Single-cell analysis of [Ca2+]i signalling in sub-fertile men: characteristics and relation to fertilization outcome.
What are the characteristics of progesterone-induced (CatSper-mediated) single cell [Ca2+]i signals in spermatozoa from sub-fertile men and how do they relate to fertilizing ability? Single cell analysis of progesterone-induced (CatSper-mediated) [Ca2+]i showed that reduced progesterone-sensitivity is a common feature of sperm from sub-fertile patients and is correlated with fertilization rate. Stimulation with progesterone is a widely used method for assessing [Ca2+]i mobilization by activation of CatSper in human spermatozoa. Although data are limited, sperm population studies have indicated an association of poor [Ca2+]i response to progesterone with reduced fertilization ability. This was a cohort study using semen samples from 21 donors and 101 patients attending the assisted conception unit at Ninewells Hospital Dundee who were undergoing ART treatment. Patients were recruited from January 2016 to June 2017. Semen donors and patients were recruited in accordance with local ethics approval (13/ES/0091) from the East of Scotland Research Ethics Service (EoSRES) REC1. [Ca2+]i responses were examined by single cell imaging and motility parameters assessed by computer-assisted sperm analysis (CASA). For analysis, patient samples were divided into three groups IVF(+ve) (successful fertilization; 62 samples), IVF-FF (failed fertilization; eight samples) and ICSI (21 samples). A further 10 IVF samples showed large, spontaneous [Ca2+]i oscillations and responses to progesterone could not be analysed. All patient samples loaded with the [Ca2+]i-indicator fluo4 responded to progesterone stimulation with a biphasic increase in fluorescence (transient followed by plateau) which resembled that seen in progesterone-stimulated donor samples. The mean normalized response (progesterone-induced increase in fluorescence normalized to resting level) was significantly smaller in IVF-FF and ICSI patient groups than in donors. All samples were further analysed by plotting, for each cell, the relationship between resting fluorescence intensity and the progesterone-induced fluorescence increment. In donor samples these plots overlaid closely and had a gradient of ≈ 2 and plots for most IVF(+ve) samples closely resembled the donor distribution. However, in a subset (≈ 10%) of IVF(+ve) samples, 3/8 IVF-FF samples and one-third of ICSI samples the gradient of the plot was significantly lower, indicating that the response to progesterone of the cells in these samples was abnormally small. Examination of the relationship between gradient (regression coefficient of the plot) in IVF samples and fertilization rate showed a positive correlation. In IVF-FF and ICSI groups, the proportion of cells in which a response to progesterone could be detected was significantly lower than in donors and IVF (+ve) patients. Approximately 20% of cells in donor, IVF(+ve) and ICSI samples generated [Ca2+]i oscillations when challenged with progesterone but in IVF-FF samples only ≈ 10% of cells generated oscillations and there was a significantly greater proportion of samples where no oscillations were observed. Levels of hyperactivated motility were lower in IVF(+ve) and IVF-FF groups compared to controls, IVF-FF also having lower levels than IVF(+ve). This is an in vitro study and caution must be taken when extrapolating these results in vivo. This study reveals important details of impaired [Ca2+]i signalling in sperm from sub-fertile men that cannot be detected in population studies. This study was funded by a MRC project grant (MR/M012492/1; MR/K013343/1). Additional funding was provided by Chief Scientist Office/NHS research Scotland.


Angiographic disease progression in medically treated adult patients with ischemic moyamoya disease without cerebral misery perfusion: supplementary analysis of a 5-year prospective cohort.
Angiographic disease progression reportedly develops in adult moyamoya disease (MMD). However, more than half of patients analyzed underwent revascularization surgery. The present supplementary analysis of a 5-year prospective cohort with follow-up using magnetic resonance angiography (MRA) and cerebral blood flow (CBF) measurements was to elucidate the incidence and clinical features of angiographic disease progression in adult patients receiving medical management alone for ischemic MMD. Sixty-eight patients without misery perfusion in the symptomatic cerebral hemispheres underwent MRA and CBF measurement using brain perfusion single-photon emission computed tomography at inclusion and at the end of the 5-year follow-up. When neurological symptoms recurred or newly developed during the 5-year follow-up period, additional MRA and CBF measurements were also performed at that time. All four patients with further ischemic events during the 5-year follow-up period exhibited angiographic disease progression on MRA at such events. Of the remaining 64 patients without further events during the 5-year follow-up period, four exhibited angiographic disease progression on MRA at the end of the 5-year follow-up. CBF was significantly lower at the time of further ischemic events or at the end of the 5-year follow-up than at inclusion in eight patients with angiographic disease progression (p = 0.0117). The incidence of angiographic disease progression was 12% for 5 years in medically treated adult patients with ischemic MMD without cerebral misery perfusion. Patients with further ischemic events always exhibited angiographic disease progression. Cerebral perfusion was reduced in patients with angiographic disease progression even when further ischemic events did not occur.


Real-world characteristics and outcomes of advanced non-small-cell lung cancer patients with EGFR exon 19 deletions or exon 21 mutations.
Aim: To estimate real-world (rw) outcomes for first-line therapy in patients with advanced EGF receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), focusing on specific mutation types. Patients & methods: Retrospective observational study (n = 244 patients). Results: Univariate/multivariate analyses showed longer rw progression-free survival (rwPFS) and rwPFS2 in patients with ex19del versus Leu858Arg mutations. Median overall survival was 12.3 months longer with ex19del versus Leu858Arg mutations (HR: 1.47 [95% CI: 0.96-2.25]; p = 0.074). With EGFR-tyrosine kinase inhibitor monotherapy, unadjusted rwPFS for ex19del mutations was longer than for Leu858Arg mutations (HR: 1.62 [95% CI: 1.03-2.56]; p = 0.036). Conclusion: In this rw cohort of patients with advanced EGFR+ NSCLC, ex19del mutations conferred a prognostic advantage over Leu858Arg mutations, with significantly better rwPFS and rwPFS2.


Photon counting, censor corrections, and lifetime imaging for improved detection in two-photon microscopy.
We present a high-speed photon counter for use with two-photon microscopy. Counting pulses of photocurrent, as opposed to analog integration, maximizes the signal-to-noise ratio so long as the uncertainty in the count does not exceed the gain-noise of the photodetector. Our system extends this improvement through an estimate of the count that corrects for the censored period after detection of an emission event. The same system can be rapidly reconfigured in software for fluorescence lifetime imaging, which we illustrate by distinguishing between two spectrally similar fluorophores in an in vivo model of microstroke.


Screening pulmonary angiogram and the effect on anticoagulation strategies in severe respiratory failure patients on venovenous extracorporeal membrane oxygenation.
Venovenous extracorporeal membrane oxygenation in the treatment of severe respiratory failure in adults continues to increase with survival improving; however, it remains associated with serious complications. The aim of this study was to evaluate the prevalence of pulmonary embolism (PE) in patients with severe respiratory failure requiring venovenous extracorporeal membrane oxygenation (VV ECMO) and in those managed with conventional mechanical ventilation. A single-center, observational cohort, retrospective study was undertaken of patients with severe respiratory failure managed with conventional ventilation or requiring ECMO in a tertiary referral university teaching hospital. We identified 343 patients with severe respiratory failure between January 2014 and December 2017. VV ECMO was used to support 290 patients and 53 were managed by conventional mechanical ventilation. The prevalence of PE was 9.6% (33/343), of which those supported with VV ECMO was 10% (29/290) and conventional ventilation 7.5% (4/53). There was no difference in survival rates between cohorts with PE versus no PE (ECMO survival to discharge P = .56; conventional ventilation survival to discharge P = .21). The prevalence of pulmonary embolism in severe respiratory failure has important clinical implications for both short and long-term anticoagulation strategies. Routine screening pulmonary angiogram is warranted in this cohort.


Nutritional responses to acute training sessions in young elite rugby players.
Acute exercise has been shown to induce nutritional adaptations in obese and lean inactive youth but it remains unclear whether youth with a high level of physical activity experience such exercise-induced energy intake and appetite modifications. 14 (15- to 16-year-old) male elite rugby players completed sessions on three separate occasions: (1) a control session (CON); (2) an exercise session (EX) and; (3) a rugby session (RUGBY). The energy induced by the rugby and exercise sessions was matched (Polar Team2 pro technology), and participants' energy intake, food preferences (ad libitum buffet meals) and appetite feelings (Visual Analogue Scales) were assessed throughout the experimental days. The energy intake during lunch and snack time was not different between conditions. Dinner time energy intake was significantly increased after RUBGY compared to CON with respectively 969 ± 145 kcal and 777 ± 183 kcal (p < 0.05). The energy intake at dinner time was significantly increased during EX (1185 ± 199 kcal) compared to both CON (p < 0.001) and RUGBY (p < 0.01). None of the appetite feelings investigated were modified between sessions. Adolescent elite rugby players regulate their energy intake differently depending on the nature of their training; independently of the energy expended. This demonstrates the need for energetic and nutritional education to optimize their physical fitness and performance.


Endovascular stent placement for venous complications following pediatric liver transplantation: outcomes and indications.
Advances in interventional radiology (IVR) treatment have notably improved the prognosis of hepatic vein (HV) and portal vein (PV) complications following pediatric living donor liver transplantation (LDLT); however, graft failure may develop in refractory cases. Although endovascular stent placement is considered for recurrent stenosis, its indications are controversial. We enrolled 282 patients who underwent pediatric LDLT in our department from May 2001 to September 2016. 22 (7.8%) HV complications occurred after LDLT. Recurrence was observed in 45.5% of the patients after the initial treatment, and 2 patients (9.1%) underwent endovascular stent placement. The stents were inserted at 8 months and 3.8 years following LDLT, respectively. After stent placement, both patients developed thrombotic obstruction and are currently being considered for re-transplantation. 40 (14.2%) PV complications occurred after LDLT. Recurrence occurred in 27.5% of the patients after the initial treatment, and 4 patients (10.0%) underwent endovascular stent treatment. The stents of all the patients remained patent, with an average patency duration of 41 months. Endovascular stent placement is an effective treatment for intractable PV complications following pediatric LDLT. However, endovascular stent placement for HV complications should be carefully performed because of the risk of intrastent thrombotic occlusion and the possibility of immunological venous injury.


Short Report: The influence of congregate setting on positive COVID-19 tests among a high-risk sample of adults with intellectual and developmental disability in Ontario.
For a number of reasons, persons with intellectual and developmental disability (IDD) are at increased risk of contracting COVID-19. This study explored the influence of congregate setting on testing positive for COVID-19 among adults with IDD in Ontario. 833 home care recipients with IDD were included, 204 were tested at least once for COVID-19. These data were linked to the homecare assessment data. The association between living in a congregate setting and receiving a positive COVID-19 test was explored using a logistic regression model among the total sample and those tested for COVID-19. 77 individuals tested positive for COVID-19 (9.24 %). Congregate setting, age, aggression, and mobility were significantly associated with receiving a positive COVID-19 test in the total sample. Among the subgroup, congregate setting and age were significant. Adults with IDD have an increased risk for positive COVID-19 tests at younger ages than other high-risk populations, such as elderly persons. These findings confirm the vulnerability of adults with IDD living in group settings to COVID-19. As such, they should be prioritized when COVID-19 prevention and public health strategies, including vaccination and boosters, are introduced.


Lack of a difference in increased capillary blood cell velocity in the skin over proximal interphalangeal joints between rheumatoid arthritis and osteoarthritis.
Early detection of synovitis in rheumatoid arthritis (RA) and distinction from osteoarthritis (OA) are important to establish the most appropriate treatment. Increased perfusion over affected joints observed by laser Doppler perfusion imaging was supposed to arise from the underlying joint, because it was detected only by a near-infrared laser and not by a less penetrating red laser source. Using laser Doppler anemometry, this study addressed two questions: (1) whether capillary blood cell velocity (CBV) is increased in the skin over finger joints affected by RA or OA; (2) whether there is a difference between RA and OA in CBV above affected proximal interphalangeal (PIP) joints. Levels of soluble adhesion molecules were measured, because they indicate rheumatoid vasculitis raising flow resistance. Thirty-one patients with RA and 20 with OA were investigated. Compared to 18 controls, CBV (mean+/-SEM) was elevated above PIP joints clinically affected by RA (0.35+/-0.06 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and over PIP (0.27+/-0.02 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and distal interphalangeal joints (0.27+/-0.02 mm/s vs. 0.17+/-0.01 mm/s; P<0.001) affected by OA. Levels of soluble adhesion molecules were not correlated with CBV over PIP joints in RA. These observations demonstrated that elevated blood cell velocity is detectable by laser Doppler anemometry in skin capillaries over interphalangeal joints affected by RA or OA and contradict the previous assumption that there is hyperemia only in the affected joint. The lack of a significant difference in CBV over PIP joints between RA and OA patients might be due to some inflammation also occurring in OA rather than to vasculitic processes in RA associated with elevated levels of soluble adhesion molecules.


Reducing the impact on renal function of kidney SABR through management of respiratory motion.
Stereotactic ablative body radiotherapy (SABR) is as a viable treatment option to treat kidney cancer. This study quantifies dose reduction to non-tumour ipsilateral kidney and estimated renal function gain from elimination of respiratory motion. We reviewed 62 previously treated kidney SABR patients. The gross tumour volume (GTV) was segmented in each phase of a four-dimensional CT (4DCT). Tumour motion amplitude (TMA) was obtained from the GTV centroid on each phase. Low modulation, motion managed (MM) plans were generated on the exhale phase image. Internal target volume (ITV)-based plans were generated on the 4DCT average intensity projection. To estimate delivered kidney dose, the ITV-based plan was copied ten times to the exhale phase image, with isocentre located at the GTV centroid position in each phase. The dose was calculated and averaged to result in non-motion managed plans. Difference in ipsilateral kidney volume receiving 50% of the prescription dose (V50%) and estimated glomerular filtration rate (GFR) change were compared between ITV and MM plans. The mean ± st.dev. TMA was 0.79 ± 0.49 cm. Removing respiratory motion reduced ipsilateral kidney V50% (slope of the difference = 12 cc/cm of TMA, Pearson-r = 0.69, p-value <10-9), and estimated GFR was improved (slope = 4.4 %/cm of TMA, Pearson-r = 0.85, p-value < 10-10). We have quantified the improvement in healthy kidney dose when removing respiratory motion from kidney SABR plans, and demonstrated an expected gain in GFR of 4.4 %/cm of motion removed.


Lactobacillus buchneri strain NRRL B-30929 converts a concentrated mixture of xylose and glucose into ethanol and other products.
Lactobacillus buchneri strain NRRL B-30929 was isolated from a fuel ethanol production facility. This heterofermentative, facultative anaerobe can utilize xylose as a sole carbon source and tolerates up to 12% ethanol. Carbohydrate utilization (API, Biomerieux) and Phenotype Microarrays (PM, Biolog) analyses indicated that the strain is able to metabolize a broad spectrum of carbon sources including various monosaccharides (C5 and C6), disaccharides and oligosaccharides, with better rates under anaerobic conditions. In pH-controlled bioreactors, the bacterium consumed xylose and glucose simultaneously at high concentrations (125 g L(-1), pH 6.0). The major fermentation products were lactate (52 g L(-1)), acetate (26 g L(-1)) and ethanol (12 g L(-1)). The strain ferments glucose alone (pH 4.0) into lactate and ethanol with a molar ratio of 1.03:1. This strain will be further explored via genetic engineering for potential applications in biomass conversion.


Interaction during online classes fosters engagement with learning and self-directed study both in the first and second years of the COVID-19 pandemic.
Maintaining students' learning engagement was a challenge in emergency online education during the pandemic. In this study, we investigated the predictors (social interaction) and outcomes (self-directed study) of engagement in online learning during the first and second years of the COVID-19 pandemic. First-year Japanese university students (N = 1167) enrolled in online classes during 2020 and 2021 responded to a questionnaire measuring perceived opportunities for social interaction during online classes, engagement with online learning, and extracurricular self-directed study time. Multi-group path analysis revealed that social interaction during online classes exhibited a positive indirect effect on self-directed study time through emotional and behavioral engagement with online learning. The positive indirect effect was significant in both the first and second years of the pandemic. The results suggest that increasing the number of opportunities for social interaction during online classes may exhibit spillover effects on learning outside the online classroom.


Comparative study of placental T2* and intravoxel incoherent motion in the prediction of fetal growth restriction.
Both transverse relaxation time (T2*) and intravoxel incoherent motion (IVIM) on magnetic resonance imaging (MRI) are promising for discriminating fetal growth restriction (FGR). We aimed to compare the utility of these two parameters and their combination in the same cohort. Twenty-seven FGR and 24 control pregnancies after 28 weeks of gestation in which both T2* and IVIM scans were performed on a 3.0 T MRI were recruited. We compared the T2* Z-score, perfusion fraction (f), diffusion coefficient (D) and pseudodiffusion coefficient (D*) between groups. Binary logistic regression analysis and areas under the curve (AUCs) with receiver operating characteristic (ROC) curve were used to evaluate the diagnostic efficacy of these parameters and their combination. Compared with normal pregnancies, T2* Z-score (0.036 ± 0.95 vs. -2.479 ± 1.56, p < 0.001), f (0.2753 ± 0.035 vs. 0.3304 ± 0.035, p < 0.001), D* (48279.82 ± 7497.36 μm2/s vs. 56167.92 ± 8549.87 μm2/s, p = 0.001) and D (1664.32 ± 288.53 μm2/s vs. 1887.15 ± 204.08 μm2/s, p = 0.002) were significantly decreased in FGR pregnancies. However, only AUC(T2* Z-score) (0.903) and AUC(f) (0.873) were good predictors of FGR. The AUC(T2* Z-score-IVIM) (0.937), calculated with the combination of T2* Z-score and f, was similar to AUC(T2* Z-score) and ACU(f). Both T2* and f were effective in discriminating FGR. However, the combination of the two parameters did not further improve diagnostic efficacy. We suggest that T2* might be more suitable for evaluating placental dysfunction, as it is fast to obtain and easy to measure.


Quantification of cell infection caused by Listeria monocytogenes invasion.
Listeria monocytogenes causes a life-threatening food-borne disease known as Listeriosis. Elderly,immunocompromised, and pregnant women are primarily the victims of this facultative intracellular Gram-positive pathogen. Since the bacteria survive intracellularly within the human host cells they are protected against the immune system and poorly accessed by many antibiotics. In order to screen pharmaceutical substances for their ability to interfere with the infection, persistence and release of L. monocytogenes a high content as say is required. We established a high content screen (HCS) using the RAW 264.7 mouse macrophage cell line seeded into 96-well glass bottom microplates. Cells were infected with GFP-expressing L. monocytogenes and stained thereafter with Hoechst 33342.Automated image acquisition was carried out by the Scan(R) screening station. We have developed an algorithm that automatically grades cells in microscopy images of fluorescent-tagged Listeria for the severity of infection. The grading accuracy of this newly developed algorithm is 97.1% as compared to a 74.3%grading accuracy we obtained using the commercial Olympus Scan(R) software.


Validation of a high-sensitivity assay for zatebradine in dried blood spots of human blood at pg/ml concentrations using HILIC-MS/MS.
One of the main reasons for the increased popularity of dried blood spots (DBS) is related to the 3Rs principles (replacement, refinement and reduction) for animal use in drug development. The small blood volume collected using this technique may have a significant impact on the assay sensitivity. An approach that made use of hydrophilic interaction chromatography (HILIC) to enhance the LC-MS assay sensitivity was explored and optimized for a tool compound. A very high-sensitivity assay in dried spots of human blood was validated in the range of 5 to 5000 pg/ml. The use of HILIC increased LC-MS sensitivity up to fivefold compared with other reversed phase chromatographic methods. The good compatibility of the DBS extracts with HILIC and the results of the assay validation for zatebradine at a very low LLOQ demonstrate the high potential and the high performance of this approach.


Xenocorneal transplantation.
Donor shortage in corneal transplantation is a significant problem in Asian countries and is an emerging issue worldwide. This review will discuss current knowledge of the pathogenesis of the rejection mechanism, recent advances in xenocorneal transplantation, and feasibility of porcine xenocorneal graft. α-Gal epitopes which are expressed on the porcine cornea, however less than in other vascularized organs. A small animal model provided evidence of complement-mediated or antibody-mediated rejection in porcine xenocorneal transplantation. Recent progress in genetic engineering of the pig or biomedical engineering for removal of the α-Gal epitope appears to have resulted in reduction of antibody-mediated rejection. Porcine corneal xenograft is not rejected hyperacutely in all animal models. T cells predominantly mediate xenocorneal rejection through various animal models. Survival of lamellar fresh porcine grafts is longer than that of full-thickness fresh porcine grafts. Decellularized porcine grafts also demonstrate significantly longer survival than fresh grafts do. Recent studies have documented the potential of the porcine corneal graft as a substitute for use in human allograft and have highlighted the mechanisms of rejection of xenocorneal transplantation. Antibody-mediated or complement-mediated xenogeneic rejection should be further explored in a large animal model.


Does freeze-substitution reveal the hydrophobic nature of interprotofilament bonding in microtubules?
The massive system of microtubules in the ovarioles of Notonecta glauca has been prepared for electron microscopy by means of freeze-substitution. With this technique the protofilaments comprising the microtubule walls can be observed in positive image, indicating that the procedure provides a valuable method for observing microtubule substructure. Surprisingly though, the cryoprotectants, which are an integral part of the method, caused a rearrangement of the microtubules from their usual pattern in the ovarioles. These observations, we believe, provide an insight into intra- and intermicrotubule interactions respectively.


Efficiency of work production by spastic muscles.
The present study compared the muscular efficiency in spastic and healthy lower limbs producing the same mechanical work. Sixteen chronic post-stroke hemiparetic and spastic patients and 14 age-matched healthy subjects were submitted to a submaximal stepwise exercise testing on a bicycle ergometer, pedalling with only one lower limb. Net energetic expenditure was computed from oxygen consumption above resting values. Electrical activity of antagonistic muscles in the thigh and in the shank was recorded and co-contraction was defined as the percentage of the pedalling cycle when antagonistic muscles were activated simultaneously. The efficiency was calculated as the ratio between the mechanical work done on the ergometer and the net energetic expenditure. Spasticity was quantitatively evaluated by measuring passive ankle plantar flexor muscle stiffness. The working capacity of the patients' paretic lower limb was very low (<40W). The energy expenditure increased linearly as a function of work intensity, without statistical difference between the patients paretic lower limb (PPL), the patients healthy lower limb (PHL) and the healthy subjects lower limb (HSL). Shank co-contraction was 2.9 times greater in PPL (p<0.05) and 2.3 times greater in PHL (p<0.05) than in HSL. Thigh co-contraction was also 1.8 times greater in PPL than in HSL (p<0.05). The ankle plantar flexor muscle stiffness was statistically greater in PPL than in PHL and HSL (p<0.05). The efficiency was not statistically different between the three groups (p=0.155). In conclusion, the efficiency of work production by paretic and spastic lower limb muscles was normal ( congruent with 20%) despite significant neurological impairments.


Emergency video-assisted thoracoscopic foreign body removal and decortication of lung after chest trauma.
Video-assisted thoracoscopy can be a useful tool in selected chest trauma patients for diagnostic and therapeutic purposes. A metallic foreign body, embedded in peripheral lung parenchyma, was removed successfully with blood clot evacuation and limited decortication of lung in a hemodynamically stable 10-year-old patient using a video-assisted thoracoscopic technique.


Impact on patients triage distribution utilizing the Australasian Triage Scale compared with its predecessor the National Triage Scale.
To assess the impact of the change from the National Triage Scale (NTS) to the Australasian Triage Scale (ATS) within a hospital ED. A retrospective audit of consecutive adult patients attending the ED of Auckland Hospital from July to September 2001, during which patients were triaged according to the NTS, were compared with patients triaged according to the ATS during July to September 2002. In total, 8715 patients attended the department during July to September 2001 compared with 9047 patients during July to September 2002. There was a significant shift in the triage ratios with patient number increases of 28 and 24% in triage categories two and three, respectively, and decreases of 15 and 67% in categories four and five, respectively. The revision of the ATS has had a significant impact on the triage distribution of patients who present to ED. The change of distribution might have implications for meeting performance criteria and assessing casemix.


Nix Pro Color Sensor provides comparable color measurements to HunterLab colorimeter for fresh beef.
The HunterLab MiniScan (HunterLab) colorimeter is used in meat quality research worldwide for measuring meat color; however, the Nix Pro Color Sensor (Nix) could be a less expensive alternative that is easier to operate. Therefore, the objective of this study was to compare the two colorimeters to objectively evaluate fresh beef color. Longissimus thoracis muscle from one side of A maturity beef carcasses (n = 200) was evaluated using both the HunterLab (3 technical replicate scans) and Nix (3, 5, 7, and 9 technical replicate scans) colorimeters. The correlation between the HunterLab and Nix for L* (lightness), a* (redness), and b* (yellowness) values ranged between r = 0.80 to 0.85 and the Bland Altman Limits of Agreement analysis indicated good agreement between the Nix and HunterLab colorimeters for all the color parameters. These results indicated that the Nix colorimeter could be a viable alternative for HunterLab colorimeters.


Bioreactance and fourth-generation pulse contour methods in monitoring cardiac index during off-pump coronary artery bypass surgery.
The pulmonary artery catheter (PAC) is considered the gold standard for cardiac index monitoring. Recently new and less invasive methods to assess cardiac performance have been developed. The aim of our study was to assess the reliability of a non-invasive monitor utilizing bioreactance (Starling SV) and a non-calibrated mini-invasive pulse contour device (FloTrac/EV1000, fourth-generation software) compared to bolus thermodilution technique with PAC (TDCO) during off-pump coronary artery bypass surgery (OPCAB). In this prospective study, 579 simultaneous intra- and postoperative cardiac index measurements obtained with Starling SV, FloTrac/EV1000 and TDCO were compared in 20 patients undergoing OPCAB. The agreement of data was investigated by Bland-Altman plots, while trending ability was assessed by four-quadrant plots with error grids. In comparison with TDCO, Starling SV was associated with a bias of 0.13 L min-1 m-2 (95% confidence interval, 95% CI, 0.07 to 0.18), wide limits of agreement (LOA, - 1.23 to 1.51 L min-1 m-2), a percentage error (PE) of 60.7%, and poor trending ability. In comparison with TDCO, FloTrac was associated with a bias of 0.01 L min-1 m-2 (95% CI - 0.05 to 0.06), wide LOA (- 1.27 to 1.29 L min-1 m-2), a PE of 56.8% and poor trending ability. Both Starling SV and fourth-generation FloTrac showed acceptable mean bias but imprecision due to wide LOA and high PE, and poor trending ability. These findings indicate limited reliability in monitoring cardiac index in patients undergoing OPCAB.


Trafficking and chromatin dynamics of holocarboxylase synthetase during development of Drosophila melanogaster.
This work examines the cellular localization of holocarboxylase synthetase (HCS) and its association to chromatin during different stages of development of Drosophila melanogaster. While HCS is well known for its role in the attachment of biotin to biotin-dependent carboxylase, it also regulates the transcription of HCS and carboxylases genes by triggering a cGMP-dependent signal transduction cascade. Further, its presence in the nucleus of cells suggests additional regulatory roles, but the mechanism involved has remained elusive. In this study, we show in D. melanogaster that HCS migrates to the nucleus at the gastrulation stage. In polytene chromosomes, it is associated to heterochromatin bands where it co-localizes with histone 3 trimethylated at lysine 9 (H3K9met3) but not with the euchromatin mark histone 3 acetylated at lysine 9 (H3K9ac). Further, we demonstrate the association of HCS with the hsp70 promoter by immunofluorescence and chromatin immuno-precipitation (ChIP) of associated DNA sequences. We demonstrate the occupancy of HCS to the core promoter region of the transcriptionally inactive hsp70 gene. On heat-shock activation of the hsp70 promoter, HCS is displaced and the promoter region becomes enriched with the TFIIH subunits XPD and XPB and elongating RNA pol II, the latter also demonstrated using ChIP assays. We suggest that HCS may have a role in the repression of gene expression through a mechanism involving its trafficking to the nucleus and interaction with heterochromatic sites coincident with H3K9met3.


Investigation of the roles of dysbindin-1 and SATB2 in the progression of Parkinson's disease.
Parkinson's disease is a neurodegenerative disease that typically results in the loss of dopaminergic neurons, especially in an area of the brain known as the substantia nigra. Here, we investigated the roles of two important neuronal development proteins, dysbindin-1 and SATB2, at different stages of Parkinson's disease. Using various concentrations of a neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we established the mouse models at initial and advanced stages of the Parkinson's disease. The pole and rotarod tests were used to assess behavioral response and motor function, respectively. Histology was used to assess the disease pathology. Immunohistochemistry and Western blotting were used to analyze dysbindin-1 and SATB2 expression levels. Compared with controls, the mice in the initial and advanced stages of Parkinson's disease required 2.3-fold and 3.8-fold longer to reach the floor in the pole test. Similarly, in the rotarod test, mice in the initial (168 ± 3.73 s) and advanced stages (91 ± 5.62 s) of Parkinson's disease were less able to maintain motor stability, compared with control mice (214 ± 4.18 s). The expression levels of dysbindin-1 and SATB2 in substantia nigra tissue from control mice were limited but were substantially increased (2.4-fold and 3.6-fold, respectively) in mice in the initial stage of the Parkinson's disease. However, in the mice in the advanced stage of Parkinson's disease, dysbindin-1 expression was 1.7-fold lower, and the SATB2 expression was 1.8-fold higher, than that in the control mice. The increased expression levels of dysbindin-1 and SATB2 in the initial stage of Parkinson's disease may be due to their protective roles. However, the reduced expression levels in the advanced stage of Parkinson's disease may contribute to irreversible neuronal degeneration.


The applicability of the time/temperature superposition principle to brain tissue.
This paper deals with the mechanical characterization of brain tissue which behaves as a viscoelastic material. We focus on the linear viscoelastic behavior, which should apply for small strains at any strain rate, and demonstrate the applicability of the time/temperature superposition principle. This principle allows the opportunity to extend the range of shear rates for which the material is characterized, and makes the results applicable to impact conditions. This characterization of the linear behavior forms the basis for a further nonlinear characterization of the tissue.


The effects of low-dose 2-hydroxyethyl methacrylate on apoptosis and survival in human dental pulp cells.
2-hydroxyethyl methacrylate (HEMA) is one of the most major components in dentin bonding systems. Uncured HEMA is eluted through the dentin and harmful to pulp cells. The study aimed to investigate the death pattern, morphological change and factors of human dental pulp cells (HDPCs) cultured with low-dose HEMA. HDPCs were cultured with low-dose concentration of HEMA at 0 mM (control), 0.125 mM, 0.25 mM, 1 mM, 2 mM and 4 mM on Day 3 and 5. The cell morphology was observed with F-actin immunocytochemical staining. The flow cytometry was used to analyze the death pattern. NF-κB and Trx-1 were measured using ELISA kits. The major death pattern was early apoptosis and late apoptosis. The morphological characteristics of apoptosis were observed clearly at 4 mM on Day 3 and Day 5. The phosphorylated NF-κB normalized to total NF-κB protein was significantly higher at 2 mM and 4 mM on Day 5. There was no difference of Trx-1 on Day 3, but significantly higher at 0.25 mM and 1 mM on Day 5. The trend line of phosphorylated NF-κB and Trx-1 showed highly positive correlations with HEMA concentration. The significant cellular morphology characteristics of apoptosis can be observed at higher dose and longer period after exposed to uncured HEMA. The expression of NF-κB was following the ratio of late apoptosis at longer exposure period. Clinically, the remaining dentin thickness should be enough to decrease HEMA concentration and thus to protect pulp cells free from harm.


Complications of laparoscopic renal surgery.
Initial excitement for laparoscopy's potential to decrease patient morbidity and convalescence by avoiding a flank incision was initially tempered by concerns for increased operative time, technical complexity and the suitability of laparoscopy approaches to oncologic surgery. With experience, the benefits of laparoscopic approaches to renal surgery have become clear. As laparoscopic techniques are mastered and the indications expanded, it is important to remember that minimally invasive surgery remains associated with significant risks and potential complications. Several complications are theoretically more difficult to control laparoscopically than with open exposure. Control of bleeding, identification of injury to solid organs, and positive margins due to the lack of haptic feedback have been of special concern during the rapid advancement of laparoscopic surgical technique between 1991 and today. It is critical for the urologist to be familiar with these complications in order to maximize patients' clinical outcomes through appropriate patient selection and intraoperative planning. Know-ledge of the complications of laparoscopic renal surgery will also aid in providing patients with true informed consent and realistic surgical expectations. The purpose of this manuscript is to review the complications associated with laparoscopic renal surgery in general, with specific attention paid to laparoscopic radical, partial, pediatric, and donor nephrectomy.


Lack of predictive factors in late recurrence of stage I melanoma.
Through the UCLA tumor registry, patients treated for late-relapse malignant melanoma (after a 10-year disease-free interval) were identified and studied retrospectively. The patients were studied in regards to age, sex, primary site of the lesion, the disease-free interval, elective lymph node dissection, mode of recurrence and survival time following relapse. The histologic characteristics studied included the maximal tumor thickness, Clark's levels, rate of mitoses, and presence of ulceration. Based on the 0.84% incidence of late-relapse, the recommendation for annual life-time follow-up examinations for all patients with malignant melanoma is supported.


Determination of a reference range for fructosamine in feline serum samples.
Fructosamine, the product of a non-enzymatic reaction between glucose and serum proteins, is a component of serum which reflects long-term deviations from normal glucose and protein homeostasis. Thirty-one healthy, intact, domestic short-haired cats, living under uniform feeding and environmental conditions, were sampled to calculate a reference range for feline serum fructosamine. The results were obtained using a nitroblue tetrazolium colorimetric method. The analytical assay was evaluated by calculation of within-run and between-day variation, detection limit, and accuracy. Serum fructosamine concentrations were approximately normally distributed and the calculated reference range was 146-271 mumol/L (mean 209 mumol/L, standard deviation 31.6 mumol/L). There were no significant differences between male and female cats, or between cats older and younger than 12 months. Previously conducted studies give higher reference ranges, possibly because of differences in the test procedure and homogeneity of the test population.


An update on management of pediatric epistaxis.
To evaluate the work-up and treatment of pediatric epistaxis in an outpatient clinical setting, with a focus on the diagnostic utility and associated costs of nasal endoscopy and adjunctive laboratory data. Retrospective, case series. Children under 18 years of age seen in an outpatient clinical setting at a tertiary care hospital between 2004 and 2012 for the primary diagnosis of epistaxis were identified. Patient characteristics were analyzed from a statistical and cost perspective. A total of 175 patients with epistaxis were included. One hundred twenty-two (69.7%) were male, with a mean overall age of 9.1 years (range 5 months to 17.9 years). The duration of bleeding ranged from 0.25 to 84 months (mean 11.5 months). Nasal endoscopy was performed in 123 (70.2%) patients. Three (2.4%) had nasal polyps, and 1 (0.8%) a juvenile nasopharyngeal angiofibroma. The average age of patients with nasal masses was significantly older (16.2 years versus 10.4 years, p=0.008). Of 131 patients with available blood work, laboratory values demonstrated anemia in 27 (20.6%) patients, elevated partial thromboplastin time in 5 (3.8%), and an abnormal platelet function analysis in 1 (0.8%) patient. Those with anemia were statistically younger (p=0.001), than those with either normal labs or abnormal coagulation studies. Epistaxis resolved in 88/135 (65.2%) who had follow-up visits. The majority of pediatric epistaxis cases resolved with nasal mucosa hydration. Nasal endoscopy can be reserved for teenaged patients with epistaxis, and routine laboratory screening may be useful in select cases based on the clinical judgment.


Brachial plexus cord compression by the tendon of a pedicled latissimus dorsi flap.
A case is reported of brachial plexus cord compression resulting from an island pedicle latissimus dorsi musculocutaneous flap used to resurface a facial defect.


Tuning the response of fluid filled hydrogel core-shell structures.
Hydrogels are hydrophilic polymer networks that swell upon submersion in water. Thanks to their bio-compatibility, compliance, and ability to undergo large deformations, hydrogels can be used in a wide variety of applications such as in situ sensors for measuring cell-generated forces and drug delivery vehicles. In this work we investigate the equilibrium mechanical responses that can be achieved with hydrogel-based shells filled with a liquid core. Two types of gel shell geometries are considered - a cylinder and a spherical shell. Each shell is filled with either water or oil and subjected to compressive loading. We illustrate the influence of the shell geometry and the core composition on the mechanical response of the structure. We find that all core-shell structures stiffen under increasing compressive loading due to the load-induced expulsion of water molecules from the hydrogel shell. Furthermore, we show that cylindrical core-shell configurations are stiffer then their spherical equivalents. Interestingly, we demonstrate that the compression of a core-shell structure with an aqueous core leads to the transportation of water molecules from the core into the hydrogel. These results will guide the design of novel core-shell structures with tunable properties and mechanical responses.


Is outpatient cholecystectomy safe for the higher-risk elective patient?
This study was done to determine the safety of outpatient cholecystectomy for the higher-risk patient. All patients over age 70 or with American Society of Anesthesiologists physical status classification of 3 or greater, from all 515 consecutive patients booked for elective cholecystectomy between April 1, 1994, and March 31, 1996, were reviewed. Of 85 higher-risk patients, 77 were booked as outpatients. Sixty-one were successfully completed as outpatients, with no complications or readmissions related to their outpatient status. Of 24 admitted patients, 15 had specific indications for hospitalization. Nine were admitted for reasons of "precaution." One of these developed a complication, possibly related to her inpatient status. The other eight could have been managed as outpatients. Outpatient cholecystectomy is safe for the higher-risk patient. Patients who recover uneventfully from surgery can be discharged without harmful effects. "Precautionary" hospitalization may be harmful.


Regulation of protein kinases in exocrine secretory cells during agonist-induced exocytosis.
Stimulation of exocytosis in exocrine glands is associated with an increased phosphorylation of several particulate proteins. Irrespective of the type of secretagogue (cAMP-dependent agonists, calcium-dependent agonists, calcium ionophores, phorbol esters) exocytosis is always accompanied by an enhanced phosphorylation of the ribosomal protein S6. It is shown by an analysis of the phosphopeptide pattern of the in vivo and the in vitro phosphorylated S6 protein that the protein kinase responsible for phosphorylation of the S6 protein during enhanced exocytosis is protein kinase C. This is so irrespective of whether the agonist uses cAMP or calcium as second messenger. Experiments with isolated guinea pig parotid gland lobules reveal that not only the acetylcholine analog carbamoylcholine, but also the beta-agonist isoproterenol lead within seconds to an increased formation of diacylglycerol. As diacylglycerol increases the affinity of protein kinase C for calcium this finding would explain why the phosphorylation pattern of the S6 protein reflects activation of protein kinase C also under conditions where (as in the case of stimulation with beta-agonists) cAMP is the primary second messenger. It would further explain why the changes of the phosphorylation of individual histones observed during agonist-induced exocytosis in the parotid gland are quite similar for isoproterenol on one hand and carbamoylcholine on the other. A 22 K protein which becomes phosphorylated only when cAMP serves as second messenger is located in the membrane of the endoplasmic reticulum. A possible relationship of this protein with the calcium transport ATPase of the endoplasmic reticulum is under investigation.


Risk factors associated with longer stays in cardiovascular surgical intensive care unit after CABG.
Monitoring ICU length of stay (LOS) after CABG and examining its risk factors can guide initiatives on the improvement of care. But few have evaluated this issue to include personal and clinical factors, and demands of ICU care. This study applied Donabedian model to identify risk factors for longer ICU stays after CABG. Lifestyle, clinical factors during and after CABG, TISS were viewed as structure factors, and infection and organ failures during ICU did as process factors. This retrospective cohort study used data via medical records at a medical center. A stratified randomized sample of 230 adults from a cohort of 690 isolated CABGs was to reflect the rate of 34.7% longer than 3-day-ICU LOS. The sample comprised of longer-stay group (n = 150) and shorter-stay group (n = 80). Hierarchical logistic regression analysis revealed that potential signs of infection (3-day average WBC higher than 10,000/μL, OR: 3.41 and the body temperature higher than 38 °C, OR:5.67) and acute renal failure (OR: 8.97) remained as the most significant predicted factors of stay longer than 3 ICU days. Along with higher TISS score within 24 hours (OR:1.06), structure factors of female gender (OR:4.16) smoking(OR: 4.87), higher CCI before surgery(OR:1.49), bypass during CABG (OR:3.51) had higher odds of risk to stay longer. Further quality improvement initiatives to shorten ICU stay after CABG may include the promotion of a smoking cessation program in clinical practice, and better management of the manpower allocation, infection control and renal failure.


Chemical warfare agents.
Chemical warfare agents (CWA's) are defined as any chemical substance whose toxic properties are utilised to kill, injure or incapacitate an enemy in warfare and associated military operations. Chemical agents have been used in war since times immemorial, but their use reached a peak during World War I. During World War II only the Germans used them in the infamous gas chambers. Since then these have been intermittently used both in war and acts of terrorisms. Many countries have stockpiles of these agents. There has been a legislative effort worldwide to ban the use of CWA's under the chemical weapons convention which came into force in 1997. However the manufacture of these agents cannot be completely prohibited as some of them have potential industrial uses. Moreover despite the remedial measures taken so far and worldwide condemnation, the ease of manufacturing these agents and effectiveness during combat or small scale terrorist operations still make them a powerful weapon to reckon with. These agents are classified according to mechanism of toxicity in humans into blister agents, nerve agents, asphyxiants, choking agents and incapacitating/behavior altering agents. Some of these agents can be as devastating as a nuclear bomb. In addition to immediate injuries caused by chemical agents, some of them are associated with long term morbidities and psychological problems. In this review we will discuss briefly about the historical background, properties, manufacture techniques and industrial uses, mechanism of toxicity, clinical features of exposure and pharmacological management of casualties caused by chemical agents.


Purification and identification of two carnosine-cleaving enzymes, carnosine dipeptidase I and Xaa-methyl-His dipeptidase, from Japanese eel (Anguilla japonica).
Three enzymes, carnosine dipeptidase I (EC 220.127.116.11, CNDP1), carnosine dipeptidase II (EC 188.8.131.52, CNDP2), and Xaa-methyl-His dipeptidase (or anserinase: EC 126.96.36.199, ANSN), are known to be capable of catalyzing the hydrolysis of carnosine (β-alanyl-l-histidine), in vertebrates. Here we report the purification and identification of two unidentified carnosine-cleaving enzymes from Japanese eel (Anguilla japonica). Two different dipeptidases were successfully purified to homogeneity from the skeletal muscle; one exhibited a broad substrate specificity, while the other a narrow specificity. N-terminal amino-acid sequencing, deglycosylation analysis, and genetic analysis clearly revealed that the former is a homodimer of glycosylated subunits, encoded by ANSN, and the latter is another homodimer of glycosylated subunits, encoded by CNDP1; that is, Xaa-methyl-His dipeptidase, and carnosine dipeptidase I respectively. This is the first report on the identification of carnosine dipeptidase I from a non-mammal. Database search revealed presence of a CNDP1 ortholog only from salmonid fishes, including Atlantic salmon and rainbow trout, but not from other ray-finned fish species, such as zebrafish, fugu, and medaka whose genomes have been completely sequenced. The mRNAs of CNDP1 and ANSN are strongly expressed in the liver of Japanese eel, compared with other tissues, while that of CNDP2 is widely distributed in all tissues tested.


Biological studies of a new class of technetium complexes: the hexakis(alkylisonitrile)technetium(I) cations.
This study describes the preparation and synthesis of a new class of cationic technetium compounds, the hexakis(alkylisonitrile)technetium(+ 1) complexes, at both carrier added and no carrier added concentrations in aqueous media from pertechnetate. Biological distribution and imaging data in animals indicate that certain members of this class may be effective for cardiac imaging in man. The usefulness of these lipophilic water-soluble species for labeling mammalian cells is also reported.


Long-term monitoring of circadian rhythms in c-fos gene expression from suprachiasmatic nucleus cultures.
The AP-1 family of transcription factors has been implicated in the control of the expression of many genes in response to environmental signals. Previous studies have provided temporal profiles for c-fos expression by taking measurements from many animals at several points in time, but these studies provide limited information about dynamic changes in expression. Here, we have devised a method of continuously measuring c-fos expression. A transgenic mouse line expressing the human c-fos promoter linked to the firefly luciferase reporter gene (fos/luc) was generated to continuously monitor c-fos gene expression. A second transgenic mouse line expressing luciferase under the control of the cytomegalovirus promoter (CMV/luc) served as a control. Luminescence originating from identifiable brain regions was imaged from fos/luc brain slice cultures. Expression of the fos/luc transgene accurately reflected transcriptional responses of the endogenous c-fos gene. Dynamic changes in fos/luc expression in suprachiasmatic nuclei (SCN) explant cultures were monitored continuously, and luminescence showed almost 24 hour rhythms lasting up to five circadian cycles. In contrast, bioluminescence monitored from CMV/luc SCN explant cultures was not rhythmic. The fos/luc transgenic mouse will be useful for long-term, non-invasive monitoring of c-fos transcriptional responses to the changing cellular environment. Circadian rhythms in c-fos expression can be monitored non-invasively in real time from the SCN, clearly demonstrating that c-fos transcription is regulated by the circadian clock.


Elevated serum levels of proinflammatory cytokines and biomarkers of matrix remodeling in never-treated patients with familial hypercholesterolemia.
Familial hypercholesterolemia (FH) is a common inherited disorder of lipoprotein metabolism, whose origin involves mutations in the gene coding for the low-density lipoprotein receptor protein. Although FH is monogenic, wide variation occurs in the onset and severity of atherosclerosis in these patients. Since data on levels of inflammatory proteins and/or active factors in FH patients who have never received lipid-lowering treatment are lacking, serum levels of MMP-3, active MMP-9 and TIMP-1 as well as pro-inflammatory cytokines (TNF-alpha, IL-18) were determined in never-treated homozygous FH Moroccan patients (n=4) and compared to those of heterozygous FH subjects (n=7) and of healthy control subjects (n=5). When compared to controls, homozygous FH patients exhibited levels of active MMP-9 and TIMP-1 (p<0.05), and of both high sensitive-CRP and IL-18 which were significantly elevated (p<0.05 and p<0.01, respectively). In heterozygous FH patients, intermediate values between FH homozygotes and healthy controls were observed for these markers, with the exception of MMP-9 activity whose levels were significantly elevated (p<0.05). Multivariate analysis revealed a positive correlation between apolipoprotein B, TIMP-1 and IL-18 levels, and between hs-CRP and IL-18 (p<0.01). Although the sample size of this FH group was limited, our data suggest that nontreated homozygous FH patients, and to a lesser degree heterozygous FH patients, exhibit not only a markedly proinflammatory vascular state but also pronounced extracellular matrix remodeling, as reflected by elevated circulating levels of inflammatory cytokines and MMPs.


Insights from a Pan India Sero-Epidemiological survey (Phenome-India Cohort) for SARS-CoV2.
To understand the spread of SARS-CoV2, in August and September 2020, the Council of Scientific and Industrial Research (India) conducted a serosurvey across its constituent laboratories and centers across India. Of 10,427 volunteers, 1058 (10.14%) tested positive for SARS-CoV2 anti-nucleocapsid (anti-NC) antibodies, 95% of which had surrogate neutralization activity. Three-fourth of these recalled no symptoms. Repeat serology tests at 3 (n = 607) and 6 (n = 175) months showed stable anti-NC antibodies but declining neutralization activity. Local seropositivity was higher in densely populated cities and was inversely correlated with a 30-day change in regional test positivity rates (TPRs). Regional seropositivity above 10% was associated with declining TPR. Personal factors associated with higher odds of seropositivity were high-exposure work (odds ratio, 95% confidence interval, p value: 2.23, 1.92-2.59, <0.0001), use of public transport (1.79, 1.43-2.24, <0.0001), not smoking (1.52, 1.16-1.99, 0.0257), non-vegetarian diet (1.67, 1.41-1.99, <0.0001), and B blood group (1.36, 1.15-1.61, 0.001).


Concise syntheses of N-aryl-5,6,7-trimethoxyindoles as antimitotic and vascular disrupting agents: application of the copper-mediated Ullmann-type arylation.
In an attempt to mimic the 3,4,5-trimethoxyphenyl-Z-stilbene moiety of combretastatin A-4, a series of N-aryl-5,6,7-trimethoxyindoles were synthesized via copper-catalyzed Ullmann-type N-arylation through the corresponding 5,6,7-trimethoxyindole and aryl halides. These synthesized compounds demonstrated potent antiproliferative activity providing a novel skeleton for potent tubulin polymerization inhibitors.


Death of Lactobacillus acidophilus caused by incorporated 3H-thymine during incubation without amino acids.
Of the cells of Lactobacillus acidophilus R-26 incorporated 3H-thymine (specific radioactivity 1.57 Ci/mmol or 3.15 Ci/mmol), their transfer to a medium without essential amino acids resulted in their death. This death may be interpreted in such a way that cell damage caused by disintegration of tritium cannot be effectively repaired under conditions of amino acid deprivation. The experimental eonditions make it possible to explain this death either as a result of inhibition of protein or RNA synthesis or as a result of the absence of amino acids. These possibilities were tested in experiments, in which the synthesis of proteins and RNA was inhibited by specific inhibitors in the presence of amino acids. Under these conditions no death of cells was detected, thus indicating that free amino acids play a role in the repair of radiation damage.


Effect of "flow anoxia" and "non flow anoxia" on the NAD/NADH redox state of the intact brain cortex of the cat.
In the present study, we compared the nicotinamide adenine dinucleotide (NAD) reducing potencies of "flow anoxia" and "non flow anoxia" in the cat brain cortex. In animals anaesthetized with alpha D-glucochloralose "flow anoxia" and "non flow anoxia" were produced by ventilating for 2 and 25 min, respectively, with nitrogen gas. Following "non flow anoxia" the brain cortices of dead animals were superfused with oxygen saturated artificial cerebrospinal fluid (mock CSF), and subsequently with CSF containing various concentrations (10(-3 -10 -1) M) of potassium cyanide. NADH (reduced NAD) fluorescence of the brain cortex was measured through a cranial window with a microscope fluororeflectometer. Ventilating the animals for 2 and 25 min with nitrogen gas increased cortical NADH fluorescence (NAD reduction) by 43.5 +/- 2.8% and 135.3 +/- 6.1%, respectively. Oxygen saturated CSF superfusion of the ischemic brain cortex restored the cortical NAD/NADH redox state to the preanoxic level (oxidation of NADH). 10(-1) M cyanide, applied after superfusion of the brain cortex with oxygen saturated CSF resulted in comparable NAD reduction to that produced by "non flow anoxia". On the basis of these findings it is suggested that "non flow anoxia" leads to much greater cortical NAD reduction than "flow anoxia", because oxygen tension in the cortex may not fall to zero mm Hg during nitrogen anoxia lasting for 2 min. Besides this, a more pronounced substrate mobilization and acidosis may also contribute to the greater NAD reducing potency of "now flow anoxia".(ABSTRACT TRUNCATED AT 250 WORDS)


When fat talks, the gut listens: IRONing out metabolism.
In a new study, Zhang et al. (2021) show that reducing iron levels in adipose tissue improves metabolic function. This occurs through an interorgan communication system where signals from the adipocyte reduce intestinal lipid absorption.


Discovery of novel SecA inhibitors of Candidatus Liberibacter asiaticus by structure based design.
Candidatus Liberibacter asiaticus is the causal agent of Huanglongbing (HLB) disease of citrus. Current management practices have not been able to control HLB and stop the spread of HLB. The current study is focused on screening small molecule inhibitors against SecA protein of Ca. L. asiaticus. Homology modeling, structure based virtual screening and molecular docking methods have been used to find the novel inhibitory compounds against SecA activity at ATP binding region. At 20μm 17 compounds showed >50% inhibition and four compounds had more than 65% inhibition. The most active compound has IC(50) value of 2.5μM. The differences between the activities of the compounds are explained by their inter-molecular interactions at ATP binding site.


Remote assessments for bone conduction hearing devices during the COVID-19 pandemic.
The COVID-19 pandemic had resulted in the suspension of many routine audiology services due to the risk of cross-infections in closed spaces. This has driven the need for exploring alternatives to conventional face-to-face consultations in the hospital outpatient setting. The aim of this study was to determine the efficacy of remote consultations and assessments for patients on the waiting list for consideration of bone conduction hearing devices (BCHDs), and whether this type of consultation could continue beyond the COVID-19 era. This was a prospective cross-sectional study in a tertiary Neuro-otology Department. All new patients on the waiting list for assessment for BCHD as of 1 March 2020 were included. Patients' case notes were reviewed. All underwent a telephone consultation with an implant audiologist. If the patient wanted to go ahead with the remote trial, a BCHD sound processor on a headband would be mailed out and the patient would then have to use the device for two weeks and return the device after with their diary. There were 49 patients. The mean age was 55 (range 27-88, SD 16.3). Four did not proceed with the trial. All patients returned their devices to the department. Majority of patients (95.6%, n = 43), completed their diary. 75.6% wanted to proceed with surgery. All patients proceeding with surgery were happy with the remote assessment and would recommend this for the future. It is possible to satisfactorily assess appropriately screened patients for BCHDs remotely with a structured approach and explanation of process and expectations. It might be possible to consider this type of consultation as an option for assessing potential candidates for BCHDs beyond the COVID-19 era to reduce the number of hospital visits for patients.


Toxocara canis larvae reinfecting BALB/c mice exhibit accelerated speed of migration to the host CNS.
Using a small animal imaging system, migratory activity of Toxocara canis larvae stained by carboxyfluorescein succinimidyl ester (CFSE) was observed post primary infection (PPI) and post reinfection (PR) of BALB/c mice. Each infection was performed with 1,000 larvae per mouse. Primary infections were performed with labeled larvae, while for challenge infections the reinfecting larvae were stained by CFSE. The worm burden in mouse organs was determined during a period from 6 h to 21 days and 4 months PPI and PR. In comparison with primary infections that led to the first larvae appearance in the brain after 60 h, greatly accelerated migration of the parasites administered 3 weeks PPI to the CNS and eyes of challenged mice was noted-in both organs the larvae appeared 6 h PR. In all challenged mice, reinfecting larvae prevailed in the resident parasite population. Preliminary experiments with Toxocara cati larvae also revealed early brain involvement in primarily infected mice. Staining of T. canis larvae by CFSE had no effect on the development of a humoral antibody response against T. canis excretory-secretory antigens. In ELISA, elevated levels of specific IgG and IgG1 were noted on day 14 PPI and the levels of antibodies increased till the end of experiment. Reinfection induced an increase in the levels of both antibodies. In terms of optical density, IgG1 antibodies gave higher values in all sera examined. In ELISA for IgG antibodies, an increase in the avidity index of around 50% was detected 1 month PPI; higher-avidity antibodies were also detected in sera of reinfected animals.


Dem-Aging: autophagy-related pathologies and the "two faces of dementia".
Neuronal ceroid lipofuscinosis (NCL) is an umbrella term referring to the most frequent childhood-onset neurodegenerative diseases, which are also the main cause of childhood dementia. Although the molecular mechanisms underlying the NCLs remain elusive, evidence is increasingly pointing to shared disease pathways and common clinical features across the disease forms. The characterization of pathological mechanisms, disease modifiers, and biomarkers might facilitate the development of treatment strategies.The DEM-AGING project aims to define molecular signatures in NCL and expedite biomarker discovery with a view to identifying novel targets for monitoring disease status and progression and accelerating clinical trial readiness in this field. In this study, we fused multiomic assessments in established NCL models with similar data on the more common late-onset neurodegenerative conditions in order to test the hypothesis of shared molecular fingerprints critical to the underlying pathological mechanisms. Our aim, ultimately, is to combine data analysis, cell models, and omic strategies in an effort to trace new routes to therapies that might readily be applied in the most common forms of dementia.


Rhizobacterial Bacillus mycoides functions in stimulating the antioxidant defence system and multiple phytohormone signalling pathways to regulate plant growth and stress tolerance.
To analyse effects and mechanisms of plant growth promotion mediated by Bacillus mycoides strain A3 (BmA3), in Arabidopsis thaliana seedlings. Bacillus mycoides strain A3 (BmA3) isolated from the bamboo rhizosphere produced phytohormones, including indole-3-acetic acid (IAA) and gibberellic acid (GA), and exhibited phosphate solubilization and radical scavenging activities. A. thaliana seedlings inoculated with BmA3 exhibited an altered root architecture including an increased number of lateral roots and root hairs. Likewise, enhanced photosynthetic efficiency through the accumulation of higher levels of chlorophyll and starch, and increased plant size and fresh weight were observed in the BmA3-treated seedlings. This bacterial inoculation stimulated the antioxidant defence system by increasing the activities of catalase (CAT), guaiacol peroxidase (GPX), ascorbate peroxidase (APX) and phenylalanine ammonia-lyase (PAL). Secondary metabolites, including phenolic compounds, flavonoids and glucosinolates, were induced to higher levels in the BmA3-treated plants. Under drought and heat stresses, lower levels of H2 O2 , malondialdehyde (MDA) and electrolyte leakage were noticed in the treated seedlings. Genes involved in the signalling pathway of jasmonic acid (JA) including MYC2 and lipoxygenase 1 (LOX1) and salicylic acid (SA) including SAR DEFICIENT 1 (SARD1) and CAM-BINDING PROTEIN 60-LIKE G (CBP60G), and the antioxidant defence system including Ascorbate peroxidase (AtAPX) and alternative oxidase (AOX) were upregulated in BmA3-treated plants. Moreover, pathogenesis-related protein 1 (PR-1) and PR-2, marker genes for disease resistance, as well as DREB2A and HsFA2, which function in abiotic stress regulation, were also upregulated. BmA3 was able to activate JA and SA signalling pathways to induce plant growth and abiotic stress tolerance in A. thaliana seedlings. The plant growth promotion and increased stress tolerance induced by BmA3 were the result of the combined effects of microbial metabolites and activated host plant responses, including phytohormone signalling pathways and antioxidant defence systems.


Maximum immunobioactivity of murine small intestinal intraepithelial lymphocytes resides in a subpopulation of CD43+ T cells.
CD43 has been linked to many function-associated T cell activities. Using mAbs that recognize two different CD43 determinants, we show that, although mouse small intestinal intraepithelial lymphocytes (IELs) expressed the CD43 core molecule reactive with mAb R2/60, only about one-half of the total IELs-including some but not all of the TCRalphabeta and TCRgammadelta cells-expressed the CD43 S7(-) reactive determinant. CD43 S7(+) IELs secreted more IL-2, IL-4, IL-10, IL-17, and IFN-gamma following anti-CD3 stimulation, and were >4-fold more cytotoxic in fresh isolates and >16-fold more cytotoxic after anti-CD3 stimulation, than S7(-) IELs. S7(+) but not S7(-) IELs from the ileum of IL-10(-/-) mice spontaneously produced IFN-gamma. In vivo BrdU uptake by IELs in non-Ag-primed mice was greatest in the S7(+) population, indicating that significantly more S7(+) IELs than S7(-) IELs undergo cell expansion under normal homeostatic conditions. DNA microarray analyses showed that S7(+) IELs expressed higher levels of genes associated with activated T cells, whereas S7(-) IELs expressed genes used in the regulation of NK cells. These findings define two functionally distinct populations of IELs based on CD43 expression independent of TCR class, and they identify a subset of IELs that may serve as a target to better control intestinal inflammation.


In silico discovery of small molecules for efficient stem cell differentiation into definitive endoderm.
Improving methods for human embryonic stem cell differentiation represents a challenge in modern regenerative medicine research. Using drug repurposing approaches, we discover small molecules that regulate the formation of definitive endoderm. Among them are inhibitors of known processes involved in endoderm differentiation (mTOR, PI3K, and JNK pathways) and a new compound, with an unknown mechanism of action, capable of inducing endoderm formation in the absence of growth factors in the media. Optimization of the classical protocol by inclusion of this compound achieves the same differentiation efficiency with a 90% cost reduction. The presented in silico procedure for candidate molecule selection has broad potential for improving stem cell differentiation protocols.


Green synthesis of bio-functionalized nano-particles for the application of copper removal - characterization and modeling studies.
Green technology for the synthesis of nanoparticles has gained momentum due to its cost-effectiveness and eco-friendly nature. In this research study, silver nanoparticles (AgNps) were synthesized using an eco-friendly biological method involving the use of marine algae, Halimeda gracilis. The surface properties of the synthesized silver nanoparticles were studied using UV-visible spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy methods. During the synthesis of nano particles, the parameters namely temperature (30 °C to 90 °C), pH (6-10), silver nitrate (AgNO3) concentration (1-3 mg/ml) and quantity of algal extract (1-3 ml) were optimized to improve the production of AgNPs. The application of the synthesized silver nanoparticles for the adsorptive removal of copper from aqueous and industrial wastewater was investigated. Intra-particle diffusion mechanism was identified to be controlling step in metal removal. Regeneration of sorbent was carried out using 2.0 M HCl and the reusability was verified for 6 cycles. A removal efficiency of copper (64.8%) from electroplating wastewater demonstrated the industrial application potential of the synthesized silver nanoparticles.


Liver transplantation with donors older than 75 years.
Orthotopic liver transplantation has shown successful results over the last years. For this reason there are increased numbers of patients on waiting lists. To expand the pool of liver donors, elderly donors have been used as a strategy. We report our experience comparing donors of ≥ 75 years with younger ages for their characteristics, clinical outcomes, and survivals. From January 2001 to December 2009, we performed 174 consecutive liver transplantation from cadaveric donors in 166 patients. During this period, we used 24 liver grafts from donors ≥ 75 years. We analyzed their outcomes retrospectively, describing donors and recipient characteristics and their clinical evolution. The mean follow-up time among the entire study population was 42 ± 39 months. We observed an overall survival of 68.3% with similar incidences in both groups: 83% in the younger versus 78% in the older group at 1 year, and 69% versus 63%, at 5 years respectively. Both groups showed similar lengths of intensive care unit stay, cold and warm ischemia times, and intraoperative transfusion requirements. The older group had a total operative time than was longer and fewer hypotensive episodes than the younger group. There were no significant differences in the rates of rejection and retransplantation between the groups. The use of older donor livers was associated with a significantly higher rate of poor initial graft function (P = .027), an increased number of reinterventions (P = .013) in the older donor group, as well as more frequent vascular and biliar complications, without reaching significance. Our data suggested that donor age alone did not engendered a survival disadvantage for graft or recipient. However, careful donor selection is needed to avoid additional risk factors that can increase the morbidity or mortality of the procedure.


Tumor size and location correlate with behavior of pancreatic serous cystic neoplasms.
The majority of pancreatic serous cystic neoplasms (SCNs) are benign. However, these neoplasms can cause symptoms and rarely can be aggressive. Identification of factors associated with symptomatic or aggressive SCNs may aid management decisions. The aim of this study was to identify variables that predict aggressive SCNs. Prospective pathology database was queried for SCNs that were surgically resected at Johns Hopkins Hospital. Tumors were considered aggressive if they invaded surrounding structures and/or vessels or if they metastasized to lymph nodes or distant organs. The associations of gender, tumor size, and tumor location, with the presence or absence of symptoms and tumor behavior were examined using Fisher's exact test, logistic regression, and multivariate analyses. A total of 257 patients with SCNs underwent surgical resection. Mean tumor diameter was 4.9 cm. Tumor location in the head of pancreas (HOP) was associated with symptoms (odds ratio (OR) 1.87, 95% confidence interval (CI) 1.1-3.3). Computed tomography (CT) predicted the diagnosis of SCN in approximately a quarter of patients. Thirteen tumors (mean 10.5 cm) were considered aggressive. Multivariate analysis showed that tumor diameter (OR 1.53, 95% CI 1.24-1.89) and location of tumor in pancreatic head (OR 10.44, 95% CI 1.73-63.04) were independently associated with aggressive behavior. We describe the largest case series of patients with pathologically proven SCNs. CT performed poorly in preoperative diagnosis of SCNs. Large tumor size and head location predicted aggressive behavior. These factors should be considered in the management of patients with SCN.


Impact of aluminum exposure on oxidative stress, intestinal changes and immune responses in red swamp crayfish (Procambarus clarkii).
Aluminum (Al) is an abundant metal that has been classified as a threatening pollutant due to indiscriminate use and anthropogenic activities. This study aimed to evaluate the impacts of Al on crayfish (Procambarus clarkii), including biochemical change, histological alteration, gut microbial community diversification, and immune changes. The bioaccumulation of Al was detected in the hemolymph and intestine of crayfish after Al exposure at different time points. Results showed that Al exposure significantly induced oxidative stress and caused pathohistological changes on intestinal barrier structures in crayfish. It was found that the intestinal microbiota was affected by retained Al and the intestinal community diversity was changed after Al treated in the crayfish. Furthermore, Al exposure affected the immunity in crayfish, by altering the expression of a set of immune-related genes, as well as reducing the phenoloxidase and lysozyme activities. Moreover, Al exposure promoted hemocytes apoptosis and impaired hemophagocytic capacity against Vibro parahamolyticus, resulting in higher mortality of crayfish upon bacterial infection. Taken these results together, we conclude that excessive Al exposure caused adverse effects on multiple biological processes of crayfish and Al pollution is a potential threat to crayfish culture.


Enhanced susceptibility to the GABA antagonist pentylenetetrazole during the latent period following a pilocarpine-induced status epilepticus in rats.
A variety of acute brain insults bear the risk of subsequent development of chronic epilepsy. Enhanced understanding of the brain alterations underlying this process may ultimately lead to interventions that prevent, interrupt or reverse epileptogenesis in people at risk. Various interventions have been evaluated in rat models of symptomatic epilepsy, in which epileptogenesis was induced by status epilepticus (SE) or traumatic brain injury (TBI). Paradoxically, recent data indicated that administration of proconvulsant drugs after TBI or SE exerts antiepileptogenic or disease-modifying effects, although epilepsy is often considered to represent a decrease in seizure threshold. Surprisingly, to our knowledge, it is not known whether alterations in seizure threshold occur during the latent period following SE. This prompted us to study seizure threshold during and after the latent period following SE induced by lithium/pilocarpine in rats. Timed intravenous infusion of the GABA(A) receptor antagonist pentylenetetrazole (PTZ) was used for this purpose. The duration of the latent period was determined by continuous video/EEG monitoring. Compared to control seizure threshold determined before SE, threshold significantly decreased two days after SE, but returned to pre-SE control thereafter. Moreover, the duration of PTZ-induced seizures was significantly increased throughout the latent period, which ranged from 6 to 10 days after SE. This increased susceptibility to PTZ likely reflects the complex alterations in GABA-mediated transmission that occur during the latent period following SE. The data will allow developing dosing regimens for evaluation of whether treatment with subconvulsant doses of PTZ during the latent period affects the development of epilepsy.


Research Progress on the Role of Sirtuin 1 in Cerebral Ischemia.
A significant amount of evidence from the past few years has shown that Sirtuin 1 (SIRT1), a histone deacetylase dinucleotide of nicotinamide adenine dinucleotide (NAD+) is closely related to the cerebral ischemia. Several potential neuroprotective strategies like resveratrol, ischemia preconditioning, and caloric restriction exert their neuroprotection effects through SIRT1-related signaling pathway. However, the potential mechanisms and neuroprotection of SIRT1 in the process of cerebral ischemia injury development and recovery have not been systematically elaborated. This review summarized the the deacetylase activity and distribution of SIRT1 as well as analyzed the roles of SIRT1 in astrocytes, microglia, neurons, and brain microvascular endothelial cells (BMECs), and the molecular mechanisms of SIRT1 in cerebral ischemia, providing a theoretical basis for exploration of new therapeutic target in future.


The effect of Emdogain on ectopic bone formation in tubes of rat demineralized dentin matrix.
Emdogain (EMD) is made from enamel matrix proteins (EMPs) from the tooth germ of swine and propylene glycol alginate (PGA) as a matrix. The function of EMD is known to differentiate cells of the dental follicle into cementoblasts. However, little is known about the effect of EMD on mesenchymal cells in other tissue. The purpose of this study was to investigate whether EMD has the ability to induce hard tissue when applied with or without demineralized dentin matrix. Half of the dentin tubes prepared from rat incisors were demineralized by treatment with 0.6 N hydrochloric acid for 3 h. EMD or PGA was injected into the demineralized or non-demineralized dentin tubes, which were then transplanted into rectus abdominis muscles. Untreated dentin tubes were also transplanted as a control. Animals were killed at 7, 14 and 21 days after the implantation. Non-demineralized dentin tubes with or without EMD or PGA did not form any hard tissue. In the demineralized group, chondrogenesis in the PGA groups occurred earlier than in the EMD groups. The expression of vascular endothelial growth factor (VEGF) mRNA in the demineralized group with PGA at day 14 was the highest. The expression of osteopontin and osteocalcin mRNAs was higher in all groups at 21 days compared with 7 or 14 days. These results suggest that neither EMD nor PGA has the ability to induce hard tissue and that EMPs contained within EMD might aggregate on the dentin surface and inhibit the effect of the demineralized dentin matrix.


Toxicity of Cadmium and nickel in the context of applied activated carbon biochar for improvement in soil fertility.
Toxicity induced by heavy metals deteriorates soil fertility status. It also adversely affects the growth and yield of crops. These heavy metals become part of the food chain when crops are cultivated in areas where heavy metals are beyond threshold limits. Cadmium (Cd) and nickel (Ni) are considered the most notorious ones among different heavy metals. The high water solubility of Cd made it a potential toxin for plants and their consumers. Accumulation of Ni in plants, leaves, and fruits also deteriorates their quality and causes cancer in humans when such a Ni-contaminated diet is used regularly. Both Cd and Ni also compete with essential nutrients of plants, making the fertility status of soil poor. To overcome this problem, the use of activated carbon biochar can play a milestone role. In the recent past application of activated carbon biochar is gaining more and more attention. Biochar sorb the Cd and Ni and releases essential micronutrients that are part of its structure. Many micropores and high cation exchange capacity make it the most acceptable organic amendment to improve soil fertility and immobilize Cd and Ni. In addition to improving water and nutrients, soil better microbial proliferation enhances the soil rhizosphere ecosystem and nutrient cycling. This review has covered Cd and Ni harmful effects on crop yield and their immobilization by activated carbon biochar. The focus was made to elaborate on the positive effects of biochar on crop yield and soil health.


Osteolytic Lesion of the Maxilla in an Undiagnosed Multiple Myeloma Patient Identified Incidentally by Cone Beam Computed Tomography.
BACKGROUND Multiple myeloma is a hematological malignancy characterized by monoclonal plasma cell proliferation. Jaw lesions are found in nearly 35% of patients with symptomatic myeloma, and lesions occur in the mandible more often than in the maxilla. However, maxillary or mandibular lesions are rarely found as a primary manifestation of the disease. This report describes a case of a 65-year-old Palestinian woman with lytic lesions in the maxilla due to undiagnosed multiple myeloma identified incidentally on cone beam computed tomography (CBCT). CASE REPORT A 65-year-old Palestinian woman presented to the Oral Maxillofacial Surgery Clinic with an expansion of the maxilla which was initially thought of as an infection. CBCT imaging revealed diffuse osteolytic lesions involving multiple osseous structures. The patient was biopsied. Histopathological examination was suspicious for plasmacytic neoplasm. She was directly referred to the Hematology Department for further laboratory tests. These included complete blood count, liver function test, bone profile, protein electrophoresis, flow cytometry, and bone marrow biopsy, which were performed to confirm the diagnosis of multiple myeloma. The patient was treated with chemotherapy including zoledronic acid, dexamethasone, bortezomib, and cyclophosphamide. She went into remission for a year but unfortunately died 2 years later. CONCLUSIONS Primary myeloma of the maxilla is a rare presentation. The present report illustrates the role of CBCT imaging supported by a multidisciplinary approach to the diagnosis and management of myeloma. Consequently, it is recommended that dental practitioners be aware of radiographic features and possible oral manifestations to avoid any delay in medical intervention.


Association of prostate-specific membrane antigen with caveolin-1 and its caveolae-dependent internalization in microvascular endothelial cells: implications for targeting to tumor vasculature.
Prostate-specific membrane antigen (PSMA) is a transmembrane protein with a highly restricted profile of expression. Expression is primarily limited to secretory cells of the prostatic epithelium, with elevated levels observed in prostate cancer. As an integral membrane protein correlated with prostate cancer, PSMA offers a potentially valuable target for immunotherapy. PSMA is also detected in the neovasculature of a variety of solid tumors but not in the endothelial cells of preexisting blood vessels. Although the significance of PSMA expression in these cells remains elusive, this pattern of expression implies that PSMA may perform a functional role in angiogenesis and may offer a therapeutic target for the treatment of a broad spectrum of solid tumors. In this study, we have expressed PSMA in human microvascular endothelial cells and demonstrate that PSMA binds to caveolin-1 and undergoes internalization via a caveolae-dependent mechanism. The association between PSMA and caveolae in endothelial cells may provide important insight into PSMA function and ways to best exploit this protein for therapeutic benefit.


Early Upper Paleolithic human foot bones from Manot Cave, Israel.
The transition from the Middle Paleolithic to the Upper Paleolithic in the Levant represents a major event in human prehistory with regards to the dispersal of modern human populations. Unfortunately, the scarcity of human remains from this period has hampered our ability to study the anatomy of Upper Paleolithic populations. This study describes and examines pedal bones recovered from the Early Upper Paleolithic period at Manot Cave, Israel, from 2014 to 2017. The Manot Cave foot bones include a partial, left foot skeleton comprising a talus, a calcaneus, a cuboid, a first metatarsal, a second metatarsal, a fifth metatarsal, and a hallucal sesamoid. All these remains were found in the same archaeological unit of the cave and belong to a young adult. Shape and size comparisons with Neanderthals, Anatomically Modern Human and modern human foot bones indicate a modern human morphology. In some characteristics, however, the Manot Cave foot bones display a Neanderthal-like pattern. Notably, the Manot Cave foot is remarkable in its overall gracility. A healed traumatic injury in the second metatarsal (Lisfranc's fracture) is most likely due to a remote impact to the dorsum of the foot. This injury, its subsequent debility, and the individual's apparent recovery suggest that the members of the Manot Cave community had a supportive environment, one with mutual responsibilities among the members.


Characterizing the implications of waste dumping surrounding the Yangtze River economic belt in China.
China has prohibited an extensive list of solid waste from abroad since 2017. While China seeks to move away from being the world's dumping ground, cleaning up its own backyard is proving to be a great challenge. China's Yangtze River economic zone, which covers 11 provinces and accounts for 40% of the country's Gross Domestic Product, has been found to be alarmingly polluted: 74 million metric tons of solid wastes, including industrial solid waste, construction debris, municipal solid waste, and hazardous waste, have been disposed of by dumping. In this study, the statistics and spatial patterns of waste dumping were determined and mapped, and then the subsequent environmental impacts on the local and downstream marine ecosystem were evaluated. The results indicated the largest dumped-waste volume was found in Sichuan province (industrial solid waste) and Hubei province (solid waste mixture). The potential environmental impacts aroused by waste dumping in Hubei, Jiangxi and Sichuan provinces were serious, while the impacts in Yunnan and Zhejiang were slight. It is imperative for the Yangtze River Economic Zone to develop stringent measures for curbing the dumping of solid waste, assessing the implications from existing dumping activities, and enhancing the capacity for responsible waste management.


Sexual Violence Perpetration Within Intimate Relationships: An I3 Model Analysis of the Effects of Sexual Violence Victimization and Psychological Flexibility.
The I3 Model posits that intimate partner violence (IPV) is determined by the relative strength of instigatory, impellance, and inhibitory factors. Although much research has examined nonsexual IPV, few studies have used the I3 Model to examine sexual IPV. This study investigated the effects of sexual IPV victimization (an impellor) and psychological flexibility (an inhibitor) on sexual IPV perpetration within a dyadic framework. Participants nested within 617 intimate couples completed measures of psychological flexibility and sexual IPV perpetration and victimization. Results showed that Actor IPV victimization was positively and Actor psychological flexibility was negatively associated with Actor IPV perpetration. Among those who experienced low levels of IPV victimization, psychological flexibility inhibited IPV perpetration. This inhibiting effect did not extend to Actors who experienced high levels of IPV victimization. Findings highlight the complex interactions between I3 factors and support continued dyadic examination of IPV perpetration etiology.


Cost variation and revisit rate for adult patients with asthma presenting to the emergency department.
Asthma is common, resulting in 53 million emergency department (ED) visits annually. Little is known about variation in cost and quality of ED asthma care. We sought to describe variation in costs and 7-day ED revisit rates for asthma care across EDs. Our primary objective was to test for an association between ED costs and the likelihood of a 7-day revisit for another asthma exacerbation. We used the 2014 Florida State Emergency Department Database to perform an observational study of ED visits by patients ≥18 years old with a primary diagnosis of asthma that were discharged home. We compared patient and hospital characteristics of index ED discharges with and without 7-day revisits, then tested the association between ED revisits and index ED costs. Multilevel regression was performed to account for hospital-level clustering. In 2014, there were 54,060 adult ED visits for asthma resulting in discharge, and 1667 (3%) were associated with an asthma-related ED revisit within 7 days. Median cost for an episode of ED asthma care was $597 with an interquartile range of $371-980. After adjusting for both patient and hospital characteristics, lack of insurance was associated with higher odds of revisit (OR 1.42, 95% CI 1.18-1.71), while private insurance, female gender, and older age were associated with lower odds of revisit. Hospital costs were not associated with ED revisits (OR = 1.00; 95% CI 1.00-1.00). Hospital costs associated with ED asthma visits vary but are not associated with odds of ED revisit.


A Rational Reconfiguration of Electrolyte for High-Energy and Long-Life Lithium-Chalcogen Batteries.
Lithium-chalcogen batteries are an appealing choice for high-energy-storage technology. However, the traditional battery that employs liquid electrolytes suffers irreversible loss and shuttle of the soluble intermediates. New batteries that adopt Li+ -conductive polymer electrolytes to mitigate the shuttle problem are hindered by incomplete discharge of sulfur/selenium. To address the trade-off between energy and cycle life, a new electrolyte is proposed that reconciles the merits of liquid and polymer electrolytes while resolving each of their inferiorities. An in situ interfacial polymerization strategy is developed to create a liquid/polymer hybrid electrolyte between a LiPF6 -coated separator and the cathode. A polymer-gel electrolyte in situ formed on the separator shows high Li+ transfer number to serve as a chemical barrier against the shuttle effect. Between the gel electrolyte and the cathode surface is a thin gradient solidification layer that enables transformation from gel to liquid so that the liquid electrolyte is maintained inside the cathode for rapid Li+ transport and high utilization of active materials. By addressing the dilemma between the shuttle chemistry and incomplete discharge of S/Se, the new electrolyte configuration demonstrates its feasibility to trigger higher capacity retention of the cathodes. As a result, Li-S and Li-Se cells with high energy and long cycle lives are realized, showing promise for practical use.


[Genetic characterization of the Brucella melitensis isolates from Mongolia, Russia, and Azerbaijan].
The goal of this work was to provide comparative genetic characterization of the human and animal Brucella melitensis isolates from Mongolia, Russia and Azerbaijan using current molecular-genetic typing methods. Twenty eight Mongolian (n = 18), Russian (n = 6), and Azerbaijan (n = 4) human and animal Brucella melitensis isolates were studied using 2 molecular typing methods based on PCR for differential species and biovar specific ORF (open reading frames) molecular targets and MLVA (multiple locus variable number tandem repeats analysis) using primers to 12 known loci. The PCR was used for differential molecular targets (all B. melitensis isolates) were characterized as the B. melitensis biovar 2. The MLVA revealed 7 identical and 5 variable MLVA loci. All the isolates were classified into 25 genotypes using the dendrogram on the data of 12 loci and the cluster related to reference strain B. melitensis 63/9 biovar 2. The B. melitensis isolates having related MLVA genotypes were connected to Mongolian, Russian and Azerbaijan regions. The circulation for two B. melitensis isolates to not typical hosts as camel and yak was demonstrated using molecular typing methods. The genetic characterization of twenty eight B. melitensis isolates from different geographical regions in Mongolia, Russia, and Azerbaijan recognized genetic relationships. On the other hand, the MLVA has high discrimination power with a resulting Hunter and Gaston discriminatory index (HGDI) of 0.9841 revealing genetic diversity for the isolates forming of 25 MLVA genotypes. To improve the system of the brucellosis surveillance in Russia MLVA typing of B. melitensis isolates are necessary to investigate from the Siberian (Republics Tuva, Buryatia, and Irkutsk region) and South (Republics Dagestan, Kalmykia, and Stavropol region) Districts having frontier areas with Mongolia and Azerbaijan.


Prognostic significance of nonsustained ventricular tachycardia after revascularization.
Two randomized trials (Multicenter Automatic Defibrillator Implantation Trial [MADIT] and Multicenter Unsustained Tachycardia Trial [MUSTT]) suggest that implantable cardioverter defibrillator (ICD) placement is associated with improved survival in patients with coronary artery disease, depressed left ventricular function, and nonsustained ventricular tachycardia (VT) who also have inducible sustained VT. However, neither study directly addresses the management of such patients who develop nonsustained VT early after revascularization. We evaluated 109 consecutive patients who underwent electrophysiologic testing to evaluate nonsustained VT, which occurred 5 +/- 4 days following revascularization. Sustained monomorphic VT was inducible in 46 (42%) patients; these patients received an ICD. The remaining 63 (58%) noninducible patients received neither antiarrhythmic drug therapy nor an ICD. During 27 +/- 12 months of follow-up, 15 (33%) of 45 patients with an implanted ICD received at least one appropriate therapy from the device and 26 (24%) of the 109 study patients died. The 1- and 2-year freedom from ventricular tachycardia/fibrillation or sudden death in noninducible patients (97% and 93%) was significantly greater than that of inducible patients (84% and 71%; P = 0.001). However, no difference was observed in total mortality. Patients with nonsustained VT during the early postrevascularization period who have inducible VT have a high incidence of arrhythmic events. Although this study was not designed to assess the impact of ICD placement on the total mortality of inducible patients, the finding that one third of these patients received appropriate ICD therapy suggests that the device may have a protective effect in these patients.


The effect of cyproheptadine on the release of corticotrophin releasing factor.
The effect of cyproheptadine was tested on the neurotransmitter-induced release of corticotrophin releasing factor (CRF) from the rat hypothalamus in vitro. It was found that cyproheptadine inhibited both acetylcholine and 5-hydroxytryptamine-induced release of CRF. Cyproheptadine did not interfere with the ACTH releasing ability of CRF. These results suggest that cyproheptadine reduces the high circulating levels of ACTH in some patients suffering from Cushing's disease and Nelson's syndrome by inhibiting CRF secretion.