Genetic analyses demonstrated that amino-terminal sequences of TAg comprise a novel J-domain that mediates a specific interaction with the constitutively expressed hsc70 and show that the J-domain is also required for efficient viral DNA replication in vivo. Furthermore, we demonstrated that the J-domain of two human DnaJ homologs, HSJ1 or DNAJ2, could substitute functionally for the amino-terminus of TAg in promoting viral DNA replication. Together, our findings suggest that TAg uses its J-domain to support SV40 DNA replication in a manner that is strikingly similar to the use of Escherichia coli DnaJ by bacteriophage lambda in DNA replication. However, TAg has evolved a more efficient strategy of DNA replication through an intrinsic J-domain to associate directly with a partner chaperone protein. Our observations provide evidence of a role for chaperone proteins in the process of eukaryotic DNA replication.


Roles of prostanoids in the pathogenesis of cardiovascular diseases.
The roles of prostanoids in the pathogenesis of cardiovascular diseases and in the development of pathological conditions have been examined using mice lacking the individual, specific prostanoid receptor. Prostaglandin (PG) I2 protected the heart from ischemia-reperfusion injury in a model of acute myocardial infarction. In addition, PGI2 suppressed the development of pressure overload-induced cardiac hypertrophy. Aside from its potent vasodilatory action, PGI2 contributed critically to the development of renovascular hypertension via the activation of the renin-angiotensin-aldosterone system. Thromboxane (TX) A2 and PGF2alpha were found to be the mediators of inflammatory tachycardia under a systemic inflammatory condition induced by lipopolysaccharide. Under a septic condition leading to a vascular hypo-responsive state, TXA2 worked to maintain vascular tone by inhibiting the induction of inducible nitric oxide synthase in vascular smooth muscle cells. Mice lacking the PGE2 receptor subtype EP3 had a bleeding tendency and were resistant to thromboembolism, due to a defective activation of platelets. From these studies, the important and novel roles of prostanoids in the pathogenesis of cardiovascular diseases have been clarified.


Heterogeneity in cervical spine assessment in paediatric trauma: A survey of physicians' knowledge and application at a paediatric major trauma centre.
Evidence-based decision-making tools are widely used to guide cervical spine assessment in adult trauma patients. Similar tools validated for use in injured children are lacking. A paediatric-specific approach is appropriate given important differences in cervical spine anatomy, mechanism of spinal injury and concerns over ionising radiation in children. The present study aims to survey physicians' knowledge and application of cervical spine assessment in injured children. A cross-sectional survey of physicians actively engaged in trauma care within a paediatric trauma centre was undertaken. Participation was voluntary and responses de-idenitified. The survey comprised 20 questions regarding initial assessment, imaging, immobilisation and perioperative management. Physicians' responses were compared with available current evidence. Sixty-seven physicians (28% registrars, 17% fellows and 55.2% consultants) participated. Physicians rated altered mental state, intoxication and distracting injury as the most important contraindications to cervical spine clearance in children. Fifty-four per cent considered adequate plain imaging to be 3-view cervical spine radiographs (anterior-posterior, lateral and odontoid), whereas 30% considered CT the most sensitive modality for detecting unstable cervical spine injuries. Physicians' responses reflected marked heterogeneity regarding semi-rigid cervical collars and what constitutes cervical spine 'clearance'. Greater consensus existed for perioperative precautions in this setting. Physicians actively engaged in paediatric trauma care demonstrate marked heterogeneity in their knowledge and application of cervical spine assessment. This is compounded by a lack of paediatric-specific evidence and definitions, involvement of multiple specialties and staff turnover within busy departments. A validated decision-making tool for cervical spine assessment will represent an important advance in paediatric trauma.


Applications of monolithic columns in gas chromatography and supercritical fluid chromatography.
Porous monoliths are well-known stationary phases in high-performance liquid chromatography and capillary electrochromatography. Contrastingly, their use in other types of separation methods such as gas or supercritical fluid chromatography is limited and scarce. In particular, very few studies address the use of monolithic columns in supercritical fluid chromatography. These are limited to silica-based monoliths and will be covered in this review together with an underlying reason for this trend. The application of monoliths in gas chromatography has received much more attention and is well documented in two reviews by Svec and Kurganov published in 2008 and 2013, respectively. The most recent studies, covered in this review, build on the previous findings and on further understanding of the influence of preparation conditions on porous properties and chromatographic performance of poly(styrene-co-divinylbenzene), polymethacrylate, and silica-based monolithic columns while expanding to polymer-based monoliths with incorporated metal organic frameworks and to vinylized hybrid silica monoliths. In addition, the potential application of porous layer open tubular monolithic columns in low-pressure gas chromatography will be addressed.


In Situ Monitoring of Dynamic Photocatalysis of Metal-Organic Frameworks by Three-Dimensional Shell-Isolated Nanoparticle-Enhanced Raman Spectroscopy.
Metal-organic frameworks (MOFs) are promising as novel disinfectants due to the reactive oxygen species (ROS) produced in their photocatalytic processes. The optimal MOF is screened as the best disinfectant, representing high-efficacy production of ROS under photocatalytic conditions. However, current methods to screen abundant MOFs for disinfectant application are generally semiquantitative or ex situ methods [such as electron paramagnetic resonance (EPR) measurements], so achieving a strategy that can quantitatively screen an optimal MOF in situ and is reliable is demanded. Herein, we developed a three-dimensional (3D) shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) platform to study the dynamic photocatalytic processes of various MOFs (e.g., ZIF-67, ZIF-8, and UIO-66) in situ. This platform comprises silica shell-isolated gold nanoparticles (AuNPs) modified on silicon nanowire arrays (SiNWArs). The MOF is then self-assembled on the 3D-SHINERS substrate. Using this platform, we recorded dynamic spectroscopic evidence of ROS formation by various MOFs under sunlight irradiation. By dynamic comparison, ZIF-67 has the most robust photocatalytic efficiency, ∼1.7-fold stronger than that of ZIF-8 and ∼42.6-fold stronger than that of UIO-66. As expected, ZIF-67 displays the best antibacterial ability, up to 99% in the agar plate assay. This work provides a versatile platform for dynamically monitoring photocatalytic performance and screening antibacterial MOFs.


An improved toolbox to unravel the plant cellular machinery by tandem affinity purification of Arabidopsis protein complexes.
Tandem affinity purification coupled to mass spectrometry (TAP-MS) is one of the most advanced methods to characterize protein complexes in plants, giving a comprehensive view on the protein-protein interactions (PPIs) of a certain protein of interest (bait). The bait protein is fused to a double affinity tag, which consists of a protein G tag and a streptavidin-binding peptide separated by a very specific protease cleavage site, allowing highly specific protein complex isolation under near-physiological conditions. Implementation of this optimized TAP tag, combined with ultrasensitive MS, means that these experiments can be performed on small amounts (25 mg of total protein) of protein extracts from Arabidopsis cell suspension cultures. It is also possible to use this approach to isolate low abundant protein complexes from Arabidopsis seedlings, thus opening perspectives for the exploration of protein complexes in a plant developmental context. Next to protocols for efficient biomass generation of seedlings (∼7.5 months), we provide detailed protocols for TAP (1 d), and for sample preparation and liquid chromatography-tandem MS (LC-MS/MS; ∼5 d), either from Arabidopsis seedlings or from cell cultures. For the identification of specific co-purifying proteins, we use an extended protein database and filter against a list of nonspecific proteins on the basis of the occurrence of a co-purified protein among 543 TAP experiments. The value of the provided protocols is illustrated through numerous applications described in recent literature.


Desimplification of Single Tablet Antiretroviral (ART) Regimens-A Practical Cost-Savings Strategy?
The use of lifelong antiretroviral therapy (ART) results in increased costs of care; the ability to finance and control sustained costs of ART needs to be discussed. The Southern Alberta Clinic initiated a practical cost savings approach that switched select patients from a branded ART to a less expensive generic variation. Our approach surveyed physicians and patients on their acceptance of switching and then launched a program asking patients if they would switch to generic variations for cost control purposes. Our early findings found >50% of patients approached agreed to switch. We found no evidence of increased risk of viral breakthrough, resistance, side effects, or displeasure with generic drugs. Measured cost savings in the first year were >$1.1 million with annual projected savings of between $4.3 million and $2.6 million (in 2017 Cdn$). Our approach can provide an option for controlling costs of HIV care without compromising quality.


[Adrenal hypoplasia congenita: four new cases in children].
Adrenal hypoplasia congenita (AHC) is an extremely uncommon disease of early onset. This condition can be lethal in the absence of adapted treatment. Some of these diseases are related to changes in the gene DAX1 that encodes a member of the superfamily of hormone nuclear receptors. It is a transcriptional repressor that is central in the morphogenesis of the adrenals and the gonadic differentiation. Here we report on four cases of X- linked AHC. In the first two familial cases, mutations were identified and mothers were heterozygotes. Abnormally low levels of estriol were evidenced during the pregnancy leading to an early diagnosis and adapted care of the affected male neonates. These children are doing well with a 21-and 20 months follow-up with hormone replacement at the present time. The two last cases corresponded to a contiguous gene syndrome associating AHC to glycerol-kinase deficiency that was revealed respectively at six days and seven years of age by acute adrenal insufficiency.


Isolation and characterization of 19 highly polymorphic microsatellite markers in the devil stinger, Inimicus japonicus (Synanceiidae).
Inimicus japonicus, the devil stinger, has an extensive distribution along the coast of China, Japan and the Korean Peninsula. Nineteen highly polymorphic microsatellite markers were isolated and characterized in I. japonicus. Twenty-eight individuals from a wild population were tested for polymorphism using this set of polymorphic microsatellite markers. The number of alleles per locus ranged from 4 to 14. The ranges of observed and expected heterozygosity were 0.500-0.892 and 0.521-0.910, respectively. Significant deviations from Hardy-Weinberg equilibrium were detected at two loci. To the best of our knowledge, these were the first microsatellite loci characterized from the Synanceiidae; they can be used for estimating genetic diversity, population structure studies, parentage analysis, genetic linkage map construction, germplasm classification and identification, gene identification, quantitative trait loci mapping, and marker-assisted selection in breeding of I. japonicus and other species of this family.


National Cancer Control Programme in India: Proposal for Organization of Chemotherapy and Systemic Therapy Services.
Cancer is a major health problem in India, with an estimated incidence of 1 million cases in 2012 that is likely to double in 2035 to approximately 1.7 million. The majority of cases are diagnosed in advanced stages, and approximately two thirds of patients die as a result of their disease. The mortality-to-incidence ratio is 0.68 in India, which is far higher than that in developed countries (approximately 0.38). One of the important reasons for this discrepancy is inequitable distribution and inaccessibility of health care resources in India. One component of scarce health care resources is the low ratio of oncologists to patients with cancer (1:2,000), which leads to delivery of systemic anticancer therapy in many hospitals by health care professionals who do not have required training. Given these facts, there is a need to focus on organization of medical oncology services in terms of manpower and infrastructure to standardize the delivery of systemic anticancer therapy. Redistribution of resources can streamline the delivery of cancer care, preferably close to the patient's home. This article describes the blueprint for organization of medical oncology services and delivery of chemotherapy and other systemic therapies to Indian patients. The model uses existing health care services in the country and is a four-tiered system of increasing sophistication: District Hospitals, Medical College Hospitals, Regional Cancer Centres, and Apex Cancer Centres. Delivery of quality care to patients with cancer through standardized protocols is crucial in improving cancer outcomes in India.


Marine Biodiversity, Biogeography, Deep-Sea Gradients, and Conservation.
The oceans appear ideal for biodiversity - they have unlimited water, a large area, are well connected, have less extreme temperatures than on land, and contain more phyla and classes than land and fresh waters. Yet only 16% of all named species on Earth are marine. Species richness decreases with depth in the ocean, reflecting wider geographic ranges of deep sea than coastal species. Here, we assess how many marine species are named and estimated to exist, paying particular regard to whether discoveries of deep-sea organisms, microbes and parasites will change the proportion of terrestrial to marine species. We then review what factors have led to species diversification, and how this knowledge informs conservation priorities. The implications of this understanding for marine conservation are that the species most vulnerable to extinction will be large and endemic. Unfortunately, these species are also the most threatened by human impacts. Such threats now extend globally, and thus the only refuges for these species will be large, permanent, fully protected marine reserves.


Quantitative phosphoproteomics after auxin-stimulated lateral root induction identifies an SNX1 protein phosphorylation site required for growth.
Protein phosphorylation is instrumental to early signaling events. Studying system-wide phosphorylation in relation to processes under investigation requires a quantitative proteomics approach. In Arabidopsis, auxin application can induce pericycle cell divisions and lateral root formation. Initiation of lateral root formation requires transcriptional reprogramming following auxin-mediated degradation of transcriptional repressors. The immediate early signaling events prior to this derepression are virtually uncharacterized. To identify the signal molecules responding to auxin application, we used a lateral root-inducible system that was previously developed to trigger synchronous division of pericycle cells. To identify and quantify the early signaling events following this induction, we combined (15)N-based metabolic labeling and phosphopeptide enrichment and applied a mass spectrometry-based approach. In total, 3068 phosphopeptides were identified from auxin-treated root tissue. This root proteome dataset contains largely phosphopeptides not previously reported and represents one of the largest quantitative phosphoprotein datasets from Arabidopsis to date. Key proteins responding to auxin treatment included the multidrug resistance-like and PIN2 auxin carriers, auxin response factor2 (ARF2), suppressor of auxin resistance 3 (SAR3), and sorting nexin1 (SNX1). Mutational analysis of serine 16 of SNX1 showed that overexpression of the mutated forms of SNX1 led to retarded growth and reduction of lateral root formation due to the reduced outgrowth of the primordium, showing proof of principle for our approach.


Parathyroid ultrasonography in patients with primary hyperparathyroidism.
Ultrasonography of the neck was performed in 42 consecutive patients with primary hyperparathyroidism (PHP). In 30 patients with subsequent neck exploration, ultrasonography localised 24 of 34 parathyroid tumours correctly (71%), and in 22 patients (73%) the diagnosis PHP was confirmed by identification of at least one parathyroid tumour. In 11 patients - who were not operated - ultrasonography disclosed a parathyroid tumour in four. Of all 42 patients, ultrasonography disclosed at least one parathyroid tumour in 26 (63%). The parathyroid tumours varied in echo pattern, and localisation difficulties were in particular related to associated nodular changes of the thyroid gland and the anatomic distribution of the enlarged parathyroid tissue.


Early estimates of influenza vaccine effectiveness in Navarre, Spain: 2012/13 mid-season analysis.
We present estimates of influenza vaccine effectiveness (VE) in Navarre, Spain, in the early 2012/13 season, which was dominated by influenza B. In a population-based cohort using electronic records from physicians, the adjusted VE in preventing influenzalike illness was 32% (95% confidence interval (CI): 15 to 46). In a nested test-negative case-control analysis the adjusted VE in preventing laboratory-confirmed influenza was 86% (95% CI: 45 to 96). These results suggest a high protective effect of the vaccine.


Assessment of left ventricular hemodynamics and function of patients with uremia by vortex formation using vector flow mapping.
A novel echocardiographic method, vector flow mapping (VFM), acquires velocity vector from color Doppler velocity data. The purpose of this study was to evaluate whether VFM could provide useful information on intracardiac flow and helpful to evaluate left ventricular (LV) function. Thirty-eight patients with uremia undergoing hemodialysis and 30 healthy volunteers were enrolled. The maximum vector velocity, maximum diameter and duration of the intracardiac vortex were measured using VFM software during systole and diastole. The maximum vector velocity of the vortex and the peak velocities at the basal septum and lateral mitral annulus measured by tissue Doppler imaging (TDI) were correlated. The maximum diameter and duration of vortex formation were significantly higher in uremic patients compared with the control group during the ejection phase (40.6 ± 7.9 cm/sec vs. 28.1 ± 3.9 cm/sec; 297.1 ± 22.1 msec vs. 145.4 ± 19.3 msec, all P < 0.001). The maximal diameters of the vortex were higher in uremic patients compared with the control group during diastole (25.6 ± 3.4 mm vs. 16.4 ± 2.1 mm; 34.3 ± 3.1 mm vs. 26.8 ± 3.9 mm; 37.5 ± 2.4 mm vs. 20.9 ± 2.1 mm; all P < 0.001). The maximum vector velocities were lower in mid-diastole and late diastole (23.6 ± 2.3 cm/sec vs. 45.2 ± 3.7 cm/sec; 31.9 ± 2.9 cm/sec vs. 54.7 ± 3.2 cm/sec, all P < 0.001). There was a correlation between the maximum vector velocity of the vortex in mid-diastole and E'/A' at the septum and lateral mitral annulus (r = 0.70, r = 0.76, P < 0.001). Vortex can be utilized to provide intracardiac dynamic information using VFM and it may be a good supplement for evaluating LV function.


Mediastinal lymphangiohemangioma communicating with the left innominate vein.
The CT manifestation of lymphangiohemangioma in a 17-year-old boy is reported. A mass composed of the central malformed, dilated venous channels and peripheral unenhanced soft tissue was revealed in the anterior mediastinum. The venous feeding enhancement of the mass is very characteristic. The diagnosis of lymphangiohemangioma was made by pathologic study of the surgical specimen.


Implant therapy in a surgical specialty clinic: an analysis of patients, indications, surgical procedures, risk factors, and early failures.
The aim of this study was to analyze the patient pool referred to a specialty clinic for implant surgery over a 3-year period. All patients receiving dental implants between 2008 and 2010 at the Department of Oral Surgery and Stomatology were included in the study. As primary outcome parameters, the patients were analyzed according to the following criteria: age, sex, systemic diseases, and indication for therapy. For the inserted implants, the type of surgical procedure, the types of implants placed, postsurgical complications, and early failures were recorded. A logistic regression analysis was performed to identify possible local and systemic risk factors for complications. As a secondary outcome, data regarding demographics and surgical procedures were compared with the findings of a historic study group (2002 to 2004). A total of 1,568 patients (792 women and 776 men; mean age, 52.6 years) received 2,279 implants. The most frequent indication was a single-tooth gap (52.8%). Augmentative procedures were performed in 60% of the cases. Tissue-level implants (72.1%) were more frequently used than bone-level implants (27.9%). Regarding dimensions of the implants, a diameter of 4.1 mm (59.7%) and a length of 10 mm (55.0%) were most often utilized. An early failure rate of 0.6% was recorded (13 implants). Patients were older and received more implants in the maxilla, and the complexity of surgical interventions had increased when compared to the patient pool of 2002 to 2004. Implant therapy performed in a surgical specialty clinic utilizing strict patient selection and evidence-based surgical protocols showed a very low early failure rate of 0.6%.


Prevalence of Pancreatic Exocrine Insufficiency among Patients with Diabetes Mellitus in India.
We aimed to assess the prevalence of pancreatic exocrine insufficiency (PEI) in Indian patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) using a unique diagnostic criterion. This multicenter study included patients aged ≥18 years with diabetes for at least 5 years. The sociodemographic characteristics, lifestyle habits, and clinical characteristics of patients were assessed. Patients were administered the PEI questionnaire (PEI-Q), and fecal elastase-1 (FE) concentration was measured. Patients were diagnosed to have PEI if they satisfied any two of the following three criteria: (a) a PEI-Q total symptom score of ≥0.60; (b) presence of malnutrition using the European Society of Clinical Nutrition and Metabolism diagnostic criteria for malnutrition; or (c) FE concentration <100 μg/gm stool. This multicenter study included patients aged ≥18 years with diabetes for at least 5 years. The sociodemographic characteristics, lifestyle habits, and clinical characteristics of patients were assessed. Patients were administered the PEI questionnaire (PEI-Q), and fecal elastase-1 (FE) concentration was measured. Patients were diagnosed to have PEI if they satisfied any two of the following three criteria: (a) a PEI-Q total symptom score of ≥0.60; (b) presence of malnutrition using the European Society of Clinical Nutrition and Metabolism diagnostic criteria for malnutrition; or (c) FE concentration <100 μg/gm stool. Pancreatic exocrine insufficiency (PEI) was found to be prevalent in nearly one-fourth of Indian patients with diabetes, using composite diagnostic criteria.


Outcomes of Elective Compared to Non-Elective Fetal Reduction by Radiofrequency Ablation in Monochorionic Multifetal Pregnancies.
Higher order fetal gestation is associated with adverse pregnancy outcomes, and monochorionic (MC) pregnancies have unique complications. Multifetal pregnancy reduction (MPR) by radiofrequency ablation (RFA) may be used to optimize the outcomes of a single fetus. The purpose of this study was to determine whether pregnancy outcomes differ for elective reduction compared to reduction for medically complicated MC multifetal pregnancies. This was a retrospective cohort of patients with MC twins and higher order multiples who underwent MPR via RFA at a single institution between 2008 and 2021. Patients undergoing elective reduction were compared to patients undergoing reduction due to a complication of MC pregnancy. Pregnancy outcomes were evaluated. Forty-eight patients who underwent RFA reduction between 2008 and 2021 were included in the analysis. Sixteen patients (33.3%) underwent elective RFA for MPR, and 32 (66.7%) underwent an RFA procedure for a complicated pregnancy. All pregnancies with RFA performed for elective indication had a continuing pregnancy (live birth rate 100%). There were no reported pregnancy losses within 4 weeks of the procedure when performed for a solely elective indication (n = 0) compared to 6.3% of complicated multifetal pregnancy (n = 2; 6.3%) (p = 0.001). In this retrospective cohort study, elective reduction of MC twins using RFA was associated with no cases of fetal loss or PPROM within 4 weeks of the procedure and a 100% live birth rate.


Nutrition and prevention of ischemic stroke: present knowledge, limitations and future perspectives.
Stroke, particularly ischemic stroke, has a major impact on public health due to its high incidence, prevalence and rate of subsequent disability in Italy as in most industrialised countries. Apart from age, many modifiable factors, such as hypertension, smoking, diabetes, dyslipidemia, obesity, physical inactivity, alcohol abuse and hyperhomocysteinemia, have been recognised as playing a role in the pathogenesis of this disease. While appropriate pharmacological therapy has proven effective in the prevention of stroke in particular categories of patients, most of the above mentioned predisposing conditions are amenable to be affected by nutrition. Unequivocal demonstration of a protective or adverse role of single foods and nutrients against the risk of stroke has been however difficult to achieve due to confounding by biological variability, methodological inadequacies in the assessment of individual nutritional habits and difficulty to carry out long-term randomised controlled trials in the nutritional area. Notwithstanding, in several cases, causal relationships could be inferred from case-control and cohort studies in the presence of plausible and reproducible associations, evidence of dose-dependent effects and consistency in the results of different studies. The aim of this paper was to review present knowledge and highlight limitations and future perspectives about the role of nutrition in the prevention of ischemic stroke.


LINC00963 Promotes Cancer Stemness, Metastasis, and Drug Resistance in Head and Neck Carcinomas via ABCB5 Regulation.
Accumulating studies have indicated that long non-coding RNAs (lncRNAs) participate in the regulation of cancer stem cells (CSCs), which are crucial in tumor initiation, metastasis, relapse, and therapy resistance. In the current study, RT-PCR analysis was employed to evaluate the expression of LINC00963 in tumor tissues and oral CSCs. Stemness phenotypes and the expression of CSCs markers in oral cancer cells transfected with sh-LINC00963 were examined. Our results showed that the expression of the lncRNA LINC00963 was up-regulated in oral cancer tissues and CSCs. We found that the downregulation of LINC00963 inhibited CSC hallmarks, such as migration, invasion and colony formation capacity. Moreover, suppression of LINC00963 reduced the activity of stemness marker ALDH1, the percentage of self-renewal, chemoresistance and the expression of multidrug-resistance transporter ABCB5. Most importantly, we demonstrated that knockdown of LINC00963 decreased self-renewal, invasion and colony formation ability via ABCB5. Analysis of TCGA (the Cancer Genome Atlas) datasets suggested that the level of LINC00963 was positively correlated with the expression of the cancer stemness markers (Sox2 and CD44) and drug resistance markers (ABCG2 and ABCB5). Altogether, our results showed that suppression of LINC00963 may be beneficial to inhibit chemoresistance and cancer relapse in oral cancer patients.


Small Molecules from Deep within the Gut.
Although the influence of the human microbiome on host functions is widely recognized, the underlying molecular mechanisms are still largely unknown. A recent study by the Fischbach group now provides an experimental workflow for characterizing and evaluating the impact of microbiome-derived small molecules on host physiology.


OCA4: evidence for a founder effect for the p.D157N mutation of the MATP gene in Japanese and Korean.
Oculocutaneous albinism type 4 (OCA4) was identified as a rare form of human OCA among a group of autosomal recessive hypopigmentary disorders. Little is known about the prevailing distribution of patients of OCA4 with mutations of the MATP gene, although one Turkish, five German, one Korean, and 18 Japanese patients have been reported so far. The p.D157N mutation was previously reported to be the most frequent (0.389; 14/36) in Japanese patients and was also found in a Korean patient. On the other hand, this mutation has not been found in Turkish and German patients. We therefore investigated haplotypes of the patients who have the p.D157N mutation. The results showed that OCA4 is prevalent in East Asia including Japan and Korea likely as a result of a founder effect for the p.D157N mutation. Furthermore, it is suspected that the p.D157N mutation might have occurred on an ancestral chromosome after the divergence of Orientals and Caucasians.


Pertussis resurgence: diagnosis, treatment, prevention, and beyond.
The introduction of routine vaccination against Bordetella pertussis more than a half century ago led to a drastic decline in the number of reported cases of pertussis. It was originally believed that lifelong immunity was afforded after vaccination. Unfortunately, this belief is flawed, as the highest number of pertussis cases since 1959 was reported in 2004. This significant increase has led to additional research on immunity, vaccination, and treatment of B. pertussis in all age groups. We performed a MEDLINE search of literature from 1966-2006 to evaluate and review the existing data on immunity to and prevention or treatment of B. pertussis infections. Additional articles were identified from the bibliographies of reviewed literature. Numerous articles pertaining to these topics have been published recently. The most significant changes in the management of this infectious disease surround the new recommendations by the Advisory Committee on Immunization Practices for adult and adolescent immunizations to assist in preventing outbreaks of B. pertussis. The Centers for Disease Control and Prevention recently published guidelines updating the recommended pharmacologic agents for treatment or prevention of B. pertussis. Despite decades of successful vaccination programs, pertussis continues to be a problematic disease. Fortunately, data and vaccines are now available that make development of a pertussis booster vaccination campaign reasonable. However, until widespread compliance with such programs is achieved, clinicians need to maintain vigilance against pertussis.


Study of gene transfer in vitro and in the digestive tract of gnotobiotic mice from Lactococcus lactis strains to various strains belonging to human intestinal flora.
The use of genetically modified organisms (GMO) in dairy products requires evaluation of the DNA transfer capacity from such organisms among the human intestinal microflora. Thus, both in vitro and in vivo [in the digestive tract (DT) of mice] transfer from Lactococcus lactis donor strains of the conjugative plasmid pIL205 (CmR) and the non-conjugative plasmid pIL253 (EmR) to: (1) recipient strains isolated from human faecal flora Bacteroides sp., Bifidobacterium sp., Peptostreptococcus sp. (strictly anaerobic bacterial strains) and Enterococcus faecalis, (2) a whole human faecal flora, was studied. In both cases, no gene transfer was observed to strictly anaerobic bacterial strains. DNA transfer was only observed to the E. faecalis strain: in vivo CmR E. faecalis transconjugants were isolated from sequentially multi-associated mice and when the recipient strains associated with the mice, they were a defined mixture of Bacteroides sp., Bifidobacterium sp., Peptostreptococcus sp. and E. faecalis strains. When mice were associated with the whole human faecal flora, the plasmid pIL205 was transferred into some facultative anaerobic streptococci. It was also shown that DNA transfer occurred even when the lactococcal donor strain was transient in the DT of the gnotobiotic host animals.