A multicenter, prospective, randomized trial evaluating the X STOP interspinous process decompression system for the treatment of neurogenic intermittent claudication: two-year follow-up results.
A randomized, controlled, prospective multicenter trial comparing the outcomes of neurogenic intermittent claudication (NIC) patients treated with the interspinous process decompression system (X STOP) with patients treated nonoperatively. To determine the safety and efficacy of the X STOP interspinous implant. Patients suffering from NIC secondary to lumbar spinal stenosis have been limited to a choice between nonoperative therapies and decompressive surgical procedures, with or without fusion. The X STOP was developed to provide an alternative therapeutic treatment. METHODS.: 191 patients were treated, 100 in the X STOP group and 91 in the control group. The primary outcomes measure was the Zurich Claudication Questionnaire, a patient-completed, validated instrument for NIC. At every follow-up visit, X STOP patients had significantly better outcomes in each domain of the Zurich Claudication Questionnaire. At 2 years, the X STOP patients improved by 45.4% over the mean baseline Symptom Severity score compared with 7.4% in the control group; the mean improvement in the Physical Function domain was 44.3% in the X STOP group and -0.4% in the control group. In the X STOP group, 73.1% patients were satisfied with their treatment compared with 35.9% of control patients. The X STOP provides a conservative yet effective treatment for patients suffering from lumbar spinal stenosis. In the continuum of treatment options, the X STOP offers an attractive alternative to both conservative care and decompressive surgery.


Long-term effectiveness of an ad hoc tailored titanium implant as a spacer for microvascular decompression in the treatment of trigeminal neuralgia caused by megadolichoectatic basilar artery anomaly: 9-year follow-up.
An enlarged, elongated, ectatic, and sclerotic aberration of the vertebrobasilar system is known as a megadolichoectatic basilar artery (BA) anomaly. The anomaly is often involved in the pathological process of trigeminal neuralgia by compressing and distorting the trigeminal nerve. First-line medical treatment includes drug therapy, but a second-line surgical procedure could be effective in medication-resistant cases. The authors report the case of a 65-year-old man with a 12-year history of progressing trigeminal neuralgia who underwent microvascular decompression after the first-line drug treatment had failed. This case is unique because an in situ tailored titanium microplate was used as a spacer to alleviate compression by the BA on the trigeminal nerve. The titanium implant provided durable and sufficient retraction for the sclerotic arterial complex when the trigeminal nerve was placed in the tunnel of the implant. The 9-year follow-up examination proves the safety and long-term efficacy of titanium implants in the treatment of trigeminal neuralgia caused by a megadolichoectatic BA anomaly. The method applied in this case was not intended to be and certainly is not an alternative to routine microvascular decompression-this surgical solution may be reserved for some extreme cases.


KIF4A Promotes Clear Cell Renal Cell Carcinoma (ccRCC) Proliferation in vitro and in vivo.
To evaluate the expression in human clear cell renal cell carcinoma (ccRCC) tissues and explore the effects of kinesin family member 4A (KIF4A) on ccRCC progression. GEPIA was used to evaluate the mRNA levels of KIF4A in human ccRCC tissues from TCGA database, and Immunohistochemistry (IHC) assays were performed to assess its expression in human ccRCC tissues collected in our hospital. The clinical-pathological analysis was performed to explore the correlation with KIF4A expression. The effects of KIF4A on ccRCC cell proliferation were detected through colony formation and MTT assays. Finally, the effects of KIF4A on tumor growth were measured using a mice model. Bioinformation results showed the expression of KIF4A mRNA was upregulated in ccRCC tissues and high expression of KIF4A was related with poor prognosis in ccRCC patients. We also found a high expression of KIF4A in human ccRCC tissues collected in our hospital. We also found its expression level was correlated with clinical characteristics, including T stage (P=0.035*) and lymphatic metastasis (P=0.028*). We further confirmed that knockdown of KIF4A suppressed cell proliferation in HTB-47 and CRL-1932 cells. Furthermore, KIF4A contributes to tumor growth of ccRCC cells in mice. We found the abnormal high expression of KIF4A in human ccRCC tissues and demonstrated that KIF4A could serve as a tumor induction gene.


High-resolution three-dimensional views of membrane-associated clathrin and cytoskeleton in critical-point-dried macrophages.
We obtained high-resolution topographical information about the distribution of clathrin and cytoskeletal filaments on cytoplasmic membrane surfaces of macrophages spreading onto glass coverslips by both critical-point drying of broken-open cells and preparation of rotary platinum replicas. Irregular patches of the adherent ventral surface of the plasma membrane were exposed in these cells, and large areas of these exposed membranes were covered with clathrin-coated patches, pits, and vesicles. Various amounts of cytoskeleton were attached to the plasma membranes of these spreading cells, either as distinct starlike foci, or as individual filaments and bundles radiating out from the cytoskeletal meshwork. In newly adherent cells a well developed Golgi-GERL complex, characterized by smooth, dish-like cisternae associated with rough endoplasmic reticulum, was observed. There were many coated vesicles budding off from the Golgi cisternae, and these were predominantly of the large type (150 nm) usually associated with the plasma membrane. In critical-point-dried samples, both cytoskeleton and membranes were preserved in detail comparable to that of quick-frozen samples, after appropriate fixation. Rotary replication of critical-point-dried cells provides a rapid, easily controlled, and generally easy to perform method for obtaining samples of exposed membrane large enough to permit quantification of membrane-associated clathrin and cytoskeleton under various experimental conditions.


Rationale, Design, and Baseline Characteristics of the Prospective Japan Acute Myocardial Infarction Registry (JAMIR).
Antiplatelet therapy is a cornerstone of treatment following acute myocardial infarction (AMI). Recently, prasugrel, a new and potent antiplatelet agent, has been introduced in clinical practice. To date, however, real-world in-hospital and follow-up data in Japanese patients with AMI remain limited. To examine ischemic and bleeding events in Japanese patients with AMI and the association between these events and antiplatelet therapy. The Japan AMI Registry (JAMIR) is a multicenter, nationwide, prospective registry enrolling patients with AMI from 50 institutions. The inclusion criterion is spontaneous onset of AMI diagnosed based on either the universal definition or Monitoring Trends and Determinants in Cardiovascular disease (MONICA) criteria. The major exclusion criteria are hospital admission ≥ 24 h after onset, no return of spontaneous circulation on admission following out-of-hospital cardiopulmonary arrest, and AMI as a complication of percutaneous coronary intervention or coronary artery bypass grafting. The primary end point of the study is the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Major safety end points include major bleeding based on Thrombolysis in Myocardial Infarction (TIMI) criteria and type 3 or type 5 bleeding based on Bleeding Academic Research Consortium (BARC) criteria. Between December 2015 and May 2017, a total of 3411 patients (mean age 68.1 ± 13.2 years, 23.4% female) were enrolled in the study. Patients will be followed for 1 year. JAMIR will provide important information regarding contemporary practice patterns in the management of Japanese patients with AMI, their demographic and clinical characteristics, in-hospital and post-discharge outcomes, and how they are related to antiplatelet therapy.


Automatic adjustment of biphasic pulse duration in transthoracic defibrillation.
Many studies have proven that biphasic defibrillation pulses are more efficient than the damped sinusoid monopolar waveform. Transthoracic resistance was shown to change during the two phases. On the other hand, it was proven that transthoracic resistance plays an important role in the defibrillation process, yielding the current for selected energy or voltage. Pre-shock measurement of the resistance may lead to improved selection. Stabilized current defibrillators are of low stored-to-delivered energy ratio. Therefore, automatic dynamic adjustment of some defibrillator parameters with respect to transthoracic resistance changes seems rational. An approach is known for modifying the pulse duration, in order to deliver a selected energy. A method is proposed here and an experimental defibrillator is developed for dynamic pulse duration adjustment with the purpose of obtaining a desired optimal time-course of the cardiac cell transmembrane potential.


Outcomes with coronary artery bypass graft surgery versus percutaneous coronary intervention for patients with diabetes mellitus: can newer generation drug-eluting stents bridge the gap?
Coronary artery bypass graft surgery (CABG) compared with percutaneous coronary intervention (PCI) reduces mortality in patients with diabetes mellitus. However, prior trials compared CABG with balloon angioplasty or older generation stents, and it is not known if the gap between CABG and PCI can be reduced by newer generation drug-eluting stents. PUBMED/EMBASE/CENTRAL search for randomized trials comparing mode of revascularization in patients with diabetes mellitus. Primary outcome was all-cause mortality. Secondary outcomes were myocardial infarction, repeat revascularization, and stroke. Mixed treatment comparison analyses were performed using a random-effects Poisson regression model. Sixty-eight randomized trials that enrolled 24 015 diabetic patients with a total of 71 595 patient-years of follow-up satisfied our inclusion criteria. When compared with CABG (reference rate ratio [RR]=1.0), PCI with paclitaxel-eluting stent (RR=1.57 [1.15-2.19]) or sirolimus-eluting stent (RR=1.43 [1.06-1.97]) was associated with an increase in mortality. However, PCI with cobalt-chromium everolimus-eluting stent (RR=1.11 [0.67-1.84]) was not associated with a statistically significant increase in mortality. When compared with CABG, there was excess repeat revascularization with PCI, which progressively declined from plain old balloon angioplasty (341% increase) to bare metal stent (218% increase) to paclitaxel-eluting stent (81% increase) and to sirolimus-eluting stent (47% increase). However, for PCI with cobalt-chromium everolimus-eluting stent (RR=1.31 [0.74-2.29]), the excess repeat revascularization was not statistically significant although the point estimate favored CABG. CABG was associated with numerically higher stroke. In patients with diabetes mellitus, evidence from indirect comparison shows similar mortality between CABG and PCI using cobalt-chromium everolimus-eluting stent. CABG was associated with numerically excess stroke and PCI with cobalt-chromium everolimus-eluting stent with numerically increased repeat revascularization. This hypothesis needs to be tested in future trials.


Epigenetic Regulation of Skin Cells in Natural Aging and Premature Aging Diseases.
Skin undergoes continuous renewal throughout an individual's lifetime relying on stem cell functionality. However, a decline of the skin regenerative potential occurs with age. The accumulation of senescent cells over time probably reduces tissue regeneration and contributes to skin aging. Keratinocytes and dermal fibroblasts undergo senescence in response to several intrinsic or extrinsic stresses, including telomere shortening, overproduction of reactive oxygen species, diet, and sunlight exposure. Epigenetic mechanisms directly regulate skin homeostasis and regeneration, but they also mark cell senescence and the natural and pathological aging processes. Progeroid syndromes represent a group of clinical and genetically heterogeneous pathologies characterized by the accelerated aging of various tissues and organs, including skin. Skin cells from progeroid patients display molecular hallmarks that mimic those associated with naturally occurring aging. Thus, investigations on progeroid syndromes strongly contribute to disclose the causal mechanisms that underlie the aging process. In the present review, we discuss the role of epigenetic pathways in skin cell regulation during physiologic and premature aging.


Lead poisoning in new immigrant children from the mainland of China.
To define the prevalence, severity and risk factors for lead poisoning in new immigrant children from the mainland of China to Hong Kong, China. New immigrant children from the mainland of China under 18 years of age were invited to join the study. Their growth parameters and venous blood lead levels (BLL) were measured within 7 days of arrival. Those with elevated BLL i.e. > 10 micrograms/dl (0.48 mumol/L) were assessed for signs, symptoms and risk factors of lead poisoning. Education on the prevention of lead poisoning and follow up BLL measurements were offered until their BLL normalized. Four hundred and fifty-seven children were recruited. Among them, 18.1% and 2.6% had BLL > 0.48 and 0.71 mumol/L, respectively. None had BLL > 0.96 mumol/L. Possible risk factors included contaminated drinking water (19%), herb ingestion (17.5%), pica, playing in dumping grounds, residing near paint factories or highways, habitual inhalation of car exhaust and cooking with petroleum. Symptoms and signs included abdominal pain, headache, short stature, and learning difficulties but did not correlate with BLL. None required treatment except for counseling on the avoidance of risk factors. About 94.7% showed a reduction in BLL 2-3 months after arrival and before counseling. All had normalized BLL by 9 months except 1 who had an X-ray feature of lead line. Lead poisoning is common in new immigrant children from the mainland of China. Environmental factors were most important while behavioral factors like regular herb ingestion might have contributed to the persistence of high BLL in the minority.


Nuclear explosions and distant earthquakes: a search for correlations.
An apparent correlation between nuclear explosions and earthquakes has been reported for the events between September 1961 and September 1966. When data from the events between September 1966 and December 1968 are examined, this correlation disappears. No relationship between the size of the nuclear explosions and the number of distant earthquakes is apparent in the data.


Digital Unwrapping of the Mummy of King Amenhotep I (1525-1504 BC) Using CT.
The mummy of King Amenhotep I (18th Dynasty c.1525-1504 BC) was reburied by the 21st Dynasty priests at Deir el-Bahari Royal Cache. In 1881 the mummy was found fully wrapped and was one of few royal mummies that have not been unwrapped in modern times. We hypothesized that non-invasive digital unwrapping using CT would provide insights on the physical appearance, health, cause of death, and mummification style of the mummy of King Amenhotep I. We examined the mummy with CT and generated two- and three-dimensional images for the head mask, bandages, and the virtually unwrapped mummy. CT enabled the visualization of the face of Amenhotep I who died around the age of 35 years. The teeth had minimal attrition. There was no CT evidence of pathological changes or cause of death. The body has been eviscerated via a vertical left flank incision. The heart is seen in the left hemithorax with an overlying amulet. The brain has not been removed. The mummy has 30 amulets/jewelry pieces including a beaded metallic (likely gold) girdle. The mummy suffered from multiple postmortem injuries likely inflicted by tomb robbers that have been likely treated by 21st Dynasty embalmers. These included fixing the detached head and neck to the body with a resin-treated linen band; covering a defect in the anterior abdominal wall with a band and placing two amulets beneath; placement of the detached left upper limb beside the body and wrapping it to the body. The transversely oriented right forearm is individually wrapped, likely representing the original 18th Dynasty mummification and considered the first known New Kingdom mummy with crossed arms at the chest. The head mask is made of cartonnage and has inlaid stone eyes. The digital unwrapping of the mummy of Amenhotep I using CT sets a unique opportunity to reveal the physical features of the King non-invasively, understand the mummification style early in the 18th Dynasty, and the reburial intervention style by 21st Dynasty embalmers. This study may make us gain confidence in the goodwill of the reburial project of the Royal mummies by the 21st dynasty priests.


Pertussis-associated persistent cough in previously vaccinated children.
To evaluate the role of Bordetella pertussis infection, 96 otherwise healthy 7- to 17-year-old subjects who were suffering from a cough lasting from 2 to 8 weeks were prospectively recruited. At enrolment, a nasopharyngeal swab and an oral fluid sample were obtained to search for pertussis infection by the detection of B. pertussis DNA and/or an elevated titre of anti-pertussis toxin IgG. Evidence of pertussis infection was found in 18 (18.7 %; 95 % confidence interval, 11.5-28.0) cases. In 15 cases, the disease occurred despite booster administration. In two cases, pertussis was diagnosed less than 2 years after the booster injection, whereas in the other cases it was diagnosed between 2 and 9 years after the booster dose. This study used non-invasive testing to show that pertussis is one of the most important causes of long-lasting cough in school-age subjects. Moreover, the protection offered by acellular pertussis vaccines currently wanes more rapidly than previously thought.


Hearing loss attributable to a cerebellopontine-angle arachnoid cyst in a child.
Although hearing loss in newborns and infants is predominantly due to malformations and infections, there are other situations which may compromise hearing quality in later stages, including posterior-fossa arachnoid cysts (ACs). We report the case of an 8-year-old girl who presented with hearing loss linked to a pontocerebellar-angle AC which had been diagnosed and treated when she was 14 months old. The pathophysiology of this late AC complication is discussed. This case reminds us that a close follow-up with audiologic monitoring and/or brain stem auditory evoked response is necessary in children with posterior-fossa AC because modern neuroradiological imaging methods do not inform about cerebral and nerve functions, although they provide excellent morphological details of ACs and have improved the ease and accuracy of their early diagnosis. Therefore, surgery should be performed before complete hearing loss occurs; however, in hearing-impaired patients, it remains unclear which surgical treatment is most appropriate.


[Atypical Mycobacterias in Mexico. Incidence and epidemiology in a general hospital].
All the cultures for mycobacteriae taken from 1967 to 1973 at the Hospital General del Centro Médico Nacional del Instituto Mexicano del Seguro Social were reviewed. From 802 positive cultures, 361 (44.2 per cent) were atypical mycobacteriae. 89 per cent of them were scotochromogen, 10.3 per cent of rapid growth, one non-chromogen, and none were photochromogen. These data are in contrast with those observed in other countries. Isolation sources varied also from other reports, in this series the most common isolation were from urine specimens, sputum, feces and bone marrow. A possible explanation for that in this hospital there are very few pulmonary patients. The percentage of atypical mycobacteriae was greatest in the last two years. In bacterioscopic examination atypical micobacteriae were detected less frequently than M. tuberculosis.


Pseudopalisades in glioblastoma are hypoxic, express extracellular matrix proteases, and are formed by an actively migrating cell population.
Necrosis and vascular proliferation are the pathologic features that distinguish the most malignant infiltrative astrocytoma, glioblastoma (GBM), from those of lower grades. In GBM, hypercellular zones called pseudopalisades typically surround necrotic foci. Although these cells are known to secrete high levels of proangiogenic factors that promote tumor growth, their origins are ill defined. We propose that pseudopalisades represent differing stages and histologic samplings of astrocytoma cells migrating away from a hypoxic/anoxic focus, often triggered by a central vaso-occlusive event. This proposition is based on our findings that pseudopalisading cells are 5-50% less proliferative and 6-20 times more apoptotic than adjacent astrocytoma, indicating that cell accumulation does not result from increased proliferation or resistance to apoptosis. Coexisting inflammatory cells account for <2% of pseudopalisading cells and cannot account for hypercellularity. Pseudopalisading cells show nuclear expression of hypoxia-inducible factor 1 alpha, consistent with their hypoxic nature, and hypoxia induces a 20-60% increase in glioma cell migration in vitro. Hypoxic cells in vitro and pseudopalisades in GBM specimens show enhanced gelatinase activity, typical of an invasive phenotype. These results suggest that pseudopalisading cells are migrating at the periphery of a hypoxic center. To uncover a potential source of hypoxia and sequence of structural events leading to pseudopalisade formation, we performed a morphometric analysis of 234 pseudopalisades from 85 pretreatment GBMs. We found distorted, degenerating, or thrombosed blood vessels within the center of more than half the pseudopalisades, suggesting that at least a subset of pseudopalisades are two-dimensional histologic representations of tumor cells migrating away from a vaso-occlusive event.


[Intraneural ganglion of the peroneal nerve. A case report].
This is a report of a 70-year-old patient with spontaneous pain of the dorsum area of the left foot. A few days later there was a sudden onset of foot drop. First, an idiopathic peroneal palsy was assessed but an MRI showed a cystic tumour near the fibular head. These findings resulted in the patient attending our clinic for surgical treatment. During the operation we found an intraneural ganglion of the deep peroneal nerve and the common peroneal nerve. There was no connection with the superior tibiofibular joint. The ganglion was therefore removed. Two months after the operation the patient reported an improvement of the pain but no improvement of movement of the foot. An intraneural ganglion of the peroneal nerve derives from the superior tibiofibular joint. Given access to the articular branch, the cyst typically spreads out proximally from the deep peroneal nerve to the common peroneal nerve and to the point of the sciatic nerve. The clinical symptoms are correlated with the extent of cyst propagation. Recommended therapy would include the ligation of the aricular branch, or synovectomy, or resection of the superior tibiofibular joint and decompression of the cyst.


Behavior of Most Widely Spread Lipids in Isotropic Bicelles.
Isotropic bicelles are a widely used membrane mimetic for structural studies of membrane proteins and their transmembrane domains. Simple and cheap in preparation, they contain a patch of lipid bilayer that reproduces the native environment of membrane proteins. Despite the obvious power of bicelles in reproducing the various kinds of environments, the vast majority of structural studies employ the single lipid/detergent system. On the other hand, even if the alternative bicelle composition is used, the properties of mixtures are not characterized, and the mere presence of lipid bilayer and discoidal shape of bicelle particles is not confirmed. Here we present an extensive investigation of various bicellar mixtures and describe the behavior of bicelles with lipids other than classical DMPC, namely sphingomyelins (SM), phosphatidylethanolamines (PE), phosphatidylglycerols (PG), phosphatidylserines (PS), and cholesterol. These lipids are rarely used in modern structural biology, but can help a lot in understanding the influence of the membrane composition on the properties of both integral and peripheral membrane proteins. Additionally, the ability of diheptanoylphosphatidylcholine (DH7PC) to serve as a rim-forming agent was investigated. We followed the phase transitions as revealed by 31P NMR and size of particles measured by 1H NMR diffusion as the criteria of the proper morphology and structure of bicelles. As an outcome, we state that SM exclusively, and PG/PS in mixtures with zwitterionic lipids can form small isotropic bicelles, which reproduce the key features of lipid behavior in bilayers. Mixtures, containing exclusively the anionic lipids, fail to reveal the lipid phase transition and do not follow the size predicted for the ideal bicelle particles. PE and DH7PC are the unwanted components of bicellar mixtures, and cholesterol can be added to bicelles, however, with certain precautions. In combination with our several most recent works, this study provides a practical guide for the preparation of small isotropic bicelles.


Expression of H-2 and Moloney leukemia virus-determined cell-surface antigens in synchronized cultures of a mouse cell line.
A mouse cell line derived from bone marrow (JLS-V9) was infected in vitro with Moloney leukemia virus. After the cell-surface antigens specified by this virus appeared, cells were synchronized in mitosis by a short treatment with colcemid. The expression of H-2- and virus-determined surface antigens was monitored during one cell cycle by an indirect membrane-immunofluorescence test. The highest proportion of antigen-positive cells was found during the G1 period; the proportion dropped as the cells entered the S period, and remained low until they entered the G1 period of the next cycle. The H-2- and virus-determined surface antigens were temporally coexpressed.


Social connectedness and mental health before and during the COVID-19 pandemic in a community sample in Korea.
This study compared social connectedness patterns and examined the relationships between objective or subjective social connectedness and mental health before and during the COVID-19 pandemic among community dwelling adults in South Korea. An identical online survey was administered at two time points, in 2019 prior to the onset and again in 2021. Objective (network diversity and network size) and subjective (thwarted belongingness and perceived burdensomeness) social connectedness were measured along with positive and negative indices of mental health (depression, suicidal behavior, happiness, and life satisfaction). The results indicated that among social connectedness indices perceived burdensomeness were significantly higher during the COVID-19 pandemic compared to the prior period, while network size was smaller. Subjective social connectedness was associated with all aspects of mental health consequences, either positive or negative. Among objective social connectedness, only network diversity was significantly associated with increased happiness and life satisfaction, and objective social connectedness was not associated with depression and suicidal behavior. These associations did not differ across the two time periods. The findings, both before and during the pandemic, indicated that network diversity is an important factor for positive indices of mental health and that efforts to increase subjective social connectedness are needed to decrease the risk of depression and suicidal behavior.


Microbial adherence to vulvar epithelial cells.
Under uniform experimental conditions, different degrees of selective attachment of Staphylococcus aureus and Candida albicans to epithelial cells of the labium majus, the labium minus, and the vagina were compared and contrasted with those found in studies with cells of the buccal and nasal mucosa and forearm skin by a novel analysis of adherence density. For both micro-organisms, the larger, rougher cells of the labium majus gave the highest adherence scores matched only by the interaction of S. aureus with fully keratinised nasal epithelial cells. Increasing acidity to pH 3.5 enhanced microbial adherence to vaginal cells. Menstruation also influenced attachment; highest densities were reached between the third and fourth weeks of the cycle. Autogenous ribitol teichoic acid was found to block the attachment of S. aureus to labium majus and labium minus cells by 76% and 81% respectively, and to vaginal cells by 66%. Adherence is considered to be an important attribute of vulvar ecology and may be a determinant of infectious disease.


Inverse Relationship Between Coarse Food Grain Intake and Blood Pressure Among Young Chinese Adults.
Coarse food grains are rich in dietary fiber and contain a wide range of nutrients with potential health benefits, such as blood pressure control. Coarse food grains are very popular in China, where hypertension is a major challenge. We evaluated the associations between coarse food grain consumption and blood pressure among young Chinese adults. A total of 104 men and women aged 18-35 years, who participated in a pilot study of the Carbohydrate Alternatives and Metabolic Phenotypes study, were included in the present analysis. Food frequency questionnaires were used to collect dietary intake data. Blood pressure was measured using a digital monitor. A multivariate general linear model was used to evaluate the putative associations. Overall, 12.5% of our participants have regular habits of coarse food grain intake (at least 4 days/week). Age was positively associated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP) (all Ps for trend < 0.05). With multivariable adjustment, including for body mass index and physical activity level, the frequency of coarse food grain intake was inversely associated with both SBP and DBP (all Ps for trend < 0.05). Similar associations were observed for estimated daily coarse food grain intake with SBP (β coefficient ± SE = -0.039 ± 0.017, P = 0.024) and DBP (β coefficient ± SE = -0.033 ± 0.013, P = 0.016). In our sample of young Chinese adults, higher coarse food grain intake was associated with lower SBP and DBP.


Relationship between Ventilator-Associated Events and Timing of Rehabilitation in Subjects with Emergency Tracheal Intubation at Early Mobilization Facility.
The present study aimed to investigate the relationship between the occurrence of ventilator-associated events (VAE) in the intensive care unit and the timing of rehabilitation intervention. We included subjects who underwent emergency tracheal intubation and received rehabilitation. We performed rehabilitation according to our hospital's protocol. We assessed the mechanical ventilation parameters of inspired oxygen fraction and positive-end expiratory pressure, and a VAE was identified if these parameters stabilized or decreased for ≥2 days and then had to be increased for ≥2 days. We defined time in hours from tracheal intubation to the first rehabilitation intervention as Timing 1 and that to first sitting on the edge of the bed as Timing 2. Data were analyzed by the t-test and χ² tests. We finally analyzed 294 subjects. VAE occurred in 9.9% and high mortality at 48.3%. Median values of Timing 1 and Timing 2 in the non-VAE and VAE groups were 30.3 ± 24.0 and 30.0 ± 20.7 h, and 125.7 ± 136.6 and 127.9 ± 111.4 h, respectively, and the differences were not significant (p = 0.95 and p = 0.93, respectively). We found no significant relationship between the occurrence of VAE leading to high mortality and timing of rehabilitation intervention.


Staff attachment styles: a pilot study investigating the influence of adult attachment styles on staff psychological mindedness and therapeutic relationships.
The attachment styles of psychiatric staff are likely to impact on their capacity to form positive therapeutic relationships with patients with psychosis. Twenty staff completed a measure assessing levels of attachment anxiety and avoidance. Staff and patients completed a measure of patients' interpersonal problems and staff completed the Five-Minute Speech Sample, which was used to derive ratings of psychological mindedness and therapeutic relationships. Higher staff avoidance was associated with greater discrepancies in staff and patient ratings of patients' interpersonal problems and poorer staff psychological mindedness. Lower staff anxiety and avoidance were associated with positive therapeutic relationships. Findings warrant replication in larger samples, but suggest that staff attachment style may be important in the development of better quality staff and patient relationships.


RNA editing by ADAR1 regulates innate and antiviral immune functions in primary macrophages.
ADAR1-dependent A-to-I editing has recently been recognized as a key process for marking dsRNA as self, therefore, preventing innate immune activation and affecting the development and resolution of immune-mediated diseases and infections. Here, we have determined the role of ADAR1 as a regulator of innate immune activation and modifier of viral susceptibility in primary myeloid and lymphoid cells. We show that ADAR1 knockdown significantly enhanced interferon, cytokine and chemokine production in primary macrophages that function as antiviral paracrine factors, rendering them resistant to HIV-1 infection. ADAR1 knockdown induced deregulation of the RLRs-MAVS signaling pathway, by increasing MDA5, RIG-I, IRF7 and phospho-STAT1 expression, an effect that was partially rescued by pharmacological blockade of the pathway. In summary, our results demonstrate a role of ADAR1 in regulating innate immune function in primary macrophages, suggesting that macrophages may play an essential role in disease associated to ADAR1 dysfunction. We also show that viral inhibition is exclusively dependent on innate immune activation consequence of ADAR1 knockdown, pointing towards ADAR1 as a potential target to boost antiviral immune response.


Global transcriptome profiling and functional analysis reveal that tissue-specific constitutive overexpression of cytochrome P450s confers tolerance to imidacloprid in palm weevils in date palm fields.
Cytochrome P450-dependent monooxygenases (P450s), constituting one of the largest and oldest gene superfamilies found in many organisms from bacteria to humans, play a vital role in the detoxification and inactivation of endogenous toxic compounds. The use of various insecticides has increased over the last two decades, and insects have developed resistance to most of these compounds through the detoxifying function of P450s. In this study, we focused on the red palm weevil (RPW), Rhynchophorus ferrugineus, the most devastating pest of palm trees worldwide, and demonstrated through functional analysis that upregulation of P450 gene expression has evolved as an adaptation to insecticide stress arising from exposure to the neonicotinoid-class systematic insecticide imidacloprid. Based on the RPW global transcriptome analysis, we identified 101 putative P450 genes, including 77 likely encoding protein coding genes with ubiquitous expression. A phylogenetic analysis revealed extensive functional and species-specific diversification of RPW P450s, indicating that multiple CYPs actively participated in the detoxification process. We identified highly conserved paralogs of insect P450s that likely play a role in the development of resistance to imidacloprid: Drosophila Cyp6g1 (CYP6345J1) and Bemisia tabaci CYP4C64 (CYP4LE1). We performed a toxicity bioassay and evaluated the induction of P450s, followed by the identification of overexpressed P450s, including CYP9Z82, CYP6fra5, CYP6NR1, CYP6345J1 and CYP4BD4, which confer cross-resistance to imidacloprid. In addition, under imidacloprid insecticide stress in a date palm field, we observed increased expression of various P450 genes, with CYP9Z82, CYP4BD4, CYP6NR1 and CYP6345J1 being the most upregulated detoxification genes in RPWs. Expression profiling and cluster analysis revealed P450 genes with multiple patterns of induction and differential expression. Furthermore, we used RNA interference to knock down the overexpressed P450s, after which a toxicity bioassay and quantitative expression analysis revealed likely candidates involved in metabolic resistance against imidacloprid in RPW. Ingestion of double-stranded RNA (dsRNA) successfully knocked down the expression of CYP9Z82, CYP6NR1 and CYP345J1 and demonstrated that silencing of CYP345J1 and CYP6NR1 significantly decreased the survival rate of adult RPWs treated with imidacloprid, indicating that overexpression of these two P450s may play an important role in developing tolerance to imidacloprid in a date palm field. Our study provides useful background information on imidacloprid-specific induction and overexpression of P450s, which may enable the development of diagnostic tools/markers for monitoring the spread of insecticide resistant RPWs. The observed trend of increasing tolerance to imidacloprid in the date palm field therefore indicated that strategies for resistance management are urgently needed.


Comparative study of the carcinogenic activities of nas and some chemical carcinogens when introduced into the buccal pouch of the Syrian hamster.
Studies were carried out on the carcinogenic effects of nas, 7,12-dimethylbenz-[a]anthracene (DMBA), DMBA+nas, dimethylnitrosamine (DMNA), diethylnitrosamine (DENA), and N-methyl-N-nitrosourea (MNU) when introduced into the buccal pouch of the Syrian hamster. Nas alone induced no tumours in the buccal pouch but tumours at other sites occurred in 18.8% of the treated animals, compared with 4.4% of the controls. Three of 11 hamsters treated with DMBA alone developed tumours. No tumours appeared in the buccal pouch following treatment with DMBA + nas but they developed at other sites in 6 of the 11 hamsters treated. DMNA and DENA induced no macroscopic changes in the mucous membrane of the buccal pouch. Following DMNA administration, tumours developed only in the liver; no tumours developed following the application of DENA. Tumours developed at various sites, including the buccal pouch, in 20 of the 25 hamsters treated with MNU.


Synergistic Inhibitory Effect of Berberine and Low-Temperature Plasma on Non-Small-Cell Lung Cancer Cells via PI3K-AKT-Driven Signaling Axis.
Low-temperature plasma (LTP) is an emerging biomedical technique that has been proposed as a potential approach for cancer therapy. Meanwhile, berberine (BER), an active ingredient extracted from various medical herbs, such as Coptischinesis, has been proven antitumor effects in a broad spectrum of cancer cells. In this study, we seek to develop a novel dual cancer therapeutic method by integrating pre-administration of BER and LTP exposure and evaluating its comprehensive antitumor effect on the human non-small-cell lung cancer (NSCLC) cell lines (A549 and H1299) in vitro. Cell viability, cell cycle, cell apoptosis, and intracellular and extracellular ROS were investigated. The results showed that cotreatment of BER and LTP significantly decreased the cell viability, arrested the cell cycle in the S phase, promoted cell apoptosis, and increased intracellular and extracellular ROS. Additionally, RNA Sequencing (RNA-Seq) technology was used to explore potential mechanisms. The differentially expressed genes among different treatment groups of NSCLC cells were analyzed and were mainly enriched in the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Moreover, cotreatment of BER and LTP notably depressed the total protein expression level of PI3K and AKT with immunoblotting. In conclusion, BER and LTP have a synergistic inhibitory effect on NSCLC cells via the PI3K-AKT signaling pathway, which could provide a promising strategy for supplementary therapy in the anti-NSCLC battle.


Metabolite-Sensing G Protein-Coupled Receptors-Facilitators of Diet-Related Immune Regulation.
Nutrition and the gut microbiome regulate many systems, including the immune, metabolic, and nervous systems. We propose that the host responds to deficiency (or sufficiency) of dietary and bacterial metabolites in a dynamic way, to optimize responses and survival. A family of G protein-coupled receptors (GPCRs) termed the metabolite-sensing GPCRs bind to various metabolites and transmit signals that are important for proper immune and metabolic functions. Members of this family include GPR43, GPR41, GPR109A, GPR120, GPR40, GPR84, GPR35, and GPR91. In addition, bile acid receptors such as GPR131 (TGR5) and proton-sensing receptors such as GPR65 show similar features. A consistent feature of this family of GPCRs is that they provide anti-inflammatory signals; many also regulate metabolism and gut homeostasis. These receptors represent one of the main mechanisms whereby the gut microbiome affects vertebrate physiology, and they also provide a link between the immune and metabolic systems. Insufficient signaling through one or more of these metabolite-sensing GPCRs likely contributes to human diseases such as asthma, food allergies, type 1 and type 2 diabetes, hepatic steatosis, cardiovascular disease, and inflammatory bowel diseases.


Simulation study of seemingly Fickian but heterogeneous dynamics of two dimensional colloids.
A two-dimensional (2D) solid lacks long-range positional order and is diffusive by means of the cooperative motion of particles. We find from molecular dynamics simulations of hard discs that 2D colloids in solid and hexatic phases show seemingly Fickian but strongly heterogeneous dynamics. Beyond translational relaxation time, the mean-square displacement is linear with time, t, implying that discs would undergo Brownian diffusion and the self-part of the van Hove correlation function [G(s)(r,t)] might be Gaussian. But dynamics is still heterogeneous and G(s)(r,t) is exponential at large r and oscillatory with multiple peaks at intermediate length. We attribute the existence of several such peaks to the observation that there are several clusters of discs with discretized mobility. The cluster of marginally mobile discs grows with time and begins to percolate around translational relaxation time while clusters of fast discs emerge in the middle of the marginally mobile cluster.


Nystatin-induced liposome fusion. A versatile approach to ion channel reconstitution into planar bilayers.
A simple method is described for promoting and detecting fusion of liposomes with planar bilayer membranes. Liposomes containing ergosterol are doped with the pore-forming antibiotic nystatin, and the planar bilayer is kept ergosterol-free. Under these conditions, when a transbilayer salt gradient is applied, liposomes added to the high-salt side of the bilayer elicit the appearance of abrupt conductance jumps of 5-300 pS. The increase in conductance is transient, decaying back to baseline on the order of 10 s. Each of these "spikes" represents the fusion of a single liposome with the bilayer, resulting in the simultaneous insertion of many nystatin channels. Relaxation of the conductance back to baseline occurs because ergosterol, required for the integrity of the nystatin pore, diffuses away into the sterol-free planar bilayer after liposome fusion. When Torpedo Cl- channels are reconstituted into liposomes containing ergosterol and nystatin, fusion spikes are observed simultaneously with the appearance of Cl- channels. This method allows the calculation of the density of functional ion channels in a preparation of proteoliposomes containing reconstituted channel protein.


T antigens' role in polyomavirus transformation: c-myc but not c-fos or c-jun expression is a target for middle T.
Polyoma virus (Py) causes neoplastic transformation in vitro and multiple tumors in vivo. The role played by large and middle T antigens (LT, MT) and their mechanisms of action are focused here. Py-transformed Balb-3T3 cells become independent of platelet-derived growth factor (PDGF) for growth. JE, c-fos, c-jun and c-myc are 'immediate early' genes induced in response to PDGF. To test whether these cellular genes play a role in malignant transformation by Py, we generated a number of transfectant cell lines overexpressing LT, MT or both. Characterization of these cell lines revealed that: (a) MT but not LT causes morphological transformation, ability to grow in agarose suspension; (b) cooperation between LT and MT is evident in vitro, however, high and simultaneous LT and MT expression does not warrant tumorigenic potential; (c) MT expression does not correlate with tumorigenic potential but alters the probability of eliciting tumors; (d) JE and c-myc (but not c-fos or c-jun) are constitutively expressed in MT transfectants. MT induction is followed by c-myc induction 1.5 h later. We conclude that some of the 'immediate-early' genes may play pivotal roles in Py transformation.


Endoscopic closure of a tracheal access site using bioglue after transtracheal thoracoscopy in a nonsurvival canine model.
An ideal wound closure device would repair the wound with minimal complexity. In this report, we describe a simple wound closure method using BioGlue sealant. Eleven canines underwent transtracheal pericardial window creation under endoscopic guidance for natural orifice transluminal endoscopic surgery (NOTES). The tracheal wound was closed using BioGlue sealant. The integrity of the wound was assessed by determining the amount of air leaking under mechanical ventilation. Transtracheal thoracic exploration and pericardial window creation was successful for all of the canines, and adequate wound closure was achieved in 10 of the canines. There was 1 case of NOTES-related death arising from misplacement of the endotracheal tube in the left lower lobar bronchus. This caused a collapse of the left upper lobe and ventilatory failure. Minor lung injuries occurred in 3 canines and minor mediastinal bleeding was encountered in 1 canine during the creation of the access site. BioGlue sealant was found to be effective in sealing the tracheal wound in all but 1 of the canines. This study demonstrates that the use of the sealant is a simple and efficient means of endoscopically closing the tracheal access site in NOTES.


Perinatal Management of Fetal Tumors.
Progress in the last three decades in prenatal genetic diagnosis and advancement in prenatal imaging and characterization of fetal anomalies have allowed better preparation in family counseling and afforded the opportunity to consider prenatal treatment for congenital defects that would have fatal outcomes, among them the fetal tumors. Advances in fetal therapy and surgical approaches including minimally invasive procedures, have permitted not just the survival of rare tumor cases but improved long-term outcomes. In this review, we described some of the most common fetal tumors and their recommended management with emphasis on in utero treatment options.


Comparative study of Japanese frozen elephant trunk device for open aortic arch repairs.
We performed a multicenter prospective comparative study to determine the impact of a Japanese frozen elephant trunk device on total arch replacement compared with conventional repair without it. Between 2016 and 2019, a total of 684 patients (frozen elephant trunk procedure; n = 369; conventional repair, n = 315) from 41 institutions were enrolled. The 2 procedures were selected according to each center's strategy. The frozen elephant trunk procedure was applied more for aortic dissection, whereas the conventional repairs were predominantly performed for aneurysms. In the former, only hypothermic circulatory arrest time was reduced among the intraoperative parameters. Although there were no differences in the 30-day and in-hospital mortality rates (0.8% and 1.6%, respectively, for the frozen elephant trunk procedure vs 0.3% and 0.6%, respectively, for conventional repair), the neurologic complication rates were significantly higher in stroke (5.7% vs 2.2%; P = .022) and paraplegia (1.6% vs 0%; P = .023). In the propensity score matching analyses using 11 variables, statistical significance disappeared in the differences for mortality and neurologic morbidity (stroke and paraplegia/paraparesis) rates of 194 patients of each group, although they were still higher for the frozen elephant trunk procedure. The early outcomes of total arch replacement with the frozen elephant trunk procedure were acceptable despite its higher prevalence of emergency or redo surgery, which was comparable to that of the conventional repair. This procedure had higher rates of spinal cord injury than the conventional repair, which is a disadvantage of this approach.


Pediatric prescribing practices and the FDA Black-box warning on antidepressants.
Since the FDA Black box warning in 2004, there has been a 58% drop in antidepressant use among children and adolescents with depression. Paralleling this decrease is an associated increase in completed suicides in youth. To date, no study has examined, on a clinician level, the changes in practice that have occurred subsequent to the FDA warning. To examine changes in pediatrician clinical practice resulting from the FDA warning on antidepressants. Subjects were recruited through a national program sponsored by the Canadian Pediatric Society that regularly surveys practicing pediatricians. The mail survey inquired about knowledge of the Black-box warning, whether their practice changed and reasons for changes in prescribing practices with antidepressants after the warning. We surveyed a total of 2395 pediatricians in Canada. Of the 1748 eligible pediatricians, 670 (38%) responded.Seventy-two percent (n = 484) of respondents were aware of the FDA warning. Of the 484 respondents who were aware of the warning, 80% (n = 386) changed their prescribing practices including 32% (n = 154) who followed their patients more closely. Seven percent (n = 35) stopped treatment with SSRIs in at least one patient. Physicians who had observed worsening depression/suicidality were more likely to discontinue treatment with SSRI's compared to those who had not observed these side effects previously (25% versus 6%, p < 0.001). This is the first national study to examine individual pediatrician practice changes in antidepressant use subsequent to the FDA warning. Further research is needed to better understand the reasons for these changes to aid in the development of strategies that could help clinicians to optimally integrate these warnings into clinical practice.


A streamlined, automated workflow to screen and triage large numbers of baculoviruses for protein expression.
The baculovirus expression system is a powerful and widely used method to generate large quantities of recombinant protein. However, challenges exist in workflows utilizing either liquid baculovirus stocks or the Titerless Infected-Cells Preservation and Scale-Up (TIPS) method, including the time and effort to generate baculoviruses, screen for protein expression and store large numbers of baculovirus stocks. To mitigate these challenges, we have developed a streamlined, hybrid workflow which utilizes high titer liquid virus stocks for rapid plate-based protein expression screening, followed by a TIPS-based scale-up for larger protein production efforts. Additionally, we have automated each step in this screening workflow using a custom robotic system. With these process improvements, we have significantly reduced the time, effort and resources required to manage large baculovirus generation and expression screening campaigns.


Employment experiences of vocationally trained doctors.
To investigate the expectations and employment experiences of male and female doctors who completed vocational training in East Anglia during 1981-7 and to examine the factors which had influenced those who had changed direction early in their careers. Survey conducted by confidential postal questionnaire. Britain. 281 doctors, 233 (83%) of whom responded. Ideal choice of work on completion of vocational training; present employment; factors which had restricted present choice of work; factors associated with reported satisfaction with job. 77/83 (93%) men and 130/150 (87%) women had hoped to work in general practice (p = 0.75). A smaller proportion of women (71%; 106) than men (89%; 74) were in general practice posts (p less than 0.01); only 6% (nine) of women were on maternity leave or caring for children without paid employment. More women than men were working in medical jobs other than general practice (18% (27) women v 4% (three) men; p less than 0.01). 44/91 (49%) women with children had achieved their employment goals compared with 47/59 (80%) women without children and 55/71 (78%) men with children. 87% (72/83) of men and 65% (98/150) of women had achieved the status of principal (p less than 0.01). 162/193 (84%) doctors who had worked in general practice reported satisfaction with their jobs. Dissatisfaction was linked with doing a job different from that hoped for and with perceiving that the share of practice income did not accurately reflect their share of the practice workload. Steps need to be taken to retain women in general practice, including a statutory part time pay allowance and incentives for practices to allow flexible working hours for doctors with young children.


Spinal glial activation and cytokine expression after lumbar root injury in the rat.
This study was designed to examine the behaviorial immunohistochemical changes of spinal glial cells and spinal Interleukin (IL)-1beta expression after various nerve root injuries used as models of lumbar radiculopathy. In order to better understand the role of central inflammation in the pathophysiologic mechanisms that give rise to pain associated with lumbar radiculopathy, this research studied the relationship between pain-related behavior associated with spinal glial activation and IL-1beta expression generated by three types of nerve root injury: loose ligation with chromic gut, loose ligation with silk, and tight ligation with silk. An animal model of lumbar radiculopathy originally described by Kawakami and Weinstein involved loose ligation of unilateral L4-L6 nerve roots with chromic gut. Characterization and establishment of such an animal model of low back pain enables further investigation of the nature of the pathophysiologic mechanisms associated with lumbar radiculopathy in humans. Seventy-three rats were divided into four treatment groups. Chromic group (n = 25): The L5 nerve roots (dorsal and ventral) were exposed by hemilaminectomy and loosely ligated with chromic gut. Tight silk group (n = 18): The exposed L5 nerve roots were tightly ligated extradurally with 5-0 silk suture. Loose silk group (n = 15): two loose ligatures of 5-0 silk were placed around the exposed L5 nerve roots. Sham group (n = 15): the rats were subjected to laminectomy alone for exposing nerve roots. Following surgery, thermal hyperalgesia and mechanical allodynia was assessed time-dependently up to 42 days post operatively. At 1, 3, 7, 14, and 42 days postoperatively, the rats in each group were perfused with fixative. The L5 spinal cord segments was harvested and cryosectioned for glial and cytokine immunohistochemistry. In the chromic and the tight silk group, an immediate and sustained mechanical allodynia was observed in the ipsilateral hind paw up to 35 days postoperatively. The loose silk group also showed an immediate mechanical allodynia that subsided by 14 days postoperatively. Sham-treated animals exhibited mild mechanicalallodynia for the initial 7 days after the surgery. Thermalhyperalgesia was evident in the three primary treatment groups, but not in the sham-treated rats. OX-42 expression was elevated in the gray matter of the L5 spinal section by 3 days in the chromic, the tight silk, and the loose silk groups as compared to the sham group. Astrocytic activation increased over time in all groups except the sham group. There was no direct correlation between degree of microglial response and severity of pain behaviors. In contrast, astrocytic activation demonstrated a direct relationship with the elevation of mechanical allodynia for the first 7 days. In addition, spinal IL-1beta protein expression was increased bilaterally in the superficial layer of the dorsal horn and cell nuclei of the ventral horns in the ligature treated groups as compared with the sham group. Direct mechanical and/or chemical injury to lumbar roots in the rat gives rise to pain behavior suggestive of lumbar radiculopathy. The finding that glial activation and enhanced IL-1beta expression are observed in the spinal cord after root injury supports a central, neuroimmune component in the generation of lumbar radiculopathy. A further understanding of the immunologic consequences of root injury may lead to further development and the novel use of selective cytokine-inflammatory inhibitors for the treatment of low back pain associated with radiculopathy.


Cerebrospinal fluid circulation: evaluation by single-photon and positron emission tomography.
Gamma camera cisternography after intrathecal administration of 111In-DTPA is a widely used and well established technique for studies of cerebrospinal fluid (CSF) circulation. The radiation dose from 111In, however, is a limiting factor that sometimes seriously affects the image quality and, hence, correct interpretation. This investigation was designed to assess the value of tomographic techniques for studies of CSF flow. Single-photon emission computed tomography (SPECT) was performed on 15 patients by means of the Karolinska Hospital rotating gamma camera system after injection of 111In-DTPA or 99mTc-DTPA. The combination of SPECT and 99mTc-DTPA proved to be a valuable technique. It permits a clear evaluation of the location of the isotope intracranially and its precise relation to the ventricles. Positron emission tomography (PET) applied after intrathecal administration of 68Ga-EDTA demonstrates that small amounts of radioactivity can be registered and that PET is a promising technique for the evaluation of CSF dynamics.


Diagnostic yield of emergency department arch-to-vertex CT angiography in patients with suspected acute stroke.
Our aim was to investigate how often relevant diagnostic findings in an arch-to-vertex CTA scan, obtained specifically as part of the acute stroke CT protocol, are located in the head, neck, and upper chest regions. Radiology reports were reviewed in 302 consecutive patients (170 men, 132 women; median ages, 66 and 73 years, respectively) who underwent emergency department investigation of suspected acute stroke between January and July 2010. Diagnostic CTA findings relevant to patient management were recorded for the head, neck, and chest regions individually. Additionally, the contributions to the total CTA scan effective dose were estimated from each of the 3 anatomic regions by using the ImPACT CT Dose Calculator. Of the 302 patients, 161 (54%) had relevant diagnostic findings in the head; 94 (31%), in the neck; and 4 (1%), in the chest. The estimated contributions to the total CTA scan dose from each body region, head, neck, and upper chest, were 14 ± 2%, 33 ± 5%, and 53 ± 6%, respectively. Most clinically relevant findings are in the head and neck, supporting inclusion of these regions in arch-to-vertex CTA performed specifically in patients with acute stroke in the emergency department. Further studies are required to investigate extending the scan to the upper chest because only 1% of patients in our study had clinically relevant findings in the mediastinum, yet half the CTA effective dose was due to scanning in this region.


Comparison of subclavian vein to inferior vena cava collapsibility by ultrasound in acute heart failure: A pilot study.
Management of acute decompensated heart failure (ADHF) requires accurate assessment of relative intravascular volume, which may be technically challenging. Inferior vena cava (IVC) collapsibility with respiration reflects intravascular volume and right atrial pressure (RAP). Subclavian vein (SCV) collapsibility may provide an alternative. The purpose of this study was to examine the relationship between SCV collapsibility index (CI) and IVC CI in ADHF. This was a prospective study of non-ventilated patients with ADHF who had paired IVC and SCV ultrasound assessments. As SCV CI is highly position-dependent, measurements were performed supine at 30-45°. Thirty-three patients were included with 36 encounters. The sample size was adequately powered for receiver-operator characteristic (ROC) analysis. SCV CI correlated with IVC CI during relaxed breathing (R = .65, n = 36, p < .001) and forced inhalation (R = .47, n = 36, p = .0036). SCV CI < 22% and >33% corresponded to IVC CI < 20% and >50% suggesting hypervolemia (sensitivity/specificity: 72%) and hypovolemia (sensitivity/specificity: 78%), respectively. Moderate to severe tricuspid regurgitation (TR) compared to less than moderate TR was associated with lower SCV CI (medians: 12.4% vs. 25.3%, p = .022) and IVC CI (medians: 9.6% vs. 35.6%, p = .0012). SCV CI and IVC CI were not significantly different among chronic kidney disease stages. In non-ventilated ADHF, SCV CI at 30-45° correlates with paired IVC CI, and may provide an alternative to IVC CI for assessment of relative intravascular volume, which may facilitate clinical management. Moderate to severe TR decreases SCV CI and IVC CI and may result in overestimation of relative intravascular volume.


Functional Outcomes and Complications After Salvage Total Laryngectomy for Residual, Recurrent, and Second Primary Squamous Cell Carcinoma of the Larynx and Hypopharynx: A Multicenter Retrospective Cohort Study.
Background/Purpose: We analyzed complications and functional outcomes and aimed at identifying prognostic factors for functional outcomes and complications in patients who underwent salvage total laryngectomy (STL) for residual, recurrent, and second primary squamous cell carcinoma (SCC) of the larynx and hypopharynx after initial (chemo)radiation. Methods: Retrospective cohort study of patients who underwent STL in four major Belgian reference hospitals between 2002 and 2018. Prognostic factors for functional outcomes and complications were identified with uni- and multivariable analysis. Results: A total of 405 patients were included in the final analysis. STL was performed for residual tumor (40.2%), local recurrence (40.5%), or second primary laryngeal or hypopharyngeal SCC (19.4%). Early postoperative complications were experienced by 34.2% of patients: postoperative hemorrhage occurred in 5.4%, wound infection in 16.2%, and clinical pharyngocutaneous fistula (PCF) in 25.5% of patients. Early readmission proved necessary in 15.1% of cases, most often due to late PCF development (72.2%). Patients achieved total peroral intake in 94.2% of cases. However, subjective dysphagia was reported by 31.3% of patients during follow-up. Functional speech, defined as functional communication by speech without additional aids, was reported in 86.7% of cases and was most often achieved by tracheo-esophageal puncture (TEP) (94.1%). In a multivariable model, lower preoperative hemoglobin (<12.5 g/dl) was identified as an independent prognostic factor for higher overall complication rate. No risk factors were found significant for clinical fistula formation. Vascularized tissue augmentation did not significantly prevent clinical PCF. Patients with positive section margins, patients initially treated with surgery combined with adjuvant RT (vs. radiotherapy alone), and those developing PCF after STL were less likely to achieve total peroral intake. Postoperative dysphagia proved more likely in patients who developed a PCF postoperatively, and less likely in patients who underwent STL without partial pharyngectomy and in patients with myocutaneous pectoralis major (PM) flap reconstruction, compared to muscle onlay PM flap. Achieving postoperative functional speech proved most likely in patients with smaller tumors (lower pT classification) and free section margins. Conclusion: Substantial complication rates and favorable functional outcomes are reported after STL.


Phacoemulsification induced transient swelling of corneal Descemet's Endothelium Complex imaged with ultra-high resolution optical coherence tomography.
Thickness changes of corneal sub-layers after phacoemulsification were investigated by spectral domain ultra-high resolution optical coherence tomography (UHR-OCT). The corneas (n = 26) of 26 age-related cataract surgery patients were studied. UHR-OCT was used to evaluate the thickness of Descemet's Endothelium Complex (DEC), stroma, Bowman's layer, epithelium, and full cornea at the center (CCT) before, one day after, and one week after surgery. Non-contact specular microscopy measured CCT, endothelial cell density, and morphology. The DEC, stroma, Bowman's layer, and epithelium were visualized by UHR-OCT. Before surgery, the DEC in all cases appeared as a translucent space between two smooth opaque lines. One day after surgery, the posterior corneal surfaces in half of the eyes were wavy and irregular. Compared to the baseline, one day after surgery the thickness increases of the DEC, stroma, and CCT were 4.3 ± 2.6 µm, 25.5 ± 24.9 µm, and 32.1 ± 26.6 µm, respectively (P < 0.001). The morphology of the DEC and the CCT recovered to baseline one week after surgery (P > 0.05), but endothelial cell density was 8.7% less than at baseline. There were no significant changes in Bowman's layer and epithelium after the operation. The pre-operative DEC thickness was positively correlated with the decreased endothelial cell density at 1 day after surgery (r = 0.55, P = 0.003). The DEC showed edematous thickening and different degrees of morphological changes after phacoemulsification. The DEC deformation and corneal edema recovered by one week after surgery, which indicated recovery of endothelial function. UHR-OCT is a useful tool to evaluate function of the DEC after phacoemulsification. Pre-operative DEC thickness may indicate the integrity of the endothelium and could be used for predicting endothelial cell loss after phacoemulsification.


A Statewide Model for Assisting Nursing Home Residents to Transition Successfully to the Community.
Minnesota's Return to Community Initiative (RTCI) is a novel, statewide initiative to assist private paying nursing home residents to return to the community and to remain in that setting without converting to Medicaid. The objective of this manuscript is to describe in detail RTCI's development and design, its key operational components, and characteristics of its clients and their care outcomes. Data on client characteristics and outcomes come from the Minimum Data Set, staff assessments of clients and caregivers, and Medicaid eligibility files. Most clients transitioned by the RTCI had entered the nursing facility from a hospital. Clients overwhelmingly wanted to return to the community and fit a health and functional profile making them good candidates for community discharge. Most clients went to a private residence, living alone or with a spouse; yet, adult children were the most frequent caregivers. At one year of follow-up 76% of individuals were alive and living in the community and only a small percentage (8.2%) had converted to Medicaid. The RTCI holds promise as a successful model for states to adopt in assisting individuals who are at risk to become long stay nursing home residents instead to return to the community.


Progression of hydroxychloroquine toxic effects after drug therapy cessation: new evidence from multimodal imaging.
Given the infrequent occurrence of hydroxychloroquine toxic effects, few data are available about the presenting features and long-term follow-up of patients with hydroxychloroquine retinopathy, making it difficult to surmise the clinical course of patients after cessation of drug treatment. To report functional and structural findings of hydroxychloroquine retinal toxic effects after drug therapy discontinuation. A retrospective medical record review was performed to identify patients taking hydroxychloroquine who were screened for toxic effects from January 1, 2009, through August 31, 2012, in the eye centers of Northwestern University and the University of Southern California. Northwestern University Sorrel Rosin Eye Center, Chicago, Illinois, and the Doheny Eye Institute at the University of Southern California, Los Angeles. Seven consecutive patients diagnosed as having hydroxychloroquine retinal toxic effects. Retinal toxic effects. Seven patients (1 man and 6 women) with a mean age of 55.9 years (age range, 25-74 years) developed retinal toxic effects after using hydroxychloroquine for a mean of 10.4 years (range, 3-19 years). Fundus examination revealed macular pigmentary changes in all 7 patients, corresponding to abnormal fundus autofluorescence (FAF). On spectral domain optical coherence tomography, there was outer retinal foveal resistance (preservation of the external limiting membrane and the photoreceptor layer) in 6 patients. After drug therapy discontinuation, 5 patients experienced outer retinal regeneration (3 subfoveally and 2 parafoveally), with associated functional visual improvement on static perimetry in 2 patients. Over time, FAF remained stable in 3 patients, whereas the remaining patients had a pattern of hypoautofluorescence that replaced areas of initial hyperautofluorescence (2 patients) and enlargement of the total area of abnormal FAF (2 patients). Preservation of the external limiting membrane carries a positive prognostic value in hydroxychloroquine toxic effects because it may be associated with regeneration of the photoreceptor layer and with potential functional visual improvement on static perimetry. The patterns of abnormal FAF persist despite cessation of the medication, with enlargement of the total area of abnormal FAF being the hallmark of severe toxic effects. Relative foveal resistance in hydroxychloroquine toxic effects was supported by this case series. These findings emphasize the importance of early detection and the need for correlating clinical observations with multimodal imaging, particularly FAF and spectral domain optical coherence tomography.


The In Vivo Effects of the CB1-Positive Allosteric Modulator GAT229 on Intraocular Pressure in Ocular Normotensive and Hypertensive Mice.
Orthosteric cannabinoid receptor 1 (CB1) activation leads to decreases in intraocular pressure (IOP). However, use of orthosteric CB1 agonists chronically has several disadvantages, limiting their usefulness as clinically relevant drugs. Allosteric modulators interact with topographically distinct sites to orthosteric ligands and may be useful to circumvent some of these disadvantages. The purpose of this study was to investigate the effects of the novel CB1-positive allosteric modulator (PAM) GAT229 on IOP. IOP was measured using rebound tonometry in anesthetized normotensive C57Bl/6 mice and in a genetic model of ocular hypertension [nose, eyes, ears (nee) mice] before drug administration, and at 1, 6, and 12 h thereafter. In normotensive mice, topical administration of 5 μL GAT229 alone at either 0.2% or 2% did not reduce IOP. However, a subthreshold dose (0.25%) of the nonselective orthosteric CB1 agonist WIN 55,212-2, when combined with 0.2% GAT229, significantly reduced IOP compared with vehicle at 6 and 12 h. Similarly, combination of subthreshold Δ9-tetrahydrocannabinol (a nonselective orthosteric CB1 agonist; 1 mg/kg) with topical 0.2% GAT229 produced IOP lowering at 6 h. In nee mice, administration of topical 0.2% GAT229 or 10 mg/kg GAT229 alone was sufficient to lower IOP at 6 and 12 h, and 12 h, respectively. The CB1 PAM GAT229 reduces IOP in ocular hypertensive mice and enhanced CB1-mediated IOP reduction when combined with subthreshold CB1 orthosteric ligands in normotensive mice. Administration of CB1 PAMs may provide a novel approach to reduce IOP with fewer of the disadvantages associated with orthosteric CB1 activation.


Review of the Psychodinae from Mallorca, Spain, with description of Pericoma unipennata, sp. n. (Diptera, Psychodidae).
We review the Psychodinae of Mallorca, recognising fifteen species based on recent collections and available literature. Previously unpublished data is presented for eleven species, of which Neoarisemus ibericus Wagner, 1978, Mormia tenebricosa (Vaillant, 1954), Clogmia albipunctata (Williston, 1893), Lepiseodina rothschildi (Eaton, 1913), Paramormia ustulata (Walker, 1856), Philosepedon pyrenaicus Vaillant, 1974 and Psychoda (Psycha) grisescens Tonnoir, 1922 are first records for Mallorca. An old record of Pericoma trifasciata (Meigen, 1804) is considered doubtful. Pericoma unipennata sp. n is described and illustrated based on a male collected at Deía. Distributional data are reviewed for all newly recorded species. Based on the Psychodinae fauna, the zoogeographical affinities of Mallorca are briefly discussed.


Effects of nitrogen sources on production and composition of sophorolipids by Wickerhamiella domercqiae var. sophorolipid CGMCC 1576.
The effects of nitrogen sources on growth of sophorolipid-producing yeast, Wickerhamiella domercqiae var. sophorolipid CGMCC 1576 and on production and composition of sophorolipids were studied. Organic nitrogen sources are more favorable for accumulation of biomass than inorganic ones. Presence of ammonium ion from different inorganic nitrogen sources (except NH(4)HCO(3)) greatly inhibited the production of lactonic sophorolipids. However, when organic nitrogen sources were used, lactonic sophorolipid production was strongly increased. Production of crystalline lactonic sophorolipids from organic/inorganic nitrogen sources was enhanced with the increase of pH value adjusted by sodium hydroxide or sodium citrate solution. Fourier-transform infrared (FT-IR), gas chromatography mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), and mass spectra (MS) were employed to compare the composition of sophorolipid mixture obtained from different nitrogen sources. More than 15 acidic sophorolipid molecules and only 4 lactonic sophorolipid molecules were produced by using 1.27 g/l ammonium sulfate as nitrogen source; they were separated by preparative HPLC and their structures were elucidated by MS. These results suggest extraordinary regulatory effects of nitrogen source on growth and sophorolipid synthesis of W. domercqiae var. sophorolipid.


Prevention of the Evolution of Workers' Hearing Loss from Noise-Induced Hearing Loss in Noisy Environments through a Hearing Conservation Program.
Introduction Noise-induced hearing loss (NIHL) is a serious problem for workers and therefore for businesses. The hearing conservation program (HCP) is a set of coordinated measures to prevent the development or evolution of occupational hearing loss, which involves a continuous and dynamic process of implementation of hearing conservation routines through anticipation, recognition, evaluation, and subsequent control of the occurrence of existing environmental risks or of those that may exist in the workplace and lead to workers' hearing damage. Objective The aim of this study was to evaluate the effectiveness of the HCP in preventing further hearing loss in workers with audiograms suggestive of NIHL. The audiometric tests and medical records of 28 furniture company workers exposed to noise were reviewed and monitored for 2 years. Methods This retrospective, cross-sectional study examined five audiometric tests in the medical records (on admission and every semester) of 28 workers in a furniture company (totaling 140 audiometric exams) following the introduction of the HCP. Results Data analysis showed no differences between the audiometric tests conducted on admission and those performed every semester. Conclusions The HCP implemented was effective in preventing the worsening of hearing loss in workers already with NIHL when exposed to occupational noise. Therefore, such a measure could be useful for the employment of workers with hearing loss in job sectors that have noise exposure.


The generation of concentration gradients using electroosmotic flow in micro reactors allowing stereoselective chemical synthesis.
The stereoselective control of chemical reactions has been achieved by applying electrical fields in a micro reactor generating controlled concentration gradients of the reagent streams. The chemistry based upon well-established Wittig synthesis was carried out in a micro reactor device fabricated in borosilicate glass using photolithographic and wet etching techniques. The selectivity of the cis (Z) to trans (E) isomeric ratio in the product synthesised was controlled by varying the applied voltages to the reagent reservoirs within the micro reactor. This subsequently altered the relative reagent concentrations within the device resulting in Z/E ratios in the range 0.57-5.21. By comparison, a traditional batch method based on the same reaction length, concentration, solvent and stoichiometry (i.e., 1.0:1.5:1.0 reagent ratios) gave a Z/E in the range 2.8-3.0. However, when the stoichiometric ratios were varied up to ten times as much, the Z/E ratios varied in accordance to the micro reactor i.e., when the aldehyde is in excess, the Z isomer predominates whereas when the aldehyde is in low concentrations, the E isomer is the more favourable form. Thus indicating that localised concentration gradients generated by careful flow control due to the diffusion limited non-turbulent mixing regime within a micro reactor, leads to the observed stereo selectivity for the cis and trans isomers.


Unveiling Enhanced Electrostatic Repulsion in Silica Nanosphere Assembly: Formation Dynamics of Body-Centered-Cubic Colloidal Crystals.
We demonstrate the effective establishment of long-range electrostatic interactions among colloidal silica nanospheres through acid treatment, enabling their assembly into colloidal crystals at remarkably low concentrations. This novel method overcomes the conventional limitation in colloidal silica assembly by removing entrapped NH4+ ions and enhancing the electrical double layer (EDL) thickness, offering a time-efficient alternative to increase electrostatic interactions compared with methods like dialysis. The increased EDL thickness facilitates the assembly of SiO2 nanospheres into a body-centered-cubic lattice structure at low particle concentrations, allowing for broad spectrum tunability and high tolerance to particle size polydispersity. Further, we uncover a disorder-order transition during colloidal crystallization at low particle concentrations, with the optimal concentration for crystal formation governed by both thermodynamic and kinetic factors. This work not only provides insights into assembly mechanisms but also paves the way for the design and functionalization of colloidal silica-based photonic crystals in diverse applications.


Temporal trends in the population structure of Bordetella pertussis during 1949-1996 in a highly vaccinated population.
The population structure of Bordetella pertussis in The Netherlands in 5 successive periods, encompassing 1949-1996, was analyzed by DNA typing ("fingerprinting"). In 10 years following the introduction of wide-scale vaccination in 1953, a decrease in genotypic diversity (GD) was observed, suggesting clonal expansion of strains that were adapted to vaccine-induced immunity. In subsequent periods, GD increased to prevaccination levels, probably reflecting a gradual adaptation of the B. pertussis population involving many lineages. In the 1990s, GD decreased again. This decrease coincided with an antigenic shift in the surface protein pertactin. No evidence was found for changes in DNA types or GD in 1996, when a large pertussis epidemic occurred. Thus, gradual changes in the bacterial population previous to 1996 were probably the cause of the 1996 epidemic. The results herein suggest that vaccination has selected for strains that are adapted to a highly vaccinated population. Similar changes may have occurred in other countries, explaining the reemergence of pertussis in vaccinated populations.


Exploring binding mode for styrylquinoline HIV-1 integrase inhibitors using comparative molecular field analysis and docking studies.
To understand pharmacophore properties of styrylquinoline derivatives and to design inhibitors of HIV-1 integrase. Comparative molecular field analysis (CoMFA) was performed to analyze three-dimensional quantitative structure-activity relationship (3D-QSAR) of styrylquinoline derivatives. Thirty-eight compounds were randomly divided into a training set of 28 compounds and a test set of 10 compounds. The stability of 3D-QSAR models was proved by the analysis of cross-validated and non-cross-validated methods. Moreover, the binding mode of these compounds and integrase was constructed by AutoDock program. The CoMFA model of the training compounds was reasonably predicted with cross-validated coefficient (q2) and conventional (r2) values (up to 0.696 and 0.754). Then the model was validated by the test set. The resulting CoMFA maps visualized structural requirements for the biological activity of these inhibitors. Docking results showed that a carboxyl group at C-7 and a hydroxyl group at C-8 in the quinoline subunit, bound closely to the divalent metal cofactor (Mg2+) around the integrase catalytic site. Moreover, there is a linear correlation between the binding energy of the inhibitors with integrase and their inhibitory effect. The present study indicated that the CoMFA model together with docking results could give us helpful hints for drug design as well as interpretation of the binding affinity between these inhibitors and integrase.


Validation of Cross-Individual Pain Assessment with Individual Recognition Model from Electroencephalogram.
Cross-individual pain assessment models based on electroencephalography (EEG) allow pain assessment in individuals who cannot report pain (e.g., unresponsive patients). The main obstacle to the generalisation of pain assessment models is the individual variation of brain responses to pain. Hence, we took the individual variation into account in cross-individual model development. We developed two convolutional neural networks (CNN) sharing an encoder architecture. One CNN predicts pain, while the other predicts the identity of an individual. We performed a leave-one-out (LOO) test with the exclusion of each subject and applied evidence accumulation to it for validating the pain prediction model's performance, where the binary classifier involves the states of pain (Hot) and resting state (Eyes-open). The mean accuracy produced by the LOO tests was 57.81% (max: 73.33%), and the mean accuracy of evidence accumulation achieved 69.75% (max: 100.00%). The individual recognition model achieved an accuracy of 99.63%. Nevertheless, when we acquired the most similar subject to a novel subject using the individual recognition model, where the most similar subject was used to train a subject-wise pain prediction model. The accuracy of predicting the pain-related conditions of the novel subject by the subject-wise model was only 53.73% (max: 79.50%). Therefore, the approach to utilising the features related to individual variation extracted by the CNN model needs more investigation for improving cross-individual pain assessment.Clinical relevance- This model can be applied to assess pain from EEG signals at the bedside with future improvement, which can help caretakers of unresponsive patients.


Evidence for permanent enhancement of residual ADH induced by antidiuretic agents (chlorpropamide, carbamazepine, clofibrate) in patients with pituitary diabetes insipidus.
Excretion of free water was studied in 7 patients with pituitary diabetes insipidus before treatment and after withdrawal of antidiuretic drugs (chlorpropamide, carbamazepine, clofibrate) used on a long-term basis. A statistically significant decrease in free water clearance was found after 2-4 weeks of withdrawal of antidiuretic agents. This was considered as a clinical evidence for the permanently enhanced release of residual ADH induced by chlorpropamide, carbamazepine and clofibrate in patients with partial defect in ADH secretion.


Use of a monoclonal antibody in the detection of HBsAg in the liver by immunofluorescence.
IF and IP techniques using conventional antibodies have been successfully applied in the detection of tissue HBsAg. However, they present problems related to specificity and sensitivity as well as in the recognition of the membranous expression of HBsAg. In this study two monoclonal antibodies to HBsAg have been used in the indirect IF and IP techniques for HBsAg demonstration in cryostat and paraffin sections of liver and other tissues (kidney, skin). The results were compared for specificity, sensitivity and histochemical patterns to those obtained by the same techniques with conventional anti-HBs antibodies of human and animal origin (rabbit, guinea-pig, baboon). IF staining with 1:40 dilution of an IgG2a monoclonal anti-HBs (5 C3) using a second layer of absorbed FITC-conjugated anti-mouse antibody, was superior as compared to IP and IF with conventional antibodies. It worked successfully both on frozen and paraffin sections. The main advantages compared to conventional antibodies were: absolute specificity with completely negative background staining, clear-cut demonstration of weak HBsAg reactions usually unrecognizable by conventional antibodies to HBsAg and unequivocal recognition of the membranous HBsAg expression on the surface of hepatocytes. The latter was frequently observed not only in patients with chronic liver disease but also in healthy HBsAg carriers, thus suggesting that surface expression of HBsAg is unrelated to the pathogenesis of HBV-induced chronic liver damage.


"What else is there to do?"--A qualitative study of the barriers to soldiers stopping smoking.
To investigate the impact of Army life on soldiers' motivation for stopping smoking. A two stage study using a questionnaire to identify smokers in a British Army infantry battalion of 560 soldiers based in the United Kingdom with either a low or high intention to quit smoking, followed by semi-structured interviews of a purposive sample of 18 respondents. 31.3% of soldiers were current smokers. In addition to recognised barriers to stopping smoking, the interview data revealed structural and cultural barriers, some of which are unique to the Army. Structural barriers included an increased opportunity to smoke in terms of time, place, and cost. Cultural barriers included peer pressure, the smoking norm, and a lack of discouragement from the 'regimental family'. These barriers to stopping smoking often arise from established British Army values and standards. For example, the need for punctuality requires early arrival at destinations, which in turn, provides an increased time opportunity to smoke. Other attitudes that the Army wishes to encourage, such as building teamwork and interdependence, can also be enhanced through smoking. Whilst the numerous, previously identified barriers to stopping smoking exist within and outside the armed forces, specific additional barriers arise from the structure and culture of the Army. Changes in the structure of daily life within the Army may reduce the barriers to stop smoking. Army clinicians also play an important part in soldiers' stopping smoking and an increased understanding of the specific barriers to stopping smoking may help them to support soldiers more effectively.


An overview of war-related thermal injuries.
Thermal injuries have always been a source of morbidity and mortality in times of war. Historically, they constitute 5% to 20% of all injuries and approximately 4% mortality. Although burn patients constitute a small number of casualties, they consume a disproportionate amount of resources and require specialized care. The current conflicts in the Middle East report similar numbers for thermal injuries despite improvement in predeployment education to reduce noncombat-related burns, flame retardant military clothing, and decline of war patterns usually associated with increased thermal injuries. However, the increased use of improvised explosive devices and vehicle-borne improvised explosive devices presents a new source of potential thermal injury. Indeed, the burden of explosion-related burns has increased as has its associated Injury Severity Score. As has been the case in previous conflicts, most burns are hand and head burns. Although usually not life threatening, burns to hands and face lead to significant physical and psychologic morbidities. In this paper, we will review the currently available literature on war-related thermal injuries in Operation Iraqi and Operation Enduring Freedom. We will describe the epidemiology of burn injuries, prewar preparation to prevent and treat thermal injuries, and the assessment, triage, and final treatment of burn patients. In addition, we will discuss the associated physical and psychologic morbidities and, finally, the role of plastic surgeon in burn rehabilitation and reconstruction.


Win-loss parameters for right-censored event data, with application to recurrent events.
The win ratio has become a popular method for comparing multiple event data between two groups in clinical cohort studies. The win ratio compares the event data in prioritized order, where the first prioritized event is death and a typical example for the second prioritized event is hospitalization. Literature is sparse on inference for win and loss parameters, including the win ratio, for censored event data. Inference for two prioritized censored event times has been developed for independent right-censoring. Many clinical studies include recurrent event data such as hospitalizations. In this article, we suggest inference for win-loss parameters for death and a recurrent event outcome under independent right-censoring. The small sample properties of the proposed method are studied in a simulation study showing that the variance formula is accurate even for small samples. The method is applied on a data set from a randomized clinical trial.


Hypothalamic expression of serotonin 1A, 2A and 2C receptor and GAD67 mRNA in female cynomolgus monkeys with different sensitivity to stress.
Like women, female cynomolgus monkeys show differential sensitivity to stress-induced reproductive dysfunction. A combined social and metabolic stress (mild diet+moderate exercise+relocation) will rapidly induce anovulation in a third of female cynomolgus monkeys (stress-sensitive; SS); a third will ovulate once and then become anovulatory (medium stress-resilient; MSR) and a third are highly stress-resilient (HSR) and exhibit normal menstrual cycles through two stressed menstrual cycles. In a non-stressed menstrual cycle, SS animals have lower levels of estrogen and progesterone, lower activity of the serotonin system and lower expression of genes related to the serotonin system in the dorsal raphe nucleus. In this study, we examined the expression of 5HT1A, 5HT2A, 5HT2C receptors and GAD67 in the hypothalamus of SS, HSR and MSR monkeys using in situ hybridization. SS monkeys exhibited higher expression of 5HT2A mRNA in the paraventricular nucleus (PVN), higher expression of 5HT2C and GAD67 in the infundibulum, as well as higher expression of GAD67 in the posterior hypothalamus (PH), compared with HSR monkeys. However, the expression of 5HT1A mRNA in the ventromedial nucleus (VMN) was not different between groups. We speculate that the serotonin and GABA systems may be altered in the stress-response and reproductive-related circuits of SS monkeys, and may be participating in altering the sensitivity of the reproductive system to stress in these individuals.


Overcoming barriers to prevention, care, and treatment of hepatitis C in illicit drug users.
Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) in the United States and other developed countries. HCV infection is a complex and challenging medical condition in injection drug users (IDUs). Elements of care for hepatitis C in illicit drug users include prevention counseling and education; screening for transmission risk behavior; testing for HCV and human immunodeficiency virus infection; vaccination against hepatitis A and B viruses; evaluation for comorbidities; coordination of substance-abuse treatment services, psychiatric care, and social support; evaluation of liver disease; and interferon-based treatment for HCV infection. Caring for patients who use illicit drugs presents challenges to the health-care team that require patience, experience, and an understanding of the dynamics of substance use and addiction. Nonetheless, programs are successfully integrating hepatitis C care for IDUs into health-care settings, including primary care, methadone treatment and other substance-abuse treatment programs, infectious disease clinics, and clinics in correctional facilities.


Drug utilization review of sedative/hypnotic agents in Texas Medicaid patients. Texas Medicaid Vendor Drug Program Drug Utilization Review Board.
To assess use of sedative/hypnotic agents in Texas Medicaid patients and evaluate practitioner receptiveness to intervention letters concerning sedative/hypnotic prescribing generated by the Texas Medicaid Drug Utilization Review (DUR) Board. Retrospective DUR. Texas Medicaid retrospective DUR program. 244 Texas Medicaid patients and 291 Texas physicians. Patient profiles for Texas Medicaid patients were reviewed retrospectively to quantify sedative/hypnotic prescribing practices. Intervention letters were prepared and sent to physicians directly involved in the care of patients receiving excessive sedative/hypnotic therapy. Physician responses were categorized based on information presented in the intervention letter and circumstances surrounding the identified patient. Prescribing practices were assessed approximately 1 year after the intervention to determine the impact of intervention letters on prescribing. Physician response to intervention letter. Responses were received from 208 of 291 physicians (71.5%). Approximately 40% of physicians agreed in principle with the suggestions offered by the Texas Medicaid DUR Board to minimize chronic sedative/hypnotic use. Almost one-half of these physicians had discontinued sedative/hypnotic therapy for the identified patients 1 year after the intervention. Approximately 9% justified continued sedative/hypnotic use based on patient diagnosis or refractory response to treatment, and 55 physicians (26.4%) were unwilling to alter therapy because of patient-specific factors. Through the use of retrospective DUR, Texas Medicaid patients receiving excessive amounts of sedative/hypnotic agents were identified and improvements in sedative/hypnotic therapy were initiated. DUR can be useful not only in identifying problem areas, but also in encouraging physicians to modify prescribing practices through educational means.


Profilometry with a coherence scanning microscope.
Coherence scanning microscopy is a new technique in high resolution imaging. It shares many of the features of confocal microscopy but uses coherence effects to enhance the lateral and longitudinal resolution rather than physical apertures. This approach has two significant implications for profilometry: the longitudinal resolution is decoupled from the lateral resolution, and interference effects can be used to further enhance the longitudinal resolution. We detail the features of coherence scanning profilometry and give some examples.


Activation of compensatory pathways via Rac2 in the absence of the Cdc42 effector Wiskott-Aldrich syndrome protein in Dendritic cells.
There is extensive crosstalk between different Rho GTPases, including Cdc42, Rac1, and Rac2, and they can activate or inhibit the activity of each other. Dendritic cells express both Rac1 and Rac2. Due to posttranslational modification of lipid anchors, Rac1 localizes mainly to the plasma membrane whereas Rac2 localizes to the phagosomal membrane where it assembles the NADPH complex. Our recent study of primary immunodeficiency disease caused by mutations in the Cdc42 effector Wiskott-Aldrich syndrome protein (WASp) has shed light on the compensatory mechanisms between Rho GTPases and their effector proteins. WASp-deficient dendritic cells have increased localization and activity of Rac2 to the phagosomal membrane and this allows antigen to be presented on MHC class I molecules to activate cytotoxic CD8+ T cells. This study reveals an intricate balance between Rac2 and WASp signaling pathways and provides an example of compensatory pathways in cells devoid of the Cdc42 effector WASp.


Estimating the relative risk of pancreatic cancer associated with exposure agents in job title data in a hierarchical Bayesian meta-analysis.
The study demonstrates the application of a hierarchical Bayesian meta-analysis of epidemiologic studies that show an association between pancreatic cancer risk and job titles, using a job-exposure matrix to estimate risks for occupational exposure agents. Altogether 261 studies published from 1969 through 1998 on pancreatic cancer and job titles were identified. When proportional studies are excluded, 77 studies were informative for 9 selected occupational agents. These studies included more than 3799 observed pancreatic cancer cases. Hierarchical Bayesian models were used for job titles (lower-level data) and agents (higher-level data), the latter from a Finnish job-exposure matrix. Non-Bayesian random effects models were applied for job titles to check consistency with the Bayesian results. The results suggest that occupational exposures to chlorinated hydrocarbon compounds may increase the risk of pancreatic cancer; the meta-relative risk (MRR) was 2.21 [95% credible interval (CrI) 1.31-3.68]. A suggestive weak excess was found for exposure to insecticides (MRR 1.95, 95% CrI 0.51-7.41). Hierarchical models are applicable in meta-analyses when studies addressing the agent(s) under study are lacking or are very few, but several studies address job titles with potential exposure to these agents. Hierarchical meta-analytic models involving durations and intensities of exposure to occupational agents from a job-exposure matrix should be developed.