Selective overproduction of 5-enol-pyruvylshikimic acid 3-phosphate synthase in a plant cell culture which tolerates high doses of the herbicide glyphosate.
Cultured cells of the higher plant Corydalis sempervirens Pers. which had been adapted to growing in the presence of 5 mM glyphosate (N-[phosphonomethyl]-glycine), a herbicide and a potent specific inhibitor of the shikimate pathway enzyme 5-enol-pyruvylshikimate-3-phosphate (EPSP) synthase, had a nearly 40-fold increased level of the extractable activity of EPSP synthase. Activities of five other shikimate pathway enzymes were, however, similar in the adapted and nonadapted cells, and the concentrations of the free aromatic amino acids in the two cell lines were also similar. EPSP synthases purified from glyphosate-adapted, as well as nonadapted cells, had identical physical, kinetic, and immunological properties, which indicated that the glyphosate-sensitive enzyme was overproduced in the adapted culture. Overproduction of EPSP synthase in the adapted culture was unequivocally established by two-dimensional polyacrylamide gel electrophoresis, as well as by one-dimensional sodium dodecyl sulfate-gradient gel electrophoresis and quantitation of EPSP protein by immunoassay after transfer to nitrocellulose membranes. While about 0.06% of the total soluble protein from nonadapted cells was EPSP synthase protein, the proportion was 2.6% in the adapted cells. In vivo pulse-labeling experiments with [35S]methionine established that the adapted cells have an increased rate of EPSP synthase protein synthesis.


Recording and reproducing the diurnal oviposition rhythms of wild populations of the soft- and stone- fruit pest Drosophila suzukii.
Drosophila suzukii is a horticultural pest on a global scale which causes both yield and economic losses on a range of soft- and stone-fruit. Tackling this pest is problematic but exploiting behavioral rhythms could increase the impact of control. To do this, a better understanding of behavioral patterns is needed. Within this study we aimed to investigate rhythms in reproductive behavior of wild D. suzukii under natural conditions in the field. Environmental parameters were also recorded to decipher how they influence these rhythms. Assays were then performed on laboratory cultures, housed under artificial conditions mimicking the temperature and light cycles, to see if these patterns were reproducible and rhythmic. We were able to promote field like oviposition patterns within the laboratory using realistic temperature and light cycles regardless of variations in other factors including substrate, humidity, and lighting type. Locomotion activity was also recorded under these mimicked conditions to identify how this behavior interacts with oviposition rhythms. Both our field and laboratory assays show that oviposition behavior is likely under the control of the circadian clock and primarily occurs during the day. However, consistent with prior reports we observed that these patterns become crepuscular when day-time temperature peaks exceeded 30°C. This was also found within locomotion rhythms. With an increased understanding of how these behaviors are influenced by environmental conditions, we highlight the importance of using realistic temperature and light cycles when investigating behavioral patterns. From an increased understanding of D. suzukii behavior we increase our ability to target the pest in the field.


Minimally invasive reoperative aortic valve replacement.
The operative mortality associated with repeat heart valve surgery is supposedly higher than the mortality associated with the primary operation. However, controversy still surrounds the risk factors and optimal surgical approach for patients requiring repeat cardiac surgery, particularly for those requiring aortic valve replacements (AVR). While the standard approach generally utilizes full sternotomy and peripheral cannulation, alternative approaches such as minimally invasive sternotomy may play an increasingly important role in this field. This study compares the advantages and disadvantages of a minimally invasive approach in redo AVR with the standard approach, highlighting difficulties and potential solutions.


Parents' Anticipated Discussions About Death With Young Children.
Guided by family communication patterns theory and terror management theory this mixed-methods investigation explored how parents (N = 112) of young children (ages 3-6) described the way they would discuss death when it comes up in conversations. Responses were coded inductively, resulting in four themes: explanations that death is inevitable, explanations that death is in the distance, the use of religion to frame discussions of death, and finally, discussing afterlife connections to deceased family members. Logistic regression analyses were used to evaluate whether parents' conformity or conversation orientations were associated with the frequency with which parents discussed death with their child and the content of parent vignette responses. Quantitative analysis revealed parents' conversation orientations were associated with the frequency with which they discussed death with their child and conformity orientations were associated with parents' use of religion and discussing afterlife connections to deceased family members in their responses.


The promoter regulatory regions of the genes for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) from the chicken and the rat have different species-specific roles in gluconeogenesis.
Hepatic expression of the gene for phosphoenolpyruvate carboxykinase (GTP) (PEPCK-C) (EC 188.8.131.52) in birds occurs prior to birth and decreases to negligible levels before hatching, whereas in mammals the gene for PEPCK-C in the liver is expressed at birth and is active throughout the life of the animal. The administration of cyclic AMP to adult chickens results in the induction of transcription of the gene for PEPCK-C and the transient accumulation of PEPCK-C mRNA in the liver. DNase I footprint analysis of 330 bp of the avian PEPCK-C promoter immediately 5' of the start-site of transcription indicated the presence of several protein binding domains, purified CAAT/enhancer binding protein alpha, cAMP regulatory element binding protein and nuclear factor-1 bound to these regions of the promoter. Sequences corresponding to an hepatic nuclear factor-1 binding domain and to the insulin response sequence, previously identified in the rat PEPCK-C promoter, were also found in the chicken PEPCK-C promoter. Co-transfection of an expression vector for CAAT/enhancer binding protein alpha or CAAT/enhancer binding protein beta markedly stimulated transcription from both the chicken and rat PEPCK-C promoters in human hepatoma cells. Sequences involved in the regulation of gene transcription by cyclic AMP and insulin were found to reside between -210 and +1 of the avian PEPCK-C promoter. In general, transcription from the avian promoter was more sensitive to inhibition by insulin than was noted for the rat PEPCK-C promoter, which may explain in part the lack of expression of the gene for PEPCK-C in the livers of adult birds.


Characteristics and seasonal variations of PM2.5, PM10, and TSP aerosol in Beijing.
To investigate the seasonal characteristics and the sources of elements and ions with different sizes in the aerosols in Beijing. Samples of particulate matters (PM2.5), PM10, and total suspended particle (TSP) aerosols were collected simultaneously in Beijing from July 2001 to April 2003. The aerosol was chemically characterized by measuring 23 elements and 18 water-soluble ions by inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and ion chromatography (IC), respectively. The samples were divided into four categories: spring non-dust, spring dust, summer dust, and winter dust. TSP, PM10, and PM2.5 were most abundant in the spring dust, and the least in summer dust. The average mass ratios of PM > 10, PM2.5-10, and PM2.5 to TSP confirmed that in the spring dust both the large coarse (PM > 10) and fine particles (PM2.5) contributed significantly in summer PM2.5, PM2.5-10, and PM > 10 contributed similar fractions to TSP, and in winter much PM2.5. The seasonal variation characteristics of the elements and ions were used to divide them into four groups: crustal, pollutant, mixed, and secondary. The highest levels of crustal elements, such as Al, Fe, and Ca, were found in the dust season, the highest levels of pollutant elements and ions, such as As, F-, and Cl-, were observed in winter, and the highest levels of secondary ions (SO4(2-), NO3-, and NH4+) were seen both in summer and in winter. The mixed group (Eu, Ni, and Cu) showed the characteristics of both crustal and pollutant elements. The mineral aerosol from outside Beijing contributed more than that from the local part in all the reasons but summer, estimated using a newly developed element tracer technique.


A comparative study of the quality of care and glycemic control among ambulatory type 2 diabetes mellitus clients, at a Tertiary Referral Hospital and a Regional Hospital in Central Kenya.
Peripheral public health facilities remain the most frequented by the majority of the population in Kenya; yet remain sub-optimally equipped and not optimized for non-communicable diseases care. We undertook a descriptive, cross sectional study among ambulatory type 2 diabetes mellitus clients, attending Kenyatta National Referral Hospital (KNH), and Thika District Hospital (TDH) in Central Kenya. Systematic random sampling was used. HbA1c was assessed for glycemic control and the following, as markers of quality of care: direct client costs, clinic appointment interval and frequency of self monitoring test, affordability and satisfaction with care. We enrolled 200 clients, (Kenyatta National Hospital 120; Thika District Hospital 80); Majority of the patients 66.5% were females, the mean age was 57.8 years; and 58% of the patients had basic primary education. 67.5% had diabetes for less than 10 years and 40% were on insulin therapy. The proportion (95% CI) with good glycemic was 17% (12.0-22.5 respectively) in the two facilities [Kenyatta National Hospital 18.3% (11.5-25.6); Thika District Hospital 15% (CI 7.4-23.7); P = 0.539]. However, in Thika District Hospital clients were more likely to have a clinic driven routine urinalysis and weight, they were also accorded shorter clinic appointment intervals; incurred half to three quarter lower direct costs, and reported greater affordability and satisfactions with care. In conclusion, we demonstrate that in Thika district hospital, glycemic control and diabetic care is suboptimal; but comparable to that of Kenyatta National Referral hospital. Opportunities for improvement of care abound at peripheral health facilities.


Geranium leaf assisted biosynthesis of silver nanoparticles.
Development of biologically inspired experimental processes for the synthesis of nanoparticles is evolving into an important branch of nanotechnology. In this paper, we report on the use of Geranium (Pelargonium graveolens) leaf extract in the extracellular synthesis of silver nanoparticles. On treating aqueous silver nitrate solution with geranium leaf extract, rapid reduction of the silver ions is observed leading to the formation of highly stable, crystalline silver nanoparticles in solution. Transmission electron microscopy analysis of the silver particles indicated that they ranged in size from 16 to 40 nm and were assembled in solution into quasilinear superstructures. The rate of reduction of the silver ions by the geranium leaf extract is faster than that observed by us in an earlier study using a fungus, Fusarium oxysporum, thus highlighting the possibility that nanoparticle biosynthesis methodologies will achieve rates of synthesis comparable to those of chemical methods. This study also represents an important advance in the use of plants over microorganisms in the biosynthesis of metal nanoparticles.


Histologic upgrading in patients eligible for active surveillance on saturation biopsy.
We evaluated the risk of histologic upgrading and upstaging in patients who met strict active surveillance (AS) criteria on saturation biopsy and elected to undergo radical prostatectomy. A retrospective review was conducted of 362 consecutive, individual patients who underwent transrectal ultrasound guided saturation biopsy (32 cores) between 2006 and 2013. Thirty-one patients (9%) were eligible for AS based on Hopkins criteria for very low risk (VLR): stage T1c, prostate-specific antigen (PSA) density ≤ 0.15 ng/mL2, Gleason ≤ 6, ≤ 2 cores and ≤ 50% core. Twenty patients (64%) elected radical prostatectomy, 2 (7%) elected radiation treatment and 9 (29%) elected AS (n = 9, 29%). Radical prostatectomy results were used to evaluate for upgrading and upstaging. Patient and saturation biopsy characteristics were similar amongst radical prostatectomy, radiation and AS patients. Mean age was 63 years (range 50-75) and 27 patients (87%) had a prior negative biopsy. Median time to prostatectomy was 3 months (range 1-46). Upgrading (Gleason ≥ 7) was identified in 40% (n = 8) of patients: Gleason 3+4 (n = 7) and Gleason 4+3 (n = 1). Upstaging (≥ T3) was not identified. Mean follow up was 47 months (range 11-99) for all patients. No patient developed biochemical recurrence or required salvage treatment. Despite increased prostate sampling, patients who met strict AS criteria on saturation biopsy were at high risk for Gleason upgrading, but fortunately at low risk for upstaging and biochemical recurrence. Patients contemplating AS based on saturation biopsy results should be counseled appropriately. MRI-TRUS fusion biopsy may be an alternative to saturation biopsy until proven otherwise.


A narrative review of fathers' involvement during labour and birth and their influence on decision making.
to identify and critically review the research literature that has examined fathers׳ involvement during labour and birth and their influence on decision making. the review follows the approach of a narrative review. Systematic searches of electronic databases Social Services Abstract, Sociological Abstracts, ASSIA, CINAHL Medline, Cochrane library, AMED, BNI, PsycINFO, Embase, Maternity and Infant care, DH-Data and the Kings Fund Database were combined with manual searches of key journals and reference lists. Studies published between 1992 and 2013 examining fathers׳ involvement during intrapartum care were included in the review. the findings of this review suggest that fathers׳ level of involvement during labour ranges from being a witness or passive observer of labour and birth to having an active supporting and coaching role. The findings also suggest that there are a number of facilitators and barriers to fathers׳ involvement during labour and birth. There are a limited number of studies that have examined fathers׳ involvement in decision making and specifically how fathers׳ influence decision making during labour and birth. future research needs to address the gap in the literature regarding fathers׳ involvement and influence on decision making to help midwives and obstetricians understand the process in order enhance the transition to parenthood for women and men.


Distribution of acetylcholinesterase (Ace-1R) target-site G119S mutation and resistance to carbamates and organophosphates in Anopheles gambiae sensu lato populations from Cameroon.
Cameroon is considering the implementation of indoor residual spraying (IRS) as a complementary measure to control malaria in the context of high pyrethroid resistance in major malaria vectors. Non-pyrethroid insecticide classes such as organophosphates and carbamates may be utilized in IRS due to widespread pyrethroid resistance. However, the success of this strategy depends on good knowledge of the resistance status of malaria vectors to carbamates and organophosphates. Here, we assessed the susceptibility profile of Anopheles gambiae sensu lato with respect to carbamates and organophosphate and the distribution of the molecular mechanism underlying resistance to these insecticides. Anopheles gambiae s.l. mosquitoes were collected from nine settings across the country and bio-assayed with bendiocarb, propoxur and pirimiphos-methyl. The Ace-1 target-site G119S mutation was genotyped using a TaqMan assay. To investigate the polymorphism in the Ace-1 gene, a region of 924 base pairs in a sequence of the gene was amplified from both live and dead females of An. gambiae exposed to bendiocarb. Pirimiphos-methyl induced full mortality in An. gambiae s.l. from all study sites, whereas for carbamates, resistance was observed in four localities, with the lowest mortality rate recorded in Mangoum (17.78 ± 5.02% for bendiocarb and 18.61 ± 3.86% for propoxur) in the southern part of Cameroon. Anopheles coluzzii was found to be the predominant species in the northern tropical part of the country where it is sympatric with Anopheles arabiensis. In the localities situated in southern equatorial regions, this species was predominant in urban settings, while An. gambiae was the most abundant species in rural areas. The G119S Ace-1 target-site mutation was detected only in An. gambiae and only in the sites located in southern Cameroon. Phylogenetic analyses showed a clustering according to the phenotype. The occurrence of the Ace-1 target-site substitution G119S in An. gambiae s.l. populations highlights the challenge associated with the impending deployment of IRS in Cameroon using carbamates or organophosphates. It is therefore important to think about a resistance management plan including the use of other insecticide classes such as neonicotinoids or pyrrole to guarantee the implementation of IRS in Cameroon.


Trends in Texas high school student enrollment in mathematics, science, and CTE-STEM courses.
In the context of Texas of the USA, House Bill 5 signifies a major policy shift requiring entering high school students starting in fall 2014 to choose an endorsement, like science, technology, engineering, and mathematics (STEM) being one of them, to provide students with earlier exposure to a coherent course sequence. As we barely understand students' choices before the endorsement requirement, this study explored 6 years of data (2008-2013) on high school student enrollment rates in mathematics, science, and career and technical education (CTE)-STEM courses to set out the baseline of the trends in STEM course enrollment in Texas. The enrollment rates of the STEM-related courses had wide variations by types of courses, gender, and race/ethnicity. Overall, student enrollment rates increased across time in selective and advanced mathematics, science, and CTE-STEM courses, which indicates a promising prospect for the STEM pipeline. However, there were exceptions in several courses with gender and racial/ethnic differences in the trends. Gender disparity was greater in advanced science courses than advanced mathematics courses, and collectively, gender gap in CTE-STEM courses increased greater than advanced mathematics and advanced science courses across years. While racial/ethnic differences were constant across years in both advanced mathematics and advanced science courses, the differences were rising in CTE-STEM courses in recent years. As little is known about students' preferences in course-taking in STEM courses at the state level, the findings on the trends in students' STEM course-taking, disaggregated by gender and race/ethnicity, can provide needed insights on what institutional K-12 changes would be effective for impacting the STEM pipeline.


[Strategy for the use of chondroprotectors in osteoarthrosis].
Symptomatic slow-acting drugs (chondroprotectors) as different dosage forms have widespread application in the treatment of osteoarthrosis (OA) at different locations. The literature review considers their possible effect on carbohydrate metabolism, which is particularly important due to the high prevalence of diabetes mellitus in patients with OA. Current clinical recommendations for the use of chondroprotectors in the therapy of OA are given.


The proliferative effect of synthetic N-POMC(1-28) peptides in rat adrenal cortex: a possible role for cyclin E.
Modified synthetic N-POMC(1-28) without disulfide bridges has been shown to act as an adrenal mitogen. Cyclins and their inhibitors are the major cell cycle controls, but in the adrenal cortex the effect of ACTH and N-POMC on the expression of these proteins remains unclear. In this work, we evaluate the effect of different synthetic N-POMC peptides on the S-phase of the cell cycle. In addition, we examine the cyclin E expression in rat adrenal cortex. Rats treated with dexamethasone were injected with ACTH and/or synthetic modified N-POMC and/or synthetic N-POMC with disulfide bridges. DNA synthesis was determined by BrdU incorporation and protein expression was analyzed by immunoblotting and immunohistochemistry. The results showed that similarly to modified N-POMC without disulfide bridges, administration of synthetic N-POMC with disulfide bridges and the combination of ACTH and N-POMC promoted an increase of BrdU-positive nuclei in adrenal cortex. However, the proliferative effect of N-POMC was comparable to that of ACTH only in the zona glomerulosa. An increase in cyclin E expression was observed 6 h after N-POMC treatment in the outer fraction of the adrenal cortex, in agreement with immunohistochemical findings in the zona glomerulosa. In summary, the effect of synthetic N-POMC with disulfide bridges was similar to modified synthetic N-POMC, increasing proliferation in the adrenal cortex, confirming previous evidence that disulfide bridges are not essential to the N-POMC mitogenic effect. Moreover, cyclin E appears to be involved in the N-POMC- and ACTH-stimulated proliferation in the zona glomerulosa of the adrenal cortex.


Characterization of the luteinizing hormone response to continuous infusions of gonadotropin releasing hormone using perifused pituitaries from intact, ovariectomized and steroid-treated rats.
Anterior pituitary glands obtained from rats at various stages of the estrous cycle and from short-term ovariectomized (OVX) rats with or without physiological replacement of estradiol-17 beta (E2) and/or progesterone (P), were perifused in vitro with continuous infusions (4 h) of gonadotropin releasing hormone (GnRH) (12 ng/h). In all treatment groups the in vitro pattern of luteinizing hormone (LH) release in response to GnRH was characterized by an initial low rate of LH release (initial phase; 20-70 min) followed by a significant augmented rate of secretion during the late phase (120-240 min) with the exception of the estrous and OVX + P groups in which LH was released at a constant rate. The total amount of LH released in response to GnRH was similar for glands removed on estrus, diestrus-I (D-I) and D-II, but increased significantly for glands removed on 0900 h proestrus with a further increase at 1400 h proestrus. Ovariectomy reduced the total LH released in vitro by 50-60% and 85-90% compared with estrous, D-I, D-II and proestrous groups, respectively. In vivo treatment of OVX rats with E2 restored the in vitro LH response to levels comparable to those in the 0900 h proestrous group while treatment with P + E2 further increased the rate of LH release in the initial phase to levels similar to those observed in the 1400 h proestrous group. In all treatment groups, addition of 5 microM cycloheximide to the perifusion media significantly inhibited GnRH-stimulated LH release during the late phase without significantly altering the initial LH response except in the OVX + E2P group in which it was partially inhibited. These results demonstrate that perifused pituitaries maintain their characteristic responsiveness to GnRH in vitro. Furthermore, they indicate that LH secretion in response to continual GnRH stimulation involves protein synthesis-independent and -dependent components. E2, in vivo, enhances the magnitude of both components in response to GnRH in vitro, while E2 + P may further enhance the initial in vitro response to GnRH through a protein synthesis-dependent mechanism.


Predictors of 1-year mortality in adult lung transplant recipients: a systematic review and meta-analysis.
Upon surviving the first year post-lung transplantation, recipients can expect a median survival of 8 years. Within the first year, graft failure and multi-organ failure (possibly secondary to graft failure) are common causes of mortality. To better understand the prognosis within the first year, we plan on conducting a systematic review and meta-analysis of observational studies addressing the association between the patient, donor, and transplant operative factors and graft loss 1-year post-lung transplant. We searched MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register, and PubMed supplemental for non-MEDLINE records for observational studies identifying independent risk factors for early mortality (1 year) in adult lung transplant recipients. We plan on including cohort studies and secondary analyses of randomized controlled trials studying adult lung transplant recipients undergoing their first lung transplant, without any simultaneous organ transplant. We will conduct a random-effects meta-analysis that pools the effect estimates from all eligible studies to obtain a summary estimate and confidence interval for all independent non-therapeutic factors identified in the primary studies. The results from this study may inform future guidelines on the selection of candidates and donors for transplantation and predictive model development and inform the decision-making process that the physician and patient undertake together. Furthermore, through the conduction of this review, we can identify the limitations with the current best evidence, which will encourage the need for studies with a better methodology to reassess the predictors of mortality.


Beyond the familial: The development of emotional communication with mothers, fathers, and strangers.
Interaction with unfamiliar partners is a component of social life from infancy onward. Yet little is known about preverbal communication with strangers. This study compared the development of infant communication with strangers to communication with mothers and fathers and examined the contribution of temperament to partner-specific communication patterns. A sample of 58 infants was observed at four and eight months during separate home-based face-to-face interactions with three partners (mother, father, and stranger). Infant visual, facial, and vocal communication behaviors were coded microanalytically. Each parent reported on infant temperament at both ages. Multilevel regression analyses indicated that infants gazed longer at strangers than at fathers, exhibited less smiling to strangers than to mothers, and produced fewer vocalizations with strangers than with either parent. Both age and temperament moderated these differences. Vocal communication with fathers became more frequent at eight months; smiling to mothers was accentuated among infants with higher levels of temperamental surgency. Importantly, levels of communication behaviors with strangers were concurrently and longitudinally associated with those with mothers and fathers. Overall, findings suggest that infant emotional communication patterns are modulated by individual temperamental differences and are reproduced in and over time, though at different levels, when interacting with novel partners.


Profiles of medicinal cannabis patients attending compassion centers in rhode island.
Little is understood regarding medicinal marijuana dispensary users. We sought to characterize socio-demographics and reasons for medicinal marijuana use among medical cannabis dispensary patients in Rhode Island. Participants (n=200) were recruited from one of two Compassion Centers in Rhode Island and asked to participate in a short survey, which included assessment of pain interference using the Brief Pain Inventory (BPI). The majority of participants were male (73%), Caucasian (80%), college educated (68%), and had health insurance (89%). The most common reason for medicinal marijuana use was determined to be chronic pain management. Participants were more likely to have BPI pain interference scores of > 5 if they were older (OR: 1.36, 95% CI: 1.04-1.78) or reported using cannabis as a substitute for prescription medications (OR: 2.47, 95% CI: 1.23-4.95), and were less likely to have interference scores of >5 if they had higher income levels (OR: 0.53, 95% CI: 0.40-0.70) or reported having ever received treatment for an alcohol use disorder. One-fifth of participants had a history of a drug or alcohol use disorder. Most participants report that medicinal cannabis improves their pain symptomology, and are interested in alternative treatment options to opioid-based treatment regimens.


The orientation of iron-sulphur clusters in membrane multilayers prepared from aerobically-grown Escherichia coli K12 and a cytochrome-deficient mutant.
1. Membrane particles prepared from ultrasonically-disrupted, aerobically-grown Escherichia coli were centrifuged on to a plastic film that was supported perpendicular to the centrifugal field to yield oriented membrane multilayers. In such preparations, there is a high degree of orientation of the planes of the membranes such that they lie parallel to each other and to the supporting film. 2. When dithionite- or succinate-reduced multilayers are rotated in the magnetic field of an e.p.r. spectrometer, about an axis lying in the membrane plane, angular-dependent signals from an iron-sulphur cluster at g(x)=1.92, g(y)=1.93 and g(z)=2.02 are seen. The g=1.93 signal has maximal amplitude when the plane of the multilayer is perpendicular to the magnetic field. Conversely, the g=2.02 signal is maximal when the plane of the multilayer is parallel with the magnetic field. 3. Computer simulations of the experimental data show that the cluster lies in the cytoplasmic membrane with the g(y) axis perpendicular to the membrane plane and with the g(x) and g(z) axes lying in the membrane plane. 4. In partially-oxidized multilayers, a signal resembling the mitochondrial high-potential iron-sulphur protein (Hipip) is seen whose g(z)=2.02 axis may be deduced as lying perpendicular to the membrane plane. 5. Appropriate choice of sample temperature and receiver gain reveals two further signals in partially-reduced multilayers: a g=2.09 signal arises from a cluster with its g(z) axis in the membrane plane, whereas a g=2.04 signal is from a cluster with the g(z) axis lying along the membrane normal. 6. Membrane particles from a glucose-grown, haem-deficient mutant contain dramatically-lowered levels of cytochromes and exhibit, in addition to the iron-sulphur clusters seen in the parental strain, a major signal at g=1.90. 7. Only the latter may be demonstrated to be oriented in multilayer preparations from the mutant. 8. Comparisons are drawn between the orientations of the iron-sulphur proteins in the cytoplasmic membrane of E. coli and those in mitochondrial membranes. The effects of diminished cytochrome content on the properties of the iron-sulphur proteins are discussed.


Heterotopic Triplet Pregnancy in Gonadotropin Stimulation Cycle: A Case Report.
Heterotopic pregnancy is defined as the simultaneous presence of 2 or more pregnancies at different implantation sites, most commonly one intrauterine and one ectopic. Triplet heterotopic pregnancy refers to the presence of specifically 3 concurrent gestations with at least 1 being abnormally implanted. Heterotopic pregnancy is a potentially life-threatening condition that requires thorough diagnostic workup and prompt intervention. We report the fourth case of triplet heterotopic pregnancy after ovarian stimulation with gonadotropins. A 24-year-old woman, G0, presented at 6 weeks of gestation with bilateral tubal ectopic pregnancies and a nonviable intrauterine pregnancy (IUP) after gonadotropin stimulation cycle. Bilateral tubal pregnancies were removed laparoscopically and the nonviable IUP via dilation and curettage. Although rare, heterotopic pregnancy of 2 or more gestations must be kept in mind when managing patients undergoing treatment with ART. Careful examination of bilateral adnexa and consideration of uterine sampling at the time of surgery for ectopic pregnancy is advisable, even for patients with few or no risk factors.


Purification of a phospholipase C from rat liver cytosol that acts on phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate.
A soluble phospholipase C from rat liver was purified to homogeneity using phosphatidylinositol 4,5-bisphosphate (PIP2) as substrate. After ammonium sulfate fractionation, the purification involved chromatography on phosphocellulose, DEAE-Sepharose CL-6B, hydroxylapatite, Reactive Blue 2 dye-linked agarose, and Mono S cation exchanger. Under the conditions of the assay, the pure enzyme had a specific activity of 407 mumol/mg protein/min. It migrated as a single band with a molecular mass of 87 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The water-soluble product formed during the hydrolysis of PIP2 by the purified enzyme was inositol 1,4,5-trisphosphate. The enzyme shows one-half of maximum velocity at 2 microM Ca2+ with PIP2 as substrate. Between 0 and 100 microM Ca2+, the enzyme shows approximately the same activity with phosphatidylinositol 4-phosphate (PIP) as it does with PIP2, and very low activity with phosphatidylinositol. The enzyme is activated by low concentrations of basic proteins; for example, with PIP2 as substrate, 1 microgram/ml histone activates the enzyme 3.6-fold. The enzyme shows an almost absolute requirement for monovalent salts which can be met by different alkali metal halides. A second, minor peak of PIP2-hydrolyzing phospholipase C activity was resolved during chromatography of the enzyme on hydroxylapatite. The substrate specificity suggests that PIP and PIP2 are normal substrates of this enzyme. Under physiological conditions of activation, the enzyme may therefore generate inositol 1,4-bisphosphate and inositol 1,4,5-trisphosphate in amounts determined by the ratio of PIP and PIP2 present in the cellular membranes.


Cell signaling stabilizes morphogenesis against noise.
Embryonic development involves gene networks, extracellular signaling, cell behaviors (cell division, adhesion, etc.) and mechanical interactions. How should these be coordinated to lead to complex and robust morphologies? To explore this question, we randomly wired genes and cell behaviors into a huge number of networks in EmbryoMaker. EmbryoMaker is a computational model of animal development that simulates how the 3D positions of cells, i.e. morphology, change over time due to such networks. We found that any gene network can lead to complex morphologies if this activates cell behaviors over large regions of the embryo. Importantly, however, for such complex morphologies to be robust to noise, gene networks should include cell signaling that compartmentalizes the embryo into small regions where cell behaviors are regulated differently. If, instead, cell behaviors are equally regulated over large regions, complex but non-robust morphologies arise. We explain how compartmentalization enhances robustness and why it is a general feature of animal development. Our results are consistent with theories proposing that robustness evolved by the co-option of gene networks and extracellular cell signaling in early animal evolution.


Apoptosis in regenerating and denervated, nonregenerating urodele forelimbs.
Denervated limbs of larval salamanders fail to regenerate if amputated and, unlike adult limbs, undergo regression. The cellular basis of the tissue loss is poorly understood. We used TUNEL staining of larval axolotl limbs fixed and sectioned at intervals after bilateral amputation and unilateral denervation to investigate the role of apoptosis during normal limb regeneration and denervated limb regression. In the first week after amputation a small percentage of apoptotic cells was found in both innervated and denervated limbs. During the second week the apoptotic index remained low in the mitotically active mesenchymal cells of the regenerating limbs, but increased twofold in the nondividing, dedifferentiated cells of the regressing limbs. TUNEL-positive cells resembling apoptotic bodies were restricted primarily to the dedifferentiated area beneath the wound epithelium, but were also present within the wound epithelium itself. Macrophages were identified immunohistochemically and were also found in increased numbers in distal areas of the denervated regressing limbs. The results suggest a role for apoptosis in the early phase of normal regeneration and indicate that denervated limb regression involves an increased rate of apoptosis and removal of apoptotic bodies by macrophages and the wound epithelium.


Characterization of the bafilomycin biosynthetic gene cluster from Streptomyces lohii.
New hope for old bones: The plecomacrolide bafilomycin has been explored for decades as an anti-osteoporotic. However, its structural complexity has limited the synthesis of analogues. The cloning of the bafilomycin biosynthetic gene cluster from the environmental isolate Streptomyces lohii opens the door to the production of new analogues through bioengineering.


Effect of an Interactive Website to Engage Patients in Advance Care Planning in Outpatient Settings.
Online programs may help to engage patients in advance care planning in outpatient settings. We sought to implement an online advance care planning program, PREPARE (Prepare for Your Care; http://www.prepareforyourcare.org), at home and evaluate the changes in advance care planning engagement among patients attending outpatient clinics. We undertook a prospective before-and-after study in 15 primary care clinics and 2 outpatient cancer centers in Canada. Patients were aged 50 years or older (primary care) or 18 years or older (cancer care) and free of cognitive impairment. They used the PREPARE website over 6 weeks, with reminders sent at 2 or 4 weeks. We used the 55-item Advance Care Planning Engagement Survey, which measures behavior change processes (knowledge, contemplation, self-efficacy, readiness) on 5-point scales and actions relating to substitute decision makers, quality of life, flexibility for the decision maker, and asking doctors questions on an overall scale from 0 to 21; higher scores indicate greater engagement. In total, 315 patients were screened and 172 enrolled, of whom 75% completed the study (mean age = 65.6 years, 51% female, 35% had cancer). The mean behavior change process score was 2.9 (SD 0.8) at baseline and 3.5 (SD 0.8) at follow-up (mean change = 0.6; 95% CI, 0.49-0.73); the mean action measure score was 4.0 (SD 4.9) at baseline and 5.2 (SD 5.4) at follow-up (mean change = 1.2; 95% CI, 0.54-1.77). The effect size was moderate (0.75) for the former and small (0.23) for the latter. Findings were similar in both primary care and cancer care populations. Implementation of the online PREPARE program in primary care and cancer care clinics increased advance care planning engagement among patients.


Systematic review of postoperative rehabilitation interventions after cranial cruciate ligament surgery in dogs.
To critically evaluate the evidence for rehabilitation interventions following surgery for cranial cruciate ligament disease (CCLD) in dogs. Systematic review. Google Scholar and Pubmed databases were searched for studies evaluating postoperative CCLD rehabilitation interventions from 1990 until March 2020 per the international Prospective Register of Systematic Reviews (PROSPERO). Each study was assigned a level of evidence score from I to IV and a risk of bias (RoB) score by 2 reviewers, and by a third reviewer, when consensus was not reached. Nineteen studies met the inclusion criteria. Twelve comprised randomized, controlled trials (Level II), 6 were nonrandomized or nonblinded (Level III), and one was retrospective (Level IV). Nine studies had high RoB scores. Sixteen studies yielded positive results. Therapeutic exercise had the most studies with positive results but all had high RoB. Cold compression therapy had 3 supporting studies (2 Level II, low RoB). Extracorporeal shockwave yielded 2 positive Level II studies (low-moderate and high-moderate RoB) and photobiomodulation had 1 positive study (Level II, low RoB) with objective outcomes. A negative outcome was noted in 1 photobiomodulation study. There was 1 supporting study on electrical stimulation and there was none on low-intensity pulsed ultrasound. This systematic review supports the use of rehabilitation interventions in recovery of postoperative CCLD in dogs; however, many studies had a high risk of bias. There is a lack of class I level evidence in veterinary rehabilitation. This study supports therapeutic exercise and cold compression therapy for postoperative CCLD rehabilitation. Existing studies on other modalities are limited and demonstrate conflicting results.


Alignment of the amino terminal amino acid sequence of human cytochrome c oxidase subunits I and II with the sequence of their putative mRNAs.
Thirteen of the first fifteen amino acids from the NH2-terminus of the primary sequence of human cytochrome c oxidase subunit I and eleven of the first twelve amino acids of subunit II have been identified by microsequencing procedures. These sequences have been compared with the recently determined 5'-end proximal sequences of the HeLa cell mitochondrial mRNAs and unambiguously aligned with two of them. This alignment has allowed the identification of the putative mRNA for subunit I, and has shown that the initiator codon for this subunit is only three nucleotides away from the 5'-end of its mRNA; furthermore, the results have substantiated the idea that the translation of human cytochrome c oxidase subunit II starts directly at the 5'-end of its putative mRNA, as had been previously inferred on the basis of the sequence homology of human mitochondrial DNA with the primary sequences of the bovine subunit.


Computer tracking of moving point targets in space.
An adaptive algorithm based on the maximum likelihood ratio is described in this correspondence. The algorithm detects low-intensity targets and tracks their paths. The charged-coupled device (CCD) mosaic sensor collects photons from the targets and the sky background. The algorithm computes the noise statistics, simulates the target pattern, correlates the received data with the target patterns, compares with the corresponding threshold, and prints out the positions and paths of the targets when present.


An unusual cause of hypercalcemia in polycythemia vera: parathyroid adenoma.
In this paper we describe a patient with polycythemia vera (PV), who presented with hypercalcemia due to a parathyroid adenoma. In November 1999, the patient was admitted to our hospital with meteorism and constipation. Her physical examination revealed plethora and hepatosplenomegaly. Laboratory data revealed hyperparathyroidism in addition to PV: Rbc 8 x 10(6)/mm3, Hct 63.7%, serum calcium 13.4 mg/dl, serum phosphorus 1.2 mg/dl, albumin 4.25 mg/dl, and alkaline phophatase activity 433 U/l. Intact Parathyroid Hormone level (iPTH) was 376 pg/ml (n.v.12-72 pg/ml). Twenty-four hour urinary calcium excretion was higher than normal (900 mg). A parathyroid adenoma was detected with Tc-99m sesta-MIBI scanning under the left lobe of the thyroid gland and an ultrasonographic examination of the neck also supported the diagnosis. The patient was recommended for surgery. The histopathological examination confirmed the diagnosis. Postoperatively, iPTH dropped to 53.4 pg/ml at the 15 th minute and to 33.5 pg/ml at the first hour. The calcium level was 7.5 mg/dl one hour after the operation. Five days later, Hct was 40.8%. This case represents a rare association between PV and primary hyperparathyroidism, and may provide evidence for a causal link between PTH and polycythemia vera in our patient. In conclusion, this case indicates that the differential diagnosis of hypercalcemia and polycythemia vera should also include the possibility of a parathyroid tumor in addition to malignancy.


Blood Metabolite Signatures of Metabolic Syndrome in Two Cross-Cultural Older Adult Cohorts.
Metabolic syndrome (MetS) affects an increasing number of older adults worldwide. Cross-cultural comparisons can provide insight into how factors, including genetic, environmental, and lifestyle, may influence MetS prevalence. Metabolomics, which measures the biochemical products of cell processes, can be used to enhance a mechanistic understanding of how biological factors influence metabolic outcomes. In this study we examined associations between serum metabolite concentrations, representing a range of biochemical pathways and metabolic syndrome in two older adult cohorts: The Tsuruoka Metabolomics Cohort Study (TMCS) from Japan (n = 104) and the Baltimore Longitudinal Study of Aging (BLSA) from the United States (n = 146). We used logistic regression to model associations between MetS and metabolite concentrations. We found that metabolites from the phosphatidylcholines-acyl-alkyl, sphingomyelin, and hexose classes were significantly associated with MetS and risk factor outcomes in both cohorts. In BLSA, metabolites across all classes were uniquely associated with all outcomes. In TMCS, metabolites from the amino acid, biogenic amines, and free fatty acid classes were uniquely associated with MetS, and metabolites from the sphingomyelin class were uniquely associated with elevated triglycerides. The metabolites and metabolite classes we identified may be relevant for future studies exploring disease mechanisms and identifying novel precision therapy targets for individualized medicine.


Long-term results of the treatment of primary hyperhidrosis with oxybutynin: follow-up of 1,658 cases.
Hyperhidrosis (HH) is characterized by exaggerated sweating in a specific region due to hyperfunction of the sweat glands. In the late 2000s, we started treating patients with an anticholinergic, oxybutynin, that was not being used until then. To present, after 12 years of utilizing this medication in our service, the substantial experience obtained with the use of oxybutynin as an initial treatment of HH in a large series of 1,658 patients. We analyzed 1,658 patients treated with oxybutynin for HH from May 2006 to June 2018. The patients were divided into four groups according to the main site of HH: the plantar group, the axillary group, the facial group, and the palmar group. To measure the degree of satisfaction, a quality of life (QoL) questionnaire was used. Pre-treatment QoL was poor or very poor in more than 94% of the cases, and the palmar group had the worst quality of life. After treatment, we observed an improvement in the quality of life in 77% of patients. More than 70% of the patients in all groups present moderate or optimal subjective clinical improvement in sweating after treatment. The group with the best result was the facial group. Intense dry mouth was reported in 24.9% of all patients in all groups. This study included a large number of patients followed for a long period and demonstrated the good effectiveness of treatment with oxybutynin for hyperhidrosis in the main sites of sweating.


Mutations in coagulation factors in women with unexplained late fetal loss.
Factor V and prothrombin-gene mutations are independent risk factors for venous thrombosis; it is debated whether a mutation in the gene encoding methylenetetrahydrofolate reductase, an enzyme involved in homocysteine metabolism, also increases the risk of venous thrombosis. Whether any of these mutations is associated with an increased risk of late fetal death is not known. We studied 67 women with a first episode of unexplained late fetal loss (fetal death after 20 weeks or more of gestation) and 232 women who had had one or more normal pregnancies and no late fetal losses. All the women were tested for the presence of three gene mutations. Women with other thrombophilic conditions were excluded from the study. Eleven of the 67 women with late fetal loss (16 percent) and 13 of the 232 control women (6 percent) had either the factor V or the prothrombin mutation. The relative risks of late fetal loss in carriers of the factor V and prothrombin mutations were 3.2 (95 percent confidence interval, 1.0 to 10.9) and 3.3 (95 percent confidence interval, 1.1 to 10.3), respectively. Thirteen percent of the women whose fetuses died and 20 percent of the control women were homozygous for the mutation in the methylenetetrahydrofolate reductase gene (relative risk, 0.8; 95 percent confidence interval, 0.5 to 1.2). Both the factor V and the prothrombin mutations are associated with an approximate tripling of the risk of late fetal loss.


"Passing Down Pollution": (Inter)generational Toxicology and (Epi)genetic Environmental Health.
Concern about the harmful health effects of industrial pollution is increasingly taking on an intergenerational dimension. In environmental health sciences such as toxicology, this has resulted in emphasizing the influence of toxic chemicals, substances, and situations across generations. Toxic relationalities are now being explored through research on gene-environment interaction, including toxicogenomics and epigenetic research through animal experiments and birth cohort studies. Based on fieldwork conducted among reproductive and developmental toxicologists working in Nanjing, China, this article shows how toxicological research both expresses and produces renewed anxieties about "passing down pollution." These toxicological accounts of intergenerational harm problematically work through overly simplistic renderings of reproduction and biological relatedness. But they also have the potential to catalyze creative understandings of toxic relationalities and responsibilities at a moment when making kin is increasingly seen as key to securing livable futures. [toxicology, environment, epigenetics, kinship, China].


Report from the National Institute of Allergy and Infectious Diseases workshop on "Atopic dermatitis and the atopic march: Mechanisms and interventions".
Atopic dermatitis (AD) affects up to 20% of children worldwide and is an increasing public health problem, particularly in developed countries. Although AD in infants and young children can resolve, there is a well-recognized increased risk of sequential progression from AD to other atopic diseases, including food allergy (FA), allergic rhinitis, allergic asthma, and allergic rhinoconjunctivitis, a process referred to as the atopic march. The mechanisms underlying the development of AD and subsequent progression to other atopic comorbidities, particularly FA, are incompletely understood and the subject of intense investigation. Other major research objectives are the development of effective strategies to prevent AD and FA, as well as therapeutic interventions to inhibit the atopic march. In 2017, the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases sponsored a workshop to discuss current understanding and important advances in these research areas and to identify gaps in knowledge and future research directions. International and national experts in the field were joined by representatives from several National Institutes of Health institutes. Summaries of workshop presentations, key conclusions, and recommendations are presented herein.


The online competition between pro- and anti-vaccination views.
Distrust in scientific expertise1-14 is dangerous. Opposition to vaccination with a future vaccine against SARS-CoV-2, the causal agent of COVID-19, for example, could amplify outbreaks2-4, as happened for measles in 20195,6. Homemade remedies7,8 and falsehoods are being shared widely on the Internet, as well as dismissals of expert advice9-11. There is a lack of understanding about how this distrust evolves at the system level13,14. Here we provide a map of the contention surrounding vaccines that has emerged from the global pool of around three billion Facebook users. Its core reveals a multi-sided landscape of unprecedented intricacy that involves nearly 100 million individuals partitioned into highly dynamic, interconnected clusters across cities, countries, continents and languages. Although smaller in overall size, anti-vaccination clusters manage to become highly entangled with undecided clusters in the main online network, whereas pro-vaccination clusters are more peripheral. Our theoretical framework reproduces the recent explosive growth in anti-vaccination views, and predicts that these views will dominate in a decade. Insights provided by this framework can inform new policies and approaches to interrupt this shift to negative views. Our results challenge the conventional thinking about undecided individuals in issues of contention surrounding health, shed light on other issues of contention such as climate change11, and highlight the key role of network cluster dynamics in multi-species ecologies15.


The influence of maternal iron deficiency anaemia on the haemoglobin concentration of the infant.
Serum ferritin, iron, and haemoglobin (Hb) values of 27 pregnant women who did not receive oral iron therapy during pregnancy, and Hb of their normal full-term babies were determined. Maternal blood samples were obtained at 16 and 24 weeks of pregnancy and infants' blood samples were obtained at the first day and 3 months of life. Mothers were divided into two groups according to their serum ferritin values. By analysing the results we were not able to detect any correlation between maternal ferritin, Hb, and newborn gestational age, and Hb and birth weight. The same was found when the groups were compared by a maternal serum ferritin above and below 12 ng/ml.


Persistence of ethyl carbamate-induced DNA damage in vivo as indicated by sister chromatid exchange analysis.
Various treatment protocols were designed to investigate sister chromatid exchanges (SCEs) induced over successive posttreatment cell cycles in bone marrow and alveolar macrophage cells following treatment of C57BL/6J X DBA/2J F1 mice by i.p. injection of ethyl carbamate (3.3 mmol/kg). The same initial extent of alkylation in bone marrow and alveolar macrophages was suggested by identical SCE frequencies produced in both cell types by a one-cycle exposure protocol. The relatively lower responses in bone marrow cells by all other protocols may be a result of its faster mean population-cycling time. Second- and third-division cell SCE data produced by the various protocols indicate persistence of SCE-inducing lesions with no evidence of repair. In spite of the demonstrated lack of repair, first-cycle ethyl carbamate treatment was less effective than was second-cycle treatment in inducing SCEs. These results could not be attributed to selection of less-damaged cells over 2 cycles or to enhanced bromodeoxyuridine sensitivity in the second-cycle treatment protocol. It is speculated that the apparent cancellation of SCEs occurring over two successive cycles in the two-cycle exposure protocol may indicate the transient presence of ethyl carbamate-induced DNA interstrand cross-links. A possible mechanism of action of ethyl carbamate involving the formation of a transient cross-link and a persistent DNA monoadduct is postulated.


Infected cell killing by HIV-1 protease promotes NF-kappaB dependent HIV-1 replication.
Acute HIV-1 infection of CD4 T cells often results in apoptotic death of infected cells, yet it is unclear what evolutionary advantage this offers to HIV-1. Given the independent observations that acute T cell HIV-1 infection results in (1) NF-kappaB activation, (2) caspase 8 dependent apoptosis, and that (3) caspase 8 directly activates NF-kappaB, we questioned whether these three events might be interrelated. We first show that HIV-1 infected T cell apoptosis, NF-kappaB activation, and caspase 8 cleavage by HIV-1 protease are coincident. Next we show that HIV-1 protease not only cleaves procaspase 8, producing Casp8p41, but also independently stimulates NF-kappaB activity. Finally, we demonstrate that the HIV protease cleavage of caspase 8 is necessary for optimal NF-kappaB activation and that the HIV-1 protease specific cleavage fragment Casp8p41 is sufficient to stimulate HIV-1 replication through NF-kappaB dependent HIV-LTR activation both in vitro as well as in cells from HIV infected donors. Consequently, the molecular events which promote death of HIV-1 infected T cells function dually to promote HIV-1 replication, thereby favoring the propagation and survival of HIV-1.


Dental insurance and dental service use by U.S. women of childbearing age.
Oral health has a significant effect on health, and for women, poor oral health can lead to poor birth outcomes and can affect their child's health. Nursing interventions to improve the oral health of at-risk women have the potential to increase maternal and child systemic and oral health. The identification of women at a high risk for poor oral health is a necessary to develop and evaluate these interventions. This study examined the factors related to dental insurance and dental service use for women of childbearing age in the United States. A secondary analysis of the 2003-2004 National Health and Nutrition Examination Survey was completed to examine the predisposing, enabling, and need variables associated with dental insurance status and dental service use in a representative random sample of 1,071 women. The results showed that over 40% of women had no dental insurance. Women with less education, lower income, and dental need were significantly less likely to have dental insurance. Dental utilization by the uninsured was low and a racial/ethnic disparity was noted. A lack of dental insurance and dental service utilization is a significant concern. Nurses working with low-income women should educate the population about oral health and advocate for policies to increase dental insurance coverage.


An assessment of geographical access and factors influencing travel time to emergency obstetric care in the urban state of Lagos, Nigeria.
Previous efforts to estimate the travel time to comprehensive emergency obstetric care (CEmOC) in low- and middle-income countries (LMICs) have either been based on spatial models or self-reported travel time, both with known inaccuracies. The study objectives were to estimate more realistic travel times for pregnant women in emergency situations using Google Maps, determine system-level factors that influence travel time and use these estimates to assess CEmOC geographical accessibility and coverage in Lagos state, Nigeria. Data on demographics, obstetric history and travel to CEmOC facilities of pregnant women with an obstetric emergency, who presented between 1st November 2018 and 31st December 2019 at a public CEmOC facility were collected from hospital records. Estimated travel times were individually extracted from Google Maps for the period of the day of travel. Bivariate and multivariate analyses were used to test associations between travel and health system-related factors with reaching the facility >60 minutes. Mean travel times were compared and geographical coverage mapped to identify 'hotspots' of predominantly >60 minutes travel to facilities. For the 4005 pregnant women with traceable journeys, travel time ranges were 2-240 minutes (without referral) and 7-320 minutes (with referral). Total travel time was within the 60 and 120 minute benchmark for 80 and 96% of women, respectively. The period of the day of travel and having been referred were significantly associated with travelling >60 minutes. Many pregnant women living in the central cities and remote towns typically travelled to CEmOC facilities around them. We identified four hotspots from which pregnant women travelled >60 minutes to facilities. Mean travel time and distance to reach tertiary referral hospitals were significantly higher than the secondary facilities. Our findings suggest that actions taken to address gaps need to be contextualized. Our approach provides a useful guide for stakeholders seeking to comprehensively explore geographical inequities in CEmOC access within urban/peri-urban LMIC settings.


Broadband polarization-entangled source for C+L-band flex-grid quantum networks.
The rising demand for transmission capacity in optical networks has motivated steady interest in expansion beyond the standard C-band (1530-1565 nm) into the adjacent L-band (1565-1625 nm) for an approximate doubling of capacity in a single stroke. However, in the context of quantum networking, the L-band has yet to be fully leveraged with the suite of advanced tools for characterization and management available from classical lightwave communications. In this work, we demonstrate an ultrabroadband two-photon source integrating both C- and L-band wavelength-selective switches for complete control of spectral routing and allocation across 7.5 THz in a single setup. Polarization state tomography of all 150 pairs of 25-GHz-wide channels reveals an average fidelity of 0.98 and total distillable entanglement greater than 181 kebits/s. This source is explicitly designed for flex-grid optical networks and can facilitate optimal utilization of entanglement resources across the full C+L-band.


Enhancement of alpha- and beta-adrenoceptor responses by elevations in vascular tone in pulmonary circulation.
The influence of increases in vascular tone on responses to selective alpha 1- and alpha 2-adrenoceptor agonists, norepinephrine, epinephrine, and isoproterenol was investigated in the feline pulmonary vascular bed. Under resting tone conditions with constant pulmonary blood flow and left atrial pressure, intralobar injections of the alpha 1-adrenoceptor agonists, phenylephrine and methoxamine, and the alpha 2-adrenoceptor agonists, UK 14304 and B-HT 933, increased lobar arterial pressure. When pulmonary vascular resistance was raised to a high steady level, vasoconstrictor responses to the alpha 2-adrenoceptor agonists were markedly increased, responses to methoxamine were increased to a lesser extent, and pressor responses to phenylephrine and epinephrine were reversed. These vasodilator responses to phenylephrine and epinephrine at elevated vascular tone were blocked by propranolol. Moreover, after beta-adrenoceptor blockade, vasoconstrictor responses to phenylephrine, epinephrine, and norepinephrine were also greater at elevated tone than at resting tone. Vasodilator responses to the beta-adrenoceptor stimulant, isoproterenol, were enhanced at higher levels of vasoconstrictor tone and were blocked by propranolol and by albuterol, a selective beta 2-adrenoceptor antagonist. The enhanced vasoconstrictor responses to the alpha 2-adrenoceptor agonists were selectively blocked by yohimbine, whereas the enhanced responses to the alpha 1-adrenoceptor agonists and, for the most part, the vasoconstrictor responses to norepinephrine and epinephrine, were blocked by prazosin. The present data support the hypothesis that postjunctional alpha 1- and alpha 2-adrenoceptors mediating vasoconstriction and beta 2-adrenoceptors mediating vasodilation are present in the feline pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)


Importance of the surface area ratio on cytokines production by human monocytes in vitro induced by various hydroxyapatite particles.
A possible complication associated with the implantation of hydroxyapatite (HA)-based prosthesis is the release of particles. Those particles can be phagocyted by monocytes that are among the first cells to colonize the inflammatory site. The activated monocytes produce inflammatory mediators, such as cytokines, which cause osteoclasts activation. It has previously been demonstrated using a surface area ratio (ratio of the total surface of the given particles to the surface area of cells) of 1 to 1 that there was a correlation between the expression and production of cytokines induced by HA. The present work studies the effect of physical characteristics of HA particles on the production of various inflammatory cytokines (tumour necrosis factor-alpha, interleukin (IL)-6, and IL-8) and anti-inflammatory cytokine (IL-10). However, the experiments were performed using a surface area ratio of 10 to 1. Our data demonstrate that all the particles, whatever their characteristics, induced a high expression of cytokines but the production was different, meaning that there was a post-transcriptional regulation. The size and sintering temperature seemed to be a characteristics that were less important compared to the shape; the needle particles appeared to induce the most important production of all the cytokines studied.


Increasing earnings of social security disability income beneficiaries with serious mental disorder.
Persons with severe and persistent mental disorders (SPMD) have extremely low earnings levels and account for 29.1 percent of all U.S. Social Security Disability Income (SSDI) disabled worker beneficiaries under age 50. Social insurance and disability policy experts pointed to several factors that may contribute to this situation, including disincentives and obstacles in the SSDI program, as well as lack of access to evidence-based behavioral-health interventions. In response, the Social Security Administration (SSA) funded the Mental Health Treatment Study (MHTS) demonstration that included 2,238 beneficiaries of SSDI whose primary reason for disability is SPMD. The demonstration, implemented in 23 different localities, consisted of two evidence-based services (individual placement and support supported employment (IPS-SE), systematic medication management (SMM)), and provision or coverage of additional behavioral-health services (OBH). This study focused on estimating MHTS intervention effects on earnings in the intervention period (two-years). The main outcome variable was self-reported average monthly earnings. Subjects were randomly assigned to intervention or control groups. Data were drawn from the baseline survey, seven follow-up quarterly surveys, a final follow-up survey, and SSA administrative data. In all surveys, respondents were asked about earnings prior to the interview. Dependent variables were average past-30-days earnings reported in all follow-up surveys, similar averages for the first four follow-ups and for the last four follow-ups, fraction of surveys with prior earnings above SSA's substantial gainful activity (SGA) threshold, and final-follow-up earnings for the past 90 days. Regression analyses compared earnings of intervention vs. control group subjects. Covariates included baseline values of: (i) beneficiary demographic and social characteristics; (ii) beneficiary physical and mental health indicators; (iii) beneficiary recipiency history; (iv) beneficiary pre-recruitment and baseline earnings; and (v) local labor-market unemployment rates. Results show significant positive MHTS earnings impacts. Estimated annual increases of earnings range from USD791 (based on the 2-year average) to USD1,131 (based on the final quarter of Year 2). Effects on the fraction of quarters with earnings exceeding SGA are positive and significant but very small in magnitude. The consistent increase in earnings impacts over the study period suggests the possibility of even larger impacts with longer-term interventions. The moderate size of the intervention impacts may partly be explained by a study population that already had an average of 9 years on SSDI, and whose labor-supply decisions continued to be affected by concerns about possible loss of benefits. Limitations are that (i) earnings effects of specific intervention components cannot be estimated since all treatment subjects received the same package of services, and (ii) study results may not generalize to the majority of the beneficiary population due to selection effects in beneficiaries' participation decisions. Replication of the MHTS on a broader scale should show similar positive earnings impacts for a substantial number of beneficiaries with characteristics similar to the study population. Future studies should consider reducing policy barriers to labor supply of persons with SPMD. Future studies should consider longer-term interventions, or at least measuring impacts for follow-up periods greater than two years.


Developing a vaccine against aspergillosis.
Although there is considerable experimental data to support the idea, bringing a fungal vaccine to fruition has been elusive. Moreover, vaccinating the immunocompromised, susceptible to an opportunistic disease such as invasive aspergillosis, seems formidable. However, pioneering studies using Aspergillus particulate forms or homogenates, and recently, recombinant proteins, have demonstrated feasibility. Moreover, T cell receptors also recognize glycotopes if presented in the appropriate MHC-binding context. The potential role of induced antibody has been appreciated only recently. Recent studies in our laboratory with heat-killed Saccharomyces (HKY) have raised the possibility of development of a panfungal vaccine. This yeast may be nature's experimental reagent, to show the way to a protective protein-carbohydrate conjugate vaccine. Subcutaneous HKY is an effective vaccine against Aspergillus, Coccidioides or Candida challenge. We have learned the protective moiety is in the cell wall, and proteins, glucan and lipid all seem important. We have also found the cell wall glycans alone, mannan or glucan, as a vaccine each provide significant protection. This leads to consideration of the importance of glycosylated proteins and glycan polymer-protein conjugates in vaccine development. We think the most productive route to a fungal-specific vaccine may be a conjugate vaccine that combines the optimally configured glycan with a specific immunogenic protein. Our work so far suggests that some proteins may be sufficiently cross-immunogenic, such that combined with the appropriate glycan, it may be possible to develop a pan-fungal vaccine.


Lymphomatoid papulosis. Case reports and literature review.
Five new cases of lymphomatoid papulosis are reported. This entity can apparently be divided into at least two subtypes. In one group of patients, papulopustular lesions resembling those of pityriasis lichenoides develop that resolve spontaneously within a few weeks. The lesions contain an epidermotropic dermal infiltration composed predominantly of abnormal lymphocytes. The other group of patients displays larger, more persistent lesions that contain a nonepidermotropic dermal infiltration composed predominantly of histiocytes. Lymphoma eventually develops in about 10% of the patients with lymphomatoid papulosis.


The arthroscopic management of osteochondritis dissecans of the adolescent elbow.
The management of avascular necrosis of the capitellum of the adolescent elbow continues to be a dilemma. This article is a critical retrospective analysis of 12 pediatric patients (mean age at surgery 14.5 years) who underwent arthroscopic debridement alone followed by early range of motion. Follow-up at a mean of 3.2 years (range, 2.0 to 5.7 years) indicated that the average flexion contracture improved from 23 degrees preoperatively to 10 degrees postoperatively. All patients had remodeling of the capitellum by plain radiographs; however, five patients had associated enlargement of the radial head. Eleven patients had minimal mechanical symptoms after the procedure and were highly satisfied. One patient had substantial enlargement of the radial head with continued loss of supination and mechanical symptoms requiring radial head resection 2 years after the index procedure. Five patients had a triangular avulsion fragment present off the lateral capsule. A statistically significant worse subjective outcome was associated with the presence of this fragment (P < .005). There were no complications.


Cool Temperature Enhances Growth, Ferulic Acid and Flavonoid Biosynthesis While Inhibiting Polysaccharide Biosynthesis in Angelica sinensis.
Angelica sinensis, a perennial herb that produces ferulic acid and phthalides for the treatment of cardio-cerebrovascular diseases, prefers growing at an altitude of 1800-3000 m. Geographical models have predicted that high altitude, cool temperature and sunshade play determining roles in geo-authentic formation. Although the roles of altitude and light in yield and quality have been investigated, the role of temperature in regulating growth, metabolites biosynthesis and gene expression is still unclear. In this study, growth characteristics, metabolites contents and related genes expression were investigated by exposing A. sinensis to cooler (15 °C) and normal temperatures (22 °C). The results showed that plant biomass, the contents of ferulic acid and flavonoids and the expression levels of genes related to the biosynthesis of ferulic acid (PAL1, 4CLL4, 4CLL9, C3H, HCT, CCOAMT and CCR) and flavonoids (CHS and CHI) were enhanced at 15 °C compared to 22 °C. The contents of ligustilide and volatile oils exhibited slight increases, while polysaccharide contents decreased in response to cooler temperature. Based on gene expression levels, ferulic acid biosynthesis probably depends on the CCOAMT pathway and not the COMT pathway. It can be concluded that cool temperature enhances plant growth, ferulic acid and flavonoid accumulation but inhibits polysaccharide biosynthesis in A. sinensis. These findings authenticate that cool temperature plays a determining role in the formation of geo-authentic and also provide a strong foundation for regulating metabolites production of A. sinensis.


Analysis of Prognostic Risk Factors of Sepsis Patients in Intensive Care Unit Based on Data Analysis.
In this paper, a data-enabled analysis of the prognostic risk factors of sepsis patients in the intensive care unit is presented. For this purpose, we have selected 220 sepsis patients, preferably those admitted to the intensive care unit for treatment in a tertiary a hospital in Tianjin from June 2018 to June 2019 and received complete data as the research objects, to explore the prognostic risk factors of sepsis patients in the intensive care unit. All patients met the SSC sepsis diagnosis guidelines and recorded the patients' age, gender, underlying disease, and infection site. Laboratory indicators, such as blood routine, electrolytes, arterial blood gas, liver function, and renal function, were collected within 24 hours of admission. Furthermore, the corresponding specimens were cultured for pathogenic microorganisms according to the site of infection. The LAC value was measured at admission and 24 h after admission, and the 24 h lactate clearance rate was calculated. The Acute Physiological and Chronic Health Status Score II (APACHE-II) and SOFA score were calculated, which were based on the worst value of the index within 24 hours after admission. According to the prognosis of patients during hospitalization, they are divided into two groups: (i) survival group and (ii) death group. We entered all the data into Excel and used SPSS21.0 statistical software for data analysis and processing. Quantitative data are tested for normality. Quantitative data for normal distribution are expressed as mean ± standard deviation, and normal distribution and uniform variance are measured. The factors affecting the prognosis of patients with sepsis were first subjected to a single-factor logistic regression analysis, and a multiple logistic regression analysis was performed on the basis of the significance of the single-factor analysis. The results found that the prognosis of patients with sepsis in the ICU is affected by multiple factors such as underlying diseases, infectious microorganisms, comorbidities, and interventional therapy. APACHE-II score, 24 h lactate clearance rate, ARDS, and DIC are independent risk factors that affect the prognosis of ICU patients.


A Comparative Study of Deep Learning Methods for Multi-Class Semantic Segmentation of 2D Kidney Ultrasound Images.
Ultrasound (US) imaging is a widely used medical imaging modality for the diagnosis, monitoring, and surgical planning for kidney conditions. Thus, accurate segmentation of the kidney and internal structures in US images is essential for the assessment of kidney function and the detection of pathological conditions, such as cysts, tumors, and kidney stones. Therefore, there is a need for automated methods that can accurately segment the kidney and internal structures in US images. Over the years, automatic strategies were proposed for such purpose, with deep learning methods achieving the current state-of-the-art results. However, these strategies typically ignore the segmentation of the internal structures of the kidney. Moreover, they were evaluated in different private datasets, hampering the direct comparison of results, and making it difficult to determination the optimal strategy for this task. In this study, we perform a comparative analysis of 7 deep learning networks for the segmentation of the kidney and internal structures (Capsule, Central Echogenic Complex (CEC), Cortex and Medulla) in 2D US images in an open access multi-class kidney US dataset. The dataset includes 514 images, acquired in multiple clinical centers using different US machines and protocols. The dataset contains the annotation of two experts, but 321 images with complete segmentation of all 4 classes were used. Overall, the results demonstrate that the DeepLabV3+ network outperformed the inter-rater variability with a Dice score of 78.0% compared to 75.6% for inter-rater variability. Specifically, DeepLabV3Plus achieved mean Dice scores of 94.2% for the Capsule, 85.8% for the CEC, 62.4% for the Cortex, and 69.6% for the Medulla. These findings suggest the potential of deep learning-based methods in improving the accuracy of kidney segmentation in US images.Clinical Relevance- This study shows the potential of DL for improving accuracy of kidney segmentation in US, leading to increased diagnostic efficiency, and enabling new applications such as computer-aided diagnosis and treatment, ultimately resulting in improved patient outcomes and reduced healthcare costs.1.


Cyclooxygenase as a target in lung cancer.
Preclinical studies suggest that cyclooxygenase (COX)-2 may be involved in the molecular pathogenesis of some types of lung cancer. Most of the available studies point to its involvement in non-small cell lung cancer. Survival of patients with non-small cell lung cancer expressing high levels of COX-2 is markedly reduced. Treatment of humans with the selective COX-2 inhibitor celecoxib augments the antitumor effects of chemotherapy in patients with non-small cell lung cancer. COX-2 has been shown to regulate some aspects of tumor-associated angiogenesis. Most of the results we have published point to effects on the regulation of vascular endothelial growth factor. However, prostaglandins derived from COX-2 affect other signaling pathways as well, such as the epidermal growth factor and its receptor. Others have recently shown that non-small cell lung cancer exhibits a COX-2 downstream enzyme expression pattern that is altered in lung tumor cells and tumor-supplying vessels. Therefore, COX-2 and prostaglandins may have a major impact on lung tumor progression and tumor-associated inflammation. Clinical trials currently underway are exploring the potential of targeting COX-2 in lung cancer.


Awareness, knowledge, attitude, and skills regarding telemedicine among Syrian healthcare providers: A cross-sectional study.
After the widespread of coronavirus disease (COVID-19) around the globe, it was imperative to establish preventative measures to restrict the virus's transmission. The purpose of this research was to present an overview of the awareness, knowledge, attitude, and abilities of Syrian physicians about telemedicine technology. An online cross-sectional study was conducted from April 1 to May 15, 2022. The questionnaire was taken from published study, and the inclusion criteria consist the Syrian doctors who worked in hospitals during the COVID-19 pandemic, mainly those who had direct contact with patients. Among 385 responses, 52.72% of them were females, 83.9% of them were aged less than 30 years old, and 66% were working in the governmental sector; 66% of participants have moderate knowledge about using computers and the internet, 80% have heard about telemedicine. Despite that, 95.1% of participants have not attended any training workshop on telemedicine, and most of them have reported no availability of a telemedicine unit in their department. Only 31.7% participants have shown high awareness of telemedicine. Furthermore, no significant correlation was identified between the academic level with the age and telemedicine awareness, knowledge, attitude, or computer skills. Despite that, there was an obvious correlation between age and computer skills (P-value < 0.05). There was a significant correlation between the medical specialty and awareness, and computer abilities, especially the anesthesiology (88.5 ± 5.2), (84 ± 8.7), respectively. Spearman's rho test showed mild positive significant association in various subscales (awareness and experience, experience and skills, knowledge and attitude, knowledge and skills, and attitude and skills). The study results demonstrate that most of the participating clinical doctors have a neutral view of telemedicine, even though they do not know much about it and do not have considerable experience with it. It is practical to educate and train academic staff, practicing physicians, residents and medical students within the clinical stages about telemedicine.


Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous p.R1419H ABCC8 mutation: an unusual clinical picture.
Inheritance of two pathogenic ABCC8 alleles typically causes severe congenital hyperinsulinism. We describe a girl and her father, both homozygous for the same ABCC8 mutation, who presented with unusual phenotypes. Single nucleotide polymorphism microarray and Sanger sequencing were performed. Western blot, rubidium efflux, and patch clamp recordings interrogated the expression and activity of the mutant protein. A 16-month-old girl of consanguineous descent manifested hypoglycemia. She had dysregulation of insulin secretion, with postprandial hyperglycemia followed by hypoglycemia. Microarray revealed homozygosity for the regions encompassing KCNJ11 and ABCC8. Her father had developed diabetes at 28 years of age. Sequencing of ABCC8 identified a homozygous missense mutation, p.R1419H, in both individuals. Functional studies showed absence of working KATP channels. This is the first description of a homozygous p.R1419H mutation. Our findings highlight that homozygous loss-of-function mutations of ABCC8 do not necessarily translate into early-onset severe hyperinsulinemia.


Direct profiling and identification of peptide expression differences in the pancreas of control and ob/ob mice by imaging mass spectrometry.
Imaging mass spectrometry (IMS) technology utilizes MALDI MS to map molecules of interest in thin tissue sections. In this study, we have evaluated the potential of MALDI IMS to study peptide expression patterns in the mouse pancreas under normal and pathological conditions, and to in situ identify peptides of interest using MS/MS. Different regions of the pancreas of both control and ob/ob mice were imaged, resulting in peptide-specific profiles. The distribution of ions of m/z 3120 and 3439 displayed a striking resemblance with Langerhans islet's histology and, following MS/MS fragmentation and database searching were identified as C-peptide of insulin and glicentin-related polypeptide, respectively. In addition, a significant increase of the 3120 peak intensity in the obese mice was observed. This study underscores the potential of MALDI IMS to study the contribution of peptides to pancreas pathology.


Oral Radiology Safety Standards Adopted by the General Dentists Practicing in National Capital Region (NCR).
With advancement in diagnostic techniques, the utilization of radiologic examination has risen to many folds in the last two decades. Ionizing radiations from the radiographic examination carry the potential for harm by inducing carcino-genesis in addition to the diagnostic information extracted. Radiation doses utilized in the course of dental treatment might be low for individual examinations but patients are exposed to repeated examinations very often and many people are exposed during the course of dental care. Therefore, principles of radiation protection and safety are necessary for the dentists to follow to ensure minimum and inevitable exposure. The aim of this study was to investigate the knowledge and behaviour of general dentists practicing in the National Capital Region (NCR) regarding radiation safety during oral radiographic procedures. The study was a questionnaire based cross-sectional study. A total of 500 general dentists were contacted to participate in the study. The target population entailed of general dentists practicing in the National Capital Region. Data was computed and tabulated in Microsoft excel sheet and statistical analysis was performed with the help of SPSS version 21.0. The total response rate recovered was 70.6% and the respondents comprised of 59% and 41% males & females respectively. Only 64.8% of the general dentists contemplated thyroid to be the most important organ for radiation protection. Only 28.8% of the general dentists followed the position & distance rule appropriately. The results showed that the knowledge and behaviour of the general dentists and the practices adopted by them regarding radiation safety is not satisfactory. To ensure the following of basic and necessary guidelines for radiation safety and protection, strict rules with penalties should be implemented by the state councils and new and interesting methods of education for this spectrum of the field should be introduced.


Limitations of student-driven formative assessment in a clinical clerkship. A randomised controlled trial.
Teachers strive to motivate their students to be self-directed learners. One of the methods used is to provide online formative assessment material. The concept of formative assessment and use of these processes is heavily promoted, despite limited evidence as to their efficacy. Fourth year medical students, in their first year of clinical work were divided into four groups. In addition to the usual clinical material, three of the groups were provided with some form of supplementary learning material. For two groups, this was provided as online formative assessment. The amount of time students spent on the supplementary material was measured, their opinion on learning methods was surveyed, and their performance in summative exams at the end of their surgical attachments was measured. The performance of students was independent of any educational intervention imposed by this study. Despite its ready availability and promotion, student use of the online formative tools was poor. Formative learning is an ideal not necessarily embraced by students. If formative assessment is to work students need to be encouraged to participate, probably by implementing some form of summative assessment.


Oral health of substance-dependent individuals: impact of specific substances.
Little is known about how different types of substances affect oral health. Our objective was to examine the respective effects of alcohol, stimulants, opioids, and marijuana on oral health in substance-dependent persons. Using self-reported data from 563 substance-dependent individuals, we found that most reported unsatisfactory oral health, with their most recent dental visit more than 1 year ago. In multivariable logistic regressions, none of the substance types were significantly associated with oral health status. However, opioid use was significantly related to a worse overall oral health rating compared to 1 year ago. These findings highlight the poor oral health of individuals with substance dependence and the need to address declining oral health among opioid users. General health and specialty addiction care providers should be aware of oral health problems among these patients. In addition, engagement into addiction and medical care may be facilitated by addressing oral health concerns.


Molecular characterization of 39 de novo sSMC: contribution to prognosis and genetic counselling, a prospective study.
Small supernumerary marker chromosomes (sSMCs) are structurally abnormal chromosomes that cannot be characterized by karyotype. In many prenatal cases of de novo sSMC, the outcome of pregnancy is difficult to predict because the euchromatin content is unclear. This study aimed to determine the presence or absence of euchromatin material of 39 de novo prenatally ascertained sSMC by array-comparative genomic hybridization (array-CGH) or single nucleotide polymorphism (SNP) array. Cases were prospectively ascertained from the study of 65,000 prenatal samples [0.060%; 95% confidence interval (CI), 0.042-0.082]. Array-CGH showed that 22 markers were derived from non-acrocentric markers (56.4%) and 7 from acrocentic markers (18%). The 10 additional cases remained unidentified (25.6%), but 7 of 10 could be further identified using fluorescence in situ hybridization; 69% of de novo sSMC contained euchromatin material, 95.4% of which for non-acrocentric markers. Some sSMC containing euchromatin had a normal phenotype (31% for non-acrocentric and 75% for acrocentric markers). Statistical differences between normal and abnormal phenotypes were shown for the size of the euchromatin material (more or less than 1 Mb, p = 0.0006) and number of genes (more or less than 10, p = 0.0009). This study is the largest to date and shows the utility of array-CGH or SNP array in the detection and characterization of de novo sSMC in a prenatal context.


Meta-Analysis of the Antidepressant Effects of Acute Sleep Deprivation.
To provide a quantitative meta-analysis of the antidepressant effects of sleep deprivation to complement qualitative reviews addressing response rates. English-language studies from 1974 to 2016 using the keywords sleep deprivation and depression searched through PubMed and PsycINFO databases. A total of 66 independent studies met criteria for inclusion: conducted experimental sleep deprivation, reported the percentage of the sample that responded to sleep deprivation, provided a priori definition of antidepressant response, and did not seamlessly combine sleep deprivation with other therapies (eg, chronotherapeutics, repetitive transcranial magnetic stimulation). Data extracted included percentage of responders, type of sample (eg, bipolar, unipolar), type of sleep deprivation (eg, total, partial), demographics, medication use, type of outcome measure used, and definition of response (eg, 30% reduction in depression ratings). Data were analyzed with meta-analysis of proportions and a Poisson mixed-effects regression model. The overall response rate to sleep deprivation was 45% among studies that utilized a randomized control group and 50% among studies that did not. The response to sleep deprivation was not affected significantly by the type of sleep deprivation performed, the nature of the clinical sample, medication status, the definition of response used, or age and gender of the sample. These findings support a significant effect of sleep deprivation and suggest the need for future studies on the phenotypic nature of the antidepressant response to sleep deprivation, on the neurobiological mechanisms of action, and on moderators of the sleep deprivation treatment response in depression.


Mitogenic activity and cytokine levels in non-healing and healing chronic leg ulcers.
The cause of impaired healing in chronic leg ulcers is not known. However, recent attempts to modify the healing process have focused on adding growth factors to stimulate healing and have failed to produce dramatic improvements in healing. This study used a unique model of chronic wound healing in humans to obtain wound fluid samples from chronic venous leg ulcers that had changed from a nonhealing to a healing phase. These samples were used to assess cytokine and growth factor levels, and mitogenic activity in these nonhealing and healing chronic wounds. The pro-inflammatory cytokines interleukin-1, interleukin-6 and tumor necrosis factor-alphawere found to be present in significantly higher concentrations in wound fluid from nonhealing compared to healing leg ulcers. There were detectable levels but, no significant change in the levels of platelet derived growth factor, epidermal growth factor, basic fibroblast growth factor or transforming growth factor-betaas ulcers healed. Wound fluid was added to fibroblasts in vitro to assess mitogenic activity. There was a significantly greater proliferative response to healing wound fluid samples compared to nonhealing samples. These results suggest that healing may be impaired by inflammatory mediators rather than inhibited by a deficiency of growth factors in these chronic wounds.


CXCR5-transduced bone marrow-derived dendritic cells traffic to B cell zones of lymph nodes and modify antigen-specific immune responses.
Skin-derived migratory dendritic cells (DC), in contrast to bone marrow-derived DC (BMDC), express CXCR5, respond to the chemokine CXC ligand 13 (CXCL13) in vitro, and are capable of migrating to B cell zones (BCZ) in lymph nodes (LN) in vivo. Herein, we analyzed the surface phenotype of skin-derived migratory DC and found that 15-35% of MHC class II(high) cells showed high levels of expression of CXCR5 but expressed low levels of DEC205, a suggested characteristic of dermal-type DC in mice. To study the effects of CXCR5 on the trafficking dynamics of DC, we stably expressed CXCR5 in BMDC by retroviral gene transduction. CXCR5 was detected by flow cytometry on transduced cells, which responded to CXCL13 in vitro in chemotaxis assays (3-fold over nontransduced BMDC, p < 0.01). When injected into the footpads of mice, approximately 40% of injected CXCR5-BMDC were observed in BCZ of draining LN. Mice were vaccinated with CXCR5- and vector-BMDC that were pulsed with keyhole limpet hemocyanin (KLH) to induce Ag-specific cellular and humoral immune responses. Mice injected with CXCR5-BMDC (vs vector-BMDC) demonstrated marginally less footpad swelling in response to intradermal injection of KLH. Interestingly, significantly higher levels of KLH-specific IgG (p < 0.05) and IgM (p < 0.01) were found in the serum of mice injected with CXCR5-BMDC compared with mice immunized with vector-transduced BMDC. Thus, CXCR5 is predominantly expressed by dermal-type DC. Moreover, CXCR5 directs BMDC to BCZ of LN in vivo and modifies Ag-specific immune responses induced by BMDC vaccination.


Simulating stochastic adsorption of diluted solute molecules at interfaces.
This report uses Monte Carlo simulations to connect stochastic single-molecule and ensemble surface adsorption of molecules from dilute solutions. Monte Carlo simulations often use a fundamental time resolution to simulate each discrete step for each molecule. The adsorption rate obtained from such a simulation surprisingly contains an error compared to the results obtained from the traditional method. Simulating adsorption kinetics is interesting in many processes, such as mass transportation within cells, the kinetics of drug-receptor interactions, membrane filtration, and other general reaction kinetics in diluted solutions. Thus, it is important to understand the origin of the disagreement and find a way to correct the results. This report reviews the traditional model, explains the single-molecule simulations, and introduces a method to correct the results of adsorption rate. For example, one can bin finer time steps into time steps of interest to simulate the fractal diffusion or simply introduce a correction factor for the simulations. Then two model systems, self-assembled monolayer (SAM) and biosensing on the patterned surface, are simulated to check the accuracy of the equations. It is found that the adsorption rate of SAM is highly dependent on the conditions and the uncertainty is large. However, the biosensing system is relatively accurate. This is because the concentration gradient near the interface varies significantly with reaction conditions for SAMs while relatively stable for the biosensing system.


The parasitic isopod Mothocya nana drives dietary shifts and poorer condition of Brazilian silversides Atherinella brasiliensis.
Cymothoids are ectoparasites that may attach to various parts of the fish for molting and reproductive purposes, thus increasing the energetic costs of the host. This study investigated the influence of the parasitic isopod Mothocya nana on the physiological condition and diet of adult Brazilian silversides Atherinella brasiliensis at a sandy beach in southeastern Brazil. We collected 268 A. brasiliensis individuals, of which 230 fish were non-parasitized (mean ± SE total weight [TW] = 16.92 ± 0.38 g; total length [TL] = 127 ± 0.88 mm) and 38 were parasitized by up to 2 isopods (TW = 15.89 ± 0.79 g; TL = 126 ± 1.96 mm). Parasitic prevalence (P) and intensity (I) reached highest values in June 2015 (P = 20.88%; I = 1.31) and were slightly higher on males (P = 17.39%; I = 1.33) than on females (P = 13.07%; I = 1.27). Parasitized fish revealed poorer condition than non-parasitized ones, among which male hosts were especially burdened by M. nana's attachment. The condition factor, the eviscerated condition factor and the fullness index each showed a decreasing trend according to the parasite's development and offspring weight (i.e. increase in egg and larval weight). Parasitized and non-parasitized Brazilian silversides fed mainly on microcrustaceans, but the first group showed reduced phytoplankton intake and was associated with fewer trophic categories in comparison to non-parasitized fish. These dietary shifts revealed correlation with the poorer physiological condition reported for infected A. brasiliensis, whose decreased feeding efficiency is likely related to potential impairment of the filter-feeding mechanism and/or altered behaviour due to pressure atrophy and the increased energetic costs imposed by M. nana's development.