Proteases from dengue, West Nile and Zika viruses as drug targets.
Proteases from flaviviruses have gained substantial interest as potential drug targets to combat infectious diseases caused by dengue, West Nile, Zika and related viruses. Despite nearly two decades of drug discovery campaigns, promising lead compounds for clinical trials have not yet been identified. The main challenges for successful lead compound development are associated with limited drug-likeness of inhibitors and structural ambiguity of the protease target. This brief review focuses on the available information on the structure of flavivirus proteases and their interactions with inhibitors and attempts to point the way forward for successful identification of future lead compounds.


Obesity increases heart failure incidence and mortality: observational and Mendelian randomization studies totalling over 1 million individuals.
Whether high body mass index (BMI) causally influences development and prognosis of heart failure has implications for clinical practice. We tested the hypotheses that high BMI causally influences heart failure incidence and mortality. Using observational and Mendelian randomization causal, genetic analyses, we studied 106 121 individuals from the Copenhagen General Population Study, 18 407 from the Copenhagen City Heart Study, and 977 323 from publicly available databases. In observational analyses in the Copenhagen studies with 10 years of median follow-up, multivariable adjusted hazard ratios per 1 kg/m2 increment of BMI were 1.06 (95% confidence interval: 1.05-1.07; P < 0.001; n = 124 528; events = 6589) for heart failure incidence, 1.04 (1.03-1.06; P < 0.001; n = 124 528; events = 1237) for heart failure mortality, and 1.01 (1.00-1.01; P < 0.001; n = 124 528; events = 24 144) for all-cause mortality. In genetic analyses in the Copenhagen studies, the age and sex adjusted causal risk ratios per 1 kg/m2 increment of BMI were 1.19 (1.05-1.36; P = 0.008; n = 118 200; events = 6541) for heart failure incidence, 1.27 (0.82-1.98; P = 0.28; n = 118 200; events = 889) for heart failure mortality, and 1.11 (1.02-1.22; P = 0.022; n = 118 200; events = 16 814) for all-cause mortality. Finally, combining genetic data from the Copenhagen studies, the Genetic Investigation of ANthropometric Traits, the Heart Failure Molecular Epidemiology for Therapeutic Targets, and the UK Biobank, the unadjusted causal risk ratios per 1 kg/m2 increment of BMI were 1.39 (1.27-1.52; P < 0.001; n = 1 095 523; events = 53 850) for heart failure incidence, 1.18 (1.00-1.38; P = 0.05; n = 576 853; events = 2373) for heart failure mortality, and 1.02 (1.00-1.04; P = 0.03; n = 576 853; events = 44 734) for all-cause mortality. High BMI causally increases the risk of both heart failure incidence and mortality.


Eduard Strasburger (1844-1912): founder of modern plant cell biology.
Eduard Strasburger, director of the Botany Institute and the Botanical Garden at the University of Bonn from 1881 to 1912, was one of the most admirable scientists in the field of plant biology, not just as the founder of modern plant cell biology but in addition as an excellent teacher who strongly believed in "education through science." He contributed to plant cell biology by discovering the discrete stages of karyokinesis and cytokinesis in algae and higher plants, describing cytoplasmic streaming in different systems, and reporting on the growth of the pollen tube into the embryo sac and guidance of the tube by synergides. Strasburger raised many problems which are hot spots in recent plant cell biology, e.g., structure and function of the plasmodesmata in relation to phloem loading (Strasburger cells) and signaling, mechanisms of cell plate formation, vesicle trafficking as a basis for most important developmental processes, and signaling related to fertilization.


[Comparative measurement of cocaine and its metabolites in blood, cerebrospinal fluid and the brain].
This study investigated the transfer of cocaine and its metabolites from plasma into the cerebrospinal fluid. The concentration of cocaine and its metabolites in plasma and cerebrospinal fluid was determined by radioimmunoassay because this method only, the sum of the drug and metabolites restored. In sheeps a sublethal cocaine hydrochloride dose (2,4 mg/kg b. wt.) was administered intraarterial daily for up to 8 days. In the first hours after administration the concentration of cocaine in cerebrospinal fluid was low. It is supposed that a barrier against the transport of cocaine from blood into cerebrospinal fluid exists. After intrathecal administration a delay of transport could from CSF to blood not be seen.


Unraveling a two-step oxidation mechanism in electrochemical Cu-MOF synthesis.
To employ the full potential of electrochemical (ec) synthesis to grow metal-organic frameworks (MOFs) in more complex organizations at the mesoscale, it is vital to understand the underlying crystallization reaction pathway. For the MOF most typically grown electrochemically, CuBTC, we systematically investigated the role of oxygen species in the synthesis.


Estimating False Discovery Proportion Under Arbitrary Covariance Dependence.
Multiple hypothesis testing is a fundamental problem in high dimensional inference, with wide applications in many scientific fields. In genome-wide association studies, tens of thousands of tests are performed simultaneously to find if any SNPs are associated with some traits and those tests are correlated. When test statistics are correlated, false discovery control becomes very challenging under arbitrary dependence. In the current paper, we propose a novel method based on principal factor approximation, which successfully subtracts the common dependence and weakens significantly the correlation structure, to deal with an arbitrary dependence structure. We derive an approximate expression for false discovery proportion (FDP) in large scale multiple testing when a common threshold is used and provide a consistent estimate of realized FDP. This result has important applications in controlling FDR and FDP. Our estimate of realized FDP compares favorably with Efron (2007)'s approach, as demonstrated in the simulated examples. Our approach is further illustrated by some real data applications. We also propose a dependence-adjusted procedure, which is more powerful than the fixed threshold procedure.


Quantitative analysis of annexin V-membrane interaction by flow cytometry.
We constructed a green fluorescent phosphatidylserine (PS)-binding probe, which was generated by fusing enhanced green fluorescent protein (EGFP) to the C terminus of human annexin V (anxV). With this probe, we investigated anxV-membrane interaction under different calcium and anxV-EGFP concentrations through flow cytometry (FCM). A mathematical description of the binding characteristics is proposed and validated to quantify the relationship concerning the relative concentration of membrane-bound anxV (B), calcium concentration ([C]), and protein concentration ([P]). Further analyses reveal that [Formula: see text] is linear with [Formula: see text] or [Formula: see text] when [P] and [C] are fixed, respectively, which indicates that the anxV-membrane binding reaction may involve sequential multiple steps. Our study provides a reference for application of anxV in apoptosis detection. The mathematical expression facilitates exploration of the possible interactions between calcium, anxV, and membrane. The corresponding mathematical analysis strengthens the interpretation of the interaction data.


[Health-related quality of life in children with spina bifida].
There are no studies on the health-related quality of life (HRQoL) in German children with a myelomeningocele (MMC). This study aims to obtain generalizable epidemiological data on the HRQoL of such children. KINDL-R questionnaires were filled out and clinical findings on typical MMC disabilities were also documented. Of the 115 families contacted, 70 MMC families responded (response rate 61%). Normative KINDL-R data from a sample of healthy children served as reference. No differences in clinical data were found when comparing responders and non-responders. KINDL total scores as well as scores across all scales were highly concordant for parental reporting and self-reporting. Despite the fact that children with MMC often suffer from severe physical limitations, their HRQoL is not necessarily lower than that of healthy children.


Behavior and toxicity assessment of copper nanoparticles in aquatic environment: A case study on red swamp crayfish.
With the wide use of copper nanoparticles (CuNPs) in various industrial and commercial applications, they inevitably enter the aquatic environment. However, their behavior in the aquatic environment and potential toxicity to aquatic organisms remain little known. In this study, we investigated the behavior of CuNPs in freshwater, as well as the toxicity and bioaccumulation of CuNPs and copper sulfate (CuSO4), used as a positive control for copper ions toxicity, in red swamp crayfish (Procambarus clarkii). The results showed that CuNPs released copper ions into freshwater and aggregated rapidly in freshwater, and their release of copper ions and aggregation slowed down at a higher concentration of CuNPs. The calculated 72-h LC50 values for crayfish were 1.18 and 0.54 mg/L for CuNPs and CuSO4, respectively. Cu accumulation in the gill and hepatopancreas from CuSO4 treatments was significantly higher than that from CuNPs, and the highest Cu bioaccumulation level in crayfish was found in the gill, followed by hepatopancreas and muscle with the exposure of copper. The activities of the antioxidative enzymes in the crayfish significantly decreased after exposure to CuNPs for 48 h, compared to the control (without CuNPs or CuSO4). Histological examination revealed that there was no significant alteration of hepatopancreas in the crayfish exposed to CuNPs. Meanwhile, the growth of crayfish was not significantly inhibited by CuNPs. These results suggested that CuNPs exposure can induce oxidative stress in the crayfish, gill is the main tissue for their accumulation, and their toxicity is mainly caused by the released copper ions.


Invasion of maritime chaparral by the introduced succulentCarpobrotus edulis : The roles of fire and herbivory.
Invasion by the alien succulent,Carpobrotus edulis, has become a common occurrence after fire in maritime chaparral in coastal California, USA. We studied post-burnCarpobrotus establishment in chaparral that lackedCarpobrotus plants before the fire and compared seedbank and field populations in adjacent burned and unburned stands.Carpobrotus seeds were abundant in deer scat and in the soil before burning. Burning did not enhance germination: many seeds were apparently killed by fire and seed bank cores taken after fire revealed no germinable seeds. Laboratory tests showed that temperatures over 105°C for five minutes killedCarpobrotus seeds. In a field experiment involving use of herbivore exclosures, we found that herbivory was an important source of mortality for seedlings in both burned and unburned chaparral. All seedlings, however, died outside of the burn regardless of the presence of cages. Establishment there is apparently limited by factors affecting plant physiology. In the burned area, seedlings that escaped herbivory grew very rapidly. Overall, it appears that herbivory limited seedling establishment in both burned and unburned sites but that the post-burn soil environment supportedCarpobrotus growth in excess of herbivore use, thus promoting establishment.


Catalytic Roles of Mn(II) and Fe(III) in the Reduction of Cr(VI) by Mandelic Acid under an Irradiation of Simulated Solar Light.
The catalytic roles of manganese(II) [Mn(II)] and iron(III) [Fe(III)] in the reduction of hexavalent chromium [Cr(VI)] by mandelic acid, both with and without the presence of light, was investigated through a series of batch experiments. The results demonstrated that both Mn(II) and Fe(III) could markedly accelerate the photoreduction of Cr(VI) by mandelic acid; additionally, the catalysis of Fe(III) was superior to that of Mn(II). Without the presence of light, Mn(II) still enhanced the reduction of Cr(VI) by mandelic acid, but Fe(III) did not exert any impact on the reaction. When compared with the activities of phenylacetic acid, it was concluded that the catalytic roles of both Mn(II) and Fe(III) in the reduction of Cr(VI) were directly related to the α-OH group and not to the carboxyl group. The photoreduction of Cr(VI) by mandelic acid, assisted by Mn(II), followed pseudo-first-order kinetics at the initial stage of the reaction, but in the presence of Fe(III) it followed a pseudo-zero-order model.


Hyperlipidemia, COVID-19 and acute pancreatitis: A tale of three entities.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the ongoing pandemic of coronavirus disease 2019 (COVID-19), which presented as not only respiratory symptoms, but various digestive manifestations including pancreatic injury and acute pancreatitis (AP). The underlying mechanism is still unclear. Hypertriglyceridemia has become one of the leading causes of AP in recent years and hyperlipidemia is highly reported in COVID-19 cases. The current narrative review aimed to explore the associations between AP, COVID-19 and hyperlipidemia. Substantial cases of COVID-19 patients complicated with AP were reported, while the incidence of AP in the COVID-19 population was relatively low. Hyperlipidemia was common in COVID-19 patients with a pooled incidence of 32.98%. Hyperlipidemia could be a mediating factor in the pathogenesis of AP in COVID-19 patients. Further studies are warranted to clarify the relationship among AP, lipid metabolism disorders and COVID-19.


Risk factors for mortality of severe trauma based on 3 years' data at a single Korean institution.
This study aimed to determine the mortality rate in patients with severe trauma and the risk factors for trauma mortality based on 3 years' data in a regional trauma center in Korea. We reviewed the medical records of severe trauma patients admitted to Ajou University Hospital with an Injury Severity Score (ISS) > 15 between January 2010 and December 2012. Pearson chi-square tests and Student t-tests were conducted to examine the differences between the survived and deceased groups. To identify factors associated with mortality after severe trauma, multivariate logistic regression was performed. There were 915 (743 survived and 172 deceased) enrolled patients with overall mortality of 18.8%. Age, blunt trauma, systolic blood pressure (SBP) at admission, Glasgow Coma Scale (GCS) at admission, head or neck Abbreviated Injury Scale (AIS) score, and ISS were significantly different between the groups. Age by point increase (odds ratio [OR], 1.016; P = 0.001), SBP ≤ 90 mmHg (OR, 2.570; P < 0.001), GCS score ≤ 8 (OR, 6.229; P < 0.001), head or neck AIS score ≥ 4 (OR, 1.912; P = 0.003), and ISS by point increase (OR, 1.042; P < 0.001) were significant risk factors. In severe trauma patients, age, initial SBP, GCS score, head or neck AIS score, and ISS were associated with mortality.


Effect of whole linseed and rumen-protected conjugated linoleic acid enriched diets on feedlot performance, carcass characteristics, and adipose tissue development in young Holstein bulls.
Forty-eight young Holstein bulls (slaughtered at 458.6±9.79 kg body weight) were used to evaluate the effect of whole linseed and conjugated linoleic acid (CLA) supplementation on animal performance, adipose tissue development, and carcass characteristics. The animals were fed with one of four isoenergetic and isoproteic diets: control (0% linseed, 0% CLA), linseed (10% linseed, 0% CLA), CLA (0% linseed, 2% CLA), and linseed plus CLA (10% linseed, 2% CLA). Animal performance and carcass characteristics were unaffected by diet composition. Adding linseed or CLA to the concentrate diet did not result in significant differences in adipocyte size and number or lipogenic enzyme activity. However, while the frequency distribution of subcutaneous adipocyte diameters followed a normal distribution, the frequency distribution of intramuscular adipocyte diameters was not normal in any dietary group (skewness coefficients: 0.8, 1.2, 0.9, 0.8 for control, linseed, CLA, and linseed plus CLA, respectively; P<0.05), indicative of adipocyte proliferation in the intramuscular adipose tissue.


Difference in the outcomes of anterior tenting and wrapping techniques for acellular dermal matrix coverage in prepectoral breast reconstruction.
Acellular dermal matrices (ADMs) play an essential role in prepectoral implant-based breast reconstructions; however, the most appropriate method for ADMs is unknown. We conducted a retrospective analysis of our institutional database. Patients who underwent mastectomy and prepectoral breast reconstruction using tissue expanders or breast implants covered with ADMs between March 2018 and June 2021 were included. Patient characteristics, postoperative complications, and long-term outcomes were investigated. In total, 112 patients (126 breasts) were included. The anterior tenting and wrapping techniques were used in the reconstruction of 32 (25.3%) and 94 (74.7%) breasts, respectively. Using propensity score matching, nine breasts were selected for each technique within the direct-to-implant reconstruction group, while 16 breasts were selected for each technique within the 2-stage reconstruction group. The choice of technique (anterior vs. wrapping) in implementing ADM did not generate any significant differences in postoperative complications, including seroma formation and capsular contracture, for the direct-to-implant and 2-stage reconstruction groups. Regarding the direct-to-implant reconstruction group, the average postoperative drain volume was less in the anterior tenting group than that in the wrapping group (anterior tenting vs. wrapping; 495.09 ± 156.118 mL vs. 673.43 ± 307.954 mL, p = 0.006), but the difference was insignificant after propensity score matching. We report our experience with covering prosthetic devices with ADMs during postmastectomy breast reconstruction. No differences in the postoperative drain volume or postoperative outcomes were found between the study groups. Future studies are needed to determine the method that provides the most satisfactory results.


Coded waveforms for optimised air-coupled ultrasonic nondestructive evaluation.
This paper investigates various types of coded waveforms that could be used for air-coupled ultrasound, using a pulse compression approach to signal processing. These are needed because of the low signal-to-noise ratios that are found in many air-coupled ultrasonic nondestructive evaluation measurements, due to the large acoustic mismatch between air and many solid materials. The various waveforms, including both swept-frequency signals and those with binary modulation, are described, and their performance in the presence of noise is compared. It is shown that the optimum choice of modulation signal depends on the bandwidth available and the type of measurement being made.


Papillary thyroid carcinoma of childhood and adolescence: a 30-year experience at the Istituto Nazionale Tumori in Milan.
Survival rates are reportedly excellent for papillary thyroid carcinomas (PTCs) in childhood/adolescence, despite their strong tendency to spread. The aim of this study was to verify this assumption in a single-institution series spanning a 30-year period with a very long follow-up. From 1968 to 2001, 74 cases of thyroid carcinoma were collected. The papillary histological type was confirmed in 42 cases with available slides; we recorded the sex, age at diagnosis, age of menarche, tumor side and size, TNM/pTNM classification, multicentricity, vascular invasion, type of surgery, post-operative complications, post-surgical therapies and outcome up to May 31, 2004. The female/male ratio was 2.2; pT4, pN1 and M1 cases were 52%, 95%, and 12% (four in lungs and one in bone), respectively. Total thyroidectomy was performed in 33 patients, hemithyroidectomy in 8, and a biopsy in 1 inoperable case. Nine patients (21%) relapsed, six in the cervical lymph nodes and three in the lungs. After a median follow-up of 189 months, all patients were alive, two of them with evidence of disease. Overall and progression-free survival curves were independent of sex, age, TNM/pTNM classification, or type of surgery. Overall survival was also independent of recurrence. Unlike its adult counterpart, PTC of childhood and adolescence is a cancer with a high frequency of spread, but an excellent outcome irrespective of sex, age at diagnosis, TNM/pTNM classification, type of surgery, recurrence. Since pediatric PTCs proved highly responsive to hormone manipulation, it is worth considering a different therapeutic approach from adult cases.


Clinical scale production of an improved retroviral vector expressing the human multidrug resistance 1 gene (MDR1).
Retroviral vectors are currently the most important and best characterized tools for ex vivo genetic modification of hematopoietic progenitor/stem cells. As a prerequisite for clinical applications, large volumes of high-titer vector supernatants have to be generated in compliance with 'GMP' guidelines. This goal can be reached using a carefully selected producer cell clone and a conventional large-scale cell culture system. The retroviral vector SF1m provides efficient expression of the human multidrug resistance 1 (MDR1) gene in hematopoietic progenitor/stem cells in vitro and in NOD/SCID mouse repopulating human cells in vivo. Currently, a clinical phase I/II study is in preparation to test whether intensified consolidation chemotherapy is enabled by autologous transplantation of peripheral blood progenitor/stem cells that have been genetically modified with SF1m. Using multi-tray cell factories >19 l of serum-free vector containing supernatant were generated from cells of a previously established SF1m-producer clone, based on the PG13 packaging cell line. Testing of the final samples revealed sufficient quality (>1.5 x 10(6) infectious particles/ml) for clinical scale transduction of CD34+ cells. Results from the production runs and the applied biosafety concept are described.


Testicular Localization and Potential Function of Vimentin Positive Cells during Spermatogonial Differentiation Stages.
Vimentin is a type of intermediate filament (IF) and one of the first filaments expressed in spermatogenesis. Vimentin plays numerous roles, consisting of the determination of cell shape, differentiation, cell motility, the maintenance of cell junctions, intracellular trafficking, and assisting in keeping normal differentiating germ cell morphology. This study investigated the vimentin expression in two populations of undifferentiated and differentiated spermatogonia. We examined vimentin expression in vivo and in vitro by immunocytochemistry (ICC), immunohistochemistry (IMH), and Fluidigm real-time polymerase chain reaction. IMH data showed that the high vimentin expression was localized in the middle of seminiferous tubules, and low expression was in the basal membrane. ICC analysis of the colonies by isolated differentiated spermatogonia indicated the positive expression for the vimentin antibody, but vimentin's expression level in the undifferentiated population was negative under in vitro conditions. Fluidigm real-time PCR analysis showed significant vimentin expression in differentiated spermatogonia compared to undifferentiated spermatogonia (p < 0.05). Our results showed that vimentin is upregulated in the differentiation stages of spermatogenesis, proving that vimentin is an intermediate filament with crucial roles in the differentiation stages of testicular germ cells. These results support the advanced investigations of the spermatogenic process, both in vitro and in vivo.


Personality, symptom, and demographic correlates of perceived efficacy of selective serotonin reuptake inhibitor monotherapy among current users with low mood: A data-driven approach.
Selective serotonin reuptake inhibitors (SSRIs) are often the first-line treatment option for depressive symptoms, however their efficacy varies across patients. Identifying predictors of response to SSRIs could facilitate personalised treatment of depression and improve treatment outcomes. The aim of this study was to develop a data-driven formulation of demographic, personality, and symptom-level factors associated with subjective response to SSRI treatment. Participants were recruited online and data were collected retrospectively through an extensive digital mental health questionnaire. Extreme gradient boosting classification with nested cross-validation was used to identify factors distinguishing between individuals with low (n=37) and high (n=111) perceived benefit from SSRI treatment. The algorithm demonstrated a good predictive performance (test AUC=.88±.07). Positive affectivity was the strongest predictor of response to SSRIs and a major confounder of the remaining associations. After controlling for positive affectivity, as well as current wellbeing, severity of current depressive symptoms, and multicollinearity, only low positive affectivity, chronic pain, sleep problems, and unemployment remained significantly associated with diminished subjective response to SSRIs. This was an exploratory analysis of data collected at a single time point, for a study which had a different primary aim. Therefore, the results may not reflect causal relationships, and require validation in future prospective studies. Furthermore, the data were self-reported by internet users, which could affect integrity of the dataset and limit generalisability of the results. Our findings suggest that demographic, personality, and symptom data may offer a potential cost-effective and efficient framework for SSRI treatment outcome prediction.


Readily improvised wrench for reduction of fractures during closed intramedullary nailing.
Overhead frame traction equipment can be used to build an adjustable, radiolucent, sterilizable, reduction device. The method achieves a quick and easy reduction of the fracture for passage of intramedullary nailing guide wires.


"Trojan Horse" Phototheranostics: Fine-Engineering NIR-II AIEgen Camouflaged by Cancer Cell Membrane for Homologous-Targeting Multimodal Imaging-Guided Phototherapy.
Multimodal phototheranostics on the basis of a single molecule with one-for-all characteristics represents a convenient approach for effective cancer treatment. In this report, a versatile molecule featured by aggregation-induced emission, namely DHTDP, synchronously enabling second near-infrared (NIR-II) fluorescence emission and efficient photothermal conversion is developed by elaborate structural modulation. By camouflaging DHTDP nanoparticles with cancer cell membrane, the resultant biomimetic nanoparticles exhibit significantly both facilitated delivery efficiency and homologous targeting capability, and afford precise imaging guidance and maximize therapeutic outcomes in form of NIR-II fluorescence imaging (FLI)-photoacoustic imaging (PAI)-photothermal imaging (PTI) trimodal imaging-guided photothermal therapy (PTT). This study presents the first example of biomimetic multimodal phototheranostics loaded by homogeneity-targeting cell membrane, thus brings a new insight into the exploration of superior phototheranostics for practical cancer theranostics.


2-D differential membrane proteome analysis of scarce protein samples.
Proteome studies with small sample amounts are difficult to perform, especially when membrane proteins are the focus of interest. In our study a new method for the analysis of scarce membrane protein samples combining large gel 2-D-CTAB/SDS-PAGE with fluorescence dye saturation labelling (satDIGE) was developed, allowing a highly sensitive differential analysis of different cell states. After Triton X-114 phase partitioning, enriched membrane protein samples of T cells were labelled at cysteine residues using fluorescence dyes and separated by large gel 2D-CTAB/SDS-PAGE. For a differential analysis 3 mug protein was found to be sufficient to detect proteins in a widespread well-separated diagonal spot pattern.


Contrast, spatial frequency and test duration effects on the tilt aftereffect: implications for underlying mechanisms.
The tilt aftereffect (TAE) was measured with a forced-choice technique for gratings of different spatial frequencies, contrasts and adapting and test durations. At short test durations, a 2 c/deg grating gave a larger TAE than a 10 c/deg, while at long test durations the opposite occurred. Low contrast gratings tended to give smaller TAEs at short test durations, and larger TAEs at long durations, than high contrast. A longer adapting duration tended to produce larger TAEs at low contrast for any test duration, but larger TAEs at high contrast only at long test durations. We suggest that the spatial frequency effect reflects differential excitation by the test stimuli of transient and sustained channels, and that the contrast effects reflect both a non-linearity in the relationship between excitation and inhibition, and the adapting effects of the test grating.


Risk-dependent conditional survival analysis and annual hazard rate of inflammatory breast cancer.
The real-time prognosis of patients with inflammatory breast cancer (IBC) after surviving for several years was unclear. We aimed to estimate survival over time in IBC using conditional survival (CS) and annual hazard functions. This study recruited 679 patients diagnosed with IBC between 2010 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. We used the Kaplan-Meier method to estimate overall survival (OS). CS was the probability of surviving for another y years after surviving for x years after the diagnosis, and the annual hazard rate was the cumulative mortality rate of follow-up patients. Cox regression analyses were used to identify prognostic factors, and changes in real-time survival and immediate mortality in surviving patients were assessed within these prognostic factors. CS analysis showed real-time improvement in survival, with 5-year OS updated annually from the initial 43.5% to 52.2%, 65.3%, 78.5%, and 89.0% (surviving 1-4 years, respectively). However, this improvement was relatively small in the first two years after diagnosis, and the smoothed annual hazard rate curve showed increasing mortality during this period. Cox regression identified seven unfavorable factors at diagnosis, but only distant metastases remained after five years of survival. Analysis of the annual hazard rate curves showed that mortality continued to decrease for most survivors, except for metastatic IBC. Real-time survival of IBC improved dynamically over time, and the magnitude of this improvement was non-linear, depending on survival time and clinicopathological characteristics.


Modification of Drosophila cell surfaces by concanavalin A.
The effect of Con A on the surface morphology of cultured cells of Drosophila melanogaster growing on coverglasses was examined by scanning electron microscopy. With low lectin concentrations (5--10 microgram/ml) surface filaments disappeared and the cells flattened and spread against the glass surface. Cytoplasmic fusion bridges were observed in areas where cells made contact. Concentrations of Con A ranging between 50--500 microgram/ml caused cell shrinkage and surface distortions without cell flattening and filament loss. These morphologic effects were not apparent if Con A binding sites were blocked by preincubation with alpha-methyl-D-mannopyranoside before application to the cell cultures. However, once the Con A-mediated changes were in effect, the cells failed to show recovery when they were returned to growth medium and a majority of the cells on the coverglasses degenerated. Presumably the cells whose morphology appears unaffected by Con A treatment are the survivors that repopulate cultures returned to growth medium.


Concurrent exercise does not prevent recognition memory deficits induced by beta-amyloid in rats.
Alzheimer's disease affects thousands of people worldwide. Alternatives aiming to prevent the disease or reduce its symptoms include different physical exercise configurations. Here we investigate the potential of concurrent exercise to prevent recognition memory deficits in an Alzheimer's disease-like model induced by the hippocampal beta-amyloid (Aβ) injection in Wistar rats. We demonstrate that the concurrent exercise, which included running and strength exercises performed in the same exercise session, is ineffective in preventing recognition memory deficits in the Aβ rats. Besides, higher levels of reactive oxygen species were found in the concurrent exercise group's hippocampus. The running exercise administrated alone prevented recognition memory impairments.


Comparable prognosis in different neonatal histidine-tryptophan-ketoglutarate dosage management.
Histidine-tryptophan-ketoglutarate (HTK) is a solution commonly used for organ transplantation. However, there is no certified fixed regimen for on-pump heart surgery in neonates. We aimed to retrospectively evaluate the outcomes related to different HTK dosages and to analyze the safety of high-dosage perfusion. A total of 146 neonates who underwent on-pump heart surgery with single-shot HTK perfusion were divided into two groups according to HTK dosages: a standard-dose (SD) group (n = 63, 40 mL/kg < HTK ≤ 60 mL/kg) and a high-dose (HD) group (n = 83, HTK >60 mL/kg). Propensity score matching (PSM) was performed to control confounding bias. The SD group had a higher weight (3.7 ± 0.4 vs. 3.4 ± 0.4 kg, P < 0.0001), a lower proportion of complete transposition of the great artery (69.8% vs. 85.5%, P = 0.022), a lower cardiopulmonary bypass (CPB) time (123.5 [108.0, 136.0] vs. 132.5 [114.8, 152.5] min, P = 0.034), and a lower aortic x-clamp time (82.9 ± 27.1 vs. 95.5 ± 26.0 min, P = 0.005). After PSM, 44 patients were assigned to each group; baseline characteristics and CPB parameters between the two groups were comparable. There were no significant differences in peri-CPB blood product consumption after PSM (P > 0.05). The incidences of post-operative complications were not significantly different between the two groups. There were no significant differences in ventilation time, intensive care unit stay, and post-operative hospital stay (P > 0.05). Follow-up echocardiography outcomes at 1 month, 3 to 6 months, and 1 year showed that left ventricular ejection fraction and end-diastolic dimension were comparable between the two groups. In neonatal on-pump cardiac surgery patients, single-shot HD (>60 mL/kg) HTK perfusion had a comparable heart protection effect and short-term post-operative prognosis as standard dosage perfusion of 40 to 60 mL/kg. Thus, this study provides supporting evidence of the safety of HD HTK perfusion.


The Budget Impact Analysis of Adopting Direct Oral Anticoagulants for Stroke Prevention in Nonvalvular Atrial Fibrillation Patients in Malawi.
This study aimed to estimate the budget impact of adopting direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation in Malawi after the inclusion of DOACs in the World Health Organization's essential medicine list. A model was developed in Microsoft Excel. An eligible population of 201 491 was adjusted with 0.05 % incidence rate and mortality rates yearly according to the treatments. The model estimated the implication of supplementing rivaroxaban or apixaban to the standard treatment mix (also the comparator), thus warfarin and aspirin. The current market share of 43% aspirin and 57% warfarin was adjusted proportionally with 10% DOAC uptake in the first year and 5% annually over the subsequent 4 years. Clinical events of stroke and major bleeding from the ROCKET-AF and ARISTOTLE trials were used because health outcome indicators affect resource utilization. The analysis was conducted solely from the Malawi Ministry of Health perspective and it considered direct costs over 5 years. The sensitivity analysis involved varying drug costs, population, and care costs from both public and private sectors. The research suggests that despite potential savings of $6 644 141 to $6 930 812 in stroke care because of fewer stroke events, the total Ministry of Health healthcare budget (approximately $260 400 000) may increase by between $42 488 342 to $101 633 644 in 5 years because drug acquisition costs are greater than savings. With a fixed budget and current DOACs prices, Malawi can consider using DOACs in patients at the highest risk while waiting for cheaper generic versions.


Comparison of peri- and intraoperative outcomes of open vs robotic-assisted partial nephrectomy for renal cell carcinoma: a propensity-matched analysis.
Partial nephrectomy (PN) is the gold standard surgical treatment for resectable renal cell carcinoma (RCC) tumors. However, the decision whether a robotic (RAPN) or open PN (OPN) approach is chosen is often based on the surgeon's individual experience and preference. To overcome the inherent selection bias when comparing peri- and postoperative outcomes of RAPN vs. OPN, a strict statistical methodology is needed. We relied on an institutional tertiary-care database to identify RCC patients treated with RAPN and OPN between January 2003 and January 2021. Study endpoints were estimated blood loss (EBL), length of stay (LOS), rate of intraoperative and postoperative complications, and trifecta. In the first step of analyses, descriptive statistics and multivariable regression models (MVA) were applied. In the second step of analyses, to validate initial findings, MVA were applied after 2:1 propensity-score matching (PSM). Of 615 RCC patients, 481 (78%) underwent OPN vs 134 (22%) RAPN. RAPN patients were younger and presented with a smaller tumor diameter and lower RENAL-Score sum, respectively. Median EBL was comparable, whereas LOS was shorter in RAPN vs. OPN. Both intraoperative (27 vs 6%) and Clavien-Dindo > 2 complications (11 vs 3%) were higher in OPN (both < 0.05), whereas achievement of trifecta was higher in RAPN (65 vs 54%; p = 0.028). In MVA, RAPN was a significant predictor for shorter LOS, lower rates of intraoperative and postoperative complications as well as higher trifecta rates. After 2:1 PSM with subsequent MVA, RAPN remained a statistical and clinical predictor for lower rates of intraoperative and postoperative complications and higher rates of trifecta achievement but not LOS. Differences in baseline and outcome characteristics exist between RAPN vs. OPN, probably due to selection bias. However, after applying two sets of statistical analyses, RAPN seems to be associated with more favorable outcomes regarding complications and trifecta rates.


99mTc-DTPA(Sn) dry-kit preparation. Quality control and clearance studies.
The preparation technique for 99m-Tc-DTPA(Sn)-complex has been studied in detail in order to find the optimal conditions for preparation. The concentration of DTPA should be at least 10 mM, and that of Sn(II) less than 1 mM, in order to obtain a reproducible high-labelling yield. A dry sterile kit was prepared of 39.3 mg H-5DTPA and 2.3 mg SnCl-2 with 2H-2O in a 10 ml vial. The 99m-Tc-DTPA(Sn) was prepared by adding the 99m-Tc-eluate to the vial. After 1 min the solution was sterile-filtered and was ready for use. The plasma clearance of 99m-Tc-DTPA(Sn) in man determined by blood-sampling up to 200 minutes after administration shows a good correlation to endogenous creatinine clearance (r plus 0.93). The plasma disappearance curve studied during 24 h is, however, a sum of three exponentials corresponding to biological half-times of 18 plus or minus 8 min, 105 plus or minus 9 min and 17 plus or minus 4 h. The slow third component representing about 2% is assumed to be due to binding of 99m-Tc to plasma proteins. The absorbed radiation dose calculated for whole body is 8 mrad/mCi, kidneys 50 mrad/mCi, bladder 300 mrad/mCi, ovaries 17 mrad/mCi and testes 11 mrad/mCi. This agent is a valuable radiopharmaceutical for renovascular clinical problems. Scintigraphic imaging of the aorta, kidneys, ureters and bladder (for residual urinary volume-determination) could be performed.


Separation of plastics: The importance of kinetics knowledge in the evaluation of froth flotation.
Froth flotation is a promising technique to separate polymers of similar density. The present paper shows the need for performing kinetic tests to evaluate and optimize the process. In the experimental study, batch flotation tests were performed on samples of ABS and PS. The floated product was collected at increasing flotation time. Two variables were selected for modification: the concentration of the depressor (tannic acid) and airflow rate. The former is associated with the chemistry of the process and the latter with the transport of particles. It was shown that, like mineral flotation, plastics flotation can be adequately assumed as a first order rate process. The results of the kinetic tests showed that the kinetic parameters change with the operating conditions. When the depressing action is weak and the airflow rate is low, the kinetic is fast. Otherwise, the kinetic is slow and a variable percentage of the plastics never floats. Concomitantly, the time at which the maximum difference in the recovery of the plastics in the floated product is attained changes with the operating conditions. The prediction of flotation results, process evaluation and comparisons should be done considering the process kinetics.


Women's susceptibility to tobacco carcinogens and survival after diagnosis of lung cancer.
It has been hypothesized that women are more susceptible to tobacco carcinogens than men, but after diagnosis of lung cancer, they have better survival rates than men. To add to the evidence on the lung cancer risk of women who smoke and their survival after diagnosis of lung cancer, conditional on other prognostic indicators and compared with men of the same age who smoke. Nonexperimental, etiologic study with prospective collection of data based on baseline computed tomographic screening for lung cancer and follow-up of diagnosed cases of lung cancer in North America in 1993-2005. A total of 7498 women and 9427 men were screened, all of whom were asymptomatic, aged at least 40 years, and had a history of cigarette smoking. Comparing women with men, the prevalence odds ratio (OR) for screen-detectable lung cancer (conditional on age and smoking history) and the hazard ratio of fatal outcome of lung cancer (conditional on smoking history, disease stage, tumor cell type, and resection). Lung cancer was diagnosed in 156 women and 113 men (rates of 2.1% and 1.2%, respectively). The prevalence OR comparing women with men was 1.9 (95% confidence interval [CI], 1.5-2.5). The hazard ratio of fatal outcome of lung cancer comparing women with men was 0.48 (95% CI, 0.25-0.89). Women appear to have increased susceptibility to tobacco carcinogens but have a lower rate of fatal outcome of lung cancer compared with men.


Ketosis resistance in the male offspring of protein-malnourished rat dams.
Plasma beta-hydroxybutyrate concentrations were measured in the offspring of rats that were fed either a control (20% protein) diet or low-protein (8% protein) diet during pregnancy and lactation. Low-protein offspring had significantly lower plasma beta-hydroxybutyrate compared with controls in the fed state (P < .04) and after fasting for 24 hours (P < .001) and 48 hours (P < .04). There were no differences in blood glucose, acetoacetate, plasma glucagon, cholesterol, or glycerol between control and low-protein offspring. However, plasma nonesterified fatty acids (NEFAs) were significantly higher in low-protein offspring in the fed state (P < .05). In contrast, plasma triglycerides and insulin were significantly lower in low-protein offspring compared with controls when fed (P < .001) and after a 24-hour fast (P < .001). These results suggest that poor maternal and early postnatal nutrition can have long-term effects on ketone body metabolism in the offspring during adulthood. This apparent ketosis resistance is similar to that observed in some forms of human diabetes.


Cold water immersion in recovery following a single bout resistance exercise suppresses mechanisms of miRNA nuclear export and maturation.
Cold water immersion (CWI) following intense exercise is a common athletic recovery practice. However, CWI impacts muscle adaptations to exercise training, with attenuated muscle hypertrophy and increased angiogenesis. Tissue temperature modulates the abundance of specific miRNA species and thus CWI may affect muscle adaptations via modulating miRNA expression following a bout of exercise. The current study focused on the regulatory mechanisms involved in cleavage and nuclear export of mature miRNA, including DROSHA, EXPORTIN-5, and DICER. Muscle biopsies were obtained from the vastus lateralis of young males (n = 9) at rest and at 2, 4, and 48 h of recovery from an acute bout of resistance exercise, followed by either 10 min of active recovery (ACT) at ambient temperature or CWI at 10°C. The abundance of key miRNA species in the regulation of intracellular anabolic signaling (miR-1 and miR-133a) and angiogenesis (miR-15a and miR-126) were measured, along with several gene targets implicated in satellite cell dynamics (NCAM and PAX7) and angiogenesis (VEGF and SPRED-1). When compared to ACT, CWI suppressed mRNA expression of DROSHA (24 h p = 0.025 and 48 h p = 0.017), EXPORTIN-5 (24 h p = 0.008), and DICER (24 h p = 0.0034). Of the analyzed miRNA species, miR-133a (24 h p < 0.001 and 48 h p = 0.007) and miR-126 (24 h p < 0.001 and 48 h p < 0.001) remained elevated at 24 h post-exercise in the CWI trial only. Potential gene targets of these miRNA, however, did not differ between trials. CWI may therefore impact miRNA abundance in skeletal muscle, although the precise physiological relevance needs further investigation.


Parameters affecting successful transplantation of frozen-thawed human fetal ovaries into immunodeficient mice.
To compare the development and survival of human fetal follicles frozen-thawed with dimethylsulfoxide (DMSO) and propandiol (PROH) in immunodeficient mice, to study the effects of host treatment with FSH, and to compare kidney and subcutaneous transplantation. Controlled histologic study. Major tertiary care and referral academic center.Twenty-one women undergoing second-trimester pregnancy termination. Microscopic morphometric analysis and immunocytochemistry for proliferating-cell nuclear antigen in human fetal ovaries grafted into immunodeficient mice. Renal grafts that were frozen-thawed with DMSO rather than PROH survived better in the hosts (79.6% compared with 58.8%), but significantly more follicles were identified in grafts frozen-thawed with PROH (P<.001). Follicular development was observed only in FSH-treated hosts, and follicular survival and development was better in the kidney than the subcutaneous site. This is the first report showing development of human fetal follicles in immunodeficient mice. Freezing-thawing with PROH seems to support development and survival better than with DMSO. The kidney is a better transplantation site than the subcutaneous site, probably because of its superior vascularization. Administration of FSH to the host is essential for follicular development. Follicular development and growth was better in ovarian grafts from older fetuses, as they contained more formed follicles.


Dementia in the Bangladeshi diaspora in England: A qualitative study of the myths and stigmas about dementia.
Although Bangladeshis are three times more likely to be carers than White British, Bangladeshi family carers are the most deprived, neglected, and effectively a hidden group in the United Kingdom.1 There is a paucity of research within the Bangladeshi community that is capable of explaining and predicting the experiences and concerns of Bangladeshi family carers providing care for their relatives with dementia. The purpose of this study is to explore the perspectives of Bangladeshi family carers' knowledge and day-to-day experiences living in England. This is a qualitative study involving semistructured face-to-face interviews with six Bangladeshi family carers living in London and Portsmouth. Interviews were recorded with the consent and transcribed verbatim. Data were managed by using NVivo software, and thematic analysis was performed. This paper explores that most carers have a lack of knowledge and awareness of the symptoms of dementia. The results of this study are in contrast to previous studies, where South Asian carers perceived dementia as being possessed by evil spirits or God's punishment for previous life's sins; this study reveals that Bangladeshi family carers believed dementia was a medical condition. Unlike earlier South Asian studies, however, all family carers in this study also believed that there was no stigma attached to dementia. Further research is warranted to investigate the religious beliefs, familism, and interpersonal motives as theoretical perspectives to explain how Bangladeshi family carers negotiate and construct their caregiving roles for their relatives with dementia.


Infection with Kaposi's sarcoma-associated herpesvirus (KSHV) and human immunodeficiency virus (HIV) in relation to the risk and clinical presentation of Kaposi's sarcoma in Uganda.
A case-control study from Uganda found that the risk of Kaposi's sarcoma increased with increasing titre of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) latent nuclear antigens, independently of HIV infection. Clinically, widespread Kaposi's sarcoma was more frequent among patients with HIV infection than in those without, but was not related to anti-KSHV antibody titres.


Compositional Design of Dielectric, Ferroelectric and Piezoelectric Properties of (K, Na)NbO₃ and (Ba, Na)(Ti, Nb)O₃ Based Ceramics Prepared by Different Sintering Routes.
Lead free piezoelectric materials are being intensively investigated in order to substitute lead based ones, commonly used in many different applications. Among the most promising lead-free materials are those with modified NaNbO₃, such as (K, Na)NbO₃ (KNN) and (Ba, Na)(Ti, Nb)O₃ (BTNN) families. From a ceramic processing point of view, high density single phase KNN and BTNN ceramics are very difficult to sinter due to the volatility of the alkaline elements, the narrow sintering temperature range and the anomalous grain growth. In this work, Spark Plasma Sintering (SPS) and high-energy ball milling (HEBM), following heat treatments (calcining and sintering), in oxidative (O₂) atmosphere have been used to prepare single phase highly densified KNN ("pure" and Cu2+ or Li1+ doped), with theoretical densities ρth > 97% and BTNN ceramics (ρth - 90%), respectively. Using BTTN ceramics with a P4mm perovskite-like structure, we showed that by increasing the NaNbO₃ content, the ferroelectric properties change from having a relaxor effect to an almost "normal" ferroelectric character, while the tetragonality and grain size increase and the shear piezoelectric coefficients (k15, g15 and d15) improve. For KNN ceramics, the results reveal that the values for remanent polarization as well as for most of the coercive field are quite similar among all compositions. These facts evidenced that Cu2+ may be incorporated into the A and/or B sites of the perovskite structure, having both hardening and softening effects.


The Effect of Laminectomy with Instrumented Fusion Carried into the Thoracic Spine on the Sagittal Imbalance in Patients with Multilevel Ossification of the Posterior Longitudinal Ligament.
To determine if there is a difference in either the cervical alignment or the clinical outcomes in cervical ossification of the posterior longitudinal ligament (OPLL) patients who underwent laminectomy with instrumented fusion (LIF) ending at C6 , C7 , or proximal thoracic spine for the treatment of multilevel OPLL, and to find out the appropriate distal fusion level. This was a single-center retrospective study. In total, 36 patients with cervical OPLL who underwent three or more level LIF in our institution between January 2015 and January 2017 were enrolled. They were divided into three groups according to their distal ends: C6 (nine females and 11 males, 60.45 ± 9.68 years old), C7 (four females and six males, 61.60 ± 10.29 years old), and T-group (two females and four males, 64.33 ± 8.12 years old). Radiographic (compression level, classification of OPLL, occupying rate, C2-7 cobb angle, C2-7 sagittal vertical axis, and fusion level) and clinical outcomes (NDI score, operative time, and blood loss) were compared. Predictors of postoperative sagittal imbalance were also identified according to if the postoperative C2-7 SVA was greater than 40 mm. The sensitivity and specificity of preoperative parameters predicting postoperative cervical stability were evaluated via the receiver operating characteristic (ROC) curve. All patients were followed up at least 1 year. The blood loss in T group was significantly more than C6 or C7 group. The length of fusion level became significantly longer when the caudal level extended to the thoracic spine. The age, preoperative SVA, and NDI score at follow-up were significantly greater in the imbalance group. At the final follow-up, the cervical lordosis tended to be straight and the C2-7 SVA tended to be greater when the caudal level of fusion was extended to upper thoracic segment. Further ROC curve analysis suggested that patients' age had a sensitivity of 75.00%, specificity of 79.17% for cervical stability, and the AUC was 0.844 (P < 0.01), with the cutoff value for age being 66.5 years old. For preoperative SVA, the sensitivity was 58.30%, and specificity was 91.70%, with the AUC of 0.778 (P < 0.01). The cutoff value for preoperative SVA was 30.4 mm. Although posterior fusion terminating in the thoracic spine was not superior to the cervical spine for patients with multilevel OPLL, for elderly patients (>67 years) with great preoperative SVA (>30 mm), terminating at C6 was recommended to limit the invasion of cervical extensor muscles, provided the decompression was adequate.


Increased electrical nerve stimulation threshold of the sciatic nerve in patients with diabetic foot gangrene: a prospective parallel cohort study.
Peripheral neuropathy may affect nerve conduction in patients with diabetes mellitus. This study was designed to test the hypothesis that the electrical stimulation threshold for a motor response of the sciatic nerve is increased in patients suffering from diabetic foot gangrene compared to non-diabetic patients. Prospective non-randomised trial with two parallel groups. Two university-affiliated hospitals. Patients scheduled for surgical treatment of diabetic foot gangrene (n = 30) and non-diabetic patients (n = 30) displaying no risk factors for neuropathy undergoing orthopaedic foot or ankle surgery. The minimum current intensity required to elicit a typical motor response (dorsiflexion or eversion of the foot) at a pulse width of 0.1 ms and a stimulation frequency of 1 Hz when the needle tip was positioned under ultrasound control directly adjacent to the peroneal component of the sciatic nerve. The non-diabetic patients were younger [64 (SD 12) vs. 74 (SD 7) years] and predominantly female (23 vs. 8). The geometric mean of the motor stimulation threshold was 0.26 [95% confidence interval (95% CI) 0.24 to 0.28] mA in non-diabetic and 1.9 (95% CI 1.6 to 2.2) mA in diabetic patients. The geometric mean of the electrical stimulation threshold was significantly (P < 0.001) increased by a factor of 7.2 (95% CI 6.1 to 8.4) in diabetic compared to non-diabetic patients. The electrical stimulation threshold for a motor response of the sciatic nerve is increased by a factor of 7.2 in patients with diabetic foot gangrene, which might hamper nerve identification.


Prognostic significance of p16 in locally advanced squamous cell carcinoma of the head and neck treated with concurrent cisplatin and radiotherapy.
Human papillomavirus (HPV)-related squamous cell cancer of the head and neck (SCCHN) has emerged as a distinct clinical entity. The expression of p16 protein can be used as a surrogate for HPV status. p16 immunohistochemistry (IHC) was assessed in archival paraffin-embedded material for 55 patients with locally advanced SCCHN treated with a uniform regimen of cisplatin and radiation. HPV status was assessed by colorimetric in situ hybridization (CISH) and polymerase chain reaction (PCR). Compared with p16- and HPV-negative patients, the p16- and HPV-positive patients had improved overall survival, disease-free survival, and locoregional recurrence rates. p16 IHC may serve as a useful surrogate and prognostic marker for patients with HPV-related SCCHN treated with cisplatin and radiation.


Simultaneous expression of the SP-peptidergic and noradrenergic phenotypes in rat sympathetic neurons.
We previously observed that substance P (SP) levels in the rat superior cervical ganglion (SCG) rise sharply when the ganglion is maintained in vitro. To define the cellular localization of SP, sections of cultured SCG were stained for the possible dual presence of SP and tyrosine hydroxylase (TOH). Immunoreactivity to both SP and TOH was present in the majority of principal neurons. This observation suggests that principal sympathetic neurons can express simultaneously both the noradrenergic and SP-peptidergic phenotypes.


Intensive dietary intervention by a dietitian as a case manager among community dwelling older adults: the EDIT study.
Clinical trials that have assessed the best approach for treating under-nutrition in old age are scarce. To determine the impact of an intensive nutritional intervention program led by a dietitian on the health and nutritional status of malnourished community dwelling older adults. Sixty-eight eligible participants (age<75) were randomly assigned to a Dietetic Intervention Treatment (DIT), an intensive nutritional intervention led by a dietitian, or a Medical Treatment (MT), a physician-led standard care group, with an educational booklet regarding dietary requirements and recommendations for older adults. An additional 59 eligible participants who were unable to participate in the randomization were included as a non-randomized "untreated nutrition" group (UNG). Over the 6-month follow-up, the DIT group showed significant improvement in cognitive function (from 25.8±4.5 to 26.8±4, p=0.04), and depression score (from 7.3±3.9 to 5.4±3.9, p=0.04) compared with the change in the other 2 groups. The DIT group showed a significant improvement in intake of carbohydrates (+15% vs. +1% in the MT and +3% in the UNG), protein (+8% vs. +2% in the MT and -3% in the UNG), vitamin B6 (+20% vs. +7% in the MT and +8% in the UNG), and vitamin B1 (+22% vs. +11% in the MT and 0% in the UNG). The DIT group had a significantly lower cost of physician visits than the other 2 groups ($172.1±232.0 vs. $417.2±368.0 in the MT and $428.1±382.3 in the UNG, p=0.005). Intensive dietary intervention was moderately effective in lowering cost of services used and improving medical and nutritional status among community dwelling older adults.


Early post-mortem formation of carbonate concretions around tusk-shells over week-month timescales.
Carbonate concretions occur in sedimentary rocks of widely varying geological ages throughout the world. Many of these concretions are isolated spheres, centered on fossils. The formation of such concretions has been variously explained by diffusion of inorganic carbon and organic matter in buried marine sediments. However, details of the syn-depositional chemical processes by which the isolated spherical shape developed and the associated carbon sources are little known. Here we present evidence that spherical carbonate concretions (diameters φ : 14 ~ 37 mm) around tusk-shells (Fissidentalium spp.) were formed within weeks or months following death of the organism by the seepage of fatty acid from decaying soft body tissues. Characteristic concentrations of carbonate around the mouth of a tusk-shell reveal very rapid formation during the decay of organic matter from the tusk-shell. Available observations and geochemical evidence have enabled us to construct a 'Diffusion-growth rate cross-plot' that can be used to estimate the growth rate of all kinds of isolated spherical carbonate concretions identified in marine formations. Results shown here suggest that isolated spherical concretions that are not associated with fossils might also be formed from carbon sourced in the decaying soft body tissues of non-skeletal organisms with otherwise low preservation potential.


Ankle sprains and instability in dancers.
Ankle inversion injuries are the most common traumatic injuries in dancers. Ankle stability is integral to normal mobilization and to minimizing the risk for ankle sprain. The ability of the dynamic and static stabilizers of the ankle joint to maintain their structural integrity is a major component of the normal gait cycle. In the world of dance, this quality assumes even greater importance given the range of movement and stresses imposed on the ankle during various dance routines.


Long-term effects of cytostatic agents on the hemopoietic stroma: a comparison of four different assays.
We have compared four assays to detect hemopoietic stromal damage induced by various cytostatic agents in young (4-week old) and adult (12-week old) mice. These assays included: (a) quantitation of the hemopoietic stem cell content of subcutaneously implanted spleens and femurs, (b) quantitation of fibroblastic colony-forming units per femur and spleen, (c) quantitation of the growth of normal hemopoietic progenitor cells in irradiated cytostatic drug-treated mice, and (d) measurement of splenic hemopoietic stem cell accumulation in response to bacterial lipopolysaccharide-induced hemopoietic stress. Busulfan caused a short- and long-term hemopoietic stromal defect. However, the four assays used showed different kinetics and severity of the stromal damage. Cyclophosphamide treatment resulted in a short-term stromal damage which was repaired within one week to three months, depending on the assay used. Methotrexate and vincristine did not cause long-term stromal damage as measured by the four assays used, whereas a short-term splenic stromal damage was detected using the subcutaneous implantation technique. No significant differences in stromal sensitivity to drug treatment were observed between young and adult mice. The presented data suggest that the four assays used to study stromal integrity measure different components of the hemopoietic microenvironment, and indicate that the use of a single assay may well lead to erroneous interpretations.


Genomic analysis of gene expression relationships in transcriptional regulatory networks.
From merging several data sources, we created an extensive map of the transcriptional regulatory network in Saccharomyces cerevisiae, comprising 7419 interactions connecting 180 transcription factors (TFs) with their target genes. We integrated this network with gene-expression data, relating the expression profiles of TFs and target genes. We found that genes targeted by the same TF tend to be co-expressed, with the degree of co-expression increasing if genes share more than one TF. Moreover, shared targets of a TF tend to have similar cellular functions. By contrast, the expression relationships between the TFs and their targets are much more complicated, often exhibiting time-shifted or inverted behavior. Further information is available at http://bioinfo.mbb.yale.edu/regulation/TIG/


Synthesis under microwave irradiation of [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazoles and other diazoles bearing indole moieties and their antimicrobial evaluation.
Microwave-assisted synthesis of some novel compounds, namely, 3-(2-methyl-1H-indol-3-yl)-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a,b was accomplished via bromination of 2-methyl-3-[4-(arylideneamino)-5-mercapto-4H-[1,2,4]triazol-3-yl]-1H-indoles 3a,b. Also, new [1,3,4]thiadiazoles 12a,b, [1,2,4]triazoles 15a,b and [1,3,4]oxadiazoles 19a,b, with indole moieties, were prepared by cyclization of 1-[(2-methyl-1H-indole)-3-carbonyl]thiosemicarbazides 8a,b under microwave irradiation using different reaction conditions. Moreover, reaction of acid hydrazide 7 with ethyl 2-(N-phenylhydrazono)-3-oxobutanoate (20) gave the respective phenylhydrazonopyrazole derivative 21 under the reaction conditions employed. The structures of the synthesized compounds were assigned based on elemental analyses and spectral data (IR, (1)H-NMR, (13)C-NMR, MS). The antifungal and antibacterial activities of the new products were also evaluated.


Circulating mid-regional proadrenomedullin is a predictor of mortality in patients with COVID-19: a systematic review and meta-analysis.
Although there is increasing understanding of the changes in the laboratory parameters of Coronavirus disease 2019 (COVID-19), the correlation between circulating Mid-regional Proadrenomedullin (MR-proADM) and mortality of patients with COVID-19 is not fully understood. In this study, we conducted a systematic review and meta-analysis to evaluate the prognostic value of MR-proADM in patients with COVID-19. The PubMed, Embase, Web of Science, Cochrane Library, Wanfang, SinoMed and Chinese National Knowledge Infrastructure (CNKI) databases were searched from 1 January 2020 to 20 March 2022 for relevant literature. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to assess quality bias, STATA was employed to pool the effect size by a random effects model, and potential publication bias and sensitivity analyses were performed. 14 studies comprising 1822 patients with COVID-19 met the inclusion criteria, there were 1145 (62.8%) males and 677 (31.2%) females, and the mean age was 63.8 ± 16.1 years. The concentration of MR-proADM was compared between the survivors and non-survivors in 9 studies and the difference was significant (P < 0.01), I2 = 46%. The combined sensitivity was 0.86 [0.73-0.92], and the combined specificity was 0.78 [0.68-0.86]. We drew the summary receiver operating characteristic (SROC) curve and calculated the area under curve (AUC) = 0.90 [0.87-0.92]. An increase of 1 nmol/L of MR-proADM was independently associated with a more than threefold increase in mortality (odds ratio (OR) 3.03, 95% confidence interval (CI) 2.26-4.06, I2 = 0.0%, P = 0.633). The predictive value of MR-proADM for mortality was better than many other biomarkers. MR-proADM had a very good predictive value for the poor prognosis of COVID-19 patients. Increased levels of MR-proADM were independently associated with mortality in COVID-19 patients and may allow a better risk stratification.


Comparison of an absolute and surrogate measure of relative translucency in dental ceramics.
The objective was to compare absolute translucency with a frequently used surrogate measure of relative translucency (contrast ratio) from 14 all-ceramic materials having a wide range of translucencies. Standardized disks were fabricated from fourteen ceramics, varying both thickness (0. 3mm, 0.5 mm, 1.0 mm, and 1.5 mm) and chroma (high and low). Absolute translucency (percent transmission) was measured using a spectroradiometer with an integrating sphere. Relative translucency was measured using a spectrophotometer as contrast ratio (contrast ratio; ratio of L* values recorded on black and white backgrounds). Non-linear regression was used to compare measurements of absolute versus relative values for each of the spectrophotometers. Contrast ratio was not able to characterize translucency across the range of materials studied and became less sensitive with increasing opacity. A non-linear correlation was found between percent transmission and contrast ratio down to 50% transmission (r(2)=0.97) and contrast ratio was insensitive to transmission differences below 50% transmission. Contrast ratio is not a direct measure of translucency and cannot be used below 50% transmission.


Rhizobacter gummiphilus NS21 has two rubber oxygenases (RoxA and RoxB) acting synergistically in rubber utilisation.
Biodegradation of poly(cis-1,4-isoprene) (rubber) by Gram-negative bacteria has been investigated on the enzymatic level only in Steroidobacter cummioxidans 35Y (previously Xanthomonas sp. 35Y). This species produces two kinds of rubber oxygenases, RoxA35Y and RoxB35Y, one of which (RoxB35Y) cleaves polyisoprene to a mixture of C20- and higher oligoisoprenoids while the other (RoxA35Y) cleaves polyisoprene and RoxB35Y-derived oligoisoprenoids to the C15-oligoisoprenoid 12-oxo-4,8-dimethyltrideca-4,8-diene-1-al (ODTD). ODTD can be taken up by S. cummioxidans and used as a carbon source. Gram-positive rubber-degrading bacteria employ another type of rubber oxygenase, latex clearing protein (Lcp), for the initial oxidative attack of the polyisoprene molecule. In this contribution, we examined which type of rubber oxygenase is present in the only other well-documented Gram-negative rubber-degrading species, Rhizobacter gummiphilus NS21. No homologue for an Lcp protein but homologues for a putative RoxA and a RoxB protein (the latter identical to a previously postulated LatA-denominated rubber cleaving enzyme) were identified in the genome of strain NS21. The roxANS21 and roxBNS21 genes were separately expressed in a ∆roxA35Y/∆roxB35Y background of S. cummioxidans 35Y and restored the ability of the mutant to produce oligoisoprenoids. The RoxANS21 and RoxBNS21 proteins were each purified and biochemically characterised. The results-in combination with in silico analysis of databases-indicate that Gram-negative rubber-degrading bacteria generally utilise two synergistically acting rubber oxygenases (RoxA/RoxB) for efficient cleavage of polyisoprene to ODTD.


The effect of water storage on nanoindentation creep of various CAD-CAM composite blocks.
To study the effect of water storage (3 months) on the creep deformation of various CAD-CAM composite structures at the nanoscale and compare it to that at the macroscale. Seven CAD-CAM blocks were investigated: five resin-composite blocks (RCB), one polymer-infiltrated ceramic network (PICN) block, and one ceramic-filled polyetheretherketone (PEEK) block. Specimens of each material (n = 6) were separated into two groups (n = 3) according to their storage conditions (24 h dry storage at 23˚C and 3 months storage in 37˚C distilled water). Nano-indentation creep measurements were undertaken (creep depth measured in µm) using a nanoindenter (Nanovea) equipped with Berkovich three-sided pyramidal diamond tip. The machine was set for the chosen parameters: a load of 20 gf, a pause of 20 s, and the material type. Thirty indentations on 3 samples were made for each material for each test. Data were analysed using two-way ANOVA followed by one-way ANOVA and Bonferroni post hoc tests and independent t-test (< 0.05) for comparisons between the materials. The nanoindentation creep depth after 24 h storage ranged from 0.09 to 0.33 μm and increased after 3 months storage in distilled water to between 0.28 and 3.46 μm. There was a statistically significant difference in nanoindentation creep behaviour between the two storage conditions for each investigated material (independent t-test) and between all materials (Bonferroni post hoc). There was a non-significant negative correlation between nanoindentation creep (µm) and filler weight% at 24 h dry storage but a significant correlation at 3 months of water storage. A further non-significant positive correlation between nanoindentation creep (µm) and bulk compressive creep (%) was found. The PICN material showed superior dimensional stability in terms of nanoindentation creep depth in both storage conditions. Other composite blocks showed comparable performance at 24 h dry condition, but an increased nanoindentation creep upon water storage.


(-)-Epicatechin 3-O-gallate ameliorates the damages related to peroxynitrite production by mechanisms distinct from those of other free radical inhibitors.
This study was carried out to elucidate whether the protective activity of (-)-epicatechin 3-O-gallate (ECg) against excessive peroxynitrite (ONOO(-)) production, is distinct from the activity of several well-known free radical inhibitors, the ONOO(-) inhibitors ebselen and uric acid, the superoxide anion (O(2)(-)) scavenger copper zinc superoxide dismutase (CuZnSOD) and the selective inducible nitric oxide synthase inhibitor L-N(6)-(1-iminoethyl)lysine hydrochloride (L-NIL). To generate ONOO(-), male Wistar rats (n = 6/group) were subjected to ischaemia-reperfusion process together with lipopolysaccharide (LPS) injection. Although ECg did not scavenge the ONOO(-) precursors nitric oxide (NO) and O(2)(-), it reduced the 3-nitrotyrosine level, a property similar to that of uric acid, but distinct from L-NIL. In addition, the elevation in myeloperoxidase activity was reversed by the administration of ECg, uric acid and SOD, but not by that of L-NIL. Furthermore, ECg was the more potent scavenger of the ONOO(-) decomposition product, the hydroxyl radical (*OH), than any other free radical inhibitor tested. The LPS plus ischaemia-reperfusion process resulted in renal dysfunction, estimated by measuring the parameters of renal function--serum urea nitrogen and creatinine levels. However, administration of ECg ameliorated renal dysfunction more than that of the other free radical inhibitors. Moreover, ECg reduced the excessive uric acid level, while the others did not, suggesting a property of ECg distinct from the others. Furthermore, proteinuria, which was demonstrated by the low- and high-molecular weight (LMW and HMW) protein bands of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern, caused by LPS plus ischaemia-reperfusion, was attenuated by administration of ECg and L-NIL, after which the HMW band intensities decreased and LMW protein bands were absent. This study indicates that, in an in-vivo model of ONOO(-) generation, ECg, L-NIL and uric acid exert stronger protective activity against ONOO(-)-induced oxidative damage than SOD and ebselen, and that the mechanism whereby ECg protects against ONOO(-) is distinct from that of L-NIL or uric acid.


Very Early Pouchitis Is Associated with an Increased Likelihood of Chronic Inflammatory Conditions of the Pouch.
Chronic inflammatory conditions of the pouch are common after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We aimed to investigate the relationship between acute pouchitis within 180 days of the final stage of IPAA surgery (very early pouchitis) and the future development of chronic antibiotic dependent pouchitis (CADP) and Crohn's-like disease of the pouch (CLDP). We performed a retrospective cohort study, evaluating patients who underwent proctocolectomy with IPAA between January 1, 2004 and December 31, 2016. Multivariable logistic regression was used to evaluate the relationship between very early pouchitis and the development of CADP and CLDP. Among 626 patients undergoing IPAA for UC, 137 (22%) developed very early pouchitis, 75 (12%) developed CADP, and 59 (9%) developed CLDP in a median follow-up of 5.18 years (interquartile range 0.94-10.8 years). Very early pouchitis was associated with a significant increase in the odds of developing CADP (adjusted odds ratio [aOR3.65, 95% CI 2.19-6.10) as was primary sclerosing cholangitis (aOR 3.97, 95% CI 1.44-11.0). Very early pouchitis was associated with increased odds for developing CLDP (aOR 2.77, 95% CI 1.54-4.98) along with a family history of inflammatory bowel disease (aOR 2.10, 95% CI 1.11-3.96). In this cohort, very early pouchitis was associated with an increased risk of developing CADP and CLDP. These findings highlight very early pouchitis as a unique risk factor for chronic inflammatory conditions of the pouch and the need for future studies evaluating potential strategies for secondary prophylaxis strategies in this population.


Enhanced performance for the analysis of prostaglandins and thromboxanes by liquid chromatography-tandem mass spectrometry using a new atmospheric pressure ionization source.
Eicosanoids, including prostaglandins and thromboxanes are lipid mediators synthetized from polyunsaturated fatty acids. They play an important role in cell signaling and are often reported as inflammatory markers. LC-MS/MS is the technique of choice for the analysis of these compounds, often in combination with advanced sample preparation techniques. Here we report a head to head comparison between an electrospray ionization source (ESI) and a new atmospheric pressure ionization source (UniSpray). The performance of both interfaces was evaluated in various matrices such as human plasma, pig colon and mouse colon. The UniSpray source shows an increase in method sensitivity up to a factor 5. Equivalent to better linearity and repeatability on various matrices as well as an increase in signal intensity were observed in comparison to ESI.


The mediating effect of allostatic load on the relationship between neighborhood perceptions and depression.
Neighborhood perceptions is an important predictor of both allostatic load in the form of biological dysregulation and major depressive disorder. Furthermore, biological dysregulation is predictive of major depressive disorder. Yet to date, the use of biological dysregulation as one potential causal pathway linking neighborhood perceptions to depression has not been explored. This study examined the relationship between neighborhood perception, biological dysregulation in the form of allostatic load, and depression among individuals who participated in the three waves of the Midlife Development in the United States study (1996-2014). Two-to-one propensity score matching was employed prior the use of causal mediation analyses. Lower neighborhood perceptions at wave one were associated with increased allostatic load at wave two. Allostatic load at wave two is associated with depression at wave three. The mediation analysis shows that 6.0% of the relationship between neighborhood perception and depression is mediated by biological dysregulation. These results can inform future prevention and treatment methods by supporting efforts to integrate individuals and community-level interventions to aid in addressing both the environmental conditions and biological factors associated with depression.


Indoor and outdoor pollutants and the upper respiratory tract.
The health effects of both indoor and outdoor air pollutants are of increasing concern. The health effects of outdoor air pollutants traditionally have been assessed through measurements of lower respiratory tract changes. However, it has been shown that one outdoor air pollutant, sulfur dioxide, decreases nasal mucus flow and increases nasal airway resistance. Along with cigarette smoke, indoor air pollutants such as formaldehyde, cadmium, and ammonium or sulfate ions have been shown to alter upper airway mucociliary function. Emissions from wood stoves are known to irritate the upper airways. Measurement of nasal airway resistance using posterior rhinomanometry allows quantification of nasal function. This technique recently has been used to demonstrate that adolescents with allergic asthma have increased work of breathing after inhalation of 0.5 ppm sulfur dioxide. Another study using posterior rhinomanometry showed that clerical workers had increased work of breathing after exposure to carbonless copy paper as compared with bond paper. This brief review of upper respiratory tract changes after pollutant exposure should serve as a reminder that a complete clinical history must include questions designed to ascertain the patient's exposure history to both outdoor and indoor air pollutants. These exposures can have a major impact on the health of the upper respiratory system.


Merging Information From Infrared and Autofluorescence Fundus Images for Monitoring of Chorioretinal Atrophic Lesions.
To develop a method for automated detection and progression analysis of chorioretinal atrophic lesions using the combined information of standard infrared (IR) and autofluorescence (AF) fundus images. Eighteen eyes (from 16 subjects) with punctate inner choroidopathy were analyzed. Macular IR and blue AF images were acquired in all eyes with a Spectralis HRA+OCT device (Heidelberg Engineering, Heidelberg, Germany). Two clinical experts manually segmented chorioretinal lesions on the AF image. AF images were aligned to the corresponding IR. Two random forest models were trained to classify pixels of lesions, one based on the AF image only, the other based on the aligned IR-AF. The models were validated using a leave-one-out cross-validation and were tested against the manual segmentation to compare their performance. A time series from one eye was identified and used to evaluate the method based on the IR-AF in a case study. The method based on the AF images correctly classified 95% of the pixels (i.e., in vs. out of the lesion) with a Dice's coefficient of 0.80. The method based on the combined IR-AF correctly classified 96% of the pixels with a Dice's coefficient of 0.84. The automated segmentation of chorioretinal lesions using IR and AF shows closer alignment to manual segmentation than the same method based on AF only. Merging information from multimodal images improves the automatic and objective segmentation of chorioretinal lesions even when based on a small dataset. Merged information from multimodal images improves segmentation performance of chorioretinal lesions.


Cerebellar herniation and infarction as a complication of an occult postoperative lumbar dural defect.
A patient who underwent lumbar spine surgery sustained an occult dural injury. After unrecognized suction drainage of cerebrospinal fluid through a surgical drain, caudal herniation of the cerebellum with superior cerebellar infarction developed. This mechanism should be considered in patients in whom acute mental status changes develop after spinal surgery.


Light-induced changes in corneal iridescence in fish.
The cornea of the goby Pomatoschistus minutus is iridescent. Spectral reflectance measurements show that the colour of the iridescence responds to light shifting to longer wavelengths when illuminated and shifting to shorter wavelengths when dark adapted. After 2-3 hr dark adaptation the iridescence is no longer visible.


Effects of antihypertensive drugs on ultrasound production and cardiovascular responses in 15-day-old rats.
When exposed to extreme cold or injected with the alpha(2)-adrenoceptor agonist, clonidine, infant rats emit ultrasonic vocalizations (USVs). Based upon the cardiovascular changes that accompany these two manipulations, especially decreased venous return, it was hypothesized that USVs are the acoustic by-product of the abdominal compression reaction (ACR), a maneuver that increases venous return. If this hypothesis is correct, then other anithypertensive drugs that decrease venous return should evoke USVs. In Experiment 1, sodium nitroprusside (SNP, 400 microg/kg), a direct-acting dilator of arteries and veins, was administered to 15-day-old rats under thermoneutral conditions while cardiac rate and ultrasound production were monitored. In Experiment 2, femoral artery pressure was monitored after SNP administration. Infants responded to SNP administration with decreased arterial pressure and tachycardia and, in addition, significantly increased ultrasound production. In Experiment 3, chlorisondamine (5 mg/kg), a ganglionic blocker that causes vasodilation and bradycardia, and hydralazine (20 mg/kg), a selective dilator of arteries, was administered to 15-day-olds. As predicted, chlorisondamine evoked ultrasound production and hydralazine did not. These results introduce SNP and chlorisondamine as only the second and third known agents capable of independently evoking USVs in thermoneutral conditions, and provide further support for the notion that ultrasound production is triggered by decreased venous return.


Concept of the term long lie: a scoping review.
The term "long lie" is often used when individuals who have fallen are unable to stand up on their own, so they have to lie unintentionally for a longer period of time until they are noticed and can be helped. Although long lie can lead to both short- and long-term physical and psychological effects, little is known about what describes the term. The aim of this review is to identify what characterizes the term. Using the Arksey and O'Malley's framework for scoping reviews in accordance with the modified Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, a systematic search was conducted for papers and gray literature that define, explain, or describe a long lie. The literature research was conducted via seven databases and Google Scholar. The search yielded 921 hits, of which 22 research papers are included; most studies were published after 2010. Emergency medicine and public health in particular have studied long lies and have found that it does not only affect the older adults who have fallen and cannot stand up on their own because of their frailty but also individuals with restricted mobility, which can be related to several reasons. The results show that a standard concept of a long lie is lacking. The duration of lying and the location alone are not relevant criteria. Further factors (helplessness, psychological and physical consequences, etc.) should also be taken into account.


Potential use of human interleukin 2 as an adjunct for the therapy of neoplasia, immunodeficiency and infectious disease.
Experimental and clinical systems have been developed to analyze both the in vitro and in vivo effects of highly purified interleukin 2 (IL2) as a potential therapeutic adjunct for neoplasia, immunodeficiency and infectious disease. Animal models, clinical in vitro studies, as well as preliminary clinical trials of IL2 in vivo show that this lymphokine may provide a necessary signal for the activation of thymus-derived T cells in immunologically-compromised hosts.


Surgical treatment of a primary cardiac lymphoma presenting with tamponade physiology.
Primary cardiac lymphomas (PCL) are rare cardiac neoplasms that carry an ominous prognosis. They occur more frequently in immunocompromised patients. We report on an immunocompetent 67-year-old who presented with dyspnea and dysphagia. Echocardiographic evidence of impending cardiac tamponade and obstruction of the inferior vena cava (IVC) with the tumor was seen. The deteriorating hemodynamics of our patient prompted an urgent surgical intervention. Pathohistological diagnosis showed diffuse large B-cell lymphoma of centroblastic subtype. Chemotherapy remains the standard treatment of PCL, with surgery reserved for relieving life-threatening complications of the neoplasm.


Gut colonization by aerobic microorganisms is associated with route and type of nutrition in premature neonates.
We hypothesized that the beneficial effects of early enteral compared with parenteral feeding are related to the increased variety of aerobic microorganisms that colonize the gut. Our aim was to describe the relationship, first, between the type of feeding and mucosal colonization and, second, between the type of feeding and the development of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm neonates. In total, 159 neonates aged 72 hours or less with risk factors for early-onset sepsis were recruited to a prospective 2-center study. Rectal swabs were collected on admission and twice per week thereafter. The feeding regimen was recorded for the first 7 days and categorized into total parenteral nutrition (TPN) and 2 regimens of enteral nutrition, that is, breast milk containing regimen (BMCR), for which breast milk constituted at least 11% of the enteral diet, or formula. Herein, 70 neonates received formula, 48 received BMCR, and 41 received TPN; 69 cases of LOS and 15 cases of NEC were observed in 50 neonates. A multiple logistic regression analysis indicated that formula and BMCR were associated with 4- to 5-fold increases in colonization by Gram-negative bacteria (odds ratio [OR], 4.52; 1.87-10.95, and OR, 4.95; 1.90-12.87, respectively) and 5 to 9 times higher odds of colonization by Gram-positive microorganisms (OR, 5.75; 1.89-16.72, and OR, 8.61; 2.52-29.36, respectively) compared with TPN. The only difference between BMCR and the other feeding groups was the higher colonization with Staphylococcus haemolyticus in the latter (formula-OR, 6.24; 1.73-22.50; TPN-OR, 2.75; 1.08-6.97). Compared with BMCR, TPN was associated with an increased odds of LOS (OR, 3.04; 1.02-9.07) and an increased odds of death (19.75; 3.64-107.12) compared with formula. Although early enteral feeding is associated with a higher odds of colonization with opportunistic microorganisms, it should be preferred over TPN whenever feasible, due to the favorable effect on the prevention of LOS.


[Age-related characteristics of the effect of deafferentation of the mandible on the metabolism of sulfate, citrate, phosphorus and calcium in the bones].
Mineral metabolism in the bones of 1- and 3-month rats reacts to a different extent to cutting the lower alveolar nerve. After deafferentation of the lower jaw, the decrease in the intensity of incorporation of the intraperitoneally injected [3-14C]-citrate and [35S]-sulphate in the bones is more significant in 1-month animals as compared to that in older ones. Deafferentation increased utilization of Na2H32PO4 and 45CaCl2 in the bones of younger rats, but decreased incorporation of 32P and remained unchanged incorporation of 45Ca in 3-month animals.


In vitro exposure of male and female mice gametes to cadmium chloride during the fertilization process, and its effects on pregnancy outcome.
The effect of cadmium chloride (Cd) on gamete fusion in vitro was evaluated, with further observations of the embryonic development and assessment of the pregnancy outcome of the in vitro fertilized mice. Oocytes were recovered from superovulated B6C3F1 females. Of 1210 control oocytes, 53.2% cleaved into two-cell stage embryos. Of these, 46.6% developed into blastocyst stage embryos which were then surgically transferred to pseudopregnant female CD-1 mice. Of a total of 63 implanted embryos, 8 (12.7%) developed in utero to live fetuses. Teratological examinations of these "test-tube" mice revealed no signs of abnormalities caused by in vitro culture. Male and female gametes were exposed to 0.4, 0.8, or 1.6 microM of Cd and a decrease in sperm motility was noted in the 1.6 microM group. Nevertheless, even in the highest concentration used, 56.4% of the ova cleaved into the two-cell stage, thus indicating no effect of Cd on initial gamete interaction. Gametes that had been treated with 0.4 and 0.8 microM Cd developed to blastocysts at rates comparable to that of the controls. In the 1.6 microM group, however, only one (3.2%) of the two-cell embryos developed to the blastocyst stage. Blastocysts from 0.4 microM Cd-treated gametes were then transferred to surrogate dams. Statistically significant blastocyst losses were recorded during the implantation period, whereas the pregnancy rate and the numbers of resorbed and live fetuses, were comparable to those of the controls. The offspring exhibited no malformations, and their body weights remained within the control values.


Ultrasound-targeted microbubble destruction improved the antiangiogenic effect of Endostar in triple-negative breast carcinoma xenografts.
Ultrasound-targeted microbubble destruction (UTMD) has been reported to be a meritorious technique for drug targeting delivery. In this study, we aimed to evaluate the synergistic antiangiogenic effect of UTMD combined with Endostar on triple-negative breast carcinoma tumors. The lipid-shelled microbubbles (MBs) conjugated with Endostar were constructed using a biotin-avidin bridging chemistry method, and the morphological characteristics and drug-conjugating content were determined. MBs were administered intravenously to nude mice bearing MDA-MB-231 breast carcinoma xenografts and ultrasound exposure followed. The tumor microcirculation was observed by contrast-enhanced ultrasonography (CEUS) and the Endostar biodistribution was detected by enzyme-linked immunosorbent assay. Twenty-four breast carcinoma-bearing nude mice were divided into four groups. After treatment, every 3 days for 15 days the in vivo antitumor effects were assessed by calculating the tumor growth inhibition rate (TGIR). The tumor microcirculation was observed by CEUS, the tumor microvessel density (MVD) was calculated by immunohistochemistry under a microscope, and the vascular endothelial growth factor (VEGF) gene expression was detected by real-time quantitative polymerase chain reaction. The prepared Endostar-conjugated MBs were round and well-dispersed with a mean size of 2.8 ± 0.7 µm and a drug conjugating content of 800.72 ± 70.53 µg/108 MBs. UTMD blocked the tumor microcirculation, and improved Endostar release in the targeted tumor tissue with a drug content of 1.12 ± 0.43 µg/gram protein, which was about three times higher than that in Endostar group or Endostar conjugated MBs group. Endostar-conjugated MBs combined with UTMD treatment achieved the optimal antitumor effects in vivo with a TGIR of 46.29%, and apparent antiangiogenic effects with minimal tumor blood perfusion, MVD and VEGF gene expression level. UTMD can improve Endostar delivery in the targeting tumor tissue and mediate synergistic antiangiogenetic and antitumor effects, which may be a potential therapeutic strategy for refractory breast cancer.


Dermatoglyphics on volar skin of mice: the normal pattern.
Mouse volar skin has many protrusions, both large and small. They can be observed more clearly after removal of the epidermis, as they are chiefly constructed of dermal structures. They form "dermatoglyphs." This report describes the normal pattern of these protrusions to establish a normal standard for detection of abnormalities. Limbs of young and adult mice were fixed in 10% formalin and treated with 5% KOH to remove the epidermis layer. They were observed under a dissecting microscope after toluidine blue staining, or by scanning electron microscopy. Several limbs were used for light microscopic observation. Four types of protrusions are observed. 1) Digital pads: single large pads on each digital tip. They locate over the distal phalanx. 2) Interdigital pads and carpal (tarsal) pads (or thenar and hypothenar pads): large pads similar to digital pads. There are five on the palm and six on the sole. 3) Caterpillar pads: elongated thin protrusions on the ventral side of the digits. They form stripes transverse to the axis of the digits. 4) Cobblestone pads: many small protrusions between the interdigital and carpal (tarsal) pads. "Caterpillar pads" and "cobblestone pads" are reported here for the first time. Each pad contains sweat glands and has sweat duct openings and dermal ridges on its top. A detailed description of the normal pattern is indispensable for identification of abnormal patterns. The present description, therefore, can be used as a normal standard when genetically or environmentally induced anomalies are assessed.


Psychological and social support associations with mortality and cardiovascular disease in middle-aged American Indians: the Strong Heart Study.
Our study examined psychosocial risk and protective features affecting cardiovascular and mortality disparities in American Indians, including stress, anger, cynicism, trauma, depression, quality of life, and social support. The Strong Heart Family Study cohort recruited American Indian adults from 12 communities over 3 regions in 2001-2003 (N = 2786). Psychosocial measures included Cohen Perceived Stress, Spielberger Anger Expression, Cook-Medley cynicism subscale, symptoms of post-traumatic stress disorder, Centers for Epidemiologic Studies Depression scale, Short Form 12-a quality of life scale, and the Social Support and Social Undermining scale. Cardiovascular events and all-cause mortality were evaluated by surveillance and physician adjudication through 2017. Participants were middle-aged, 40% male, with mean 12 years formal education. Depression symptoms were correlated with anger, cynicism, poor quality of life, isolation, criticism; better social support was correlated with lower cynicism, anger, and trauma. Adjusted time-to-event regressions found that depression, (poor) quality of life, and social isolation scores formed higher risk for mortality and cardiovascular events, and social support was associated with lower risk. Social support partially explained risk associations in causal mediation analyses. Altogether, our findings suggest that social support is associated with better mood and quality of life; and lower cynicism, stress, and disease risk-even when said risk may be increased by comorbidities. Future research should examine whether enhancing social support can prospectively reduce risk, as an efficient, cost-effective intervention opportunity that may be enacted at the community level.


Inhibition of tumor growth and metastasis establishment by adenovirus-mediated gene transfer delivery of the antiangiogenic factor 16K hPRL.
Tumor metastases, the most fearsome aspect of cancer, are generally resistant to conventional therapies. Angiogenesis is a crucial aspect of tumor growth and metastatic dissemination. Antiangiogenic therapy, therefore, holds potential as an attractive strategy for inhibiting metastasis development. Human 16K PRL (16K hPRL), a potent inhibitor of angiogenesis, has been demonstrated to prevent tumor growth in two xenograft mouse models, but whether it also affects tumor metastasis is unknown. In this study we will investigate the ability of 16K hPRL to prevent the establishment of metastasis. We demonstrate that 16K hPRL administered via adenovirus-mediated gene transfer, inhibits tumor growth by 86% in a subcutaneous (SC) B16-F10 mouse melanoma model. Computer-assisted image analysis shows that 16K hPRL treatment results in a reduction of tumor-vessel length and width, leading to a 57% reduction of average vessel size. In a pre-established tumor model, moreover, 16K hPRL can significantly delay tumor development. Finally, for the first time, we provide evidence that 16K hPRL considerably reduces the establishment of B16-F10 metastasis in an experimental lung metastasis model. Both the number and size of metastases are reduced by 50% in 16K hPRL-treated mice. These results highlight a potential role for 16K hPRL in anticancer therapy for both primary tumors and metastases.