Interaction of the human body and surfaces of different stiffness during drop jumps.
The purpose of this study was to examine two hypotheses: (a) the stiffness of the surface influences the leg stiffness of the subjects during drop jumps, and (b) drop jumping performance (jumping height and energy rates of the subject's center of mass during the contact phase) increases when decreasing surface stiffness due to a greater energy storage capacity of the surface for a given acting force. Ten female subjects performed a series of drop jumps from 40-cm height onto two sprung surfaces with different stiffness. Those trials of each subject displaying the maximal mechanical power during the upward phase were analyzed. The ground reaction forces were measured using a force plate. Sagittal kinematics of the subject's body positions and the deformation of the surface were recorded using two high-speed video cameras. On the soft surface, the jumping height and the energy rates of the subjects during the contact phase were greater than on the hard one. The energy delivered by the subjects during the upward phase, the leg and joint stiffness, as well as the range of motion of the subjects remained unchanged for both surfaces. The absolute energy loss is lower for the hard surface, but the jumping performance is greater for the soft one. The reason is a higher ratio of positive to negative mechanical work done by the subjects during the contact phase. The adjustment of the subjects to different surfaces is not only dependent on the stiffness of the surface but also on the intensity of the movement.


Emotional determinants of infant-mother attachment.
The present study examined the assumption that emotion-related characteristics of mothers and infants contribute to the development of infant-mother attachment in the first year of life. Mothers' emotion and personality characteristics were assessed with expressive-behavior ratings and self-report scales. Infant characteristics were measured by emotion and temperament questionnaires (mother report) and objective coding of facial expressions of emotions. Attachment classifications were determined by means of the Strange Situation procedure, and a continuous-variable index of attachment security was derived by a discriminant function procedure. Mothers' emotion experiences, expressive behaviors, and personality traits were significant predictors of the level of security of the infant-mother attachment. Infants' expressive and temperamental characteristics as rated by their mothers were also significant predictors of attachment security.


Success of scaphoid nonunion surgery is independent of proximal pole vascularity.
We followed 35 consecutive patients with scaphoid nonunions in a prospective longitudinal registry. All nonunions were treated with curettage, non-vascularized autogenous grafting and headless screw fixation. Preoperative magnetic resonance imaging, intraoperative bleeding points and histopathological analysis of cancellous bone in the proximal pole were recorded as measures of viability. Healing was categorized as ≥50% bony bridging on computed tomographic images in the plane of the scaphoid. Nine of 23 proximal poles demonstrated ischaemia on magnetic resonance imaging but none were interpreted as infarcted. Twenty-eight of 33 were found to have impaired vascularity as assessed by intraoperative bleeding. Fourteen of 32 demonstrated ≥50% trabecular necrosis and four of 33 demonstrated ≥50% tissue necrosis on histopathological analysis. Thirty of 33 demonstrated focal or robust remodelling activity. Despite pathological evidence of impaired vascularity in over half of the patients, 33 of the 35 scaphoids had healed by 12 weeks. We conclude that proximal pole infarction is decidedly rare and that vascularized bone grafting is seldom required. IV.


[Clinical and evolutive study of plasma cell leukemia. Apropos of 9 cases].
Nine patients were diagnosed with plasma cell leukemia (PCL) from 1982-1995 at our hospital. Seven patients had primary PCL and the other two patients a secondary from. In this study the clinical and analytical features are reported, as well as the therapy and response obtained in these patients. Also, the karyotype findings in bone marrow of four of these patients are reported. At diagnosis, the most common symptom was bone pain which was associated with osteolytic lesions or diffuse bone demineralization. Analytical features were similar to those reported in other series of patients with PCL. Different therapeutical regimens were used, and VAD was the most commonly employed. Two patients underwent consolidation therapy with autologous transplantation of hemopoietic stem cells. The mean survival time was 5.5 months. Although PCL prognosis associated with chemotherapy is still poor, myeloablative therapy with hemopoietic support can increase the survival length in these patients.


Autoantibodies from Patients with Scleroderma Renal Crisis Promote PAR-1 Receptor Activation and IL-6 Production in Endothelial Cells.
Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc). Autoantibodies (Abs) against endothelial cell antigens have been implicated in SSc and SRC. However, their detailed roles remain poorly defined. Pro-inflammatory cytokine interleukin-6 (IL-6) has been found to be increased in SSc, but its role in SRC is unclear. Here, we aimed to determine how the autoantibodies from patients with SSc and SRC affect IL-6 secretion by micro-vascular endothelial cells (HMECs). Serum IgG fractions were isolated from either SSc patients with SRC (n = 4) or healthy individuals (n = 4) and then each experiment with HMECs was performed with SSc-IgG from a separate patient or separate healthy control. IL-6 expression and release by HMECs was assessed by quantitative reverse transcription and quantitative PCR (RT-qPCR) and immunoassays, respectively. The mechanisms underlying the production of IL-6 were analyzed by transient HMEC transfections with IL-6 promoter constructs, electrophoretic mobility shift assays, Western blots and flow cytometry. Exposure of HMECs to IgG from SSc patients, but not from healthy controls, resulted in a time- and dose-dependent increase in IL-6 secretion, which was associated with increased AKT, p70S6K, and ERK1/2 signalling, as well as increased c-FOS/AP-1 transcriptional activity. All these effects could be reduced by the blockade of the endothelial PAR-1 receptor and/or c-FOS/AP-1silencing. Autoantibodies against PAR-1 found in patients with SSc and SRC induce IL-6 production by endothelial cells through signalling pathways controlled by the AP-1 transcription factor. These observations offer a greater understanding of adverse endothelial cell responses to autoantibodies present in patients with SRC.


Over-expression of IL-18, ICE and IL-18 R in testicular tissue from sexually immature as compared to mature mice.
In this study we examined the cellular origin and the expression levels of interleukin-18 (IL-18), IL-18 receptor (IL-18R) and IL-1beta-converting enzyme (ICE), which activates pro-IL-18, during normal maturation of murine testis. The levels of IL-18, IL-18R and ICE were significantly higher in testicular tissues and homogenates (but not in the spleen or liver) from sexually immature than mature mice. Immunohistochemical staining of testicular tissues from sexually immature and mature mice shows that testicular germ cells and Leydig cells/interstitial cells express higher levels of IL-18, as compared to other testicular cells. Peritubular cells of sexually immature and mature mice also expressed IL-18. Our results demonstrate, for the first time, over-expression of the IL-18 family in testicular tissues of sexually immature mice, as compared to mature mice, as well as the expression of IL-18 in the different stages of differentiation of testicular germ cells. Thus, our results may indicate involvement of the endocrine system (gonadotropins and testosterone) in the regulation of the testicular IL-18 family, which could be involved in the regulation of testicular functions, development and spermatogenesis under physiological conditions.


Practice-based skill acquisition of pushrim-activated power-assisted wheelchair propulsion versus regular handrim propulsion in novices.
Regular handrim wheelchair (RHW) propulsion is straining for the upper extremities and wheelchair users often experience overuse problems. A recent advancement in wheelchair technology that could assist users is the pushrim-activated power-assisted wheelchair (PAPAW). PAPAWs are challenging to control, yet it is unclear how people learn to use a PAPAW. The purpose of this study is to examine early skill acquisition through practice in PAPAWs and compare it with RHWs. Twenty-four able-bodied novices were randomly allocated to either the RHW group or the PAPAW group. The experiment consisted of five sessions with three blocks of 4 min steady-state practice at 1.11 m/s and 0.21 W/kg. Finally, a transfer to the other mode was made. Data were collected with a drag-test, breath-by-breath spirometry, and a motion capture system. The last minute of each four-minute block was used for analysis. A mixed analysis of variance (ANOVA) was used to test for group, time, and interaction effects. Both groups improved their (assisted) mechanical efficiency, reduced their stroke rate, right-left and forward-backward deviation on the treadmill, and had a lower rate of perceived exertion (RPE) over time. (Assisted) mechanical efficiency was higher for the PAPAW group than for the RHW group and RPE was lower. However, left-right and forward-backward deviation was also found to be higher in the PAPAW group. At the group level the energetic cost of RHW and PAPAW propulsion can be lowered through low-intensity practice in novice users. The PAPAW is more 'efficient' than the RHW given the reduced energy requirement of the user from the motor assist, but more difficult to control. Future studies on PAPAWs should focus on the control needs of the user and their interaction with the power-assist technology.


Hsp27 regulates epithelial mesenchymal transition, metastasis, and circulating tumor cells in prostate cancer.
Defining the mechanisms underlying metastatic progression of prostate cancer may lead to insights into how to decrease morbidity and mortality in this disease. An important determinant of metastasis is epithelial-to-mesenchymal transition (EMT), and the mechanisms that control the process of EMT in cancer cells are still emerging. Here, we report that the molecular chaperone Hsp27 (HSPB1) drives EMT in prostate cancer, whereas its attenuation reverses EMT and decreases cell migration, invasion, and matrix metalloproteinase activity. Mechanistically, silencing Hsp27 decreased IL-6-dependent STAT3 phosphorylation, nuclear translocation, and STAT3 binding to the Twist promoter, suggesting that Hsp27 is required for IL-6-mediated EMT via modulation of STAT3/Twist signaling. We observed a correlation between Hsp27 and Twist in patients with prostate cancer, with Hsp27 and Twist expression each elevated in high-grade prostate cancer tumors. Hsp27 inhibition by OGX-427, an antisense therapy currently in phase II trials, reduced tumor metastasis in a murine model of prostate cancer. More importantly, OGX-427 treatment decreased the number of circulating tumor cells in patients with metastatic castration-resistant prostate cancer in a phase I clinical trial. Overall, this study defines Hsp27 as a critical regulator of IL-6-dependent and IL-6-independent EMT, validating this chaperone as a therapeutic target to treat metastatic prostate cancer.


Staff experience, knowledge and attitudes regarding the management of adolescent patients in adult mental health units.
Inpatient psychiatric care of adolescents should, where possible, be provided in specialized units. However, admission of adolescent patients to adult mental health units does occur. There is a paucity of data about this practice. This study collates information about the experience, attitudes and knowledge of clinical staff regarding the care of adolescent patients in adult psychiatry units within Northern Sydney Central Coast Area Health Service (NSCCHS). A survey was emailed to all clinical staff with employer accessible email addresses in NSCCHS. The response rate was 29% (n = 108). The majority of respondents believed their wards were "not at all" (30.7%) or "only a little" (57.4%) equipped to care for adolescent patients. The majority felt "moderately" (39.6%) or "very" (16.8%) confident to care for these patients; however, a significant proportion (43.2%) lacked confidence. There was no significant difference across the responses of psychiatrists, psychiatry registrars and nursing staff to these questions. The majority felt the objectives of these admissions were met "only a little" (47.4%) or "not at all" (16.5%). Many concerns regarding the admission of adolescents to adult wards were reported. Generally, staff were not in favour of admitting adolescent patients to adult mental health units apart from in exceptional circumstances. Staff harboured concerns about several aspects of care for adolescents in adult wards.


Automated breast mass detection in 3D reconstructed tomosynthesis volumes: a featureless approach.
The purpose of this study was to propose and implement a computer aided detection (CADe) tool for breast tomosynthesis. This task was accomplished in two stages-a highly sensitive mass detector followed by a false positive (FP) reduction stage. Breast tomosynthesis data from 100 human subject cases were used, of which 25 subjects had one or more mass lesions and the rest were normal. For stage 1, filter parameters were optimized via a grid search. The CADe identified suspicious locations were reconstructed to yield 3D CADe volumes of interest. The first stage yielded a maximum sensitivity of 93% with 7.7 FPs/breast volume. Unlike traditional CADe algorithms in which the second stage FP reduction is done via feature extraction and analysis, instead information theory principles were used with mutual information as a similarity metric. Three schemes were proposed, all using leave-one-case-out cross validation sampling. The three schemes, A, B, and C, differed in the composition of their knowledge base of regions of interest (ROIs). Scheme A's knowledge base was comprised of all the mass and FP ROIs generated by the first stage of the algorithm. Scheme B had a knowledge base that contained information from mass ROIs and randomly extracted normal ROIs. Scheme C had information from three sources of information-masses, FPs, and normal ROIs. Also, performance was assessed as a function of the composition of the knowledge base in terms of the number of FP or normal ROIs needed by the system to reach optimal performance. The results indicated that the knowledge base needed no more than 20 times as many FPs and 30 times as many normal ROIs as masses to attain maximal performance. The best overall system performance was 85% sensitivity with 2.4 FPs per breast volume for scheme A, 3.6 FPs per breast volume for scheme B, and 3 FPs per breast volume for scheme C.


Mandibular melanotic neuroectodermal tumor of infancy treated conservatively with enucleation.
Melanotic neuroectodermal tumor of infancy (MNTI) is an uncommon, rapidly growing neoplasm of neural crest origin that primarily develops in the maxilla of infants during their first year of life. Mandibular lesions are rare and account for about 6% of all cases. Radical surgical excision is usually curative, but patients should be followed up closely because recurrence may occur in approximately 10% to 20% of cases. In this study, we report a case of mandibular MNTI in a 4-month-old male patient that was conservatively treated with enucleation and curettage and has shown no recurrence 11 years after surgery. Review of the English-language literature revealed that of more than 350 cases of MNTI reported so far, only 23, including the present one, have been encountered in the mandible. Most patients (91.3%) were younger than 1 year, whereas the male-to-female ratio was 1.3:1. Most lesions were treated with wide surgical excision, with only 2 cases being conservatively treated with enucleation. Recurrence was noted in 36.8% of cases at less than 3 months postoperatively. In conclusion, MNTI lesions in the mandible, albeit rare, show high recurrence rate. However, small-size mandibular MNTI lesions may be successfully treated with conservative enucleation. Close follow-up is highly recommended, in particular during the first 6 postoperative months.


Effectiveness of the head-shaking method combined with cisternal irrigation with urokinase in preventing cerebral vasospasm after subarachnoid hemorrhage.
The head-shaking method combined with cisternal irrigation has been proposed to be effective in preventing cerebral vasospasm after subarachnoid hemorrhage (SAH) by facilitating rapid washout of the clot from the subarachnoid space. This study was conducted to evaluate the effectiveness of this method. The inclusion criteria included the following: 1) Fisher Grade 3 SAH on admission computerized tomography (CT) scans; 2) aneurysm secured within 48 hours of SAH onset; and 3) no focal deficit and ability to obey commands within 24 hours postsurgery. Two hundred thirty patients treated between 1994 and 2002 fulfilled the criteria. Because only one machine was available and it required I month of maintenance every other month, 114 patients underwent irrigation combined with the head-shaking method (head-shaking group), whereas the remaining 116 patients received cisternal irrigation alone (control group). There were no significant differences in sex, age, site of aneurysm, or preoperative grade between the two groups. The incidence of symptomatic vasospasm with or without infarction, cerebral infarction on CT scans, and permanent ischemic neurological deficit was 25.7, 17.7, and 8.8%, respectively, in the control group and 15.2, 4.5, and 2.7% in the head-shaking group. The difference was statistically significant for symptomatic vasospasm, cerebral infarction, and permanent ischemic neurological deficit (p < 0.05). In a multivariate backward stepwise logistic regression analysis, absence of head shaking was the only variable that was predictive of permanent ischemic neurological deficit (p = 0.061). The outcomes evaluated using the modified Rankin Scale were better in the head-shaking group (p = 0.051). The head-shaking method significantly reduced the incidence of symptomatic vasospasm, cerebral infarction, and permanent ischemic neurological deficit and improved the clinical outcomes in patients who underwent cisternal irrigation therapy after aneurysmal SAH.


STUDIES ON THE LYMPHOCYTOSIS INDUCED IN MICE BY BORDETELLA PERTUSSIS.
1. Intravenous injection into mice of phase I Bordetella pertussis vaccine resulted in a striking hyperleucocytosis with a predominating lymphocytosis. Intraperitoneal inoculation was less effective, and subcutaneous administration was inactive. 2. Active immunization prevented the hyperleucocytosis; passive immunization was less effective. 3. Reticuloendothelial blockage reduced the effect of the vaccine. 4. Extirpation of the spleen or thymus did not alter the leucocyte response. 5. Histologic studies suggested that the increase in circulating lymphocytes resulted from release of cells from lymphoid organs, including the thymus.


Detection of Additional Primary Neoplasms on 18F-Fluciclovine PET/CT in Patients with Primary Prostate Cancer.
The aim of this study was to evaluate the detection rate of incidental second primary neoplasms in patients with prostate cancer on 18F-fluciclovine PET/CT. Methods: Imaging reports and patient demographic data were retrospectively reviewed from 663 clinical 18F-fluciclovine PET/CT studies, performed in 601 patients for the assessment of their prostate cancer (643 - recurrence evaluation, 20 - initial staging) from August 2016 to April 2021. Maximum SUV (SUVmax) of the suspected second neoplasms was determined. The results of 18F-fluciclovine PET/CT were correlated with clinical and radiologic studies to determine the nature of the suspected second neoplasms. Results: Fifty-five patients (9.1%) had findings suggestive of a second neoplasm. Thirty-nine of 55 had a known second neoplasm diagnosed before the PET/CT. An incidental second primary neoplasm was first suspected on 18F-fluciclovine PET/CT in 16 of 601 patients (2.7%). Three of the 16 patients had PET/CT suggestive of a meningioma that was corroborated on MRI. Of the remaining 13 patients, 11 had a tissue diagnosis confirming a malignancy. Second malignancies included renal cell carcinoma (RCC; 5/11; 45.5%), urothelial carcinoma (n = 2), multiple myeloma, chondrosarcoma, cutaneous squamous cell carcinoma, and squamous cell carcinoma of the esophagus and lung (n = 1, each; except for 1 patient with both esophageal and lung carcinomas). Among histopathologically confirmed malignancies, clear-cell RCC had the lowest uptake (SUVmax 3.4), and cutaneous squamous cell carcinoma had the highest uptake (SUVmax 13.6). Of the 2 patients with no histopathologic confirmation, 1 had ultrasound and MRI findings corroborating the diagnosis of RCC. The other patient had a solitary lung nodule suggestive of primary lung carcinoma and elected to undergo observation. Conclusion: Incidental findings consistent with a second primary neoplasm are not infrequently seen on 18F-fluciclovine PET/CT performed for assessment of prostate cancer (9.1%). Of the incidentally detected primary cancers, RCC was the most common (45.5%). These findings indicate the need for a careful analysis of 18F-fluciclovine PET/CT images, due to the broad tumor imaging capabilities of this radiotracer.


Understanding the impact of the central atom on the ionic liquid behavior: phosphonium vs ammonium cations.
The influence of the cation's central atom in the behavior of pairs of ammonium- and phosphonium-based ionic liquids was investigated through the measurement of densities, viscosities, melting temperatures, activity coefficients at infinite dilution, refractive indices, and toxicity against Vibrio fischeri. All the properties investigated are affected by the cation's central atom nature, with ammonium-based ionic liquids presenting higher densities, viscosities, melting temperatures, and enthalpies. Activity coefficients at infinite dilution show the ammonium-based ionic liquids to present slightly higher infinite dilution activity coefficients for non-polar solvents, becoming slightly lower for polar solvents, suggesting that the ammonium-based ionic liquids present somewhat higher polarities. In good agreement these compounds present lower toxicities than the phosphonium congeners. To explain this behavior quantum chemical gas phase DFT calculations were performed on isolated ion pairs at the BP-TZVP level of theory. Electronic density results were used to derive electrostatic potentials of the identified minimum conformers. Electrostatic potential-derived CHelpG and Natural Population Analysis charges show the P atom of the tetraalkylphosphonium-based ionic liquids cation to be more positively charged than the N atom in the tetraalkylammonium-based analogous IL cation, and a noticeable charge delocalization occurring in the tetraalkylammonium cation, when compared with the respective phosphonium congener. It is argued that this charge delocalization is responsible for the enhanced polarity observed on the ammonium based ionic liquids explaining the changes in the thermophysical properties observed.


Pre- and postischemic effects of the NMDA receptor antagonist dizocilpine maleate (MK-801) on collateral cerebral blood flow.
The authors studied the effects of pre- and postischemic administration of dizocilpine maleate (MK-801) on collateral and regional cerebral blood flow (CBF). The ischemic penumbra appears to benefit most from the neuroprotective effects of MK-801. The precise mechanism by which MK-801 provides this neuroprotection remains controversial. Alterations in CBF have been demonstrated with MK-801 administration, but whether the response is an increase or decrease in flow has remained unclear. A left-sided craniectomy was performed in 20 dogs. A branch of the middle cerebral artery (MCA) was cannulated and collateral blood supply-dependent tissue (CDT) was identified using the "shadow flow" technique. Regional CBF was measured using radiolabeled microspheres. Six dogs received MK-801 (1 mg/kg administered intravenously) before they underwent MCA branch occlusion; the remaining 14 dogs received MK-801 after they underwent MCA occlusion. Cerebral blood flow and vascular pressures were measured 30 and 60 minutes after MK-801 administration. In animals that received MK-801 before MCA occlusion, CBF did not change significantly from baseline values before or after occlusion. In contrast, in animals that received MK-801 after MCA occlusion, CBF was significantly reduced in all regions of the brain, including the CDT. Collateral blood supply-dependent tissue showed a 51.7% reduction in flow, whereas normal CBF was reduced by 29.7%. The MK-801 induced cerebral vasoconstriction in both groups. The neuroprotective effects of MK-801 do not appear to be caused by the augmentation of collateral or global cerebral circulation and, in fact, may block the glutamate-mediated vasodilation that occurs during ischemia.


Membrane and culture fluid proteins of nine human T lymphoblastoid cell lines.
Proteins form the membranes and culture media of nine, human T lymphoblastoid cell lines and of the myeloid line K562 were analyzed after 35S-methionine metabolic labeling, by electrophoresis in SDS polyacrylamide gradient gels. A monotonous consistency was present among these cell lines in their synthesis of membrane proteins, with only few variations in the expression of most proteins. In contrast, the synthesis of culture supernatant proteins was found to differ substantially among the cell lines. Proteins of 35,000 and 36,000 daltons were most prominently synthesized by cell line 1301. Proteins of 50,000 daltons were abundantly synthesized by SKW 3 and 8402. Proteins of 65,000 daltons were best synthesized by Jurgat, 1301 and CEM. Few of the membrane proteins which were abundantly synthesized by mitogen-activated normal T lymphocytes were expressed on the cultured cell lines. The view was proposed that cultured T lymphoblastoid malignancies do do not represent static vignettes of stages of differentiation of normal T lymphocytes.


Primary architecture and energy requirements of Type III and Type IV secretion systems.
Many pathogens use Type III and Type IV protein secretion systems to secrete virulence factors from the bacterial cytosol into host cells. These systems operate through a one-step mechanism. The secreted substrates (protein or nucleo-protein complexes in the case of Type IV conjugative systems) are guided to the base of the secretion channel, where they are directly delivered into the host cell in an ATP-dependent unfolded state. Despite the numerous disparities between these secretion systems, here we have focused on the structural and functional similarities between both systems. In particular, on the structural similarity shared by one of the main ATPases (EscN and VirD4 in Type III and Type IV secretion systems, respectively). Interestingly, these ATPases also exhibit a structural resemblance to F1-ATPases, which suggests a common mechanism for substrate secretion. The correlation between structure and function of essential components in both systems can provide significant insights into the molecular mechanisms involved. This approach is of great interest in the pursuit of identifying inhibitors that can effectively target these systems.


Changes in Sexual Fantasy and Solitary Sexual Practice During Social Lockdown Among Young Adults in the UK.
Pandemic-related social lockdown limited many sexual behaviors, but to date, no study has examined the perceived impact of social lockdown due to COVID-19 on sexual fantasy and solitary sexual behavior. The present study sought to examine the perceived impact of social lockdown on sexual fantasy and solitary sexual behavior among UK young adults in various living situations. A convenience sample of 565 adults aged 18-32 and living in the UK completed anonymous, web-based, study-specific questionnaires between May 14 and 18, 2020, 7 weeks after social lockdown was initiated. Mixed-method analyses were conducted. The study presents qualitative and quantitative data. Criterion variables were measured dichotomously as increases (vs no change) in sexual fantasy and increases (vs no change) in pornography consumption. Predictor variables were living arrangement, relationship status, and postlockdown changes in masturbation and pornography consumption. Of all, 34.3% engaged in more sexual fantasizing during lockdown; women were more likely than men to report this increase. Living context and relationship status were predictors of increased fantasizing. Of all, 30.44% reported an increase in at least one solitary sexual practice. This increase was associated with an increase in sexual fantasizing and also with increased pornography consumption. Nineteen percent of participants reported an increase in pornography use, with men being more likely than women to report this increase. Participants mostly attributed their increases to boredom, increased free time, and replacing partnered sex. Shifts in sexual fantasizing and solitary sexual practices were predicted by living arrangements, relationship status, and gender. The present findings suggest that the assessment of sexual fantasy and solitary sexual activities may benefit patients presenting with pandemic-related stress. Although mostly exploratory, significant changes in sexual fantasy and solitary sexual practices were observed. A cross-sectional design, convenience sampling, and study-specific measures are limitations. Cascalheira CJ, McCormack M, Portch E, et al. Changes in Sexual Fantasy and Solitary Sexual Practice During Social Lockdown Among Young Adults in the UK. J Sex Med 2021;9:100342.


From sediment to tissue and tissue to sediment: an evaluation of statistical bioaccumulation models.
Biota-sediment accumulation factors (BSAFs) and biota-sediment accumulation regressions (BSARs) are statistical models that may be used to estimate tissue chemical concentrations from sediment chemical concentrations or vice versa. Biota-sediment accumulation factors and BSARs are used to fill tissue concentration data gaps, set sediment preliminary remediation goals (PRGs), and make projections about the effectiveness of potential sediment cleanup projects in reducing tissue chemical concentrations. We explored field-based, benthic invertebrate biota-sediment chemical concentration relationships using data from the US Environmental Protection Agency (USEPA) Mid-Continent Ecology Division (MED) BSAF database. Approximately two thirds of the 262 relationships investigated were very poor (r(2) < 0.3 or p-value ≥ 0.05); for some of the biota-sediment relationships that did have a significant nonzero slope (p-value < 0.05), lipid-normalized tissue concentrations tended to decrease as the colocated organic carbon (OC)-normalized sediment concentration increased. Biota-sediment relationships were further evaluated for 3 of the 262 datasets. Biota-sediment accumulation factors, linear regressions, model II regressions, illustrative sediment PRGs, and confidence intervals (CIs) were calculated for each of the three examples. These examples illustrate some basic but important statistical practices that should be followed before selecting a BSAR or BSAF or relying on these simple models of biota-sediment relationships to support consequential management decisions. These practices include the following: one should not assume that the relationship between chemical concentrations in tissue and sediment is necessarily linear, one should not assume the model intercept to be zero, and one should not place too much stock on models that are heavily influenced by one or a few high chemical concentration data points. People will continue to use statistical models of field-based biota-sediment chemical concentration relationships to support sediment investigations and remedial action decisions. However, it should not be assumed that the models will be reliable. In developing and applying BSAFs and BSARs, it is essential that best practices are followed and model limitations and uncertainties are understood, acknowledged, and quantified as much as possible.


Evaluation of opt-out inpatient HIV screening at an urban teaching hospital.
This study evaluated opt-out inpatient HIV screening delivered by admitting physicians, and compared number of HIV tests and diagnoses to signs and symptoms-directed HIV testing (based on physician orders) in the emergency department (ED). The opt-out inpatient HIV screening program was conducted over a one year period in patients who were admitted to the 386-bed University of California San Diego (UCSD) teaching hospital. Numbers of HIV tests and diagnoses were compared to those observed among ED patients who underwent physician-directed HIV testing during the same time period. Survey data were collected from a convenience sample of patients and providers regarding the opt-out testing program. Among 8488 eligible inpatients, opt-out HIV testing was offered to 3017 (36%) patients, and rapid antibody testing was performed in 1389 (16.4%) inpatients, resulting in 6 (0.4% of all tests) newly identified HIV infections (5/6 were admitted through the ED). Among 27,893 ED patients, rapid antibody testing was performed in 88 (0.3%), with 7 (8.0% of all tests) new HIV infections identified. HIV diagnoses in the ED were more likely to be men who have sex with men (MSM) (p = 0.029) and tended to have AIDS-related opportunistic infections (p = 0.103) when compared to HIV diagnoses among inpatients. While 85% of the 150 physicians who completed the survey were aware of the HIV opt-out screening program, 44% of physicians felt that they did not have adequate time to consent patients for the program, and only 30% agreed that a physician is best-suited to consent patients. In conclusion, the yield of opt-out HIV rapid antibody screening in inpatients was comparable to the national HIV prevalence average. However, uptake of screening was markedly limited in this setting where opt-out screening was delivered by physicians during routine care, with limited time resources being the major barrier.


Characterization of Gallium Indium Phosphide and Progress of Aluminum Gallium Indium Phosphide System Quantum-Well Laser Diode.
Highly ordered gallium indium phosphide layers with the low bandgap have been successfully grown on the (100) GaAs substrates, the misorientation toward [01-1] direction, using the low-pressure metal organic chemical vapor deposition method. It is found that the optical properties of the layers are same as those of the disordered ones, essentially different from the ordered ones having two orientations towards [1-11] and [11-1] directions grown on (100) gallium arsenide substrates, which were previously reported. The bandgap at 300 K is 1.791 eV. The value is the smallest ever reported, to our knowledge. The high performance transverse stabilized AlGaInP laser diodes with strain compensated quantum well structure, which is developed in 1992, have been successfully obtained by controlling the misorientation angle and directions of GaAs substrates. The structure is applied to quantum dots laser diodes. This paper also describes the development history of the quantum well and the quantum dots laser diodes, and their future prospects.


Predictive power of hepatitis B 1762T/1764A mutations in plasma for hepatocellular carcinoma risk in Qidong, China.
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality with nearly 700,000 deaths occurring annually. Hepatitis B virus (HBV) is a major contributor to HCC and acquired mutations in the HBV genome may accelerate its pathogenesis. In this study, a matched case-control investigation of 345 men who died of HCC and 625 controls were nested within a cohort of male hepatitis B surface antigen (HBsAg) carriers from Qidong, China. Matched preserving odds ratios (ORs) were used as a measure of association and 95% confidence intervals (CIs) as a measure of precision. Real-time polymerase chain reaction allowed for a quantitative comparison of the levels of the HBV 1762(T)/1764(A) mutation in cases and controls. A total of 278 (81%) of the cases were positive for the HBV 1762(T)/1764(A) mutation compared with 250 (40%) of the controls. The matched preserving OR of 6.72 (95% CI: 4.66 to 9.68) strongly indicated that cases were significantly more probably than controls to have the mutation. Plasma levels of DNA harboring the HBV mutation were on average 15-fold higher in cases compared with controls (P < 0.001). Most strikingly, the level of the mutation in the 20 controls who later developed and died of HCC were on average 274-fold higher than controls who did not develop HCC. Thus, within this cohort of HBsAg carriers at high risk of developing HCC, individuals positive for the HBV 1762(T)/1764(A) mutation at enrollment were substantially more probably to subsequently develop HCC, with a higher concentration of the mutation in plasma enhancing predisposition for cancer development.


Nonlinear restoration of noisy images.
The restoration of images degraded by an additive white noise is performed by nonlinearly filtering a noisy image. The standard Wiener approach to this problem is modified to take into account the edge information of the image. Various filters of increasing complexity are derived. Experimental results are shown and compared to the standard Wiener filter results and other earlier attempts involving nonstationary filters.


Mitochondrial ATP-Pi exchange complex and the site of uncoupling of oxidative phosphorylation.
Five enzyme complexes, which are concerned with electron transport and oxidative phosphorylation, have been isolated from beef heart mitochondria. Enzyme complexes I, II, III and IV are the electron transfer complexes discovered in 1961. Complex V is an energy-conserving complex. It catalyzes ATP-Pi exchange and ATP hydrolysis. The exchange reaction is sensitive to uncouplers, rutamycin, valinomycin plus K-+, dicyclorexylcarboditmide, arsenate, azide, and adenylyl imidodiphosphate. It is also specific for ATP; ITP, GTP and UTP are essentially ineffective. Studies with the photoaffinity labeling uncoupler, 2-azido-4-nitrophenol (NPA), have shown that the mitochondrial uncoupler-binding sites are located exclusively in complex V. Complexes I, III and IV, which carry the three coupling sites of the respiratory chain, had negligible capacity for the binding of NPA, whereas the uncoupler-binding capacity of complex V appeared to be increased two- to threefold as compared to mitochondria. Complexes I, II, III, IV and V are obtained from the same batch of mitochondria by a simple fractionation procedure, which employs cholate, deoxycholate, ammonium acetate and ammonium sulfate. Studies with NPA have shown that mitochondria contain per milligram protein about 0.6 nmole of uniformly reacting uncoupler binding site. All of the uncouplers tested appeared to interact competitively with this site. Photoaffinity labeling with tritiated NPA has shown that a major portion of NPA binds to a polypeptide of molecular weight between 26,000 and 30,000. Other studies on the mechanism of uncoupling have shown that picrate is a membrane-impermeable uncoupler. It cannot uncouple mitochondria. However, it is an effective uncoupler of ATP synthesis and ATP-induced transhydrogenation or reverse electron transfer when used in conjunction with sonicated submitochondrial particles, which have an inside-out orientation of the inner membrane with respect to the medium. In these particles, picrate binds to the same uncoupler-binding site as NPA and other uncouplers. However, unlike the membrane-permeable uncouplers, picrate is a poor protonophore. It has a very small effect on the proton permeability of phosphorylating submitochondrial vesicles, even at two to three times the concentration needed for complete uncoupling. The increase in the proton permeability of submitochondrial vesicles caused by such high concentrations of picrate (500 mum) can be achieved with approximately 5 mum 2,4-dinitrophenol. At this concentration, dinitrophenol results in only about 20% uncoupling.


How can we keep patients with dementia safe in our acute hospitals? A review of challenges and solutions.
Maintaining patient safety in acute hospitals is a global health challenge. Traditionally, patient safety measures have been concentrated on critical care and surgical patients. In this review the medical literature was reviewed over the last ten years on aspects of patient safety specifically related to patients with dementia. Patients with dementia do badly in hospital with frequent adverse events resulting in the geriatric syndromes of falls, delirium and loss of function with increased length of stay and increased mortality. Contributory factors include inadequate assessment and treatment, inappropriate intervention, discrimination, low staff levels and lack of staff training. Unfortunately there is no one simple solution to this problem, but what is needed is a multifactorial, multilevel approach at the seven levels of care - patient, task, staff, team, environment, organisation and institution. Improving safety and quality of care for patients with dementia in acute hospitals will benefit all patients and is an urgent priority for the NHS.


Synthesis, visible light photocleavage, antiproliferative and cellular uptake properties of ruthenium complex [Ru(phen)2(mitatp)]2+.
A new ruthenium complex [Ru(phen)(2)(mitatp)](2+) (phen = 1,10-phenanthroline, mitatp = 5-methoxy-isatino[1,2-b]-1,4,8,9-tetraazatriphenylene) has been synthesized and characterized. The interaction of the complex with DNA has been studied and the results indicate that [Ru(phen)(2)(mitatp)](2+) could efficiently photocleave pBR322 DNA under irradiation at visible light and the singlet oxygen (1)O(2) was proved to be reactive species in the photocleavage process. The cytotoxicity has also been evaluated by MTT method, and [Ru(phen)(2)(mitatp)](2+) shows prominent anticancer activity against various cancer cells. Live cell imaging study and flow cytometric analysis demonstrate that the complex could cross cell membrane accumulating in the nucleus and inducing cell death by induction of G0/G1 cells cycle arrest and apoptosis.


Misinterpretation of Frozen Section in Endometrial Cancer Cases: Does It Have Any Effect on Disease-free and Overall Survival?
The aim of this study was to assess whether misinterpretation of frozen sections in endometrial cancer cases is associated with survival and determine the factors leading to mismatch. One hundred fifty endometrial cancer cases treated in Zeynep Kamil Maternity and Children's Health Training and Research Hospital between January 2010 and December 2014 were included in the study. Frozen sections and final histopathologic reports were screened from a prospectively collected database and analyzed on whether mismatch between the initial and the final reports has any impact on disease-free survival. There were 31 patients with mismatched frozen sections with the final report, whereas in 119 patients, frozen sections and final reports were consistent. The recurrence-free survival time was similar between groups (51 vs. 49, P=0.813). Overall survivals were also similar between groups (55 vs. 52, P=0.880). Frozen section misinterpretation does not affect disease-free and overall survival in endometrial cancer cases.


Context-aware Multimodal Auditory BCI Classification through Graph Neural Networks.
The prospect of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) in the presence of topological information of participants is often left unexplored in most of the brain-computer interface (BCI) systems. Additionally, the usage of these modalities together in the field of multimodality analysis to support multiple brain signals toward improving BCI performance is not fully examined. This study first presents a multimodal data fusion framework to exploit and decode the complementary synergistic properties in multimodal neural signals. Moreover, the relations among different subjects and their observations also play critical roles in classifying unknown subjects. We developed a context-aware graph neural network (GNN) model utilizing the pairwise relationship among participants to investigate the performance on an auditory task classification. We explored standard and deviant auditory EEG and fNIRS data where each subject was asked to perform an auditory oddball task and has multiple trials regarded as context-aware nodes in our graph construction. In experiments, our multimodal data fusion strategy showed an improvement up to 8.40% via SVM and 2.02% via GNN, compared to the single-modal EEG or fNIRS. In addition, our context-aware GNN achieved 5.3%, 4.07% and 4.53% higher accuracy for EEG, fNIRS and multimodal data based experiments, compared to the baseline models.


Applicability of induced sputum for molecular dosimetry of exposure to inhalatory carcinogens: 32P-postlabeling of lipophilic DNA adducts in smokers and nonsmokers.
The lung is a major target organ for smoking-associated cancer. We examined the applicability of induced sputum for molecular dosimetry of exposure to tobacco smoke-related carcinogens. Sputum induction was performed by inhalation of 4.5% saline delivered from an ultrasonic nebulizer for a period of up to 21 min in a group of smoking (n = 20) and nonsmoking (n = 24) healthy individuals. Samples were analyzed for total and differential cell counts and cell viability. Subsequently, DNA contents of the samples were isolated, and measurement of lipophilic DNA adducts was done by the 32P-postlabeling assay using nuclease P1 (NP1) and butanol enrichment methods. All subjects tolerated the induction procedure without experiencing any troublesome symptoms, and 90% of smokers (18 of 20) and 88% of nonsmokers (21 of 24) succeeded in producing sufficient amounts of sputum. Total cell counts and percentages of viable cells in smokers were higher than those in nonsmokers (6.7+/-6.0 versus 4.7+/-6.0 x 10(6), P = 0.40 and 80+/-15 versus 63+/-17, P = 0.01, respectively). In cell differentials, smokers had lower percentages of bronchoalveolar macrophages and higher percentages of neutrophils (69+/-24 versus 92+/-5, P = 0.002 and 26+/-26 versus 4+/-4, P = 0.008, respectively). Using the NP1 digestion method, all smokers and only one nonsmoker showed a diagonal radioactive zone in their adduct maps; adduct levels in smokers were higher than those in nonsmokers (3.1+/-1.4 versus 0.6+/-0.8/10(8) nucleotides; P = 0.0007), and also, adduct levels were significantly related to smoking indices. Applying the butanol extraction method, however, only half of the smokers and three nonsmokers showed the diagonal radioactive zone in their adduct maps; adduct levels in smokers were higher than those in nonsmokers (4.6+/-3.7 versus 1.0+/-1.9/10(8) nucleotides; P = 0.02), and the levels of adducts were significantly related to the smoking indices. There was a correlation between the levels of adducts determined by the two enrichment methods (r = 0.7; P = 0.02). Paired comparison showed no differences between the levels of adducts measured by the two methods (P = 0.55). We conclude that induced sputum can serve for molecular dosimetry of inhalatory exposure to carcinogens and that the NP1 version of the 32P-postlabeling assay is a choice of preference for studying smoking-induced DNA adducts in the lower respiratory tract.


Layered graph matching with composite cluster sampling.
This paper presents a framework of layered graph matching for integrating graph partition and matching. The objective is to find an unknown number of corresponding graph structures in two images. We extract discriminative local primitives from both images and construct a candidacy graph whose vertices are matching candidates (i.e., a pair of primitives) and whose edges are either negative for mutual exclusion or positive for mutual consistence. Then we pose layered graph matching as a multicoloring problem on the candidacy graph and solve it using a composite cluster sampling algorithm. This algorithm assigns some vertices into a number of colors, each being a matched layer, and turns off all the remaining candidates. The algorithm iterates two steps: 1) Sampling the positive and negative edges probabilistically to form a composite cluster, which consists of a few mutually conflicting connected components (CCPs) in different colors and 2) assigning new colors to these CCPs with consistence and exclusion relations maintained, and the assignments are accepted by the Markov Chain Monte Carlo (MCMC) mechanism to preserve detailed balance. This framework demonstrates state-of-the-art performance on several applications, such as multi-object matching with large motion, shape matching and retrieval, and object localization in cluttered background.


Decreased abundance of trefoil factor 1 transcript in the majority of gastric carcinomas.
Gastric carcinoma is one of the leading causes of cancer-related death worldwide, but the mechanisms underlying its development and progression still remain largely uncharacterized. As loss of trefoil factor 1 (TFF1) expression leads to neoplastic growth in the antropyloric mucosa of mice, the authors sought to comprehensively study the human TFF1 gene in primary gastric carcinomas. The authors studied the human TFF1 gene in primary gastric carcinomas and normal gastric mucosa at the DNA, RNA, and protein levels through DNA sequencing, quantitative real-time reverse transcriptase-polymerase chain reaction, and immunohistochemistry. Strikingly, TFF1 mRNA expression was significantly decreased in all 37 gastric carcinomas studied compared with normal gastric mucosa. Furthermore, six tumor/normal pairs with available histologic samples demonstrated a marked decrease in protein expression in tumor samples. Screening of the entire TFF1 coding region in a panel of 42 human gastric tumors did not reveal any somatic mutations, although a few rare germline sequence variants were identified. These findings demonstrated a significant decrease in the TFF1 transcript in the majority of human gastric carcinomas along with a corresponding reduction in protein expression, both of which occurred in the absence of gene mutation. Dysregulation of TFF1 expression at the transcript level was a critical event in the development of most gastric carcinomas.


Characterization of kinetic folding intermediates of recombinant canine milk lysozyme by stopped-flow circular dichroism.
The intermediate in the equilibrium unfolding of canine milk lysozyme induced by a denaturant is known to be very stable with characteristics of the molten globule state. Furthermore, there are at least two kinetic intermediates during refolding of this protein: a burst-phase (first) intermediate formed within the dead time of stopped-flow measurements and a second intermediate that accumulates with a rate constant of 22 s(-)(1). To clarify the relationships of these intermediates with the equilibrium intermediate, and also to characterize the structural changes of the protein during refolding, here we studied the kinetic refolding reactions using stopped-flow circular dichroism at 10 different wavelengths and obtained the circular dichroism spectra of the intermediates. Comparison of the circular dichroism spectra of the intermediates, as well as the absence of observed kinetics in the refolding from the fully unfolded state to the equilibrium intermediate, has demonstrated that the burst-phase intermediate is equivalent to the equilibrium intermediate. The difference circular dichroism spectrum that represented changes from the kinetic intermediate to the native state had characteristics of an exciton coupling band, indicating that specific packing of tryptophan residues in this protein occurred in this phase. From these findings, we propose a schematic model of the refolding of canine milk lysozyme that is consistent with the hierarchical mechanism of protein folding.


Epidemiology, detection, and management of tuberculosis among end-stage renal disease patients.
Tuberculosis (TB) remains an important problem among end-stage renal disease (ESRD) patients. We reviewed the epidemiology of TB and ESRD, investigations of TB exposures in US dialysis facilities, and published guidelines to inform screening and treatment practices among US ESRD patients. Compared to TB in the general population, ESRD patients have 6-25-fold higher TB incidence rates, and mortality during treatment is 2-3-fold higher. Most TB cases among ESRD patients (~90%) occur among non-US-born persons, and an analysis of genotyping data suggests that 80% of all cases result from latent TB infection (LTBI) reactivation. Published TB contact investigations in dialysis facilities have reported cases among ESRD patients and healthcare workers. However, transmission of TB is rare: there were no reports of secondary cases of TB because of exposure to an index-case patient and there were few TB infections, which was demonstrated by low occurrence of newly positive tuberculin skin tests (12%-16%) and conversions (8%-17%) among contacts. Targeted TB education, screening, and treatment for ESRD patients at highest risk for TB exposure (eg, non-US-born persons), using interferon-gamma release assays and short course LTBI regimens (ie, isoniazid-rifapentine weekly for 12 weeks or rifampin daily for 4 months) may be an effective overall strategy for reducing TB burden in ESRD patients.


[The tonus and relative thickness of the wall of skeletal muscle arterioles].
Inner diameter, absolute and relative wall thickness, and blood flow velocity in arterioles of different branching orders were measured in the rat skeletal (cremaster) muscle. It was found that as the branching order increased the heterogeneity of arterioles with respect to their relative wall thickness also grew. In response to papaverine-induced relaxation of the smooth muscle, there was a direct correlation between vasodilatation and the relative wall thickness. It was shown that a degree of smooth muscle shortening in different arterioles varied widely, the relative wall thickness being a measure (characteristic) of this shortening.


Aqueous Binary Mixtures of Stearic Acid and Its Hydroxylated Counterpart 12-Hydroxystearic Acid: Cascade of Morphological Transitions at Room Temperature.
Here, we describe the behavior of mixtures of stearic acid (SA) and its hydroxylated counterpart 12-hydroxystearic acid (12-HSA) in aqueous mixtures at room temperature as a function of the 12-HSA/SA mole ratio R. The morphologies of the self-assembled aggregates are obtained through a multi-structural approach that combines confocal and cryo-TEM microscopies with small-angle neutron scattering (SANS) and wide-angle X-ray scattering (WAXS) measurements, coupled with rheology measurements. Fatty acids are solubilized by an excess of ethanolamine counterions, so that their heads are negatively charged. A clear trend towards partitioning between the two types of fatty acids is observed, presumably driven by the favorable formation of a H-bond network between hydroxyl OH function on the 12th carbon. For all R, the self-assembled structures are locally lamellar, with bilayers composed of crystallized and strongly interdigitated fatty acids. At high R, multilamellar tubes are formed. The doping via a low amount of SA molecules slightly modifies the dimensions of the tubes and decreases the bilayer rigidity. The solutions have a gel-like behavior. At intermediate R, tubes coexist in solution with helical ribbons. At low R, local partitioning also occurs, and the architecture of the self-assemblies associates the two morphologies of the pure fatty acids systems: they are faceted objects with planar domains enriched in SA molecules, capped with curved domains enriched in 12-HSA molecules. The rigidity of the bilayers is strongly increased, as well their storage modulus. The solutions remain, however, viscous fluids in this regime.


A genome-wide search for genetic influences and biological pathways related to the brain's white matter integrity.
A genome-wide search for genetic variants influencing the brain's white matter integrity in old age was conducted in the Lothian Birth Cohort 1936 (LBC1936). At ∼73 years of age, members of the LBC1936 underwent diffusion MRI, from which 12 white matter tracts were segmented using quantitative tractography, and tract-averaged water diffusion parameters were determined (n = 668). A global measure of white matter tract integrity, g(FA), derived from principal components analysis of tract-averaged fractional anisotropy measurements, accounted for 38.6% of the individual differences across the 12 white matter tracts. A genome-wide search was performed with g(FA) on 535 individuals with 542,050 single nucleotide polymorphisms (SNPs). No single SNP association was genome-wide significant (all p > 5 × 10(-8)). There was genome-wide suggestive evidence for two SNPs, one in ADAMTS18 (p = 1.65 × 10(-6)), which is related to tumor suppression and hemostasis, and another in LOC388630 (p = 5.08 × 10(-6)), which is of unknown function. Although no gene passed correction for multiple comparisons in single gene-based testing, biological pathways analysis suggested evidence for an over-representation of neuronal transmission and cell adhesion pathways relating to g(FA).


Forkhead containing transcription factor Albino controls tetrapyrrole-based body pigmentation in planarian.
Pigmentation processes occur from invertebrates to mammals. Owing to the complexity of the pigmentary system, in vivo animal models for pigmentation study are limited. Planarians are capable of regenerating any missing part including the dark-brown pigments, providing a promising model for pigmentation study. However, the molecular mechanism of planarian body pigmentation is poorly understood. We found in an RNA interference screen that a forkhead containing transcription factor, Albino, was required for pigmentation without affecting survival or other regeneration processes. In addition, the body color recovered after termination of Albino double stranded RNA feeding owing to the robust stem cell system. Further expression analysis revealed a spatial and temporal correlation between Albino and pigmentation process. Gene expression arrays revealed that the expression of three tetrapyrrole biosynthesis enzymes, ALAD, ALAS and PBGD, was impaired upon Albino RNA interference. RNA interference of PBGD led to a similar albinism phenotype caused by Albino RNA interference. Moreover, PBGD was specifically expressed in pigment cells and can serve as a pigment cell molecular marker. Our results revealed that Albino controls planarian body color pigmentation dominantly via regulating tetrapyrrole biogenesis. These results identified Albino as the key regulator of the tetrapyrrole-based planarian body pigmentation, suggesting a role of Albino during stem cell-pigment cell fate decision and provided new insights into porphyria pathogenesis.


Trans fat diet induces abdominal obesity and changes in insulin sensitivity in monkeys.
There is conflicting evidence about the propensity of trans fatty acids (TFAs) to cause obesity and insulin resistance. The effect of moderately high intake of dietary monounsaturated TFAs on body composition and indices of glucose metabolism was evaluated to determine any pro-diabetic effect in the absence of weight gain. Male African green monkeys (Chlorocebus aethiops; n=42) were assigned to diets containing either cis-monounsaturated fatty acids or an equivalent diet containing the trans-isomers (approximately 8% of energy) for 6 years. Total calories were supplied to provide maintenance energy requirements and were intended to not promote weight gain. Longitudinal body weight and abdominal fat distribution by computed tomography scan analysis at 6 years of study are reported. Fasting plasma insulin, glucose, and fructosamine concentrations were measured. Postprandial insulin and glucose concentrations, and insulin-stimulated serine/threonine protein kinase (Akt), insulin receptor activation, and tumor necrosis factor-alpha concentrations in subcutaneous fat and muscle were measured in subsets of animals. TFA-fed monkeys gained significant weight with increased intra-abdominal fat deposition. Impaired glucose disposal was implied by significant postprandial hyperinsulinemia, elevated fructosamine, and trends toward higher glucose concentrations. Significant reduction in muscle Akt phosphorylation from the TFA-fed monkeys suggested a mechanism for these changes in carbohydrate metabolism. Under controlled feeding conditions, long-term TFA consumption was an independent factor in weight gain. TFAs enhanced intra-abdominal deposition of fat, even in the absence of caloric excess, and were associated with insulin resistance, with evidence that there is impaired post-insulin receptor binding signal transduction.


COVID-19 Disease and Vitamin D: A Mini-Review.
Novel coronavirus disease (COVID-19) pandemic caused by SARS-CoV-2, for which there is no effective treatment except employing prevention strategies, has already instituted significant number of deaths. In this review, we provide a scientific view on the potential role of vitamin D in SARS-CoV-2 virus/COVID-19 disease. Vitamin D is well-known to play a significant role in maintaining the immune health of an individual. Moreover, it induces antimicrobial peptide expression that can decrease viral replication and regulate the levels of pro-inflammatory/anti-inflammatory cytokines. Therefore, supplementation of vitamin D has the potential to reduce the incidence, severity and the risk of death from pneumonia resulting from the cytokine storm of many viral infections including COVID-19. We suggest that supplementation of subjects at high risk of COVID-19 with vitamin D (1.000 to 3.000 IU) to maintain its optimum serum concentrations may be of significant benefit for both in the prevention and treatment of the COVID-19.


Factors affecting plasma lipoprotein(a) levels: role of hormones and other nongenetic factors.
Lp(a) appears to be one of the most atherogenic lipoproteins. It consists of an low-density lipoprotein core in addition to a covalently bound glycoprotein, apo(a). Apo(a) exists in numerous polymorphic forms. The size of the polymorphism is mediated by the variable number of kringle-4 Type 2 repeats found in apo(a). Plasma Lp(a) levels are determined to more than 90% by genetic factors. Plasma Lp(a) levels in healthy individuals correlate significantly highly with apo(a) biosynthesis, and not with its catabolism. There are several hormones that are known to have a strong effect on Lp(a) metabolism. In certain diseases, such as kidney disease, the Lp(a) catabolism is impaired, leading to elevations that are up to a fivefold increase. Lp(a) levels rise with age but are otherwise only little influenced by diet and lifestyle. There is no safe and efficient way of treating individuals with elevated plasma Lp(a) concentrations. Most of the lipid-lowering drugs have either no significant influence on Lp(a) or exhibit a variable effect in patients with different forms of primary and secondary hyperlipoproteinemia.


A study on the GC-MS analysis of bioactive components and pancreato-protective effect of methanolic extract of Brassica oleracea L. var. botrytis.
The ever-increasing problem of pancreatitis due to alcohol abuse demands evaluation of novel drugs of plant origin. This study explores the therapeutic effects of the methanolic extract of Brassica oleraceae (MEBO) on ethanol and cerulein induced pancreatitis in rats. The MEBO was subjected to GC-MS and HPLC analysis. Male albino Wistar rats were divided into various groups, fed with alcohol (36% of total calories for 5 weeks) and cerulein (20 μg/kg b.wt i.p, weekly thrice for last three weeks) with or without MEBO (40 mg/kg b.wt). Serum lipase, amylase, IL-1β, IL-18, caspase-1, lipid peroxides, oxidative stress index and antioxidant status were assessed in pancreas. Six compounds were identified in GC-MS analysis. Co-administration of MEBO reduced the pancreatic marker enzymes in serum, IL-1β, IL-18 and caspase-1 and increased the antioxidant status of pancreas. The pancreato-protective effect of Brassica oleraceae may be attributed to well-known anti-inflammatory flavonoids, luteolin, quercetin and myricetin.


Heart rate, anxiety and performance of residents during a simulated critical clinical encounter: a pilot study.
High-fidelity patient simulation has been praised for its ability to recreate lifelike training conditions. The degree to which high fidelity simulation elicits acute emotional and physiologic stress among participants - and the influence of acute stress on clinical performance in the simulation setting - remain areas of active exploration. We examined the relationship between residents' self-reported anxiety and a proxy of physiologic stress (heart rate) as well as their clinical performance in a simulation exam using a validated assessment of non-technical skills, the Ottawa Crisis Resource Management Global Rating Scale (Ottawa GRS). This was a prospective observational cohort study of emergency medicine residents at a single academic center. Participants managed a simulated clinical encounter. Anxiety was assessed using a pre- and post-simulation survey, and continuous cardiac monitoring was performed on each participant during the scenario. Performance in the simulation scenario was graded by faculty raters using a critical actions checklist and the Ottawa GRS instrument. Data collection occurred during the 2011 academic year. Of 40 eligible residents, 34 were included in the analysis. The median baseline heart rate for participants was 70 beats per minute (IQR: 62 - 78). During the simulation, the median maximum heart rate was 140 beats per minute (IQR: 137 - 151). The median minimum heart rate during simulation was 81 beats per minute (IQR: 72 - 92), and mean heart rate was 117 beats per minute (95% CI: 111 - 123). Pre- and post-simulation anxiety scores were equal (mean 3.3, IQR: 3 to 4). The minimum and maximum Overall Ottawa GRS scores were 2.33 and 6.67, respectively. The median Overall score was 5.63 (IQR: 5.0 to 6.0). Of the candidate predictors of Overall performance in a multivariate logistic regression model, only PGY status showed statistical significance (P = 0.02). Simulation is associated with physiologic stress, and heart rate elevation alone correlates poorly with both perceived stress and performance. Non-technical performance in the simulation setting may be more closely tied to one's level of clinical experience than to perceived or actual stress.


Cost Analysis, Complications, and Discharge Disposition Associated With Simultaneous vs Staged Bilateral Total Knee Arthroplasty.
Simultaneous vs staged bilateral total knee arthroplasty (BTKA) has long been debated. The primary objective of this study was to compare actual hospital costs and complication rates in patients undergoing simultaneous BTKA (simBTKA) and staged BTKA (staBTKA) at a single institution. A total joint arthroplasty database from a single hospital was used to identify all patients who underwent primary BTKA from 2013 to 2016 and divided into simultaneous and staged groups. StaBTKA patients were included if both procedures were performed within 1 year by the same surgeon. The combined total hospital cost of both procedures was used, and inpatient rehabilitation (IPR) costs were added for all patients discharged to IPR. There were 225 simBTKA and 337 staBTKA patients. SimBTKA patients were younger (61 ± 8 vs 66 ± 8 years, P < .001), had lower body mass index (31.3 ± 5.9 vs 34.0 ± 7.2, P < .001), were more predominately male (48% vs 38%, P = .029), and more likely to require IPR as compared with staBTKA patients. There was no difference in total hospital cost for simBTKA as compared with staBTKA ($24,596 ± $5652 vs $24,915 ± $5756, P = .586). Complications were more prevalent in the simBTKA group, including venous thromboembolism (5.4% vs 1.4%, P = .006) and blood transfusions (15.8% vs 6.2%, P < .001). There were higher complication rates with no significant cost savings in actual hospital costs associated with simBTKA, when accounting for the cost of IPR, as compared with staBTKA. The total cost analysis of simBTKA vs staBTKA, using actual cost data, merits further evaluation.


Identification of an endoplasmic reticulum-resident calcium-binding protein with multiple EF-hand motifs in asexual stages of Plasmodium falciparum.
An endoplasmic reticulum-located, calcium-binding protein, with an apparent molecular weight (Mr) of approximately 40,000 (PfERC), has been identified in the asexual stages of the malaria parasite, Plasmodium falciparum. This protein appears to be equivalent to a previously described gametocyte protein, Pfs40, which was reported to be expressed on the gametocyte surface (Rawlings DJ, Kaslow DC. J Biol Chem 1992;267:3976-3982). Sequencing of the 3' end of the gene revealed the omission of a single base in the 3' region of the published sequence. The corrected gene sequence encodes a C-terminal IDEL motif, which indicates residency of the 40 kDa protein within the endoplasmic reticulum. The predicted C-terminal region also appears to contain a sixth EF-hand calcium-binding domain, which suggests that PfERC is related to previously reported ER-localized calcium-binding proteins, namely reticulocalbin and ERC-55 (Ozawa M. J. Biochem. 1995;117:1113-1119; Weis K, Griffiths G, Lamond AI. J. Biol. Chem. 1994;269:19142-19150). The presence of the 40 kDa calcium-binding protein in malaria parasites was confirmed using 45Ca2+-blotting and partial protein sequencing of the corresponding Coomassie blue-stained polypeptide. Confocal immunofluorescence microscopy of asexual stage parasites was used to show that PfERC co-localizes with the known ER-located protein, Pfgrp. Analysis of immunoblots of tightly synchronized parasites showed that expression of PfERC increases with increasing maturity of the parasite. We propose that PfERC is a member of the reticulocalbin family of calcium-binding proteins and may play a role in protein trafficking in the malaria parasite.


Pharmacology of converting enzyme inhibitors.
Angiotensin converting enzyme inhibitors were developed to prevent the in vivo generation of angiotensin II and thereby to reduce peripheral vasoconstriction. However, these compounds exert some additional effects that may or may not be angiotensin dependent. These include potential sodium diuresis, bradykinin accumulation, prostaglandin release, blunting of sympathetic activity, parasympathomimetic actions, central effects, redistribution of blood flow toward some particularly important organs. Only the comprehensive assessment of the many complex interactions that exist between the renin-angiotensin and several other regulatory systems reveals the complete therapeutic profile of this class of pharmacologic agents.


Associations between Adolescent Marijuana Use, Driving after Marijuana Use and Recreational Retail Sale in Colorado, USA.
We investigated associations between the retail distribution of recreational marijuana in Colorado and (i) past 30-day marijuana use and (ii) driving after marijuana use (DAMU) among a representative sample of public high school students using four waves of data from a state surveillance system. Past 30-day marijuana use was assessed among all sampled students (n = 85,336). DAMU was assessed among students 15 years or older who indicated driving (n = 47,518). Modified Poisson regression with robust variance estimates was used to estimate prevalence ratios (PR) comparing the pre-distribution (2013) and post-distribution (2015, 2017, 2019) periods for marijuana-related behaviors. Frequency of behavioral engagement was assessed using a multinomial approach. An estimated 20.3% of students engaged in past 30-day marijuana use and 10.5% of student drivers engaged in DAMU. Retail distribution of recreational marijuana was not significantly associated with the prevalence of any marijuana use or DAMU. However, it was associated with 1.16 (95% CI: 1.04-1.29) times the prevalence of using marijuana one or two times in the last 30 days, 1.27 (1.03, 1.55) times the prevalence of DAMU one time, and 0.82 (0.69, 0.98) times the prevalence of DAMU six or more times. No significant associations were observed for the remaining frequency categories. Approximately 1 in 10 students who drive reported DAMU. Varying prevalence in the frequency of past 30-day marijuana use and DAMU was observed following the retail distribution of recreational marijuana in Colorado. Care should be taken to properly educate adolescent drivers regarding the dangers of DAMU.


Phthalate-associated hypertension in premature infants: a prospective mechanistic cohort study.
Phthalates are associated with increased blood pressure in children. Large exposures to di-(2-ethylhexyl) phthalate (DEHP) among premature infants have been a cause for concern. We conducted a prospective observational cohort study to determine if DEHP exposures are related to systolic blood pressure (SBP) in premature infants, and if this exposure is associated with activation of the mineralocorticoid receptor (MR). Infants were monitored longitudinally for 8 months from birth. Those who developed idiopathic hypertension were compared with normotensive infants for DEHP exposures. Appearance of urinary metabolites after exposure was documented. Linear regression evaluated the relationship between DEHP exposures and SBP index and whether urinary cortisol/cortisone ratio (a surrogate marker for 11β-HSD2 activity) mediated those relationships. Urinary exosomes were quantified for sodium transporter/channel expression and interrogated against SBP index. Eighteen patients met the study criteria, nine developed transient idiopathic hypertension at a postmenstrual age of 40.6 ± 3.4 weeks. The presence of urinary DEHP metabolites was associated with prior IV and respiratory tubing DEHP exposures (p < 0.05). Both IV and respiratory DEHP exposures were greater in hypertensive infants (p < 0.05). SBP index was related to DEHP exposure from IV fluid (p = 0.018), but not respiratory DEHP. Urinary cortisol/cortisone ratio was related to IV DEHP and SBP index (p < 0.05). Sodium transporter/channel expression was also related to SBP index (p < 0.05). Increased blood pressure and hypertension in premature infants are associated with postnatal DEHP exposure. The mechanism of action appears to be activation of the MR through inhibition of 11β-HSD2.


Depressive symptoms, cognitive impairment and functional impairment in a rural elderly population in India: a Hindi version of the geriatric depression scale (GDS-H).
To measure depressive symptomatology in a largely illiterate elderly population in India, using a new Hindi version of the Geriatric Depression Scale (GDS-H), and to examine its distribution and associations with age, gender, literacy, cognitive impairment and functional impairment. A Hindi version of the Geriatric Depression Scale was developed and administered to participants along with measures of demographic characteristics, cognitive functioning and functional ability. The rural community of Ballabgarh in northern India. A community sample of 1554 mostly illiterate Hindi-speaking residents of Ballabgarh aged 55+. The Hindi version of the Geriatric Depression Scale (GDS-H); the Hindi Mental State Exam (HMSE); the Everyday Abilities Scale for India (EASI); age, gender and literacy. The GDS-H had high internal consistency and a factor structure comparable to the original English language version. The overall distribution of scores was higher than reported from other populations. Greater numbers of depressive symptoms, as measured by higher scores on the GDS-H, were associated with older age and illiteracy. Among the illiterate, there was no gender difference while among the literate, higher GDS-H scores were found among women. Cognitive impairment and functional disability were independently associated with higher scores on the GDS-H after adjustment for age, gender and literacy. A reliable and valid Hindi version of the GDS has been developed. Depressive symptoms as measured by the GDS-H were prominent in this elderly illiterate northern Indian population and strongly associated with both cognitive and functional impairment.


Identification of discriminators of hepatoma by gene expression profiling using a minimal dataset approach.
The severity of hepatocellular carcinoma (HCC) and the lack of good diagnostic markers and treatment strategies have rendered the disease a major challenge. Previous microarray analyses of HCC were restricted to the selected tissue sample sets without validation on an independent series of tissue samples. We describe an approach to the identification of a composite discriminator cassette by intersecting different microarray datasets. We studied the global transcriptional profiles of matched HCC tumor and nontumor liver samples from 37 patients using cDNA (cDNA) microarrays. Application of nonparametric Wilcoxon statistical analyses (P < 1 x 10(-6)) and the criteria of 1.5-fold differential gene expression change resulted in the identification of 218 genes, including BMI-1, ERBB3, and those involved in the ubiquitin-proteasome pathway. Elevated ERBB2 and epidermal growth factor receptor (EGFR) expression levels were detected in ERBB3-expressing tumors, suggesting the presence of ERBB3 cognate partners. Comparison of our dataset with an earlier study of approximately 150 tissue sets identified multiple overlapping discriminator markers, suggesting good concordance of data despite differences in patient populations and technology platforms. These overlapping discriminator markers could distinguish HCC tumor from nontumor liver samples with reasonable precision and the features were unlikely to appear by chance, as measured by Monte Carlo simulations. More significantly, validation of the discriminator cassettes on an independent set of 58 liver biopsy specimens yielded greater than 93% prediction accuracy. In conclusion, these data indicate the robustness of expression profiling in marker discovery using limited patient tissue specimens as well as identify novel genes that are highly likely to be excellent markers for HCC diagnosis and treatment.


Predictors of quality of life among Chinese people with schizophrenia.
This study was designed to investigate the association of quality of life, perceived stigma, and medication adherence among Chinese patients with schizophrenia, and to ascertain the predictors of quality of life. A cross-sectional correlation study was conducted with 146 participants. All participants completed self-report scales: the Schizophrenia Quality of Life Scale, Link's Stigma Scale, and the Morisky Medication Adherence Scale. Pearson parametric correlations and stepwise multiple regressions were performed. The total quality of life score and psychosocial subscale was significantly positively correlated with perceived stigma, coping orientation of withdrawal, and feelings of stigma, and negatively correlated with age and medication adherence. The means of all subscale scores except perceived devaluation-discrimination and different/guilty feelings were significantly higher than the midpoint of 2.5. The best predictors of quality of life and psychosocial domains were stigma-related feelings: feeling misunderstood, feeling different/shame, and age. Our findings suggest that an individual's negative emotional response may strengthen internalized stigma and decrease quality of life. As the best predictor, age indicated that adaptation to mental illness may relieve perceived stigma and achieve favorable quality of life.


Triparental origin of triploid onion, Allium × cornutum (Clementi ex Visiani, 1842), as evidenced by molecular, phylogenetic and cytogenetic analyses.
Reconstruction of the parental origins of cultivated plants from wild relatives, especially after long periods of domestication, is not a trivial task. However, recent advances in molecular phylogenetics, among other approaches, have proved to be very informative in analyses of the origin and evolution of polyploid genomes. An established minor garden crop, triploid onion Allium × cornutum (Clementi ex Visiani, 1842) (2n = 3x = 24), is widespread in southeastern Asia and Europe. Our previous cytogenetic analyses confirmed its highly heterozygous karyotype and indicated its possible complex triparental genome origin. Allium cepa L. and Allium roylei Stearn were suggested as two putative parental species of A. × cornutum, whereas the third parental species remained hitherto unknown. Here we report the phylogenetic analyses of the internal transcribed spacers ITS1-5.8S-ITS2 of 35S rDNA and the non-transcribed spacer (NTS) region of 5S rDNA of A. × cornutum and its relatives of the section Cepa. Both ITS and NTS sequence data revealed intra-individual variation in triploid onion, and these data clustered into the three main clades, each with high sequence homology to one of three other species of section Cepa: A. cepa, A. roylei, and unexpectedly, the wild Asian species Allium pskemense B. Fedtsh. Allium pskemense is therefore inferred to be the third, so far unknown, putative parental species of triploid onion Allium × cornutum. The 35S and 5S rRNA genes were found to be localised on somatic chromosomes of A. × cornutum and its putative parental species by double fluorescent in situ hybridisation (FISH). The localisation of 35S and 5S rDNA in A. × cornutum chromosomes corresponded to their respective positions in the three putative parental species, A. cepa, A. pskemense, and A. roylei. GISH (genomic in situ hybridisation) using DNA of the three putative parental diploids corroborated the results of the phylogenetic study. The combined molecular, phylogenetic and cytogenetic data obtained in this study provided evidence for a unique triparental origin of triploid onion A. × cornutum with three putative parental species, A. cepa, A. pskemense, and A. roylei.


Genetic Correlation of miRNA Polymorphisms and STAT3 Signaling Pathway with Recurrent Implantation Failure in the Korean Population.
The growing prevalence of in vitro fertilization-embryo transfer procedures has resulted in an increased incidence of recurrent implantation failure (RIF), necessitating focused research in this area. STAT3, a key factor in maternal endometrial remodeling and stromal proliferation, is crucial for successful embryo implantation. While the relationship between STAT3 and RIF has been studied, the impact of single nucleotide polymorphisms (SNPs) in miRNAs, well-characterized gene expression modulators, on STAT3 in RIF cases remains uncharacterized. Here, we investigated 161 RIF patients and 268 healthy control subjects in the Korean population, analyzing the statistical association between miRNA genetic variants and RIF risk. We aimed to determine whether SNPs in specific miRNAs, namely miR-218-2 rs11134527 G>A, miR-34a rs2666433 G>A, miR-34a rs6577555 C>A, and miR-130a rs731384 G>A, were significantly associated with RIF risk. We identified a significant association between miR-34a rs6577555 C>A and RIF prevalence (implantation failure [IF] ≥ 2: adjusted odds ratio [AOR] = 2.264, 95% CI = 1.007-5.092, p = 0.048). These findings suggest that miR-34a rs6577555 C>A may contribute to an increased susceptibility to RIF. However, further investigations are necessary to elucidate the precise mechanisms underlying the role of miR-34a rs6577555 C>A in RIF. This study sheds light on the genetic and molecular factors underlying RIF, offering new avenues for research and potential advancements in the diagnosis and treatment of this complex condition.


Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up.
The Diabetes Intervention Study (DIS) is a prospective population-based multicentre trial of newly detected cases of non-insulin-dependent diabetes mellitus (NIDDM). This report analyses the risk factors for subsequent coronary heart disease and all-cause death during the 11-year follow-up. The prognostic significance of the categories of the NIDDM Policy Group was validated with respect to the incidence of coronary heart disease and mortality. At baseline 1139 subjects, aged 30-55 years at the time of diabetes detection and classified as diet controlled after a 6-week screening phase, were included. Of the patients 112 (15.2%) suffered from myocardial infarction, 197 (19.82%) of 994 had died. The odds ratio for all-cause mortality compared to the general population for males at the age of 36-45 years was 5.1 and for females 7.0. In multivariate analysis age, blood pressure and smoking were independent risk factors for myocardial infarction and male sex, age, blood pressure, triglycerides, postprandial blood glucose and smoking for death, respectively. The categories of the NIDDM Policy Group target parameters for blood glucose, triglycerides and blood pressure were significant predictors of both CHD and death. Thus, it appears that in NIDDM good control of blood glucose, blood pressure and triglycerides is associated with a lower incidence of coronary heart disease and death rate respectively.


Crystal structure of conserved domains 1 and 2 of the human DEAD-box helicase DDX3X in complex with the mononucleotide AMP.
DExD-box helicases are involved in all aspects of cellular RNA metabolism. Conserved domains 1 and 2 contain nine signature motifs that are responsible for nucleotide binding, RNA binding and ATP hydrolysis. The human DEAD-box helicase DDX3X has been associated with several different cellular processes, such as cell-growth control, mRNA transport and translation, and is suggested to be essential for the export of unspliced/partially spliced HIV mRNAs from the nucleus to the cytoplasm. Here, the crystal structure of conserved domains 1 and 2 of DDX3X, including a DDX3-specific insertion that is not generally found in human DExD-box helicases, is presented. The N-terminal domain 1 and the C-terminal domain 2 both display RecA-like folds comprising a central beta-sheet flanked by alpha-helices. Interestingly, the DDX3X-specific insertion forms a helical element that extends a highly positively charged sequence in a loop, thus increasing the RNA-binding surface of the protein. Surprisingly, although DDX3X was crystallized in the presence of a large excess of ADP or the slowly hydrolyzable ATP analogue ATPgammaS the contaminant AMP was seen in the structure. A fluorescent-based stability assay showed that the thermal stability of DDX3X was increased by the mononucleotide AMP but not by ADP or ATPgammaS, suggesting that DDX3X is stabilized by AMP and elucidating why AMP was found in the nucleotide-binding pocket.


Mucosal lymphocytes in the rat small intestine: phenotypical characterization in situ.
Lymphocyte subpopulations in the intestinal mucosa of the rat were quantified in situ and compared with data obtained by other authors using enzymic or mechanical methods (Selby et al., 1984; Gibson et al., 1985) in order to assess any selective loss of cell types or contamination with lamina propria lymphocytes after these enzymic or mechanical isolation procedures. Intraepithelial lymphocytes (IEL) were predominantly of the suppressor/cytotoxic phenotype (MRC OX-8) and nearly all cells bore the pan T marker W3/13. About 10% of the IEL phenotypically belonged to the T-helper (W3/25) lineage. MRC OX-19, the rat equivalent of the mouse Lyt-1 antigen, was present on about 15% of the IEL. The main subpopulation of lamina propria T lymphocytes (T-LPL) showed a T-helper phenotype and a smaller subpopulation a suppressor/cytotoxic phenotype. Practically all T-LPL expressed the pan T marker W3/13, and half of these T cells were MRC OX-19+. The results proved to be in agreement with the data obtained after enzymic or mechanical isolation procedures and indicate that proportional contamination with LPL is not likely to occur with these methods.


Nonclinical Safety and Toxicokinetics of MnTnBuOE-2-PyP5+ (BMX-001).
BMX-001, a manganese porphyrin that has anti-inflammatory, antioxidant, and antitumor properties, is being developed as a potential therapeutic for high-grade glioma (HGG) and head and neck (H&N) cancer. An IND has been opened for BMX-001 in the treatment of HGG (NCT02655601) and another is in preparation for H&N. The safety of BMX-001 has been evaluated in a battery of nonclinical Good Laboratory Practice (GLP)-compliant studies. Systemic toxicity has been evaluated using the intended cGMP product administered subcutaneously for periods of up to 5 weeks in both the mouse and the monkey and included toxicokinetic evaluations to characterize systemic exposure and tissue distribution and clearance of BMX-001. In additional GLP studies, BMX-001 was not irritating to the skin or eye and caused no changes in cardiac rate or rhythm or blood pressure. Mixed results for genotoxicity were seen with the weight of evidence indicating that BMX-001 poses no genotoxic risk in humans. In systemic mouse and monkey studies, loading/maintenance dose no observed adverse effect levels were 12/2 mg/kg/dose and 6/2 mg/kg/dose, respectively, with maintenance doses administered every 3 days after the initial loading dose. Systemic data were used to determine a Food and Drug Administration-approved safe starting dose for the initial clinical study in patients with HGG. BMX-001 was detected in analyzed tissues, including the brain, persisting well past the short plasma clearance period. The highest levels of BMX-001 were seen in the liver and kidneys, with amounts in these tissues returning to close to undetectable levels after a 2-week cessation of dosing.


Continuous glucose monitoring in newborn infants: how do errors in calibration measurements affect detected hypoglycemia?
Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values. Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics. Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data.


microRNA profile datasets of murine macrophages infected with different strains of Leptospira spp.
MicroRNAs play an important role in the regulation of immune responses. The influence of epigenetic mechanisms, particularly RNA-mediated post-transcriptional regulation of host immune responses has been proven vital following infections by different pathogens, and bacteria can modulated host miRNAs. Global miRNA expression analysis from macrophages infected in vitro with different strains of Leptospira spp was performed using miRNA 4.1 microarray strips. Leptospirosis is a bacterial zoonosis of global importance, responsible for significant morbidity and mortality worldwide. Despite considerable advances, much is yet to be discovered about disease pathogenicity, particularly in regards to host-pathogen interactions. We present here a high-quality dataset examining the microtranscriptome of murine macrophages J774A.1 following 8h of infection with virulent, attenuated and saprophyte strains of Leptospira. Metadata files were submitted to the Gene Expression Omnibus (GEO) repository.


Differential inflammatory networks distinguish responses to bone marrow-derived versus adipose-derived mesenchymal stem cell therapies in vascularized composite allotransplantation.
Vascularized composite allotransplantation (VCA) is aimed at enabling injured individuals to return to their previous lifestyles. Unfortunately, VCA induces an immune/inflammatory response, which mandates lifelong, systemic immunosuppression, with attendant detrimental effects. Mesenchymal stem cells (MSC)-both adipose-derived (AD-MSC) and bone marrow-derived (BM-MSC)-can reprogram inflammation and have been suggested as an alternative to immunosuppression, but their mechanism of action is as yet not fully elucidated. We sought to gain insights into these mechanisms using a systems biology approach. PKH26 (red) dye-labeled AD-MSC or BM-MSC were administered intravenously to Lewis rat recipients of mismatched Brown-Norway hindlimb transplants. Short course tacrolimus (FK-506) monotherapy was withdrawn at postoperative day 21. Sera were collected at 4 weeks, 6 weeks, and 18 weeks; assayed for 29 inflammatory/immune mediators; and the resultant data were analyzed using Dynamic Network Analysis (DyNA), Dynamic Bayesian Network (DyBN) inference, and Principal Component Analysis. DyNA network complexity decreased with time in AD-MSC rats, but increased in BM-MSC rats. DyBN and Principal Component Analysis suggested mostly different central nodes and principal characteristics, respectively, in AD-MSC versus BM-MSC rats. AD-MSC and BM-MSC are associated with both overlapping and distinct dynamic networks and principal characteristics of inflammatory/immune mediators in VCA grafts with short-course tacrolimus induction therapy. The decreasing inflammatory complexity of dynamic networks in the presence of AD-MSC supports the previously suggested role for T regulatory cells induced by AD-MSC. The finding of some overlapping and some distinct central nodes and principal characteristics suggests the role of key mediators in the response to VCA in general, as well as potentially differential roles for other mediators ascribed to the actions of the different MSC populations. Thus, combined in vivo/in silico strategies may yield novel means of optimizing MSC therapy for VCA.


Inhibitory Smads and bone morphogenetic protein (BMP) modulate anterior photoreceptor cell number during planarian eye regeneration.
Planarians represent an excellent model to study the processes of body axis and organ re-specification during regeneration. Previous studies have revealed a conserved role for the bone morphogenetic protein (BMP) pathway and its intracellular mediators Smad1/5/8 and Smad4 in planarian dorsoventral (DV) axis re-establishment. In an attempt to gain further insight into the role of this signalling pathway in planarians, we have isolated and functionally characte-rized the inhibitory Smads (I-Smads) in Schmidtea mediterranea. Two I-Smad homologues have been identified: Smed-smad6/7-1 and Smed-smad6/7-2. Expression of smad6/7-1 was detected in the parenchyma, while smad6/7-2 was found to be ex-pressed in the central nervous system and the eyes. Neither single smad6/7-1 and smad6/7-2 nor double smad6/7-1,-2 silencing gave rise to any apparent disruption of the DV axis. However, both regenerating and intact smad6/7-2 (RNAi) planarians showed defects in eye morphogenesis and displayed small, rounded eyes that lacked the anterior subpopulation of photoreceptor cells. The number of pigment cells was also reduced in these animals at later stages of regeneration. In contrast, after low doses of Smed-bmp(RNAi), planarians regenerated larger eyes in which the anterior subpopulation of photoreceptor cells was expanded. Our results suggest that Smed-smad6/7-2 and Smed-bmp control the re-specification and maintenance of anterior photoreceptor cell number in S. mediterranea.


Anthropology in a postcolonial colony: Helen I. Safa's contribution to Puerto Rican ethnography.
This article assesses Helen I. Safa's legacy to anthropological thought in Puerto Rico. The first part of the article locates Safa's research on the Island within a long tradition of fieldwork by U.S. scholars since the early twentieth century. More recent research, conducted mostly by Puerto Rican women anthropologists and other social scientists, has expanded upon Safa's insights on gender and work. The second part of the essay analyzes Safa's major empirical work, The Urban Poor of Puerto Rico: A Study in Development and Inequality. Above all, this book helped overcome the theoretical impasse over the culture of poverty that characterized much of urban anthropology during the 1960s and 1970s. The article concludes with an appraisal of the relevance of Safa's work for the ethnography of contemporary Puerto Rico.