Raising the quality of care during medical missions: a survey to assess the need for clinical and anatomic pathology services in international medical missions.
Providing basic medical care to patients in underserved communities around the world is a valuable service and should not be compromised. Limited publicly available information on the use of pathology services during short-term medical missions (STMMs) shows a dire need for the improved quality of care being provided. To assess the need for clinical and anatomic pathology services in international medical missions by conducting an online survey. A survey containing 35 questions aimed to understand the current use and availability of routine laboratory tests during STMMs, identify the need for particular tests that would improve quality of care, and determine the perceived obstacles preventing the delivery of the care to underserved communities worldwide. Answers from 21 health care providers who served on 50 medical missions were assessed. Survey results revealed a significant discrepancy between the availability of pathology services in the United States and during STMMs. Statistical significance (P< .001) was found in areas of routine blood work, cytopathology, and histologic evaluation, among many others. More than half of the STMMs did not have access to basic metabolic panel, rapid hepatitis B test, and microbial cultures. Another 28% of health care providers indicated that having human immunodeficiency virus testing would have improved health care quality. Survey results show the need for improved pathology support during STMMs. The lack of precise diagnosis and disease monitoring has a negative effect on the quality of care provided during missions and the ability to enhance global health.


Edematous wall thickening of the gallbladder induced by hyperthyroidism: A case report.
Hyperthyroidism, such as Basedow disease, causes fluid retention, although the common cause is volume overload due to congestive heart failure. In addition, hyperthyroidism and Basedow disease are known to cause pulmonary hypertension. Edematous thickening of the gallbladder wall is caused by venous blood congestion. The feature of edematous wall thickening of the gallbladder on abdominal computed tomography (CT) is subserosal edema and is often accompanied by a periportal collar sign. A 30-year-old woman was referred to our hospital because of liver dysfunction, edematous gallbladder wall thickening, and fluid retention. In addition, the patient developed hyperthyroidism and heart failure. Enhanced abdominal CT revealed edematous wall thickening of the gallbladder and a periportal collar sign. We suspected that fluid retention and congestion were caused by hyperthyroidism and Basedow disease. On admission, we started thiamazole therapy for Basedow disease, and her thyroid hormone levels normalized. Abdominal CT revealed disappearance of edematous wall thickening of the gallbladder, which was likely associated with an improvement in thyroid function. The patient was discharged 10 days after admission. We encountered a case of hyperthyroidism and Basedow disease accompanied by edematous wall thickening of the gallbladder and various fluid retentions as the first symptoms. Such edematous wall thickening of the gallbladder and various fluid retentions were reduced, together with the improvement of hyperthyroidism.


Overexpression of DDB2 enhances the sensitivity of human ovarian cancer cells to cisplatin by augmenting cellular apoptosis.
Cisplatin is one of the most widely used anticancer agents, displaying activity against a wide variety of tumors. However, development of drug resistance presents a challenging barrier to successful cancer treatment by cisplatin. To understand the mechanism of cisplatin resistance, we investigated the role of damaged DNA binding protein complex subunit 2 (DDB2) in cisplatin-induced cytotoxicity and apoptosis. We show that DDB2 is not required for the repair of cisplatin-induced DNA damage, but can be induced by cisplatin treatment. DDB2-deficient noncancer cells exhibit enhanced resistance to cell growth inhibition and apoptosis induced by cisplatin than cells with fully restored DDB2 function. Moreover, DDB2 expression in cisplatin-resistant ovarian cancer cell line CP70 and MCP2 was lower than their cisplatin-sensitive parental A2780 cells. Overexpression of DDB2 sensitized CP70 cells to cisplatin-induced cytotoxicity and apoptosis via activation of the caspase pathway and downregulation of antiapoptotic Bcl-2 protein. Further analysis indicates that the overexpression of DDB2 in CP70 cells downregulates Bcl-2 expression through decreasing Bcl-2 mRNA level. These results suggest that ovarian cancer cells containing high level of DDB2 become susceptible to cisplatin by undergoing enhanced apoptosis.


Neurodegeneration in the limbic and paralimbic system in progressive supranuclear palsy.
Progressive supranuclear palsy is neuropathologically characterized by neuronal degeneration of the basal ganglia, brain stem, and cerebellum. In addition, cortical neuronal degeneration associated with neurofibrillary tangles formation has been identified over wide areas of the brain in patients with progressive supranuclear palsy. We studied the distribution of alpha B-crystallin-positive degenerating neurons in cases with progressive supranuclear palsy, and compared them with those in Pick's disease. Alzheimer's disease, senile dementia of Alzheimer type, and normal aged individuals. A large number of alpha B-crystallin-positive neurons was found in the cerebral cortices of four out of nine patients with progressive supranuclear palsy. In particular, alpha B-crystallin-positive ballooned neurons were frequently observed in deep cortical pyramidal cell layers of the limbic and paralimbic systems in these diseases. The involvement of the limbic and paralimbic systems may thus contribute to personality changes as well as to memory and cognitive impairment in some patients with progressive supranuclear palsy.


Pros and cons of antioxidant use during radiation therapy.
Radiation therapy is one of the major treatment modalities in the management of human cancer. While impressive progress like more accurate dosimetry and more precise methods of radiation targeting to tumor tissue has been made, the value of radiation therapy in tumor control may have reached a plateau. At present, two opposing hypotheses regarding the use of antioxidants during radiation therapy have been proposed. One hypothesis states that supplementation with high doses of multiple micronutrients including high dose dietary antioxidants (vitamins C and E, and carotenoids) may improve the efficacy of radiation therapy by increasing tumor response and decreasing some of its toxicity on normal cells. The other hypothesis suggests that antioxidants (dietary or endogenously made) should not be used during radiation therapy, because they would protect cancer cells against radiation damage. Each of these hypotheses is based on different conceptual frameworks that are derived from results obtained from specific experimental designs, and thus, each may be correct within its parameters. The question arises whether any of these concepts and experimental designs can be used during radiation therapy to improve the management of human cancer by this modality. This review has analyzed published data that are used in support of each hypothesis, and has revealed that the current controversies can be resolved, if the results obtained from one experimental design are not extrapolated to the other. This review has also discussed the scientific rationale for a micronutrient protocol that includes high doses of dietary antioxidants (vitamin C, vitamin E succinate and natural beta-carotene) which can be used adjunctively with radiation therapy.


The status of the Spanish language in the United States at the beginning of the 21st century.
"This study presents population projections for different linguistic components of the Spanish language group, that is, for English dominant bilinguals, Spanish dominant bilinguals and Spanish monolinguals [in the United States]. The population model combines parameters obtained from the U.S. Bureau of the Census for nonlinguistic characteristics with linguistic parameters estimated from the 1976 Survey of Income and Education. The number of persons speaking Spanish on a regular basis will climb to an estimated 16.6 million persons at the turn of the century. Further analysis reveals, however, that an additional 4.5 million persons will have left the group by ceasing to speak Spanish. In fact, in the absence of continued immigration, this language minority cannot maintain its current size and will undergo progressively more rapid decline over the course of time."


68Ga-labelled exendin-3, a new agent for the detection of insulinomas with PET.
Insulinomas are neuroendocrine tumours derived from pancreatic beta-cells. The glucagon-like peptide 1 receptor (GLP-1R) is expressed with a high incidence (>90%) and high density in insulinomas. Glucagon-like peptide 1 (GLP-1), the natural ligand of GLP-1R, is rapidly degraded in vivo. A more stable agonist of GLP-1R is exendin-3. We investigated imaging of insulinomas with DOTA-conjugated exendin-3 labelled with (68)Ga. Targeting of insulinomas with [Lys(40)(DOTA)]exendin-3 labelled with either (111)In or (68)Ga was investigated in vitro using insulinoma tumour cells (INS-1). [Lys(40)((111)In-DTPA)]Exendin-3 was used as a reference in this study. In vivo targeting was investigated in BALB/c nude mice with subcutaneous INS-1 tumours. PET imaging was performed using a preclinical PET/CT scanner. In vitro exendin-3 specifically bound and was internalized by GLP-1R-positive cells. In BALB/c nude mice with subcutaneous INS-1 tumours a high uptake of [Lys(40)((111)In-DTPA)]exendin-3 in the tumour was observed (33.5 +/- 11.6%ID/g at 4 h after injection). Uptake was specific, as determined by coinjection of an excess of unlabelled [Lys(40)]exendin-3 (1.8 +/- 0.1%ID/g). The pancreas also exhibited high and specific uptake (11.3 +/- 1.0%ID/g). High uptake was also found in the kidneys (144 +/- 24%ID/g) and this uptake was not receptor-mediated. In this murine tumour model optimal targeting of the GLP-1R expressing tumour was obtained at exendin doses < or =0.1 microg. Remarkably, tumour uptake of (68)Ga-labelled [Lys(40)(DOTA)]exendin-3 was lower (8.9 +/- 3.1%ID/g) than tumour uptake of (111)In-labelled [Lys(40)(DTPA)]exendin-3 (25.4 +/- 7.2%ID/g). The subcutaneous tumours were clearly visualized by small-animal PET imaging after injection of 3 MBq of [Lys(40)((68)Ga-DOTA)]exendin-3. [Lys(40)((68)Ga-DOTA)]Exendin-3 specifically accumulates in insulinomas, although the uptake is lower than that of [Lys(40)((111)In-DTPA)]exendin-3. Therefore, [Lys(40)((68)Ga-DOTA)]exendin-3 is a promising tracer to visualize insulinomas with PET.


A story of scrutiny and fear: Australian midwives' experiences of an external review of obstetric services, being involved with litigation and the impact on clinical practice.
to describe Australian midwives' experiences of an external review of obstetric services, involvement in legal proceedings and the impact on midwives' clinical practice and personal wellbeing. the external review process (commonly referred to as the 'Douglas Inquiry') was initiated by a state government and was in response to hospital staff and consumer complaints that focused on anomalies in client care and a significantly high rate of adverse outcomes and clinical errors. It took place within the context of a number of legal proceedings against medical practitioners. As a result, some midwives employed by the hospital were called to give evidence at a variety of legal forums. a qualitative study using an explorative descriptive design. Snowball sampling was used to invite 16 Australian midwives to participate in a tape-recorded interview. Thematic analysis and the techniques associated with constant comparison were used to analyse the data. Australian maternity tertiary referral centre. the analysis identified two overarching themes, 'A story of scrutiny' and 'A story of fear', each with a number of subthemes. 'A story of scrutiny' consists of three subthemes. 'A cloak and dagger affair' reflects the midwives' sense of being and feeling 'exposed' and 'vulnerable' whilst simultaneously being 'kept in the dark' and uninformed during the review process. The subtheme 'Being thrown to the wolves' describes the midwives' experiences of being involved, as witnesses, in medico-legal proceedings. The third subtheme, 'The Inquiry followed them home' outlines the effect on midwives' emotional wellbeing and personal relationships. The second major theme, 'A story of fear' again consists of a number of subthemes. 'Feeling unsafe at work: a culture of fear' describes the midwives' experiences of working within an environment they perceive as driven by the fear of litigation. In order to protect themselves and maintain a sense of control, the midwives adopted a number of strategies to 'feel safe' including defensive decision making and moving towards a medical philosophy of care. These concepts are captured within the subtheme 'Covering your back: setting boundaries'. The impact on relationships between midwives, women and medical practitioners is described within the subtheme 'Professional relationship: coloured by fear'. The effect on midwives' confidence and the resultant negative emotions elicited make up the subtheme 'Between a rock and a hard place: the midwives' distressing dilemma'. Finally the subtheme, 'Opting out: the changing nature of professional work practices' describes the specific professional decisions and work strategies that midwives made about their ability to continue working in an environment that they perceived as threatening. the findings suggest that the midwife participants in this small study were totally unprepared and ill equipped, both personally and professionally, to deal with the consequences of working within an environment that was the centre of a number of high profile legal proceedings and an extensive external review of obstetric services. The midwives were naïve about legal processes and unprepared for the legal 'game playing' and media attention that often accompanies court proceedings. Despite the fact that no midwife faced litigation, the participants described their work environment as becoming increasingly stressful and permeated by a culture of fear. In turn, this situation has reinforced the need for some midwives to adopt an 'institution' ideology which reinforces birth as an abnormal event that needs to be medically managed. This has led to changes in professional and personal work practices. The findings also have implications for the midwifery workforce and retention. Although the findings are context specific, this study provides valuable insight into the phenomena of fear of litigation and its impact on midwifery practice. Given the similarities concerning obstetric litigation in some other Western nations, the findings have relevance in the international midwifery arena.


Protective effects of PARP inhibitor, PJ34, is related to down-regulation of calpain and NF-κB in a mouse model of TBI.
Poly(ADP-ribose) polymerase (PARP), calpain and nuclear factor-κB (NF-κB) are reported to participate in inflammatory reactions in pathological conditions and are involved in traumatic brain injury. The objective of this study was to investigate whether PARP participated in inflammation related to calpain and NF-κB in a mouse model of controlled cortical impact (CCI). PJ34 (10 mg kg-1), a selective PARP inhibitor, was administered intraperitoneally 5 minutes and 8 hours after experimental CCI. A neurobehavioural evaluation and a histopathological analysis were then performed and the contusion volume, calpain activity and protein levels were measured in all animals. Treatment with PJ34 markedly reduced neurological deficits, decreased contusion volume and attenuated necrotic and apoptotic neuronal cell death 24 hours after CCI. The data showed that the cytosolic and nuclear fractions of calpain and NF-κB were up-regulated in the injured cortex and that these changes were reversed by PJ34. Moreover, PJ34 significantly enhanced the calpastatin and IκB levels and decreased the levels of inflammatory mediators. PARP inhibition by PJ34 suppresses the over-activation of calpain and the production of inflammatory factors that are caused by NF-κB activation and it improves neurological functioning, decreases the contusion volume and attenuates neuronal cell death in a mouse model of CCI.


Atypical persistence of tunica vasculosa lentis.
The authors report an unusual case of persistent tunica vasculosa lentis in a patient with minimal retinopathy of prematurity (ROP). A 3-month-old male infant who had been born at 31 weeks' gestation presented with a significant amount of persistent tunica vasculosa lentis and arteriolar tortuosity with minimal ROP and no plus disease. After weekly observation and no surgical intervention, the arteriolar tortuosity lessened but the tunica vasculosa lentis persisted. Persistent tunica vasculosa lentis can be mistaken for iris vascular engorgement, suggesting plus disease and high-risk prethreshold ROP. Differentiation between tunica vasculosa lentis and iris vascular engorgement, as well as correct diagnosis of plus disease, is critical when considering laser treatment for high-risk prethreshold ROP.


[The mechanism of microbial removal of Mn(Ⅱ) and its influencing factors: a review].
Manganese is an element essential for living organisms. Development of industrial technologies and exploitation of mineral resources have led to the release of large amount of Mn(Ⅱ) into the environment, posing a serious threat to human health. Bioremediation can remove the Mn(Ⅱ) from the environment rapidly and effectively without generating secondary pollution, thus received increasing attention. This review summarized the diversity and distribution of Mn(Ⅱ) removal microorganisms and the associated mechanisms, followed by discussing the effect of environmental factors on microbial Mn(Ⅱ) removal. Finally, the challenges and prospects for bioremediation of Mn(Ⅱ) polluted wastewater were proposed.


Myotilin is not the causative gene for vocal cord and pharyngeal weakness with distal myopathy (VCPDM).
Myotilin (MYOT) is a promising candidate gene for Vocal Cord and Pharyngeal Weakness with Distal Myopathy (VCPDM, also known as MPD2). Located within the minimum VCPDM candidate interval, myotilin mutations also cause a similarly progressive and adult-onset muscle disease. We examined myotilin in VCPDM patients by sequence analysis, RT-PCR, Southern blotting, and western blotting. We detected no defects in the myotilin gene, transcript, or protein in VCPDM. We also report several useful SNPs and STRs for the analysis of myotilin in muscle diseases of suspected, yet unknown genetic origin. We conclude that MYOT mutations likely are not a cause of VCPDM.


Clinical response to hypertensive hypervolemic therapy and outcome after subarachnoid hemorrhage.
Hypertensive hypervolemic therapy is widely used to treat symptomatic vasospasm after subarachnoid hemorrhage. Few data exist to support a relationship between early clinical response and mortality or functional outcome. In a prospective cohort of 580 subarachnoid hemorrhage patients, we studied 95 patients with acute symptomatic vasospasm who received stepwise volume expansion with crystalloid and/or 5% albumin solution followed by intravenous pressors to maintain systolic blood pressure between 180 and 220 mm Hg. We separately assessed the effects of volume expansion and induced hypertension on the neurological examination during the first 2 hours of each intervention. We used multivariate logistic regression analysis to calculate adjusted odds ratios assessing the relationship between clinical response to hypertensive hypervolemic therapy and 3-month outcome, as measured by the modified Rankin Scale. Of 95 patients with symptomatic vasospasm, volume expansion was used in 94% (n = 89), of whom 43% had a clinical response; 85% of the patients (n = 81) received pressors, of whom 68% responded. Early clinical improvement attributable to either volume expansion or pressors was not related to the development of infarction on computed tomography, but response to either modality within 2 hours was independently protective against death (adjusted odds ratio, 0.03; P < 0.05) and death-or-severe-disability (modified Rankin Scale score, 4-6; adjusted odds ratio, 0.1; P < 0.05) after adjusting for age, Hunt-Hess grade, angioplasty, and aneurysm size. Subarachnoid hemorrhage patients with symptomatic vasospasm who fail to demonstrate early clinical improvement in response to volume or pressor therapy are at high risk for death or disability. Urgent endovascular intervention in this high-risk patient cohort may be justified.


Psychotherapy of personality disorders.
Although personality disorders are often regarded as "untreatable" by third-party payers, there is actually a growing empirical literature suggesting that Axis II conditions may be eminently treatable by psychotherapy. This literature is critically reviewed, the implications for length of treatment are discussed, and cost-effectiveness issues are examined.


Biomechanical analysis of two standing sprint start techniques.
The purpose of this study was to examine any differences between the false step standing sprint start and a traditional forward step standing sprint start. Ten DI collegiate female soccer players performed 2 standing sprint starts (Forward step and False step). Each player was videotaped for the first 3 steps of each sprint start. Velocity, acceleration, and displacement were calculated at each of the 3 steps for both standing sprint start techniques. Velocity was significantly faster with the forward step for steps 1 and 2 but not with step 3. Displacement was significantly greater with the forward step for each of the 3 steps. Acceleration was greater with the false step for each step though differences were not significant. The results indicate the forward step outperforms the false step in both velocity and displacement. Even though the false step generates greater acceleration, the backward step drastically undercuts displacement nullifying acceleration. Controversy exists between these 2 standing sprint starts with proponents arguing for their favorite with no evidence to suggest one or the other. The results from this study suggest that the forward step is superior to the false step when the concern for an individual is to get from 1 point to the next as fast as possible.


Pediatric cardiac surgery under the parents sight: a qualitative study.
Congenital heart defects can often be corrected through surgery, providing for parents to expect a normal life, but the hospitalization experience often early, causes more pain, for which surgery is the worst moment. The aim of this study was to analyze the experience of families of children undergoing cardiac surgery and to identify the coping resources used by the families. A qualitative approach was the metodology of choice for this study, which took place with six semi-structured interviews and 100 hours of observation. Thematic analysis was used to understand the data. The results were categorized into four themes: feelings and emotions facing the illness of the child; heart disease under the watchful mother, mother and child on the ICU and coping resources. The speech of mothers demonstrated the importance of the heart due to its symbolism that enhances their emotional fragility in the face of illness. Religiosity and a solid social network of support were contributing factors for the maintenance of the adaptive behaviors. The presence of mothers in all stages of the child's treatment contributed to minimizing the suffering generated by hospitalization. The experience of families was characterized by ambivalent feelings such as fear of death, guilt and helplessness against the different stages of treatment. The anguish and anxiety prevailed in the face of unknown situations when information were required before therapeutic procedures, hospital routines and the actual life situation of the families.


Prevalence of bullying and aggressive behavior and their relationship to mental health problems among 12- to 15-year-old Norwegian adolescents.
The aim of this study was to examine the relationships between being bullied and aggressive behavior and self-reported mental health problems among young adolescents. A representative population sample of 2,464 young Norwegian adolescents (50.8% girls) aged 12-15 years was assessed. Being bullied was measured using three items concerning teasing, exclusion, and physical assault. Self-esteem was assessed by Harter's self-perception profile for adolescents. Emotional and behavioral problems were measured by the Moods and Feelings Questionnaire (MFQ) and the youth self-report (YSR). Aggressive behavior was measured by four items from the YSR. One-tenth of the adolescents reported being bullied, and 5% reported having been aggressive toward others during the past 6 months. More of the students being bullied and students being aggressive toward others reported parental divorce, and they showed higher scores on all YSR subscales and on the MFQ questions, and lower scores on the global self-worth subscale (Harter) than students not being bullied or aggressive. A few differences emerged between the two groups being bullied or being aggressive toward others: those who were aggressive showed higher total YSR scores, higher aggression and delinquency scores, and lower social problems scores, and reported higher scores on the social acceptance subscale (Harter) than bullied students. However, because social problems were demonstrated in both the involved groups, interventions designed to improve social competence and interaction skills should be integrated in antibullying programs.


Idiopathic pulmonary hemosiderosis presenting in an adult: A case report and review of the literature.
Diffuse alveolar hemorrhage (DAH) is characterized by the presence of hemoptysis, anemia, and the presence of diffuse parenchymal infiltrates on imaging studies. Idiopathic pulmonary hemosiderosis (IPH) is an uncommon cause of diffuse alveolar hemorrhage (DAH) and is classically known to present in childhood. Adult-onset IPH is extremely rare. We report the case of a 48-year-old female patient who presented with hemoptysis and acute hypoxic respiratory failure, requiring intubation and mechanical ventilation. Imaging studies showed diffuse bilateral patchy infiltrates. Bronchoalveolar lavage (BAL) confirmed the diagnosis of DAH. Extensive workup including video-assisted thoracoscopic surgical lung biopsy (VATS) failed to reveal any vasculitis, infectious, immunological or connective tissue disorder, as the underlying cause for DAH. The patient was successfully treated with high-dose steroid therapy.


Burns at the soroka university medical center - a two-year experience.
Background. Burn trauma is a major public health concern, with increased risk for burns in children. Objectives. To characterize the profile of injured burn patients and to identify patients who are prone to burn injury. Methods. This is a cross-sectional study including all patients who were admitted to the Burns and Plastic Surgery Department, Soroka University Medical Center, Israel, between 1 January 2001 and 31 December 2002. Results. Five hundred and fifty-eight patients with a mean age of 15.4 yr (SD, 19.5 yr) were included in the study. There were 348 male patients (62.4%). The cause of the burns was scalding in 314 patients (56.3%), flame in 177 (31.7%), chemicals in 31 (5.6%), explosion in 20 (3.6%), and electricity in four (0.7%). There were 325 Bedouin patients (58.2%) and 221 Jewish patients (39.6%). In Bedouins, 235 patients (72.3%) were children below 5 yr, compared to 59 Jewish patients (26.7%) (p < 0.001). Eighteen burn patients (3.2%) expired. A multivariate analysis demonstrated that age and percentage of body surface area involved in the burn were significantly associated with mortality. Conclusions. The epidemiological characteristics of the burned population in Soroka University Medical Center are described. Burn injury has become a principal public health problem, particularly in Bedouin children.


A metric space approach to the information channel capacity of spike trains.
A novel method is presented for calculating the information channel capacity of spike trains. This method works by fitting a χ-distribution to the distribution of distances between responses to the same stimulus: the χ-distribution is the length distribution for a vector of Gaussian variables. The dimension of this vector defines an effective dimension for the noise and by rephrasing the problem in terms of distance based quantities, this allows the channel capacity to be calculated. As an example, the capacity is calculated for a data set recorded from auditory neurons in zebra finch.


Silent stellate ganglion paraganglioma masquerading as schwannoma: A surgical nightmare.
A 28-year-old normotensive female presented with Horner's syndrome and paresthesia over the left side of the chest. Imaging study showed a large heterogeneous enhancing lesion in short-T1 inversion recovery sequence with flow voids in T2W sequence of magnetic resonance imaging. The lesion was located in the left-sided D1 and D2 regions extending into the neural foramina and apical part of the lung. During surgery, even minimal dissection of the tumor resulted in marked fluctuation in hemodynamic parameters, requiring temporary suspension of the surgery multiple times until hemodynamic parameters were brought under control by the anesthesiologist with drugs. The massive fluctuation in hemodynamic parameters in an unprepared and unanticipated scenario was a challenge for the anesthetist and surgeon. The tumor was radically excised with improvement of paresthesia in the immediate postoperative period, but Horner's syndrome persisted. After 18-months of follow-up, she was relieved of all symptoms including Horner's syndrome. Histopathological examination confirmed our suspicion as paraganglioma.


[The epidemiological transition in Latin America].
The changes in health conditions that have occurred in most of the countries of Latin America in the second half of the twentieth century are analyzed. "This paper analyzes the main mechanisms involved in the epidemiologic transition, which are: changes in risk factors, fertility decline and improvements in health care technology." The authors use a mortality profile ratio, obtained by dividing the mortality rate due to infectious and parasitic diseases over the mortality rate due to cardiovascular diseases and neoplasms, to analyze trends in 15 countries. "Three distinct groups can be recognized. Each of them represents a different transitional experience. Such experiences are discussed in detail, including a new 'protracted polarized model' of the epidemiologic transition, which characterizes several Latin American countries. Finally, evidence is provided to illustrate the relationship among economic development, fertility change, and mortality profiles." (SUMMARY IN ENG)


Decoration of Silica Nanoparticles on Polypropylene Separator for Lithium-Sulfur Batteries.
A SiO2 nanoparticle decorated polypropylene (PP) separator (PP-SiO2) has been prepared by simply immersing the PP separator in the hydrolysis solution of tetraethyl orthosilicate (TEOS) with the assistance of Tween-80. After decoration, the thermal stability and the electrolyte wettability of the PP-SiO2 separator are obviously improved. When the PP-SiO2 separator is used for lithium-sulfur (Li-S) batteries, the cyclic stability and rate capability of the batteries are greatly enhanced. The capacity retention ratio of the Li-S battery configured with the PP-SiO2 separator is 64% after 200 cycles at 0.2 C, which is much higher than that configured with the PP separator (45%). Moreover, the rate capacity of the Li-S batteries using the PP-SiO2 separator reaches 956.3, 691.5, 621, and 567.6 mAh g-1 at the current density of 0.2, 0.5, 1, and 2 C, respectively. The reason could be ascribed to that the polar silica coating not only alleviates the shuttle effect but also facilitates Li-ion migration.


Outlook for tuberculosis elimination in California: An individual-based stochastic model.
As part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI). To estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California. We created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained. In the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to $48 billion. These had an incremental cost per QALY of $657,000 to $3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY. Substantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks.


SYT7 plays a role in promoting thyroid cancer by mediating HMGB3 ubiquitination.
Thyroid cancer is one of the most common endocrine malignancies. It is necessary to discover more effective molecular targets for the treatment of thyroid cancer. The results of immunohistochemical staining, qPCR and Western blot indicated that the expression of SYT7 in thyroid cancer tissues and cells was higher than that in paracarcinoma tissues and normal thyroid cells. Through cell function testing experiments, it was found that SYT7 knockdown inhibited the proliferation and migration of thyroid cancer cells and promoted cell apoptosis, while SYT7 overexpression had the opposite effect. Similarly, SYT7 downregulation also suppressed tumor growth in vivo. HMGB3 was confirmed to be the downstream gene of SYT7 by GeneChip and Ingenuity Pathway Analysis. Besides, through UbiBrowser database predictions and Co-IP assays, we found that SYT7 interacted with BRCA1 to inhibit HMGB3 ubiquitination and thus upregulated the protein level of HMGB3. Similar to SYT7, HMGB3 was significantly upregulated in thyroid cancer. HMGB3 knockdown inhibited the proliferation and migration of thyroid cancer cells and promoted cell apoptosis. Furthermore, HMGB3 knockdown restored the promotion of cell proliferation and migration caused by SYT7 overexpression. SYT7 and HMGB3 were upregulated in thyroid cancer, and SYT7 regulated the expression of HMGB3 through BRCA1-mediated ubiquitination of HMGB3 to promote thyroid cancer progression.


Effects of sequential exposure to lipopolysaccharide and heat stress on dental pulp cells.
In the present study, we examined the effects of sequential exposure to bacterial lipopolysaccharide (LPS) and heat stress on dental pulp cells. LPS induced the proliferation of pulp cells through the activation of p38 MAPK. HSP27 was expressed in cells with or without LPS during the entire period of heat stress, while transiently phosphorylated by short-term heat stress. In LPS-treated cells, short-term heat stress also induced the phosphorylation of HSF1. The immediate phosphorylation of HSF1 and HSP27 in LPS-treated cells by short-term heat stress occurred dependent on the activation of p38 MAPK. However, with long-term heat stress, the activation of HSF1 and induction of HSP27 occurred independent of p38 MAPK. Further, full activation of Akt in LPS-treated cells was immediately induced by short-term heat stress and lasted during the entire period of heat stress. IkappaB alpha was induced and phosphorylated throughout sequential exposure to LPS and heat stress. These results suggest that LPS has the unique effects on the cytoprotection and the cell death of pulp cells during heat stress through the modification and the activation of heat stress responsive molecules, HSF1 and HSP27, and cell survival molecules, Akt and NF-kappaB/IkappaB alpha.


Intracranial bruit: Charles Warlow's challenge revisited.
Over 20 years ago, Charles Warlow, the founding editor of Practical Neurology, offered a copy of his stroke textbook to anyone diagnosing an intracranial arteriovenous malformation by auscultation of the skull alone. This article examines the possible diagnostic value of intracranial bruit in terms of the 2×2 contingency table for diagnostic tests and recounts an historical case.


Neurophysiological changes in deformity correction of adolescent idiopathic scoliosis with intraoperative skull-femoral traction.
Retrospective review of 36 consecutive patients undergoing coronal plane deformity correction with intraoperative skull-femoral traction between 2005 and 2008 with motor evoked potential (MEP)/somatosensory evoked potential monitoring. To determine the prevalence and significance of neurophysiological changes with intraoperative skull-femoral traction in adolescent idiopathic scoliosis. Intraoperative skeletal traction can be associated with spinal cord stretching and ischemia with resultant electrophysiological changes. The prevalence and risks of such changes and their clinical significance is unknown. Thirty-seven procedures involving 36 patients (27 females and 9 males) with a mean age of 14.8 (12-18) years were divided into two groups on the basis of the presence (group 1, n = 18 procedures) or absence (group 2, n = 19) of significant MEP changes with surgery. They were compared with patients undergoing correction without traction (group 3). Significant differences among the groups were observed in mean preoperative Cobb angle (86° vs. 70° vs. 59°), mean intraoperative posttraction Cobb angle (50.0° vs. 34.6°), traction index (0.41 vs. 0.50), flexibility index (0.14 vs. 0.27 vs. 0.25), and presence of primary lumbar curves (0% vs. 32% vs. 14%). Initial onset of MEP amplitude loss (group 1) occurred at a mean of 94 (1-257) minutes from the onset of surgery, was bilateral in 13 procedures, and improved at a mean of 5.5 (1-29) minutes after decreasing or removing the traction. At closure, complete bilateral recovery to baseline was observed in 10 procedures, recovery to >50% baseline in five, and recovery to <50% baseline in three procedures. There were no neurologic deficits in this series. Intraoperative traction is associated with frequent changes in MEP monitoring. The thoracic location of the major curve, increasing Cobb angle, and rigidity of major curve are significant risk factors for changes in MEP with traction. The presence of any MEP recordings irrespective of its amplitude at closure was associated with normal neurological function. Somatosensory evoked potential monitoring did not correlate with the traction induced MEP amplitude changes.


[Covalent drug discovery exploiting the new warheads].
Covalent drug forms a covalent bond with desease-related target proteins irreversibly inhibits their function. In order to develop a safe and non-toxic covalent drug, it is important to device new reaction chemistry that realizes a sufficient reactivity and high target selectivity for targeted protein under the complicated biological systems such as our body. Currently, new reaction chemistry is being actively developed all over the world to achieve excellent target selectivity of covalent drugs. In this essay, we intoroduce α-chlorofluoroacetamide and bicyclobutane amide as the new reactive groups for proteineous cysteine of targeted protein and their application to develop targeted covalent inhibitors for the treatment of cancer and infecsious deseases.


Acetylcholine releases endothelium-derived hyperpolarizing factor and EDRF from rat blood vessels.
1. The effects of haemoglobin and methylene blue on the acetylcholine (ACh)-induced electrical and mechanical responses of smooth muscle cells were investigated in rat aorta and rat main pulmonary artery. 2. When the endothelium was intact, ACh induced a transient hyperpolarization and sustained relaxation of tissues precontracted with noradrenaline. Both hyperpolarization and relaxation were absent in preparations without endothelium. 3. Haemoglobin and methylene blue inhibited the ACh-induced relaxation, but not the transient hyperpolarization. 4. In aorta with an intact endothelium, ACh produced an increase in both the rate of 86Rb efflux and tissue cyclic GMP levels. The changes in ion flux were unaffected by either haemoglobin or methylene blue in concentrations which almost abolished the increase in cyclic GMP concentrations. 5. In arteries with an intact endothelium, indomethacin had no effect on the ACh-induced electrical and mechanical responses or on the increase in 86Rb efflux and tissue cyclic GMP levels. 6. It is concluded that in the rat aorta and rat main pulmonary artery, ACh releases two different substances, an endothelium-derived relaxing factor (EDRF) and a hyperpolarizing factor (EDHF), from the endothelial cells. Neither substance appears to be derived from a pathway dependent on cyclo-oxygenase. EDHF seems to play a minor role in the relaxation of noradrenaline-induced contractions.


The effect of pentoxifylline (Trental) and two analogues, BL 194 and HWA 448, on the release of plasminogen activators and von Willebrand factor in rats.
The effects on fibrinolytic components of pentoxifylline (Trental), of its first metabolite BL 194 (penthydroxyfylline), and of its analogue HWA 448 (torbafylline) were studied in rats. BL 194, though not pentoxifylline and HWA 448, significantly enhanced the induced release by platelet-activating factor (PAF) of tissue-type plasminogen activator (tPA) from isolated perfused rat hindlegs. In contrast, the simultaneously induced release of von Willebrane factor (vWF) was reduced by BL 194. The effect of BL 194 on PAF-induced release of tPA and vWF could be mimicked by isobutyl-methylxanthine (IBMX), an inhibitor of phosphodiesterases. In vivo, BL 194 and pentoxifylline did not affect baseline levels of plasma tPA and PA inhibitor activity, nor did these compounds affect the in vivo induction of tPA release by PAF. Similarly, the induction by endotoxin of PA inhibitor activity was not influenced by pentoxifylline or BL 194. By its opposite effects on tPA and vWF release. BL 194 might favrorably influence the thrombotic balance.


A new method for phase identification for electron diffractionists.
An accurate analytical procedure for phase identification for electron diffractionists has been developed. The method opens new frontiers in the identification of solid-state materials, as crystalline samples in the size range 10 microns to 10 A can be accurately characterized. Research with NIST CRYSTAL DATA (a large database with chemical, physical, and crystallographic data on solid-state materials) has proved that a material can be uniquely characterized on the basis of its lattice and chemical composition. To characterize a material, it is sufficient to determine any primitive cell of the lattice and the element types present. Using a modern analytical electron microscope (AEM), the experimentalist can collect the required data on an unknown sample. The lattice information is obtained by rotation of the sample to obtain two or more planes of data. From these planes, a unit cell defining the lattice can be deduced. The chemical data are determined by energy-dispersive spectroscopy (EDS). Once the experimental data are measured, the unknown is identified against the database of knows using lattice/element-type matching techniques. The basic strategy consists of three conceptual steps. First, the unknown lattice is searched against the database to find all lattices that are the same or related; the results are kept in set 1. Second, the unknown is searched against the database to find all materials with the same or similar element types; the results are kept in set 2. Finally, the results in sets 1 and 2 are combined to obtain the answer set. Experience has proved that the procedure is highly selective and reliable.


[The characteristics of disorders of intracardiac hemodynamics and hemorheology in pulmonary heart failure].
Overall ninety patients with chronic obstructive bronchitis presenting with signs of varying degree cardiopulmonary insufficiency (CPI) were evaluated by radionuclide ventriculography with technetium pertechnetate as well as by rotational viscosimetry of blood. The degree of hemorheological derangements tended to get higher with CPI severity (light, moderately severe, severe) being accompanied by progressing impairement of systolic and diastolic functions of both ventricles of the heart. Mechanisms of compensation of endocardiac hemodynamics were realized as a result of increase in end-diastolic and end-systolic volumes of both ventricles together with changes in amplitude and time characteristics of processes of ventricular ejection and filling. Forecast of the probable course of the condition may rely upon the functional state of right as well as left ventricle of the heart.


Deep venous thrombosis in Assir region of Saudi Arabia. Case-control study.
In a five-year case-control study (1988 to 1993) at Assir Central Hospital (ACH), Abha (8,000 feet above sea level), Saudi Arabia, 92 of 129 patients suspected of deep venous thrombosis (DVT) were studied with ascending contrast venography (CV) (74 patients, 80.4%) or Doppler ultrasonography (DUS) (18 patients, 19.6%). Female-to-male ratio was 2.3 to 1. Age range of patients was twelve to ninety years; mean age was 44.45 yrs +/- 17.38 years. DVT hospital incidence was 18 per 10,000 admissions. The most common associated factors included immobilization due to chronic diseases (21.7%), trauma and surgery (19.6%), and pregnancy and oral contraceptives usage (16.3%). The most common symptom and sign were limb pain and tenderness (95.6%). Limb swelling was noted in 93.5% of patients. The left lower limb was more commonly affected than the right. There was a definite increase of DVT during the winter months. Altitude was not a contributory factor. Pulmonary embolism was the greatest complication.


A combination of two electrophoretical approaches for detailed proteome-based characterization of SCLC subtypes.
Small cell lung cancers (SCLC) are heterogeneous and tumours differ in growth characteristics and treatment resistance. To get insight into the underlying protein profiles responsible for this heterogeneity, two subtypes of SCLC cells mutually differing in chemo resistance properties and growth characteristics are analysed. Two different electrophoresis approaches in combination with mass spectrometry were used to detect differences between the SCLC cell lines GLC1 and GLC1M13: IEF/SDS-PAGE as well as cetyltrimethylammonium bromide (CTAB)-SDS-PAGE. Altogether 60 non redundant differentially expressed proteins were found of which 5 were verified by Western Blot analysis. Most of these proteins identified are involved in processes of tumour progression. Therefore, these proteins are interesting candidates for further functional analysis. Additional CTAB-SDS page is a complementary method to IEF-SDS page revealing a complete new subset of proteins differentially expressed between GLC1 and GLC1 M13 cells SCLC subtypes.


The expression profile of human peripheral blood mononuclear cell miRNA is altered by antibody-dependent enhancement of infection with dengue virus serotype 3.
Antibody-dependent enhancement (ADE) of dengue virus (DENV) infection has been identified as the main risk factor for severe dengue disease, although the underlying mechanisms leading to severe dengue fever remain unclear. MicroRNAs (miRNAs) participate in numerous pathological and biological processes, including host responses to viral infections. Here, we aimed to investigate the differences in miRNA expression patterns in human peripheral blood mononuclear cells (PBMCs) infected with DENV-3 and DENV-3-ADE at various time points employing high-throughput sequencing. According to miRNAs high-throughput sequencing, a total of 50 known miRNAs exhibited significant differences. GO (Gene Ontology) and pathway analysis of the predicted targets showed enrichment in the regulation of transcription, including multicellular organismal development, DNA-dependent transcription, negative regulation of cell differentiation and transcription. Afterwards, regulatory networks of miRNA predicted targets, miRNA transcription factors, miRNA pathways and miRNA GOs were formulated to expose the complex regulatory mechanisms of miRNAs during the infection phase. Finally, we analyzed hierarchical GO categories of the predicted targets involved in the MAPK signaling pathway, the cGMP-PKG signaling pathway, the cAMP signaling pathway, the endocytosis effect, and our analyses indicated that innate and adaptive immunity following DENV-3 and DENV-3-ADE infections may be signally distinct. Our results demonstrate a novel describing miRNA expression profiles in human PBMCs with DENV-3 and DENV-3-ADE infections using high-throughput sequencing. Our findings could provide a beneficial basis for further studies on the regulatory roles of miRNAs relevant to the different immune responses caused by DENV-3 and DENV-3-ADE infections.


Fruits and vegetables diet improves some selected haemorheological parameters predisposing to cardiovascular disease in non insulin dependent diabetes mellitus NIDDM subjects.
Fruits and vegetables have been shown to contain vital components that moderate disease conditions. However, there is dearth of information of these effects in Africans diabetic subjects. Thus, we investigated the relative effect of fruits and vegetables on some selected heamorological factors associated with cardiovascular disease in diabetic subjects. Thirty diabetic subjects were selected at the cardiovascular clinic of Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria. The subjects with mean Fasting Blood Glucose (FBG) level of 7.8 +/- 0.95 mmold L(-1) were placed on 300 g of fruits and vegetables per day, while they continued their normal medication and food intake. A significant difference (p < 0.05) was noticed between baseline and eight week values in all the parameters, Fibrinogen 262.75 +/- 2.64 to 250.57 +/- 3.98 mg dL(-1), Blood viscosity, 5.96 +/- 0.21 to 4.82 +/- 0.23 m Pas; erythrocyte sedimentation rate 49.40 +/- 2.34 to 32.8 +/- 1.26 min h(-1) and haematocrit 38.8 +/- 1.25 to 44.75 +/- 1.05%. At the eight week the fruits and vegetables were withdrawn for two weeks and the above parameters were reassessed (at the 10th week) which were compared with eight week values. Significant difference p < 0.05 was noticed in E.S.R. 32.8 +/- 1.26 to 38.8 +/- 1.23. However no significant difference (p > 0.05) was observed in haematocrit, 44.75 +/- 1.44 to 42.70 +/- 1.24, Fibrinogen, 254.5 +/- 3.98 to 250.57 +/- 3.16 mg dL(-1). The results showed that regular intake of fruits and vegetables by diabetic subjects may reduce cardiovascular risk factors.


Age differences at marriage and divorce.
This article explores the age difference of marrying and divorcing couples, calculated by subtracting the wife's age from the husband's. Age difference is of interest in the study of families and partnership behaviour. It is also important because of its link with broader socio-demographic changes, such as population ageing, delayed fertility and the provision of care. The main finding is that between 1963 and 2005, the distribution of age differences for all marriages is very similar in each year to the distribution of age differences for the subset of couples who married in that year, but have since divorced. While there is some evidence of small variations in the proportion of marriages that end in divorce by age difference, there does not seem to be evidence of a strong association.


Long-term outcome of hematopoietic stem cell transplantation for IL2RG/JAK3 SCID: a cohort report.
Hematopoietic stem cell transplantation (HSCT) cures the T-lymphocyte, B-lymphocyte, and natural killer (NK)-cell differentiation defect in interleukin-2 γ-chain receptor (IL2RG)/JAK3 severe combined immunodeficiency (SCID). We evaluated long-term clinical features, longitudinal immunoreconstitution, donor chimerism, and quality of life (QoL) of IL2RG/JAK3 SCID patients >2 years post-HSCT at our center. Clinical data were collated and patients/families answered PedsQL Generic Core Scale v4.0 questionnaires. We performed longitudinal analyses of CD3+, CD4+ naive T-lymphocyte, CD19+, and NK-cell numbers from pretransplant until 15 years posttransplant. Thirty-one of 43 patients (72%) survived. Median age at last follow-up was 10 years (range, 2-25 years). Twenty-one (68%) had persistent medical issues, mainly ongoing immunoglobulin replacement (14; 45%), cutaneous viral warts (7; 24%), short stature (4; 14%), limb lymphoedema (3; 10%), and bronchiectasis (2; 7%). Lung function was available and normal for 6 patients. Longitudinal analysis demonstrated sustained CD3+, CD19+, and NK-cell output 15 years post-HSCT. CD4+ naive lymphocyte numbers were better in conditioned vs unconditioned recipients (P, .06). B-lymphocyte and myeloid chimerism were highly correlated (ρ, 0.98; P < .001). Low-toxicity myeloablative conditioning recipients have better B-lymphocyte/myeloid chimerism and are free from immunoglobulin replacement therapy. IL2RG/JAK3 SCID survivors free from immunoglobulin replacement have normal QoL.


An invisible issue.
Awareness of sexually transmitted infections in women who have sex with women is a vital yet often invisible part of healthcare practice.


Halazepam in the management of acute alcohol withdrawal syndrome.
Eighty patients admitted to a specialized alcohol detoxification unit, who had blood alcohol levels of .15% or less and were not currently intoxicated, participated in a double-blind trial involving treatment with either halazepam or chlordiazepoxide. A flexible dosage schedule was followed for 5 days with the objective of using the largest dose on the first day, followed by daily reductions as clinically feasible. Efficacy evaluations indicated that halazepam was as effective as chlordiazepoxide in the control of symptoms in patients hospitalized for the medical management of acute alcohol withdrawal. No significant side effects were noted.


[Premature cytokinesis in pollen mother cells of transgenic tobacco plants Nicotiana tabacum L].
In majority species of dicotyledonous plants cytokinesis in PMCs occurs once after completion of two caryokinesis cycles, that is a simultaneous type. This paper represents cytological picture and frequency characteristics of abnormality which resulted in cytokinesis triggering after first meiotic division in a part of transgenic tobacco PMCs. It was shown that the main process of cytoskeleton reorganization typical for simultaneous cytokinesis remained without any alterations in such cells. However, in most cases premature cell division occurred with abnormalities such as membrane "tunnel" or "gash" formation. It was ascertained that initiation of additional round ofcytokinesis did not block nuclear cycle and cytokinesis after second meiotic division. Thus, transition of cell division from simultaneous type to successive one occurs under this abnormality.


Lethal effect of cytokine-induced nitric oxide and peroxynitrite on cultured rat cardiac myocytes.
We examined the cytotoxic effect of iNOS-generated NO in cultured cardiac myocytes treated with IL-1 beta, IFN- gamma and LPS. Treatment of the myocytes with cytokines for 48 h resulted in a marked NO production, a significant decline in cellular ATP content, and a significant increase in myocyte death with morphological characteristics of necrosis. Moreover, immunohistochemical examination showed that the cytokines caused nitrotyrosine formation in the injured myocytes. Uric acid and L-cysteine which have the ability to quench peroxynitrite significantly attenuated these cytokine-induced effects, although they did not alter NO production or the decline in cellular ATP. These data suggest that NO production induced by cytokines can not only cause deleterious effects in the myocardial energy balance but also induce myocytes necrosis, through the formation of peroxynitrite.


Emotional and physiological desensitization to real-life and movie violence.
Youth are exposed to large amounts of violence in real life and media, which may lead to desensitization. Given evidence of curvilinear associations between exposure to violence and emotional distress, we examined linear and curvilinear associations of exposure to real-life and movie violence with PTSD symptoms, empathy, and physiological arousal, as well emotional and physiological reactivity to movie violence. College students (N = 209; mean age = 18.74) reported on their exposure to real-life and televised violence, PTSD symptoms, and empathy. Then, students were randomly assigned to view a series of violent or nonviolent high-action movie scenes, providing ratings of emotional distress after each clip. Blood pressure was measured at rest and during video viewing. Results showed that with increasing exposure to real-life violence, youth reported more PTSD symptoms and greater identification with fictional characters. Cognitive and emotional empathy increased from low to medium levels of exposure to violence, but declined at higher levels. For males, exposure to higher levels of real-life violence was associated with diminishing (vs. increasing) emotional distress when viewing violent videos. Exposure to televised violence was generally unrelated to emotional functioning. However, those with medium levels of exposure to TV/movie violence experienced lower elevations of blood pressure when viewing violent videos compared to those with low exposure, and those with higher levels of exposure evidenced rapid increase in blood pressure that quickly declined over time. The results point to diminished empathy and reduced emotional reactivity to violence as key aspects of desensitization to real-life violence, and more limited evidence of physiological desensitization to movie violence among those exposed to high levels of televised violence.


Blood molecular markers associated with COVID-19 immunopathology and multi-organ damage.
COVID-19 is characterized by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand host responses to COVID-19 pathophysiology, we combined transcriptomics, proteomics, and metabolomics to identify molecular markers in peripheral blood and plasma samples of 66 COVID-19-infected patients experiencing a range of disease severities and 17 healthy controls. A large number of expressed genes, proteins, metabolites, and extracellular RNAs (exRNAs) exhibit strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients suggesting a potential impact on tissue function. Chronic activation of neutrophils, IFN-I signaling, and a high level of inflammatory cytokines were observed in patients with severe disease progression. In contrast, COVID-19-infected patients experiencing milder disease symptoms showed robust T-cell responses. Finally, we identified genes, proteins, and exRNAs as potential biomarkers that might assist in predicting the prognosis of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19.


Effects of Resistant Starch Interventions on Metabolic Biomarkers in Pre-Diabetes and Diabetes Adults.
Simple lifestyle changes can prevent or delay the onset of type 2 diabetes mellitus (T2DM). In addition to maintaining a physically active way of life, the diet has become one of the bases in managing TD2M. Due to many studies linking the ability of resistant starch (RS) to a substantial role in enhancing the nutritional quality of food and disease prevention, the challenge of incorporating RS into the diet and increasing its intake remains. Therefore, we conducted this review to assess the potential benefits of RS on metabolic biomarkers in pre-diabetes and diabetes adults based on available intervention studies over the last decade. Based on the conducted review, we observed that RS intake correlates directly to minimize possible effects through different mechanisms for better control of pre-diabetic and diabetic conditions. In most studies, significant changes were evident in the postprandial glucose and insulin incremental area under the curve (iAUC). Comparative evaluation of RS consumption and control groups also showed differences with inflammatory markers such as TNF-α, IL-1β, MCP-1, and E-selectin. Only RS2 and RS3 were extensively investigated and widely reported among the five reported RS types. However, a proper comparison and conclusion are deemed inappropriate considering the variations observed with the study duration, sample size, subjects and their metabolic conditions, intervention doses, and the intervention base products. In conclusion, this result provides interesting insights into the potential use of RS as part of a sustainable diet in diabetes management and should be further explored in terms of the mechanism involved.


Magnetization transfer ratio relates to cognitive impairment in normal elderly.
Magnetization transfer imaging (MTI) can detect microstructural brain tissue changes and may be helpful in determining age-related cerebral damage. We investigated the association between the magnetization transfer ratio (MTR) in gray and white matter (WM) and cognitive functioning in 355 participants of the Austrian stroke prevention family study (ASPS-Fam) aged 38-86 years. MTR maps were generated for the neocortex, deep gray matter structures, WM hyperintensities, and normal appearing WM (NAWM). Adjusted mixed models determined whole brain and lobar cortical MTR to be directly and significantly related to performance on tests of memory, executive function, and motor skills. There existed an almost linear dose-effect relationship. MTR of deep gray matter structures and NAWM correlated to executive functioning. All associations were independent of demographics, vascular risk factors, focal brain lesions, and cortex volume. Further research is needed to understand the basis of this association at the tissue level, and to determine the role of MTR in predicting cognitive decline and dementia.


Serologic evaluation of clinical and subclinical secondary hepatic amyloidosis in rhesus macaques (Macaca mulatta).
Secondary hepatic amyloidosis in nonhuman primates carries a grave prognosis once animals become clinically ill. The purpose of this study was to establish serologic parameters that potentially could be used to identify rhesus macaques undergoing subclinical development of secondary hepatic amyloidosis. A retrospective analysis was completed by using serum biochemical profiles from 26 histologically diagnosed amyloidotic macaques evaluated at 2 stages of disease, clinical and subclinical (3 to 32 mo prior to clinical signs of disease). Standard serum biochemistry values for cases were compared with institutional age- and gender-specific references ranges by construction of 95% confidence intervals for the difference between means. In addition, 19 histologically diagnosed amyloidotic macaques and 19 age-matched controls were assayed for changes in various parameters by using routinely banked, frozen (-80 degrees C) sera available from clinical and subclinical time points. Clinically amyloidotic animals displayed increased levels of alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, gamma glutamyltranspeptidase, and macrophage colony-stimulating factor and significantly decreased quantities of albumin and total cholesterol. Subclinical amyloidotic animals displayed increased levels of alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, and serum amyloid A and decreased concentrations of albumin and total cholesterol. The serologic parameters studied indicate a temporal relationship of these factors not previously described, show a clear pattern of disease progression, and could be useful in subclinical disease detection.


[Investigation of an acute hydrogen sulfide mixture gas poisoning in a confined space].
Hydrogen sulphide poisoning is an acute poisoning event that occurs frequently in summer. A case of acute hydrogen sulphide poisoning in a confined space in August 2018 was investigated and clinical data were analyzed. This is a typical case of acute hydrogen sulfide gas poisoning in a confined space. The main cause of the accident is the lack of occupational protection and illegal rescue. Among the 5 patients, 3 died, 1 patient had long-term sequelae of nervous system damage such as cortical blindness, and 1 patient was cured.


New Orleans soil lead (Pb) cleanup using Mississippi River alluvium: need, feasibility, and cost.
In New Orleans, LA prior to hurricane Katrina 20-30% of inner-city children had elevated blood Pb levels > or =10 microg/ dL and 10 census tracts had a median surface soil level of Pb >1000 mg/kg (2.5 times the U.S. standard). This project tests the feasibility of transporting and grading contaminated properties (n = 25) with 15 cm (6 in.) of clean Mississippi River alluvium from the Bonnet Carré Spillway (BCS) (median soil Pb content 4.7 mg/kg; range 1.7-22.8). The initial median surface soil Pb was 1051 mg/kg (maximum 19 627). After 680 metric tons (750 tons) of clean soil cover was emplaced on 6424 m2 (69 153 ft2), the median surface soil Pb decreased to 6 mg/kg (range 3-18). Interior entrance wipe samples were collected at 10 homes before and after soil treatment and showed a decreasing trend of Pb (p value = 0.048) from a median of 52 microg/ft2 to a median of 36 microg/ft2 (25th and 75th percentiles are 22 and 142 microg/ft2 and 12 and 61 microg/ft2, respectively). Average direct costs for properties with homes were $3,377 ($1.95 per square foot), with a range of $1,910-7,020, vs $2,622 ($0.61 per square foot), with a range of $2,400-3,040 for vacant lots. Approximately 40% (86,000) of properties in New Orleans are in areas of >400 mg Pb/kg soil and estimated direct costs for treatment are between $225.5 and $290.4 million. Annual costs of Pb poisoning in New Orleans are estimated at approximately $76 million in health, education, and societal harm. Urban accumulation of Pb is an international problem; for example, the new Government of Norway established a policy precedence for an isolated soil cleanup program at daycare centers, school playgrounds, and parks to protect children. New Orleans requires a community-wide soil cleanup program because of the extent and quantity of accumulated soil Pb. The post-Katrina benefits of reducing soil Pb are expected to outweigh the foreseeable costs of Pb poisoning to children returning to New Orleans.


Alendronate Enhances Functional Recovery after Spinal Cord Injury.
Spinal cord injury is a destructive disease characterized by motor/sensory dysfunction and severe inflammation. Alendronate is an anti-inflammatory molecule and may therefore be of benefit in the treatment of the inflammation associated with spinal cord injury. This study aimed to evaluate whether alendronate attenuates motor/sensory dysfunction and the inflammatory response in a thoracic spinal cord clip injury model. Alendronate was intraperitoneally administered at 1 mg/kg/day or 5 mg/kg/day from day (D) 0 to 28 post-injury (PI). The histopathological evaluation showed an alleviation of the inflammatory response, including the infiltration of inflammatory cells, and a decrease in gliosis. Alendronate also led to reductions in the levels of inflammation-related molecules, including mitogen-activated protein kinase, p53, pro-inflammatory cytokines, and pro-inflammatory mediators. Neuro-behavioral assessments, including the Basso, Beattie, and Bresnahan scale for locomotor function, the von Frey filament test, the hot plate test, and the cold stimulation test for sensory function, and the horizontal ladder test for sensorimotor function improved significantly in the alendronate-treated group at D28PI. Taken together, these results suggest that alendronate treatment can inhibit the inflammatory response in spinal cord injury thus improving functional responses.


Metaphyseal Distal Tibia Fractures: A Cohort, Single-Surgeon Study Comparing Outcomes of Patients Treated With Minimally Invasive Plating Versus Intramedullary Nailing.
The purpose of this study was to compare clinical and functional outcomes of patients with distal tibia fractures treated with minimally invasive plating (MIPO) or intramedullary nailing (IMN). Cohort study. Level II regional trauma center. Overall, 86 patients with metaphyseal distal fractures (within 5 cm of joint) with simple or no articular involvement treated by a single, fellowship trained, orthopedic trauma surgeon from 2002 to 2013. Intramedullary nailing or minimally invasive plate osteosynthesis. Clinical and radiographic results were evaluated at a minimum of 1-year follow-up. Limb-specific outcomes (American Orthopedic Foot and Ankle Surgeons' ankle-hindfoot instrument) and whole-person measures [Short Form 36 (SF-36) instrument] were assessed at the final follow-up. We studied 86 patients with distal tibia fractures treated with MIPO (43 patients) and IMN (43 patients). Thirty-seven patients in the MIPO group and 27 in the IMN group met inclusion criteria. All patients ultimately healed, with the average time to union of 23 weeks in both the groups. Complications were similar between the 2 groups (MIPO vs. IMN, respectively), including nonunion (8% vs. 7%), malalignment (3.6% vs. 3%), wound complications (3.6% vs. 3%), and infection (0% vs. 3.6%). The need for secondary procedures for the removal of implants was 25.9% in the IMN group (distal locking screws only in 6/7) versus 8.3% in the MIPO group (P = 0.05). Additionally, the American Orthopedic Foot and Ankle Surgeons and all SF-36 version 2 domain scores were quantitatively higher for the IMN group, although only Role Emotional reached a level of statistical superiority between the groups. Similar clinical results and marginally enhanced functional outcomes were seen when treating nonarticular or minimally articular metaphyseal distal tibia fractures with IMN compared with MIPO. However, patients treated with IMN required more frequent secondary surgeries for the removal of painful distal locking screws. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assembly of Two Subunits of the Cyanobacterial Photosystem I on the n-Side of Thylakoid Membranes.
Photosystem I contains several peripheral membrane proteins that are located on either positive (luminal) or negative (stromal or cytoplasmic) sides of thylakoid membranes of chloroplasts or cyanobacteria. Incorporation of two peripheral subunits into photosystem I of the cyanobacterium Synechocystis species PCC 6803 was studied using a reconstitution system in which radiolabeled subunits II (PsaD) and IV (PsaE) were synthesized in vitro and incubated with the isolated thylakoid membranes. After such incubation, the subunits were found in the membranes and were resistant to digestion with proteases and removal by 2 molar NaBr. All of the radioactive proteins incorporated in the membrane were found in the photosystem I complex. The subunit II was assembled specifically into cyanobacterial thylakoid membranes and not into Escherichia coli cell membranes or thylakoid membranes isolated from spinach. The assembly process did not require ATP or proton motive force, and it was not stimulated by ATP. The assembly of subunits II and IV into thylakoid membranes isolated from the strain AEK2, which lacks the gene psaE, was increased two- to threefold. The incorporation of subunit II was 15 to 17 times higher in the thylakoids obtained from the strain ADK3 in which the gene psaD has been inactivated. However, assembly of subunit IV in the same thylakoids was reduced by 65%, demonstrating that the presence of subunit II is required for the stable assembly of subunit IV. Large deletions in subunit II prevented its incorporation into thylakoids and assembly into photosystem I, suggesting that the overall conformation of the protein rather than a specific targeting sequence is required for its assembly into photosystem I.


Fish Segmentation in Sonar Images by Mask R-CNN on Feature Maps of Conditional Random Fields.
Imaging sonar systems are widely used for monitoring fish behavior in turbid or low ambient light waters. For analyzing fish behavior in sonar images, fish segmentation is often required. In this paper, Mask R-CNN is adopted for segmenting fish in sonar images. Sonar images acquired from different shallow waters can be quite different in the contrast between fish and the background. That difference can make Mask R-CNN trained on examples collected from one fish farm ineffective to fish segmentation for the other fish farms. In this paper, a preprocessing convolutional neural network (PreCNN) is proposed to provide "standardized" feature maps for Mask R-CNN and to ease applying Mask R-CNN trained for one fish farm to the others. PreCNN aims at decoupling learning of fish instances from learning of fish-cultured environments. PreCNN is a semantic segmentation network and integrated with conditional random fields. PreCNN can utilize successive sonar images and can be trained by semi-supervised learning to make use of unlabeled information. Experimental results have shown that Mask R-CNN on the output of PreCNN is more accurate than Mask R-CNN directly on sonar images. Applying Mask R-CNN plus PreCNN trained for one fish farm to new fish farms is also more effective.


Combined Effect of Early Physical Exercise and Stereotactic Hematoma Evacuation in Patients with Cerebral Hemorrhage Undergoing Hemodialysis.
This study investigated the combined effect of stereotactic hematoma evacuation and early postoperative physical function exercise in hemodialysis patients with cerebral hemorrhage. A retrospective study was conducted, including a total of 78 hemodialysis patients with cerebral hemorrhage treated at our hospital between January 2021 and June 2022. The patients were equally allocated to two groups based on different postoperative rehabilitation methods. The control group underwent stereotactic hematoma evacuation, while the study group received additional early postoperative physical function exercise in addition to the intervention provided to the control group. The operative conditions of both groups were recorded, and comparisons were made concerning neural function, limb function, daily activity ability, and complications. There were no significant differences between the two groups regarding operation time, intraoperative blood loss, and hematoma removal rate (P > .05). However, the study group demonstrated a significantly shorter hospital stay (12.98 ± 2.01 days) compared to the control group (15.02 ± 2.07 days), P < .05. Post-treatment, the study group exhibited substantially lower neurological function scores (NIHSS score) (6.37 ± 1.02) compared to the control group (10.03 ± 1.09), P < .05. Additionally, the study group showed significantly higher limb function scores (P < .05) and daily activity ability scores (P < .05) compared to the control group. Moreover, the incidence of complications in the study group was significantly lower than that in the control group (P < .05). Early postoperative physical function exercise following stereotactic hematoma evacuation showed beneficial effects in hemodialysis patients with cerebral hemorrhage. It effectively reduced operation time, restored nerve and limb function, improved daily activity ability, and reduced the incidence of related complications. These approaches hold crucial clinical significance.


Ionic Osmoregulation during Salt Adaptation of the Cyanobacterium Synechococcus 6311.
The mechanisms of salt adaptation were studied in the cyanobacterium Synechococcus 6311. Intracellular volumes and ion concentrations were measured before and after abrupt increases of external NaCl concentrations up to 0.6 molar NaCl. Equilibrium volumes, measured with a rapid and accurate electron spin resonance spin probe method, showed that at low NaCl concentrations the cells did not shrink as expected for an impermeable solute. However, when the NaCl concentration exceeded a critical value, volume losses occurred. These losses were not fully reversed by hypoosmotic treatment, suggesting membrane damage. The critical value of irreversible volume loss paralleled the increase in salinity during cell growth. Rapid mixing experiments showed that exposure of Synechococcus 6311 to non-damaging NaCl concentrations caused water extrusion from the cells; the volume decreases were time resolved to about 200 milliseconds. Subsequently, volumes increased rapidly as NaCl moved into the cells. Controls recovered their volumes within 15 seconds, while salt-adapted cells grown at 0.6 molar NaCl required 1 minute for volume equilibration. This decrease in the rate of cell volume recovery indicates that salt adaptation is accompanied by changes in cell membrane properties. Subsequent to these initial rapid volume changes, a more gradual sequence of ion movement and sugar accumulation was observed. Under conditions for photoautotrophic growth, significant Na(+) extrusion was observed 30 min after salt shock. Sucrose accumulation reached a maximum value after 16 hours and K(+) accumulation reached equilibrium after 40 hours. The final concentrations of K(+) and Na(+) and sucrose and glucose inside the 0.6 molar NaCl-grown cells indicate that the inorganic ions and organic ;compatible' solutes are the major osmotic species which account for the adaptation of Synechococcus 6311 to salt.


[Secondary effects associated with raltegravir].
Integrase inhibitors are a new therapeutic modality against HIV. Raltegravir is the first integrase inhibitor to have been approved by the health authorities for human use. This drug acts by inhibiting the HIV enzyme that catalyzes integration of the virus inside the genome of the host cell. In the host cell, there is no homologue to viral integrase and consequently the potential toxicity of this drug is probably low. The results of safety studies in animal models have shown that the recommended dose in humans is lower than the dose below which no secondary effects are observed. Studies of genotoxicity and carcinogenicity, as well as of fertility and embryo development, have been negative to date. During clinical trials, raltegravir has been shown to have a very good safety profile, with few adverse effects, which were mild-to-moderate and similar to those of the comparator. The most notable were diarrhea, nausea and headache. The lipid profile of raltegravir was better than that of efavirenz. In view of the above, the risk-benefit ratio for raltegravir is positive.


Readability of Cochlear Implant Brochures: A Potential Factor in Parent Decision Making.
The purpose of this study was to examine the ease of reading cochlear implant (CI) brochures provided to parents and caregivers who are making informed decisions about the management of their child's hearing loss. CI brochures from three Food and Drug Administration-approved CI manufacturers were examined: Advanced Bionics, Cochlear Americas, and MED-EL. Reading grade levels and ease of reading were analyzed using a commercially available computer software program, applying six readability formulas commonly used to examine hearing-related patient education materials (PEMs). The readability of the CI brochures exceeds the fifth- to sixth-grade reading-level guidelines. The CI brochures may be difficult for the average English-speaking adult to read with ease and requires at least a 10th-grade comparable reading level. Despite health literacy initiatives, audiology-focused PEMs continue to be created without full consideration of the burden for the reader. Authors of PEMs should consider the average reading level of the reader as a variable potentially influencing the decision-making process. Likewise, clinicians should consider the average reading level needed to understand PEMs when presenting information and resources to parents and caregivers for informed and shared decision making.


Deficiency of TNFalpha converting enzyme (TACE/ADAM17) causes a lean, hypermetabolic phenotype in mice.
Energy homeostasis involves central nervous system integration of afferent inputs that coordinately regulate food intake and energy expenditure. Here, we report that adult homozygous TNFalpha converting enzyme (TACE)-deficient mice exhibit one of the most dramatic examples of hypermetabolism yet reported in a rodent system. Because this effect is not matched by increased food intake, mice lacking TACE exhibit a lean phenotype. In the hypothalamus of these mice, neurons in the arcuate nucleus exhibit intact responses to reduced fat mass and low circulating leptin levels, suggesting that defects in other components of the energy homeostasis system explain the phenotype of Tace(DeltaZn/DeltaZn) mice. Elevated levels of uncoupling protein-1 in brown adipose tissue from Tace(DeltaZn/DeltaZn) mice when compared with weight-matched controls suggest that deficient TACE activity is linked to increased sympathetic outflow. These findings collectively identify a novel and potentially important role for TACE in energy homeostasis.


Characterization of G-protein betagamma expression in inner ear.
Heterotrimeric guanine nucleotide binding proteins (G-proteins) are composed of a diverse set of alpha, beta, and gamma subunits, which couple cell surface receptors to intracellular effectors, such as adenylyl cyclase, phospholipase Cbeta, and ion channels. Both the Galpha and the Gbetagamma dimers mediate effector activity and are believed to contribute to the complexity of the signaling pathway. Molecular and immunocytochemical techniques were employed to determine diversity of Gbeta and Ggamma subunit expression in the murine inner ear. PCR-based assessment of lambdaZAP unidirectional cDNA libraries, representing the cochlea and inner ear hair cells, indicated all five known Gbeta subunits were present in the cochlea, while only a subset of Ggamma isoforms were found. New or novel G-protein beta and gamma subunits were not detected. cDNAs representing Gbeta1-4 and Ggamma2, Ggamma3, Ggamma5, Ggamma8olf subunit transcripts were isolated. In addition, cDNAs corresponding to the Gbeta5 and Ggamma11 isoforms exhibited restricted expression to inner and outer hair cells, respectively. Antisera specific for Gbeta3, Gbeta4, Ggamma3, Ggamma5 and Ggamma11 stained spiral ganglion and neurosensory hair cells. A unique finding was the variable topological distribution of Ggamma3 in the spiral ganglion cells along the cochlear axis. Collectively, our results demonstrate a complementary as well as differential distribution pattern for Gbeta and Ggamma isoforms exists in the inner ear. The co-localization of various G-protein isoforms within the same cell type suggests specific combinatorial Gbeta and Ggamma subunit associations may preferentially be formed. Thus, the detection of multiple subunits presumably reflects the extent of the functional diversity of inner ear signaling pathways and should provide specificity of G-protein mediated pathways.


Fishing in a polluted estuary: fishing behavior, fish consumption, and potential risk.
People make subjective judgments about hazards relying on what they know and feel. These risk perceptions may be based on accurate or inaccurate information and are often optimistically biased. The existence of uncertainties in the evaluation of many environmental hazards effects how risks are perceived. This paper examines fish consumption and risk perception of urban fishermen in the New York/New Jersey estuary, in areas where there were consumption advisories. We interviewed 318 fishermen and crabbers in the Arthur Kill, Raritan Bay, and New Jersey shore. Fish were eaten an average of at least four times per month in all regions, but fishermen in the Arthur Kill fished most frequently, averaging over eight times per month. Although 60% of fishermen and crabbers in the Arthur Kill reported hearing warnings about consuming fish caught in these waters, 70% of fishermen and 76% of crabbers said they are their catch. Significantly fewer fishermen in the Bay and Shore regions had heard warnings (28% and 30%, respectively), and more reported consuming their catch (88% and 82%, respectively). In all regions, most people thought that the fish were safe to eat, many believing they were "fresher" than store bought fish. Thus, most people ignored the consumption advisories in effect for these waters. Some of these people are consuming high quantities of fish and crabs, and thus are exposed to potentially deleterious levels of contaminants. In general, people failed to consider the possibility of chronic effects and did not perceive that this enjoyable, familiar pastime could be hazardous. Further, fishermen generally had great confidence in their own knowledge, which proved to be inaccurate in many cases, and often expressed distrust in the information source (government). Clearly, simply issuing consumption advisories is insufficient to promote risk-reducing behavior.


Performance on paced serial addition tasks indicates an associative network for calculation.
Although paced serial addition (PSA) tasks are considered to be tests of general information-processing capacity, recent work suggests that performance on such tasks is influenced by arithmetic-specific variables. We designed two visual PSA experiments to determine whether the performance of normal adults would support predictions derived from the cognitive psychology of calculation. Experiment 1 showed that mixing familiar (Arabic numeral) and less familiar (Roman numeral) stimulus formats reduced scores below the averaged scores for pure Arabic and Roman lists. The Roman-Arabic order of addends was more difficult than the Arabic-Roman order. Experiment 2, which involved only Arabic numerals as addends, showed that performance could be impaired by constraining the trial-to-trial variability of sums. The results of both experiments confirm the importance of arithmetic-specific variables in PSA and provide support for an associative network model of calculation. In addition, the findings implicate interference from extraneous addends and responses as the performance-limiting factor.


Hepatic activation and inactivation of clinically-relevant vitamin D analogs and prodrugs.
Like most pharmaceutical agents, vitamin D analogs are subject to hepatic metabolism by a variety of cytochrome P450 (CYP)-based systems. Metabolism can involve activation as well as inactivation of the vitamin D analog and one of the more successful families includes the 1alpha-hydroxyvitamin D prodrugs (1alpha-OH-D2, 1alpha-OH-D3, 1alpha-OH-D4, 1alpha-OH-D5), that all require a step of activation. Some of these prodrugs are in use or clinical trial because they have a therapeutic advantage over calcitriol. However, the nature of the activation of these molecules is poorly understood, particularly with regard to the CYP isoform involved. Various transfected CYPs and hepatic cell lines combined with tandem LC-MS analysis were used to investigate the metabolism of a spectrum of vitamin D analogs, including 1alpha-OH-Ds and the topical analog, calcipotriol. In the case of the 1alpha-OH-Ds, evidence was found of multiple sites of side-chain hydroxylation consistent with the generation of more than one active form. The potential involvement of CYP27A and other putative 25-hydroxylases in 1alpha-OH-D activation was also shown, as well as the potential for CYP24 activation and inactivation. In the case of calcipotriol, the respective roles of non-vitamin D-related CYPs and CYP24 in the catabolism of this anti-psoriatic drug were dissected out using cell lines with or without CYP24 expression, allowing us to demonstrate the potential contribution of CYP24 to "vitamin D resistance". The implications of hepatic metabolism in the context of other facets thought to play a role in the mechanism of action of anticancer and antiproliferative vitamin D analogs are discussed.


Hemostatic characteristics of thawed, pooled cryoprecipitate stored for 35 days at refrigerated and room temperatures.
Cryoprecipitate's shelf life is limited due to concerns over decreased clotting factor activity and contamination with extended storage. Hemostatic characteristics of thawed cryoprecipitate stored up to 35 days at refrigerated and room temperatures were assessed. Pooled cryoprecipitate was thawed and aliquoted for storage at 1-6°C or 21-24°C. Samples were tested immediately after thawing and at 4 h, 24 h, 72 h, and weekly for 35 days. At each time point fibrinogen, factor VIII (FVIII), and von Willebrand factor (vWF) were assessed. Thrombin generation and rotational thromboelastometry (ROTEM) were also performed. Further, packed red cells, platelet concentrates, frozen plasma, and stored cryoprecipitate were combined (1:1:1:1) to simulate massive transfusion and analyzed by ROTEM. Day 35 samples were cultured for bacterial contamination. Precipitation was observed in refrigerated samples; however, these aggregates were easily resuspended upon warming in a 37°C water bath. No significant changes were observed in fibrinogen concentration or ROTEM at either temperature. FVIII and vWF declined significantly during storage. vWF, clot time, and thrombin generation were significantly better preserved with refrigeration. With simulated massive transfusion, fibrinogen function remained at or above the established range for whole blood at both storage temperatures. Bacterial contamination was not observed in cold stored or room temperature cryoprecipitate. The fibrinogen concentration and function of cryoprecipitate at extended storage durations are adequate for fibrinogen replacement in critical bleeding. These results support extension of the shelf life of cryoprecipitate when used for fibrinogen replacement.


Chromium-induced modulation in the antioxidant defense system during phenological growth stages of Indian mustard.
Chromium-induced modulation in the enzymes and metabolites of antioxidants was investigated at various phenological stages of Indian mustard (Brassica juncea (L.) Czern. & Coss. cv Pusa Jai Kisan)], grown with various levels of chromium (Cr) in pots under natural environmental conditions. Chromium accumulation in the root, stem and leaves increased with the advancement in the age of the plants. Growth of Indian mustard was not affected significantly by the supply of Cr up to the levels of 400 mg kg(-1) soil. Activities of superoxide dismutase (SOD), ascorbate peroxide (APX), catalase (CAT), and glutathione reductase (GR) increased in the leaves of Cr-treated plants, when compared with control. High activities of antioxidant enzymes supported by high Cr concentrations in roots and aerial parts (except seeds) established the Indian mustard as a potential hyperaccumulator anda hypertolerant species to Cr stress. For this study, an edible crop was chosen intentionally so as to tap maximum benefit by remediating the contaminated site on one hand and getting uncontaminated seeds to raise the next generation, on the other.


Experimental-design-guided approach for the removal of atrazine by sono-electrochemical-UV-chlorine techniques.
The aim of the present study was to investigate the electrochemical formation of free chlorine species (HOCl/ClO-) and their subsequent use for the degradation of the pesticide atrazine. Initially, the process of electrochemical-free chlorine production was investigated using a bench-scale electrochemical flow-cell. The most significant variables (electrolyte concentration ([NaCl]) and inter-electrode gap) of the process were obtained using a 23 factorial design and the optimum process conditions (1.73 mol L-1 and 0.56 cm) were determined by a central composite design. Following optimization of free chlorine production, three degradation techniques were investigated, individually and in combination, for atrazine degradation: electrochemical, photochemical and sonochemical. The method using the techniques in combination was denominated sono-photo-assisted electrochemical degradation. Constant current assays were performed and the sono-photo-assisted electrochemical process promoted more efficient removal of atrazine, achieving total organic carbon removal of ∼98% and removal of atrazine to levels below the detection limit (>99%) in under 30 min of treatment. Furthermore, the combination of three techniques displayed lower energy consumption, and phytotoxicity tests (Lactuca sativa) showed that there was no increase in toxicity.


Efficacy of prone position in acute respiratory distress syndrome: overview of systematic reviews.
To identify and integrate the available scientific evidence related to the use of the prone position in patients with acute respiratory distress syndrome for the reduction of the outcome variable of mortality compared to the dorsal decubitus position. Overview of systematic reviews or meta-analyzes of randomized clinical trials. It included studies that evaluated the use of prone positioning in patients with acute respiratory distress syndrome published between 2014 and 2016. The AMSTAR tool was used to determine the methodological quality of studies. The GRADE system was used to establish the overall quality of evidence for the mortality outcome. From the search strategy, were retrieved seven relevant manuscripts of high methodological quality. Scientific evidence supports that combined use of protective ventilatory strategy and prone positioning for periods between 16 and 20 hours in patients with acute respiratory distress syndrome and PaO2/FiO2 ratio lower than 150 mm/Hg results in significant reduction of mortality rate.


Repeat Courses of Stereotactic Radiosurgery (SRS), Deferring Whole-Brain Irradiation, for New Brain Metastases After Initial SRS.
To report the outcomes of repeat stereotactic radiosurgery (SRS), deferring whole-brain radiation therapy (WBRT), for distant intracranial recurrences and identify factors associated with prolonged overall survival (OS). We retrospectively identified 652 metastases in 95 patients treated with 2 or more courses of SRS for brain metastases, deferring WBRT. Cox regression analyzed factors predictive for OS. Patients had a median of 2 metastases (range, 1-14) treated per course, with a median of 2 courses (range, 2-14) of SRS per patient. With a median follow-up after first SRS of 15 months (range, 3-98 months), the median OS from the time of the first and second course of SRS was 18 (95% confidence interval [CI] 15-24) and 11 months (95% CI 6-17), respectively. On multivariate analysis, histology, graded prognostic assessment score, aggregate tumor volume (but not number of metastases), and performance status correlated with OS. The 1-year cumulative incidence, with death as a competing risk, of local failure was 5% (95% CI 4-8%). Eighteen (24%) of 75 deaths were from neurologic causes. Nineteen patients (20%) eventually received WBRT. Adverse radiation events developed in 2% of SRS sites. Multiple courses of SRS, deferring WBRT, for distant brain metastases after initial SRS, seem to be a safe and effective approach. The graded prognostic assessment score, updated at each course, and aggregate tumor volume may help select patients in whom the deferral of WBRT might be most beneficial.


Rat cholangiocytes absorb bile acids at their apical domain via the ileal sodium-dependent bile acid transporter.
Although bile acid transport by bile duct epithelial cells, or cholangiocytes, has been postulated, the details of this process remain unclear. Thus, we performed transport studies with [3H]taurocholate in confluent polarized monolayers of normal rat cholangiocytes (NRC). We observed unidirectional (i.e., apical to basolateral) Na+-dependent transcellular transport of [3H]taurocholate. Kinetic studies in purified vesicles derived from the apical domain of NRC disclosed saturable Na+-dependent uptake of [3H]taurocholate, with apparent Km and Vmax values of 209+/-45 microM and 1.23+/-0.14 nmol/mg/10 s, respectively. Reverse transcriptase PCR (RT-PCR) using degenerate primers for both the rat liver Na+-dependent taurocholate-cotransporting polypeptide and rat ileal apical Na+-dependent bile acid transporter, designated Ntcp and ASBT, respectively, revealed a 206-bp product in NRC whose sequence was identical to the ASBT. Northern blot analysis demonstrated that the size of the ASBT transcript was identical in NRC, freshly isolated cholangiocytes, and terminal ileum. In situ RT-PCR on normal rat liver showed that the message for ASBT was present only in cholangiocytes. Immunoblots using a well-characterized antibody for the ASBT demonstrated a 48-kD protein present only in apical membranes. Indirect immunohistochemistry revealed apical localization of ASBT in cholangiocytes in normal rat liver. The data provide direct evidence that conjugated bile acids are taken up at the apical domain of cholangiocytes via the ASBT, and are consistent with the notion that cholangiocyte physiology may be directly influenced by bile acids.