Two Candidate Meloidogyne javanica Effector Genes, MjShKT and MjPUT3: A Functional Investigation of Their Roles in Regulating Nematode Parasitism.
During parasitism, root-knot nematode Meloidogyne spp. inject molecules termed effectors that have multifunctional roles in construction and maintenance of nematode feeding sites. As an outcome of transcriptomic analysis of Meloidogyne javanica, we identified and characterized two differentially expressed genes encoding the predicted proteins MjShKT, carrying a Stichodactyla toxin (ShKT) domain, and MjPUT3, carrying a ground-like domain, both expressed during nematode parasitism of the tomato plant. Fluorescence in-situ hybridization revealed expression of MjShKT and MjPUT3 in the dorsal esophageal glands, suggesting their injection into host cells. MjShKT expression was upregulated during the parasitic life stages, to a maximum at the mature female stage, whereas MjPUT3 expression increased in third- to fourth-stage juveniles. Subcellular in-planta localization of MjShKT and MjPUT3 using a fused fluorescence marker indicated MjShKT co-occurrence with the endoplasmic reticulum, the perinuclear endoplasmatic reticulum, and the Golgi organelle markers, while MjPUT3 localized, to some extent, within the endoplasmatic reticulum and was clearly observed within the nucleoplasm. MjShKT inhibited programmed cell death induced by overexpression of MAPKKKα and Gpa2/RBP-1. Overexpression of MjShKT in tomato hairy roots allowed an increase in nematode reproduction, as indicated by the high number of eggs produced on roots overexpressing MjShKT. Roots overexpressing MjPUT3 were characterized by enhanced root growth, with no effect on nematode development on those roots. Investigation of the two candidate effectors suggested that MjShKT is mainly involved in manipulating the plant effector-triggered immune response toward establishment and maintenance of active feeding sites, whereas MjPUT3 might modulate roots morphology in favor of nematode fitness in the host roots. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study of Zanubrutinib with Rifabutin in Healthy Volunteers.
Zanubrutinib is a second-generation Bruton tyrosine kinase inhibitor that is primarily metabolized by CYP3A enzymes. Previous drug-drug interaction (DDI) studies have demonstrated that co-administration of zanubrutinib with rifampin, a strong CYP3A inducer, reduces zanubrutinib plasma concentrations, potentially impacting activity. The impact of the co-administration of zanubrutinib with less potent CYP3A inducers is unclear. This phase 1, open-label, fixed-sequence DDI study evaluated the pharmacokinetics, safety, and tolerability of zanubrutinib when co-administered with steady-state rifabutin, a known CYP3A inducer less potent than rifampin, in 13 healthy male volunteers (NCT04470908). Co-administration of zanubrutinib with rifabutin resulted in a less than 2-fold reduction of zanubrutinib exposures. Overall, zanubrutinib was well tolerated. The results of this study provide useful information for the evaluation of the DDI between rifabutin and zanubrutinib. In conjunction with safety and efficacy data from other clinical studies, these results will be taken into consideration to determine the appropriate dose recommendation of zanubrutinib when co-administered with CYP3A inducers.


Verification of dried blood spot as a sample type for HIV viral load and early infant diagnosis on Hologic Panther in Zambia.
Zambia has embarked on improving the diagnostic capacity by setting up high throughput and accurate machines in the testing process and introduction of dried blood spot (DBS) as a sample type. This was a cross sectional study to verify dried blood spot as a sample type for HIV viral load and early infant diagnosis (EID) on Hologic Panther platform and Evaluate the analytical performance (precision, linearity and measurement of uncertainty) of the Hologic Panther. The specificity and sensitivity of EID performance of Aptima Quant Dx assay on Hologic panther machine against the gold standard machine COBAS Taqman (CAP/CTM) was 100% with an overall agreement of 100%. The quantitative HIV Viral Load (VL) accuracy had a positive correlation of (0.96) obtained against the gold standard (plasma samples) run on COBAS4800 platform. Analytical performance of the Hologic panther machine was evaluated; Precision low positive repeatability 3.50154 and within lab 2.268915 at mean 2.88 concentration and precision high positive repeatability 1.116955 and within lab 2.010677 at mean 5.09 concentration were obtained confirming manufacturers claims. Uncertainty of measurement for this study was found to be ± 71 copies/ml. Linearity studies were determined and all points were within acceptable limits. We therefore recommend DBS as a sample type alternative to plasma for the estimation of HIV-1 viral load and EID diagnosis on the Hologic panther machine.


The prevention of infection in open fractures: an experimental study of the effect of fracture stability.
An experimental model of a contaminated open fracture has been developed. This model has been used to test the hypothesis that stable fixation of a contaminated open fracture will reduce its susceptibility to infection. The tibiae of male New Zealand white rabbits were fractured and then fixed with either a dynamic compression plate (stable group) or a loose-fitting intramedullary rod (unstable group). The fracture site was then inoculated with a standard inoculum of Staphylococcus aureus. There were 20 rabbits in the stable group and osteomyelitis developed in seven (35 per cent); in the unstable group 15 (71 per cent) out of 21 animals developed osteomyelitis. This difference in infection rates was statistically significant (P < 0.02). This experimental study supports the concept of stabilization of open fractures in man.


Angular velocity: a new method to improve prediction of ventricular fibrillation duration.
Ventricular fibrillation (VF) is a leading cause of sudden death. Electrical defibrillation is the primary modality of treatment, but evidence is accumulating that its use in the late stage of VF prior to providing ventilation, chest compressions and the administration of appropriate medication is detrimental. In VF of <5 min duration a 'shock first' strategy is effective. In VF of 5> min duration a 'perfuse first' approach is more effective. Because of the difficulty in determining the duration of VF in the clinical setting we have sought to develop method which analyze 5 s intervals of VF waveform and quickly provide an estimate of duration. Such methods would be useful in directing clinical interventions. Using methods of nonlinear dynamics and fractal geometry we have previously derived a quantitative measure of VF duration, namely the scaling exponent (ScE). In this study we report on a novel method also based on nonlinear dynamics, the angular velocity (AV). By constructing a flat, circular disk-shaped structure in a three-dimensional phase space and measuring the velocity of rotation of the position vector over time, a statistic is developed which rises from 58 rad/s at 1 min to 79 rad/s at 4 min and then decreases in a linear manner to 32 rad/s at 12.5 min. Using ScE and AV probability density estimated, VF of <5 min duration can be identified with 90% sensitivity on the basis of a single 5 s recording of the waveform. The combination of ScE and AV can be used in developing strategies for the treatment of VF during the different clinical phases of VF.


An unusual double supernumerary maxillary mesiodens in a Middle Iron Age skeleton from South Uist, Western Isles, Scotland.
Bilaterally occurring and fully erupted mesiodens occur infrequently in the modern population and have been little documented from past populations. This research presents an unusual case of a double maxillary mesiodens in the permanent dentition occurring in skeletal remains dating to the Middle Iron Age (250-410 AD) from South Uist, Western Isles of Scotland. Osteological analysis of an adult male included the inventory of teeth present/absent and analysis of dental pathologies (caries, calculus, periodontal disease, ante-mortem tooth loss, periapical abscesses), developmental defects and orthodontic anomalies (enamel hypoplastic defects, malposition, rotation, crowding, agenesis and supernumerary teeth). An unusual expression of double, fully erupted, mesiodens in the anterior permanent maxillary dentition representing supernumerary central incisors exists. The complete eruption had contributed to anterior displacement of one central incisor alveolar socket similar to documented modern clinical cases. Shallow sockets also implied an associated stunted development of the original central maxillary incisor roots. Occlusal enamel wear indicated the mesiodens had been abraded during mastication. Current clinical data suggest there is a much higher tendency for single mesiodens to exist rather than double and examples often fail to fully erupt into the dentition. This relative rarity may account for the few previous reports of this dental anomaly from past human remains and especially of this date. The fully erupted double example from South Uist contributes to the known evidence for orthodontic anomalies in the past.


Acute exercise as a modifier of neocortical plasticity and aperiodic activity in the visual cortex.
Long-term potentiation (LTP) is a form of neuroplasticity commonly implicated in mechanistic models of learning and memory. Acute exercise can boost LTP in the motor cortex, and is associated with a shift in excitation/inhibition (E:I) balance, but whether this extends to other regions such as the visual cortex is unknown. We investigated the effect of a preceding bout of exercise on LTP induction and the E:I balance in the visual cortex using electroencephalography (EEG). Young adults (N = 20, mean age = 24.20) engaged in 20 min of high-intensity interval training (HIIT) exercise and rest across two counterbalanced sessions. LTP was induced using a high frequency presentation of a visual stimulus; a "visual tetanus". Established EEG markers of visual LTP, the N1b and P2 component of the visual evoked potential, and an EEG-derived measure of the E:I balance, the aperiodic exponent, were measured before and after the visual tetanus. As expected, there was a potentiation of the N1b following the visual tetanus, with specificity to the tetanised stimulus, and a non-specific potentiation of the P2. These effects were not sensitive to a preceding bout of exercise. However, the E:I balance showed a late shift towards inhibition following the visual tetanus. A preceding bout of exercise resulted in specificity of this E:I balance shift to the tetanised stimulus, that was not seen following rest. This novel finding suggests a possible exercise-induced tuning of the visual cortex to stimulus details following LTP induction.


Fat/Dachsous family cadherins in cell and tissue organisation.
Precisely controlled organisation at the cellular and tissue level is crucial to establish and maintain complex organisms. The atypical cadherins Fat (Ft), Fat2 and Dachsous (Ds) contribute to this organisation by regulating growth and planar cell polarity. Here we describe the recent advances in understanding how these large cadherins coordinate these processes, and discuss additional progress extending their function in regulation of microtubules, migration and disease.


Contact inactivation of orthopoxviruses by household disinfectants.
The aim of this study is to identify common household disinfectants that combine significant activity against the type orthopoxvirus, vaccinia virus with minimal impact in terms of potential toxicity and/or damage to household or personal items. Laboratory scale experiments assessed common disinfectants containing anionic and nonionic detergents, oxygen-based bleach, potassium peroxomonosulfate, chloroxylenol or halogenated phenols. Disinfectants were assessed for their ability to inactivate the virus on contact or after a short incubation period in the presence and absence of foetal bovine serum as a potential interferant. Significant differences were observed ranging from negligible effect of detergents to complete inactivation on contact with chloroxylenol. At least one chloroxylenol-based household disinfectant is available, which inactivates vaccinia virus on contact. In the event of a release or major outbreak of a pathogenic orthopoxvirus there is likely to be significant public demand for disinfectants with activity against these viruses. The identification of common household disinfectants with such activity obviates any requirement to stockpile or distribute laboratory/industrial disinfectants for this purpose.


Studies on the mechanism by which indomethacin increases the anticancer effect of methotrexate.
The effect of indomethacin on the response of the NC carcinoma to methotrexate has been examined in vivo and in vitro. Survival was prolonged in mice treated with indomethacin 1.25 mg kg-1 twice daily plus methotrexate 4 mg kg-1 daily, compared to mice given either drug alone or controls. Indomethacin 1 microgram ml-1 increased the killing of cultured NC cells by methotrexate. This was not due to displacement of methotrexate from binding sites on the serum proteins. Nor was it due (entirely) to inhibition of prostaglandin synthesis, since flurbiprofen did not mimic the effect. Inhibition of cyclic AMP phosphodiesterase seems unlikely to explain the effect of indomethacin since theophylline had little or no effect on NC cell killing by methotrexate. Indomethacin 1 microgram ml-1 increased the accumulation of tritium in NC cells incubated with [3H]-methotrexate. In contrast, with normal epithelial cells from human embryonic intestine, indomethacin 1 microgram ml-1 did not alter the cytotoxicity of methotrexate or the accumulation of tritium during incubation with [3H]-methotrexate. The beneficial interaction between indomethacin and methotrexate may have therapeutic potential in man.


Efficacy, safety, and acceptability of polyethylene glycol 3350 without electrolytes vs magnesium hydroxide in functional constipation in children from six months to eighteen years of age: A controlled clinical trial.
There are few studies that compare polyethylene glycol (PEG) 3350 and magnesium hydroxide (MH), as long-term treatment of functional constipation (FC) in children, and they do not include infants as young as 6 months of age. Our aim was to determine the efficacy, safety, and acceptability of PEG vs MH in FC, in the long term, in pediatric patients. An open-label, parallel, controlled clinical trial was conducted on patients from 6 months to 18 years of age, diagnosed with FC, that were randomly assigned to receive PEG 3350 or MH for 12 months. Success was defined as: ≥ 3 bowel movements/week, with no fecal incontinence, fecal impaction, abdominal pain, or the need for another laxative. We compared adverse events and acceptability, measured as rejected doses of the laxative during the study, in each group and subgroup. Eighty-three patients with FC were included. There were no differences in success between groups (40/41 PEG vs 40/42 MH, p = 0.616). There were no differences in acceptability between groups, but a statistically significant higher number of patients rejected MH in the subgroups > 4 to 12 years and > 12 to 18 years of age (P = .037 and P = .020, respectively). There were no differences regarding adverse events between the two groups and no severe clinical or biochemical adverse events were registered. The two laxatives were equally effective and safe for treating FC in children from 0.5 to 18 years of age. Acceptance was better for PEG 3350 than for MH in patients above 4 years of age. MH can be considered first-line treatment for FC in children under 4 years of age.


Carboxyl-terminal truncations of human anion exchanger impair its trafficking to the plasma membrane.
The human anion exchanger AE1 (Band 3) is an abundant glycoprotein localized in plasma membrane of red cells and is responsible for the electro-neutral exchange of chloride for bicarbonate. In order to determine the role of the carboxyl-terminal tail of AE1 in its expression, function and trafficking to the plasma membrane, we generated a series of five constructs encoding truncation mutants missing the last 5 (Delta5), 11 (Delta11), 15 (Delta15), 20 (Delta20) or 35 (Delta35) amino-acids. In transiently transfected HEK 293 cells, immunoblotting of whole cell extracts showed that all the proteins were expressed at the same level as full-length AE1, except Delta20 and particularly Delta35, which showed a reduced expression. Furthermore, the last 15 amino-acids were not required for AE1 folding in the membrane, since Delta5, Delta11 and Delta15 were able to bind to an inhibitor affinity matrix, while Delta20 and Delta35 exhibited poor binding. Immunofluorescence and deglycosylation results showed that Delta15 and Delta11 were retained intracellularly, whereas a lower amount of Delta5 compared with WT trafficked to the plasma membrane. These results indicate that an intact C-terminal tail of human AE1 is important for efficient AE1 trafficking to the plasma membrane.


Decolorization and detoxication of reactive industrial dyes by immobilized fungi Trametes pubescens and Pleurotus ostreatus.
Trametes pubescens and Pleurotus ostreatus, immobilized on polyurethane foam cubes in bioreactors, were used to decolorize three industrial and model dyes at concentrations of 200, 1000 and 2000 ppm. Five sequential cycles were run for each dye and fungus. The activity of laccase, Mn-dependent and independent peroxidases, lignin peroxidase, and aryl-alcohol oxidase were daily monitored during the cycles and the toxicity of media containing 1000 and 2000 ppm of each dye was assessed by the Lemna minor (duckweed) ecotoxicity test. Both fungi were able to efficiently decolorize all dyes even at the highest concentration, and the duckweed test showed a significant reduction (p < or = 0.05) of the toxicity after the decolorization treatment. T. pubescens enzyme activities varied greatly and no clear correlation between decolorization and enzyme activity was observed, while P. ostreatus showed constantly a high laccase activity during decolorization cycles. T. pubescens showed better decolorization and detoxication capability (compared to the better known P. ostreatus). As wide differences in enzyme activity of the individual strains were observed, the strong decolorization obtained with the two fungi suggested that different dye decolorization mechanisms might be involved.


Persistent Radical Tetrathiafulvalene-Based 2D Metal-Organic Frameworks and Their Application in Efficient Photothermal Conversion.
A series of stable radical 2D metal-organic frameworks has been assembled. (m-TTFTB)3 (m-Tetrathiafulvalene-tetrabenzoate) trimer building blocks are beneficial for the stability of the radicals due to delocalization of the unpaired electron. Hexanuclear rare-earth-cluster-based 1D chains further enhance the stability of the frameworks. The radical state of the middle TTF in the trimer has been observed by the change of central C-C and C-S bond distances and the configuration of the TTF by single-crystal X-ray diffraction. The radical characteristics are also confirmed by electron paramagnetic resonance, UV/Vis-NIR absorption, and X-ray photoelectron spectroscopy experiments. Stability tests showed that the radicals are stable even in solutions and under acid/base environments (pH 1-12). Owing to efficient light absorption due to intramolecular charge transfer, low thermal conductivity, and outstanding stability, the radical 2D Dy-MOF shows excellent photothermal properties, an increase of 34.7 °C within 240 s under one-sun illumination.


Crystal structure of dihydroorotate dehydrogenase from Leishmania major.
Dihydroorotate dehydrogenase (DHODH) is the fourth enzyme in the de novo pyrimidine biosynthetic pathway and has been exploited as the target for therapy against proliferative and parasitic diseases. In this study, we report the crystal structures of DHODH from Leishmania major, the species of Leishmania associated with zoonotic cutaneous leishmaniasis, in its apo form and in complex with orotate and fumarate molecules. Both orotate and fumarate were found to bind to the same active site and exploit similar interactions, consistent with a ping-pong mechanism described for class 1A DHODHs. Analysis of LmDHODH structures reveals that rearrangements in the conformation of the catalytic loop have direct influence on the dimeric interface. This is the first structural evidence of a relationship between the dimeric form and the catalytic mechanism. According to our analysis, the high sequence and structural similarity observed among trypanosomatid DHODH suggest that a single strategy of structure-based inhibitor design can be used to validate DHODH as a druggable target against multiple neglected tropical diseases such as Leishmaniasis, Sleeping sickness and Chagas' diseases.


Equating norms between the ALS Cognitive Behavioral Screen (ALS-CBS™) and the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) in non-demented ALS patients.
The present study aimed at deriving equating norms to estimate scores on the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) based on those on the ALS Cognitive Behavioral Screen (ALS-CBS™) in an Italian cohort of non-demented ALS patients. ALS-CBS™ and ECAS scores of 293 ALS patients without frontotemporal dementia were retrospectively retrieved. Concurrent validity of the ALS-CBS™ towards the ECAS was tested by covarying for demographics, disease duration and severity, presence of C9orf72 hexanucleotide repeat expansion and behavioural features. A linear-smoothing equipercentile equating (LSEE) model was employed to derive ALS-CBS™-to-ECAS cross-walks. Gaps in LSEE-based estimation were managed via a linear regression-based equating approach. Equivalence between empirical and derived ECAS scores was tested via a two-one-sided test (TOST) procedure for the dependent sample. The ALS-CBS™ predicted the ECAS (β = 0.75), accounting for the vast majority of its variance (60% out of an R2 = 0.71). Consistently, a strong, one-to-one linear association between ALS-CBS™ and ECAS scores was detected (r = 0.84; R2 = 0.73). The LSEE was able to estimate conversions for the full range of the ALS-CBS™, except for raw scores equal to 1 and 6 - for whom a linear equating-based equation was derived. Empirical ECAS scores were equivalent to those derived with both methods. Italian practitioners and researchers have been herewith provided with valid, straightforward cross-walks to estimate the ECAS based on ALS-CBS™ scores in non-demented ALS patients. Conversions herewith provided will help avoid cross-sectional/longitudinal inconsistencies in test adoption within research, and possibly clinical, settings.


24-Month results of the BRAVO study: A prospective, multi-center study evaluating the clinical outcomes of a ventral hernia cohort treated with OviTex® 1S permanent reinforced tissue matrix.
This study evaluated the performance of OviTex® 1S (TELA Bio Inc., Malvern, PA, USA) over 24 months when used for ventral hernia repair. This was a prospective, single-arm, multi-center clinical trial (ClinicalTrials.gov/NCT03074474). A ninety-two patient cohort with ventral hernias were enrolled. The surgical approach (open, laparoscopic, or robotic) and plane of placement (retrorectus, intraperitoneal, or pre-peritoneal) were at the discretion of the surgeon. Patients were characterized as high risk for a surgical site occurrence (SSO) based on the following comorbidities: BMI between 30 and 40, active smoker, chronic obstructive pulmonary disease (COPD), diabetes mellitus, coronary artery disease, advanced age ( ≥ 75 years). Subjects underwent physical examinations to evaluate safety events and completed quality of life surveys at 1 months, 3 months, 12 months, and 24 months post-surgery. Sixty-five of the 92 enrolled patients (70.7%) completed 24-month follow-up. The Kaplan Meier estimate for risk of recurrence at day 730 (24 months) was 2.6%; among subjects who completed their 24-month visit or had a previous recurrence, the unadjusted rate of recurrence was 4.5% (3/66). SSOs were observed in 38.0% of patients (35/92). The most prevalent SSO was surgical site infection occurring in 20.7% (19/92) of patients, followed by seroma formation, which occurred in 13.0% of patients; however, only 3.3% required intervention. HerQLes and EQ-5D assessments showed improvement from baseline as soon as 3 months post-surgery. Continued improvement was observed through 24 months. Overall the BRAVO study demonstrates that use of the ovine reinforced tissue matrix OviTex 1S is a viable option for use in ventral hernia repair. Additional studies with longer term follow-up data are needed to draw definitive conclusions on the use of OviTex 1S.


Pneumatic anti-shock garment: state of the art 1988.
The responses of hypovolemic patients would be expected to be similar to experimental animals that were hypovolemic. Normovolemic patients would be expected to respond as do the normovolemic experimental animals. Hypovolemic patients do not necessarily respond the same as do normovolemic patients or volunteers. The amount of external pressure applied by the device is directly proportional to the amount of tissue pressure increase. Tissue pressure is transmitted to the vessel as reduction transmural pressure, or in change in the size of the vessels and subsequent increase in SVR. Patient response to external pressure varies with the amount of device pressure. The optimal pressure of the PASG is in the range of 60 to 80 torr. Although exceeding this value does not appear to be necessary, it is not harmful in the short term (less than 90 minutes). Using less pressure reduces the SVR and, therefore, the blood pressure response. Keeping the external pressure at approximately 40 torr appears to be ideal for hemorrhage control. Of the more than 300 articles that have appeared in the recent literature addressing the PASG, at least 190 have discussed specific scientific experiments in the animal laboratory, in the human laboratory, or in the clinical environment, in which results gathered addressed how, why, or if the PASG worked. These studies demonstrate that the PASG does, in fact, improve blood pressure, control hemorrhage, improve carotid and upper body blood flow, improve the ability of the prehospital provider to start IV lines, and improve survival (particularly short-term) with few hospital and even fewer prehospital complications. The device produces its blood pressure response by improving preload, increasing SVR, and mobilizing some blood (500 to 1,000 mL) to the upper body compartment above the device. These responses are most probably produced by decreasing the radius of the vessels compressed by the device, decreasing the compartment volume, and differentially affecting the blood flow without and within the device. Hemorrhage is controlled by increasing the external pressure on the vessel by the transmitted increased tissue pressure, reducing the vascular lumen, and reducing the area of the laceration. Short-term survival is improved by decreasing intra-abdominal hemorrhage and improving perfusion (maintaining better oxygenation in the heart-brain-lung circulation.) Long-term survival is improved because the device controls hemorrhage, maintains blood pressure, and allows delivery of the severely injured patient to the trauma center and within the hospital while awaiting an OR, as in the case of a leaking aortic aneurysm.(ABSTRACT TRUNCATED AT 400 WORDS)


Use of antibiotics in traumatic mandibular fractures: a systematic review and meta-analysis.
The treatment of traumatic mandibular fractures constitutes a significant part of the oral and maxillofacial trauma service's workload. There are potential variations in how they are managed. Patients are often admitted and given intravenous antibiotics prior to their definitive treatment. The evidence behind this is inconclusive. We performed a systematic review as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance/ PROSPERO Registered (CRD:42020201398) on the use of antibiotics in the management of mandibular fractures. We identified studies using a search algorithm within the OVID Gateway (including MEDLINE, PubMed, and Cochrane Collaborative). Studies analysing the possible impact of prophylactic antibiotics on traumatic mandibular fractures were eligible. The primary outcome was surgical site infection requiring any treatment beyond the normal postoperative protocol. Secondary outcomes included any complication requiring further intervention. From the 16 studies identified (3,285 patients), seven were randomised controlled clinical trials (RCTs) and nine were retrospective observational studies. We have identified significant between-study variation in choice of antibiotic regimen (timing, dosage, duration) and in reporting both primary and secondary outcomes. There was significant between-study heterogeneity (p = 0.02, I2 = 69%) and none of the assessed interventions was found to be superior. The evidence behind the use of prophylactic antibiotics in mandibular fractures is weak. A properly designed and powered RCT is needed, in order to standardise practice for the benefit of patients and healthcare systems.


Effect of fluoxetine on enhanced biological phosphorus removal using a sequencing batch reactor.
In this work, the potential impact of emerging pollutant Fluoxetine (FLX) on enhanced biological phosphorus removal (EBPR) was systematically investigated using the sequencing batch reactor. The experimental results showed that even 200 μg/L FLX had no significant effect on EBPR during the short-term exposure. However, in the long-term exposure test, high dosage of FLX inhibited EBPR. 200 μg/L FLX induced biological phosphorus removal efficiency dropped to 71.3 ± 2.1%, significantly lower than that of the blank. The mechanism investigation showed that high concentration of FLX reduced anaerobic phosphorus release and oxic phosphorus absorption, and the consumption of organic matter during the anaerobic period. In addition, FLX decreased the synthesis of intracellular polymer polyhydroxyalkanoates (PHA), but promoted the metabolism of glycogen and polyhydroxyvalerate. FLX reduced the activity of key enzymes in EBPR and the relative abundance of Accumulibacter, but improved the relative abundance of Candidatus Competibacter.


Treatment with insulin glargine does not suppress serum IGF-1.
A 6-8-fold higher insulin-like growth factor 1 (IGF-1) receptor binding affinity in vitro is reported for the insulin analogue glargine compared with human insulin. This study evaluates the in vivo significance by exploring the growth hormone (GH)-IGF-1 axis. Assuming a higher binding affinity of insulin glargine to pituitary IGF-1 receptors, serum IGF-1 concentrations should decrease via negative feedback. In a crossover study, insulin glargine or NPH insulin, respectively, were used in identical doses as basal insulins in treatment periods of 3 weeks. Overall glycaemic control was not different between the treatment regimens. In contrast to the hypothesis, serum IGF-1 concentrations were higher during insulin glargine treatment compared with NPH insulin in patients with Type 1 diabetes (177 +/- 18 vs. 159 +/- 18 microg/l, P < 0.02, n = 17, age 28 +/- 2 years). The effect on IGF-1 was most pronounced in male patients with Type 1 diabetes (174 +/- 11 vs. 146 +/- 10 microg/l, P < 0.02, n = 10), but was not significant in patients with Type 2 diabetes (92 +/- 9 vs. 86 +/- 8 microg/l, NS, n = 25, age 66 +/- 2 years). In contrast to our hypothesis, serum IGF-1 did not decrease, but rose during insulin glargine treatment, suggesting an absence of relevant IGF-1-like activity of glargine at the level of the pituitary. Improved plasma glucose at dawn during glargine treatment may intensify growth hormone surges and increase IGF-1 synthesis. Significant increases were seen in younger patients, compatible with the higher activity of the GH-IGF-1 axis in this age group.


[Predicting efficiency of selection on reproductive traits in the medicinal leech Hirudo medicinalis L].
A set of selection measures for increasing reproduction efficiency in Hirudo medicinalis has been developed. The optimal values of reproductive traits corresponding to the highest progeny number were determined and recommended. The probability of correlated selection response in traits "number of threads in a cocoon" and "weight of threads" was estimated. Based on earlier results on phenotypic variation and heritability of reproductive traits in medicinal leech, efficiency of different selection modes was predicted.


Effect of systemic herbicides on microbial biomass in relation to availability of some plant nutrients in an alluvial soil of West Bengal.
An experiment was conducted under laboratory conditions to investigate the effect of three herbicides, viz., fenoxaprop, pendimethalin and paraquat, at their recommended field application rates (50 g, 1.0 kg and 1.0 kg a.i. ha⁻¹, respectively), on the changes of microbial biomass C, N and P in relation to transformations and availability of plant nutrients in an alluvial soil (Typic Orchraqualf) from West Bengal, India. Application of herbicides, in general, significantly increased the microbial biomass C, N and P, resulting in greater availability of these plant nutrients in soil. The microbial biomass C was highly increased due to application of fenoxaprop (39.8%) followed by paraquat (28.2%). Application of pendimethalin led to the maximum stimulation of microbial biomass N (37.1%), while microbial biomass P was increased by 15.2% following the incorporation of paraquat into the soil. Compared to untreated control soil, the soil retained the highest amount of organic C (19.8%) when it was treated with pendimethalin. A similar trend was recorded with fenoxaprop for total N (19.6%) and exchangeable NH₄⁺ (21.3%) in soil. The stimulation of soluble NO₃⁻ was highest under fenoxaprop (22.3%) followed by paraquat (20.7%). Regarding the availability of P in soil, paraquat manifested greater stimulation (17.8%) than fenoxaprop (15.4%) or pendimethalin (13.1%). Application of paraquat also gave the highest amount of total P (17.8%) in the soil solution.


Double-Jump migration and diffusive instability.
In order to look into the stability consequences of a particular migration process in which individuals choose to settle, we formulated a continuous-time multi-species multi-patch model in which individuals migrate by one or two instantaneous jumps while making the second jump with a certain probability that possibly depends on the conditions at the end point of the first jump. It turned out that a second jump has some quantitative effects on diffusive instability even when it occurs in the absence of density-dependent mechanisms. When a second jump happens as a natural interspecific response of individuals, and such a response is sufficiently strong, it has crucial effects on diffusive instability: it leads to diffusive instability in the case of competitive interactions, whereas it annihilates diffusive instability in the case of prey-predator interactions. We demonstrated these results in the context of two specific examples.


Stereoselective acetylation of hemicellulosic C5-sugars.
The stereoselective peracetylation of α-d-xylose (1) and α-l-arabinose (4) using a combination of triethylamine and acetic anhydride in the presence or absence of a catalytic amount of dimethylaminopyridine (DMAP) is described. The peracetylated d-xylose and l-arabinose alpha pyranose anomers 2α and 5α are obtained in 97% and 56% yields respectively. The peracetylated d-xylose beta pyranose anomer 2β is obtained in 71% yield through simple modification of the reaction conditions. Details regarding synthesis and isolation optimization studies under different conditions are presented below. The stereoselective peracetylation reactions disclosed here have been used to separate mixtures of d-xylose and l-arabinose as their peracetylated derivatives 2β and 5α in 47% and 42% yields and can provide pure pentoses after deacetylation.


Effects of different resistance mechanisms on susceptibility to different classes of antibiotics in Klebsiella pneumoniae strains: a strategic system for the screening and activity testing of new antibiotics.
A strategic system for the screening and testing of new antibiotics was created to facilitate the development of antibiotics that are robustly effective against MDR bacteria. In-frame deletion, site-directed mutagenesis and plasmid transformation were used to generate genetically engineered strains with various resistance mechanisms from a fully susceptible clinical isolate of Klebsiella pneumoniae. Antimicrobial susceptibility testing and a mouse infection model were used to test antibiotics against these strains in vitro and in vivo, respectively. A total of 193 strains, including 29 strains with chromosome-mediated resistance, 33 strains with plasmid-mediated resistance and 131 strains with a combination of both resistance mechanisms were constructed; these strains covered resistance to β-lactams, quinolones, aminoglycosides, tetracyclines, folate pathway inhibitors and other antibiotics. MICs for all strains were tested, and the effects of genetic modifications on increasing the MICs were assessed. Ceftazidime and cefotaxime were used to assess the correlation between antibacterial activities in vitro and in vivo. Against a K. pneumoniae strain with blaOXA-48, ceftazidime had a lower MIC (0.5 mg/L) than cefotaxime (2 mg/L). Ceftazidime had an ED50 of 30 mg/kg, and no mice survived treatment with the same dose of cefotaxime. A positive correlation was observed between these in vitro and in vivo results. The system developed here could reduce the considerable time required to evaluate the effectiveness of new antibiotics against MDR bacteria, particularly in the early stages of drug development. This system could also be expanded as new resistance mechanisms emerge.


Progression of HIV infection among injecting drug users: indications for a lower rate of progression among those who have frequently borrowed injecting equipment.
To study markers of progression in a cohort of HIV-infected intravenous drug users (IDU). A prospective epidemiologic study. We studied progression of HIV infection among 126 IDU attending the Municipal Health Service in Amsterdam. Progression was defined as a decline of the CD4 cell count to < 200 x 10(6)/l on two consecutive follow-up visits or AIDS. Using Cox modelling, the following baseline variables were predictive of progression. Enhanced progression was associated with: age > 30 years [relative hazard (RH), 7.7 [95% confidence intervals (CI), 1.7-36.0]], core antibody negativity [RH, 5.3 (95% CI, 1.6-17.6)], CD4 cell count [for CD4 cells 350-500 x 10(6)/l, RH, 1.38 (95% CI, 0.37-5.16); for CD4 cells 200-350 x 10(6)/l, RH, 9.20 (95% CI, 2.73-31.05) compared with a CD4 count > 500 x 10(6)/l]. A lower rate of progression was associated with borrowing used injecting equipment. IDU who reported borrowing injecting equipment between 1980 and baseline 10-99 times or > 99 times had a RH of 0.44 (95% CI, 0.22-0.88) and 0.19 (95% CI, 0.03-0.37), respectively, compared with IDU who had borrowed < 10 times. p24 antigen positivity was more predictive than core antibody negativity in a model with time-dependent variables, the relative risk for p24 antigen-positive participants was 3.5 (95% CI, 1.3-9.3). Additional analysis of progression to AIDS in a larger group of IDU showed comparable results with regard to the effect of borrowing on progression. Our observation that those IDU who reported borrowing injecting equipment most frequently appeared to have the lowest rate of progression, corrected for some sources of potential confounding, requires further epidemiologic confirmation and extended laboratory studies since other sources of bias might have been present. Baseline CD4 count, age and core antibody or p24 antigen were predictive of progression in IDU. We wish to emphasize that our results do not imply that borrowing should be encouraged, but may have implications for our understanding of HIV pathogenesis.


Healthcare Utilization in Patients with Chronic Obstructive Pulmonary Disease Discharged from Coronavirus 2019 Hospitalization.
There is concern that patients with chronic obstructive pulmonary disease (COPD) are at greater risk of increased healthcare utilization (HCU) following Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-COV-2) infection. To assess whether COPD is an independent risk factor for increased post-discharge HCU. We conducted a retrospective cohort study of patients with COPD discharged home from a hospitalization due to Coronavirus Disease 2019 (COVID-19) between April 1, 2020, and March 31, 2021, using Optum's de-identified Clinformatics® Data Mart Database (CDM). COVID-19 was identified by an International Classification of Diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis code of U07.1. The primary outcome was HCU (ie, emergency department (ED) visits, readmissions, rehabilitation/skilled nursing facility (SNF) visits, outpatient office visits, and telemedicine visits) nine months post-discharge after COVID-19 hospitalization (from here on "post-discharge") in patients with COPD compared to HCU of patients without COPD. Poisson regression modeling was used to calculate relative risk (RR) and confidence interval (CI) for COPD, adjusted for the other covariates. We identified a cohort of 160,913 patients hospitalized with COVID-19, with 57,756 discharged home and 14,622 (25.3%) diagnosed with COPD. Patients with COPD had a mean age of 75.48 years (±9.49); 55.5% were female and 70.9% were White. Patients with COPD had an increased risk of HCU in the nine months post-discharge after adjusting for the other covariates. Risk of ED visits, readmissions, length of stay during readmission, rehabilitation/SNF visits, outpatient office visits, and telemedicine visits were increased by 57% (RR 1.57; 95% CI 1.53-1.60), 50% (RR 1.50; 95% CI 1.46-1.54), 55% (RR 1.55; 95% CI 1.53-1.56), 18% (RR 1.18; 95% CI 1.14-1.22), 16% (RR 1.16; 95% CI 1.16-1.17), and 28% (RR 1.28; 95% CI 1.24-1.31), respectively. Younger patients (ages 18 to 65 years), women, and Hispanic patients with COPD showed an increased risk for post-discharge HCU. Patients with COPD hospitalized with COVID-19 experienced increased HCU post-discharge compared to patients without COPD.


High-fat meal impairs vascular compliance in a subgroup of young healthy subjects.
Postprandial hypertriglyceridemia impairs endothelial function and may possibly worsen vascular compliance by increasing oxidative stress. Large (C1) and small (C2) artery compliance, glucose, insulin, and triglycerides (TGs) were measured hourly for 6 hours in 18 young healthy volunteers after a low-fat meal and a high-fat meal, with and without antioxidant vitamins. C1 and C2 declined significantly for 6 hours after fat ingestion in 8 subjects ("fat reactors") and increased in 10 ("nonreactors"). Fat reactors had higher fasting and peak serum TGs after fat loading and increased baseline glucose and insulin levels and homeostasis model assessment of insulin resistance (HOMA(IR)). Fasting insulin correlated with C1 and C2 only in fat reactors. After fat intake, plasma nitric oxide metabolites decreased more in fat reactors than in nonreactors (17.0% +/- 5.1% vs 4.8% +/- 2.1%; P < .05). In fat reactors, pretreatment with antioxidant vitamins before the high-fat meal blunted the fall in C1 but not in C2. Compliance was unchanged after the low-fat meal. Normal weight young subjects with an insulin resistance phenotype show significantly decreased vascular compliance, increased postprandial TG peaks, and markedly reduced plasma nitric oxide metabolites after a high-fat meal.


Extended spectrum beta-lactamase-producing Klebsiella pneumoniae chronic ambulatory peritoneal dialysis peritonitis treated successfully with polymyxin B.
Peritonitis is not an infrequent complication of inpatients with chronic ambulatory peritoneal dialysis (CAPD). CAPD peritonitis may be related to the catheter or secondary to perforation of an intra-abdominal viscus. The most common organisms usually associated with CAPD peritonitis are Staphylococcus aureus and Staphylococcus epidermidis (coagulase-negative staphylococci). Rarely, aerobic gram-negative bacilli have been the causative agents of CAPD peritonitis. The treatment of CAPD peritonitis usually requires removal of the peritoneal catheter and treatment with parenteral antibiotics active against the causative pathogen. We report a case of CAPD-associated peritonitis caused by an extended spectrum beta-lactamase-producing strain of Klebsiella pneumoniae. The case presented had this strain of multidrug-resistant K. pneumoniae present in blood cultures and the peritoneal fluid. Extended spectrum beta-lactamase-producing bacteria, for example, K. pneumoniae, are multidrug-resistant and sensitive to few antibiotics. This isolate was intermediately sensitive to amikacin and meropenem, but the patient did not clinically improve on these 2 antibiotics. Polymyxin B therapy was initiated after lack of clinical improvement after dialysis catheter removal and 1 week of meropenem and amikacin therapy. The patient responded rapidly to therapy with polymyxin B. Polymyxin B has a unique mechanism of action on bacterial cells and is highly active against all multidrug-resistant gram-negative organisms except Proteus species and Serratia marcescens. No toxicity was observed during therapy. Polymyxin B is being used increasingly as a therapeutic alternative to multidrug-resistant gram-negative organisms.


PRDM11 is dispensable for the maintenance and function of hematopoietic stem and progenitor cells.
Hematopoietic stem cells (HSC)(1) supply organisms with life-long output of mature blood cells. To do so, the HSC pool size has to be maintained by HSC self-renewing divisions. PRDM3 and PRDM16 have been documented to regulate HSC self-renewal, maintenance and function. We found Prdm11 to have similar expression patterns in the hematopoietic stem and progenitor cell (HSPC) compartments as Prdm3 and Prdm16. Therefore, we undertook experiments to test if PRDM11 regulates HSC self-renewal, maintenance and function by investigating the Prdm11(-/-) mice. Our data shows that phenotypic HSPCs are intact in bone marrow (BM) of one-year-old Prdm11(-/-) mice. In addition, Prdm11(-/-) mice were able to fully regenerate the hematopoietic system upon BM transplantation (BMT) into lethally irradiated mice with a mild drop in lymphoid output only. Taken together, this suggests that PRDM11, in contrast to PRDM3 and PRDM16, is not directly involved in regulation of HSPCs in mice.


Identification of donor Bacteroides vulgatus genes encoding proteins that correlate with early colonization following fecal transplant of patients with recurrent Clostridium difficile.
Due to suppressive antibiotics, patients with recurrent Clostridium difficile have gut microbial communities that are devoid of most commensal microbes. Studies have shown that most of the failures using fecal microbe transplantation (FMT) for recurrent C. difficile occur during the first 4 weeks following transplantation. To identify features of donor Bacteroides vulgatus that lead to early colonization, we used two data sets that collected fecal samples from recipients at early times points post FMT. The first analysis used the shotgun metagenomic DNA sequencing data set from Aggarwala et al. consisting of 7 FMT donors and 13 patients with recurrent C. difficile with fecal samples taken as early as 24 h post FMT. We identified 2 FMT donors in which colonization of recipients by donor B. vulgatus was detected as early as 24 h post FMT. We examined a second data set from Hourigan et al. that collected fecal samples from C. difficile infected children and identified 1 of 3 FMT that also had early colonization of the donor B. vulgatus. We found 19 genes out of 4911 encoding proteins were unique to the 3 donors that had early colonization. A gene encoding a putative chitobiase was identified that was in a gene complex that had been previously identified to enhance colonization in mice. A gene encoding a unique fimbrillin (i.e., pili) family protein and 17 genes encoding hypothetical proteins were also specific for early colonizing donors. Most of the genes encoding hypothetical proteins had neighboring genes that encoded proteins involved in mobilization or transposition. Finally, analysis of 42 paired fecal samples from the human microbiome project (HMP) found no individuals had all 19 genes while 2 individuals had none of the 19 genes. Based on the results from our study, consideration should be given to the screening of FMT donors for these B. vulgatus genes found to enhance early colonization that would be of benefit to promote colonization following FMT.


Cardiac transplantation in dogs: evaluation with gated MRI and Gd-DTPA contrast enhancement.
It is important to evaluate the severity and extent of cardiac rejection in heart transplantation. Six heterotopic heart transplantation models in the peritoneal cavity were prepared with 12 adult mongrel dogs and in vivo imaging of the donor heart was performed using gated magnetic resonance imaging, (MRI) and Gd-DTPA contrast enhancement. In cardiac rejection, high signal intensity was obtained in the rejected myocardium, especially from the right ventricular wall to the intraventricular septal wall. The rejected myocardium was clearly visualized after administration of Gd-DTPA (0.5 mmol/kg body weight) via the femoral vein in all donor hearts. The mean ratios of signal intensity calculated from the rejected and normal myocardium were also increased from 25% to 42% after administration of Gd-DTPA. On the other hand, in the cases with no rejection, whole myocardium was visualized homogeneously before and after Gd-DTPA and there was no high signal intensity. Thus, our method has the potential of assessing the extent and severity of cardiac rejection using gated MRI and Gd-DTPA contrast enhancement.


The primary structure of rat ribosomal protein L34.
The amino acid sequence of rat ribosomal protein L34 was deduced from the nucleotide sequence in a recombinant cDNA and confirmed from the NH2-terminal amino acid sequence of the protein. Ribosomal protein L34 contains 117 amino acids (the NH2-terminal methionine is removed after translation of the mRNA) and has an Mr of 13,498. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 7-9 copies of the L34 gene. The mRNA for the protein is about 630 nucleotides in length.


Caregiver and divine support: Associations with resilience among adolescents following disclosure of sexual abuse.
Social support is believed to be important for fostering adolescent resilience following sexual abuse. Caregiver support is often examined as a source of support for adolescents, but divine support (support from God or a higher power) has received scant research attention. This study examines relations of caregiver support and divine support with resilience following adolescent sexual abuse. Participants were 548 adolescents aged 11-17 (Mage = 13.78; 91% female) and their non-offending caregivers (Mage = 39.68; 79% mothers). Families were recruited from a children's advocacy center located in the southern United States following a disclosure of sexual abuse. Adolescents completed measures of caregiver and divine support and their social and academic functioning; caregivers and adolescents reported on adolescent psychological functioning. Resilience was operationalized as the absence of clinical levels of psychological symptoms together with the presence of adaptive levels of social and academic functioning. Both caregiver support (r = .19, p < .001) and divine support (r = .14, p = .001) were positively associated with resilience. Considered together in regression analyses, caregiver support (OR = 1.02, p = .001) and divine support (OR = 1.06, p = .04) were both associated with resilience. Clinicians and researchers should consider the potential contribution of caregiver and divine support to adolescent resilience following sexual abuse.


[Death certificates-an underestimated source of information for statistics, judicature, public health, and science].
The thorough external examination of a corpse and the correct completion of the death certificate are medical duties with far-reaching consequences. Data obtained from the death certificates are the basis for mortality statistics and for scientific research. They can be helpful in uncovering criminal offences or for the surveillance of medical facilities. For many years the deficiencies of external post-mortem examinations and death certificates have been discussed in professional journals.The important task of analysing all death certificates is performed by the local health authorities. This is the only opportunity for quality control and, if necessary, the doctors who issued the death certificate must be asked for corrections. This also improves the quality of the mortality statistics and contributes to the administration of justice.Additionally, important information for routine duties of the public health authorities can be obtained from the death certificates concerning the monitoring of narcotics, the supervision of medical facilities and the adherence to notification requirements for infectious diseases. Furthermore, death certificates contain relevant data for selected medical research projects.The high information content of death certificates is widely unknown and should be used by the health authorities comprehensively and systematically. Enough qualified staff needs to be allocated to further secure the important task of quality control of death certificates.


Differential expression of YAMA/CPP-32 by T lymphocytes in popliteal artery aneurysm.
We have previously demonstrated that programmed cell death, proteolytic activity, and inflammatory infiltrate in the aneurysmal wall may have a role in the pathogenesis of popliteal artery aneurysms (PAA). This investigation examines the expression of a cell death-promoting molecule, a cysteine protease, YAMA/CPP-32 in a series of PAA specimens. Twenty PAA specimens were obtained from patients undergoing elective surgical repair. Normal controls were popliteal arteries obtained from patients without PAA who were undergoing infrainguinal bypass surgery (n = 8). Standard histochemistry techniques were used to assess inflammatory infiltrates in PAA. Expression of apoptosis-promoting molecule, CPP-32, vascular smooth muscle cells (VSMC), macrophages, and T lymphocytes was detected by immunohistochemistry. There is a conspicuous disruption and fragmentation of elastic lamellae and increased inflammatory infiltrate in the PAA as compared with normal arteries. As compared with normal popliteal artery tissues, the PAA demonstrated large number of cells immunopositive for CPP-32 (60.45 +/- 4.25% P < 0.05). This study revealed significantly increased expression of CPP-32 in the T-cell population of the PAA as compared with the other cells (P < 0.01). Dual immunolabeling and investigation of serial sections demonstrated that co-expression of CPP-32 was maximum in the CD8+ subset (37 +/- 3.3% of the total CPP-32 immunoreactive cells identified). The data emphasize that the inflammatory infiltrate in the PAA walls has a significant role in the pathogenesis of this vascular disorder. Cells expressing death-promoting molecules are present in large numbers and are predominantly T lymphocytes in PAA. In addition to compromising the mechanical integrity of the vessel wall, apoptosis in the inflammatory infiltrate may contribute to the production of cytokines, activation of other signaling molecules such as stress proteins that could eventually favor PAA development.


Visual tracking of viral infection dynamics reveals the synergistic interactions between cucumber mosaic virus and broad bean wilt virus 2.
Cucumber mosaic virus (CMV) is one of the most prevalent plant viruses in the world, and causes severe damage to various crops. CMV has been studied as a model RNA virus to better understand viral replication, gene functions, evolution, virion structure, and pathogenicity. However, CMV infection and movement dynamics remain unexplored due to the lack of a stable recombinant virus tagged with a reporter gene. In this study, we generated a CMV infectious cDNA construct tagged with a variant of the flavin-binding LOV photoreceptor (iLOV). The iLOV gene was stably maintained in the CMV genome after more than four weeks of three serial passages between plants. Using the iLOV-tagged recombinant CMV, we visualized CMV infection and movement dynamics in living plants in a time course manner. We also examined whether CMV infection dynamics is influenced by co-infection with broad bean wilt virus 2 (BBWV2). Our results revealed that no spatial interference occurred between CMV and BBWV2. Specifically, BBWV2 facilitated the cell-to-cell movement of CMV in the upper young leaves. In addition, the BBWV2 accumulation level increased after co-infection with CMV.


Radiofrequency ablation for treatment of sporadic angiomyolipoma.
Symptomatic angiomyolipoma (AML) and asymptomatic AML larger than 4 cm in size are usually treated with nephron-sparing surgery or arterial embolization. We used another technique, that is, radiofrequency ablation (RFA), for treatment of a sporadic AML in a patient with a solitary kidney, in whom maximal sparing of normal renal tissue was required. Contrast-enhanced computed tomography (CT) showed an enhancing well-defined mainly lipomatous tumor, with a maximum diameter of 4.5 cm in the upper pole of the left kidney. Diagnosis of AML was confirmed with fine-needle aspiration biopsy. RFA was performed with a RF 3000 system, consisting of a generator that supplied up to 200W of power, connected to a 15-gauge LeVeen multipolar array electrode that was placed under CT-guidance centrally in the AML. Initial power was set at low power and increased with increments of 10W, according to the algorithm provided by the manufacturer, resulting in a final tumor end temperature above 65 degrees C. No complications occurred and the patient was discharged home the day after. During follow-up (12 months) function of the solitary kidney of the patient was preserved and patient did not have any AML-related symptoms develop. Contrast-enhanced CT scan showed complete (100%) tumor ablation with absence of enhancement in the tumor and decreased tumor size from 4.5 cm to 2.9 cm at 12 months. CT-guided RFA is a minimally invasive ablation procedure that allowed successful treatment of a sporadic AML in a patient with a solitary kidney. No complications occurred and no AML recurrence was observed during the 12-month follow-up.


Perioperative bone-conducted ocular vestibular-evoked myogenic potentials in otosclerosis patients.
Vestibular symptoms are seen variably in patients with otosclerosis, both in patients with the disease and in patients after treatment with stapes surgery. The goal of this study was to objectify any changes of the bone-conducted (BC) ocular vestibular evoked myogenic potentials (oVEMPs) in patients with otosclerosis before and after stapes surgery. Twenty-six healthy subjects and 27 patients with otosclerosis were tested in a tertiary care center, and 11 of the patients were tested preoperatively and postoperatively. The ears of patients were divided in 4 groups: normal ears, otosclerotic ears, ears after primary stapes surgery, and ears after revision surgery. The stimulus used in oVEMP testing was a BC stimulus delivered by a mini-shaker at stimulus frequencies of 250 and 500 Hz. oVEMP characteristics were the n1 and p1 latencies, n1 - p1 amplitude, and threshold. No significant differences were seen in all oVEMP characteristics between the 4 groups of ears without surgery nor in the ears that were tested preoperatively and postoperatively. No or undetectably little damage to the utricle is caused by both otosclerotic disease and stapes surgery. There is no additive value of screening with BC oVEMPs perioperatively in otosclerotic patients.


Identification of polymorphisms in Apolipoprotein M gene and their relationship with risk of recurrent venous thromboembolism.
Apolipoprotein M (ApoM) plasma levels have been reported to be associated with risk of venous thromboembolism (VTE) recurrence. However, the role of genetic alterations in the ApoM gene in VTE recurrence remains unknown. The aim of this study was to identify genetic aberrations in ApoM gene in VTE recurrence and their role in prediction of VTE recurrence in a prospective follow-up study of 1465 VTE patients. During follow-up, 156 (10.6 %) patients had VTE recurrence. First screening of whole ApoM gene was performed by Sanger's sequencing in selected age and sex matched non-recurrent and recurrent patients (n=95). In total six polymorphisms were identified and two polymorphisms (rs805297 and rs9404941) with minor allele frequency (MAF) ≥5 % were further genotyped in the whole cohort by Taqman PCR. ApoM rs805297 polymorphism was significantly associated with higher risk of VTE recurrence in males but not in females on both univariate (p= 0.038, hazard ratio = 1.72, confidence interval = 1.03-2.88) and on multivariate analysis adjusted with mild and severe thrombophilia, family history, location and acquired risk factors for VTE. However, ApoM rs9404941 polymorphism showed no significant association with risk of VTE recurrence in all patients as well as in different gender groups. Moreover, ApoM rs805297 and rs9404941 polymorphisms were not associated with the ApoM plasma levels. In conclusion, for the first time we have sequenced whole ApoM gene in VTE and identified six polymorphisms. ApoM rs805297 was significantly associated with higher risk of VTE recurrence in male but not in female patients.


A review of Duhuo Jisheng decoction mechanisms in intervertebral disc degeneration in vitro and animal studies.
Intervertebral disc degeneration (IVDD) has become a serious public health problem, placing a heavy burden on society and the healthcare system. Its pathogenesis is not completely clear and may be closely related to mechanical damage, inflammatory factors, oxidative stress and death of nucleus pulposus cells (NPCs). The treatment of IVDD mainly includes conservative treatment and surgery. Conservative treatment is based on hormonal and anti-inflammatory drugs and massage techniques, which can relieve the pain symptoms to a certain extent, but cannot solve the problem from the root cause. Surgical treatment is mainly by removing the herniated nucleus pulposus, but it is more traumatic for IVDD patients, expensive and not suitable for all patients. Therefore, it is extremely important to clarify the pathogenesis of IVDD, to find an effective and convenient treatment and to further elaborate its mechanism of action. The effectiveness of traditional Chinese medicine in the treatment of IVDD has been well demonstrated in clinical medical research. We have been working on the Chinese herbal formula Duhuo Jisheng Decoction, which is a common formula for the treatment of degenerative disc disease. Not only does it have significant clinical effects, but it also has few adverse effects. At present, we found that its mechanism of action mainly involves regulation of inflammatory factors, reduction of apoptosis and pyroptosis of NPCs, inhibition of extracellular matrix degradation, improvement of intestinal flora, etc. However, a few relevant articles have yet comprehensively and systematically summarized the mechanisms by which they exert their effect. Therefore, this paper will comprehensively and systematically explain on it. This is of great clinical significance and social value for elucidating the pathogenesis of IVDD and improving the symptoms of patients, and will provide a theoretical basis and scientific basis for the treatment of IVDD with traditional Chinese medicine.


IL-8 exacerbates CCl4-induced liver fibrosis in human IL-8-expressing mice via the PI3K/Akt/HIF-1α pathway.
Liver fibrosis is an excessive accumulation of extracellular matrix (ECM) due to chronic liver injury. In recent years, the mechanism of liver fibrosis has been extensively studied. Hepatic stellate cells (HSCs) play an important role in the occurrence and development of liver fibrosis because activated hepatic stellate cells could synthesize a large number of ECM and thus participate in the process of liver fibrosis. Interleukin-8 (IL-8) (deletion in mice) is a versatile chemokine that promotes inflammation and affects cell growth by activating related pathways and plays an important role in the development and progression of a variety of diseases. Notably, the expression level of IL-8 was significantly higher in patients with liver fibrosis, suggesting that it may be related to the pathogenesis of liver fibrosis. In this study, we used hydrodynamic injection to deliver the lentiviral vector LV5-hIL-8 into mice. We found that hIL-8 could aggravate carbon tetrachloride (CCl4)-induced liver fibrosis through the PI3K/Akt/HIF-1α pathway. It is characterized by excessive accumulation of ECM as well as a significant increase in markers of liver injury. In addition, in PDGF-induced HSCs, we also demonstrated that hIL-8 could aggravate ECM accumulation through the PI3K/Akt/HIF-1α pathway. In conclusion, the results of this study on hIL-8 may help to identify potential targets for the clinical treatment of liver fibrosis.


Constancy of the front surface desiccation times for Igel 67 lenses in vivo.
A simple method for judging the desiccation of a hydrophilic lens, while on the eye, is described. This involves subjective determination of the loss in "crispness" and "regularity" of the keratometer mire reflected off the anterior lens surface in between blinks. The time interval between a complete blink and the moment of loss of regularity of the reflex was monitored over a 6 month period for subjects wearing a commercially available 67% water content contact lens. This time interval appears to remain constant, and is, on average, comparable with the normal interblink period.


Diagnostic interview study of the prevalence of depression among public employees engaged in long-term relief work in Fukushima.
The Great East Japan Earthquake and in particular, the Fukushima Daiichi Nuclear Power Plant accident, have had a serious psychological impact on not only residents, but also relief workers in Fukushima. Although public employees work in highly stressful situations and play a very important role in long-term relief, their psychiatric features have yet to be clarified. The two aims of this study were to identify the current prevalence rate of depression and post-traumatic stress disorder among public employees working in the disaster area using diagnostic interviews, and to speculate on the psychosocial factors affecting their mental condition. We conducted diagnostic interviews and self-administered questionnaires with 168 public employees working in two coastal towns in Fukushima. Results showed that the current prevalence of depression among public employees is as high as 17.9%, in contrast to the relatively low prevalence of post-traumatic stress disorder (4.8%). Based on the results of self-administered questionnaires and interview contents, frequent exposure to strong complaints or anger from residents and role conflicts were considered the cause of the high prevalence of depression. The present study reveals the serious mental status of public employees working in Fukushima and sheds light on the urgent need to establish an efficient care network to provide adequate psychiatric intervention.


Coordinated development of economic growth and ecological efficiency in Jiangsu, China.
In order to realize sustainable development, ecological efficiency is particularly important and deserving of further study and discussion in China. Thus, the study proposed a comprehensive index for ecological efficiency in Jiangsu and evaluated the ecological efficiency of 13 cities in the year of 2007, 2012, and 2017 by using entropy-weighting TOPSIS method. Based on coupling model, the study discussed the interaction between economic growth and ecological efficiency in Jiangsu. The results indicated that the ecological efficiency of Jiangsu in these three years differed considerably. Ecological efficiency is the highest in central Jiangsu, whereas ecological efficiency in the northern and southern parts of Jiangsu is relatively low from the perspective of horizontal space. In terms of coupling, Wuxi and Suzhou were the stablest in southern Jiangsu. Economic growth in the central Jiangsu fluctuated, Suqian lagged. Furthermore, based on the findings, the industrial structure should be adjusted to improve ecological efficiency. In addition, the use of innovation and rational foreign direct investment and other measures should be promoted. These proposals aim at improving ecological efficiency and achieving overall sustainable development in Jiangsu, China.


Solid state thermal degradation behaviour of graft copolymers of carboxymethyl cellulose with vinyl monomers.
The graft copolymer of sodium carboxymethyl cellulose (CMC) with acrylamide (ACM), dimethylacrylamide (DMA), N-vinyl pyrrolidone (NVP), 2-acrylamido-2-methyl-1-propane sulphonic acid (AMPS) and vinyl caprolactum (VCL) were synthesized in nitrogen atmosphere by employing redox initiators. The integral procedural decomposition temperature (IPDT) of CMC and its graft copolymer with ACM, DMA, AMPS, NVP and VCL have been found to be 274°C, 375°C, 421°C, 404°C, 466°C and 331°C, respectively. The higher value of IPDT showed more thermal stability. Among all five graft copolymers, the graft copolymer of CMC with NVP is thermally more stable and VCL grafted copolymer was found least thermally stable. The higher char yield and final decomposition temperature (FDT) were obtained in the case of more thermally stable graft copolymer. All five graft copolymers have shown more than one Tmax, which suggests that degradations were multistep process.


The International Medical Graduate Perspective in Hand Surgery: Legacy and Future Challenges.
International medical graduates (IMGs) have made significant contributions in the field of hand surgery in terms of bringing in skill, innovation, research, and leadership and have gone onto mentor the next generations of hand surgeons. In this article, we have highlights some such contributions. We also highlight various pathways that IMGs take to establish their practice in the United States and the various challenges and hurdles they face.


Uptake of COVID-19 vaccination among people who inject drugs.
People who inject drugs (PWID) may be at elevated risk of adverse outcomes from SARS-CoV-2 infection; however, data on COVID-19 vaccine uptake among PWID are scarce. This study aimed to determine COVID-19 vaccine uptake among PWID, identify factors associated with sub-optimal uptake, and compare uptake to the general population. The Australian Needle Syringe Program Survey is an annual sentinel surveillance project, comprising a self-completed questionnaire and provision of a dried blood sample for HIV and HCV testing. In 2021, respondents provided information on their COVID-19 vaccination status. Multivariate logistic regression models identified correlates of vaccine uptake. Among 1166 respondents, 49% had been vaccinated and in most states and territories, vaccine uptake was significantly lower than among the general population. Independent predictors of vaccine uptake were longer duration of vaccine eligibility (AOR 3.42, 95% CI 2.65, 4.41); prior SARS-CoV-2 diagnostic testing (AOR 2.90, 95% CI 2.22, 3.79); injection of opioids (AOR 1.91, 95% CI 1.20, 3.05); and current opioid agonist therapy (AOR 1.70, 95% CI 1.23, 2.33). Women (AOR 0.70, 95% CI 0.54, 0.92) and those who reported daily or more frequent injection (AOR 0.75, 95% CI 0.57, 1.00) were significantly less likely to be vaccinated. In most Australian states and territories, uptake of COVID-19 vaccine among PWID lagged uptake among the general population. Increased efforts are required to ensure PWID have equitable access to vaccination. Vaccination programmes within harm reduction services and via outreach, coupled with increased support for peers to act as vaccine champions, are likely to reduce barriers and improve COVID-19 vaccine uptake in this population.


Indomethacin treatment for polyhydramnios. Effective but potentially dangerous?
A case of acute polyhydramnios for unknown reason was successfully treated with orally administrated indomethacin. The need for close supervision of the pregnancy, because of potential risk for oligohydramnios, is described.


Effects of alcohol on a Critical Tracking Task.
Performance on a Critical Tracking Task decreased significantly as blood alcohol levels increased.


Verisyse intraocular lens implantation in a child with anisometropic amblyopia: four-year follow-up.
A Verisyse phakic intraocular lens (pIOL) (AMO) was implanted in the eye of a 3-year-old child with unilateral high myopia and suspected dense amblyopia. Four years postoperatively, the Snellen visual acuity was 20/30 with a refraction of -1.00 -1.00 x 77 and the endothelial cell density was 3262 cells/mm(2) compared with 3092 cells/mm(2) in the right eye. The Verisyse pIOL may be a treatment option to prevent dense amblyopia in children with highly myopic anisometropia.


Pigment epithelium-derived factor may induce antidepressant phenotypes in mice by the prefrontal cortex.
Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein encoded by SERPINF1 and our previous study reported that PEDF may have antidepressant effects. As a key brain region regulating cognition, memory and emotion, the prefrontal cortex (PFC) has been studied extensively in major depressive disorder (MDD), but there are few reports on the relationship between PEDF and the PFC. In this study, enzyme-linked immunosorbent assay showed that the PEDF level was decreased in the plasma of MDD patients compared with that of healthy controls. Western blotting validated that the PEDF expression in the PFC was downregulated in the mouse chronic social defeat stress and rat chronic unpredictable mild stress models of depression. Correspondingly, normal mice overexpressing PEDF in the PFC showed depression-resistant phenotypes. We detected PFC metabolite levels by liquid chromatography-tandem mass spectrometry and found significant upregulation of 5-hydroxyindoleacetic acid, kynurenine, 5-hydroxytryptamine, ornithine and glutamine, and downregulation of 5-hydroxytryptophan, glutamic acid and aspartic acid in PEDF-overexpressing mice compared with control mice, in which no such changes were detected. Combined with the above findings, this provides an insight into a potential mechanism of the antidepressant effects of PEDF via the PFC, which may help to improve understanding of depression pathophysiology.


Disaster preparedness and response practices among providers from the Veterans Health Administration and Veterans with spinal cord injuries and/or disorders.
Few empirical studies have examined the disaster preparedness and response practices of individuals with spinal cord injuries and/or disorders (SCI/D) and the healthcare providers who serve them. This study was conducted to understand the experiences of Veterans Health Administration (VHA) providers and Veterans with SCI/D in recent natural disasters, and to identify lessons learned for disaster preparedness and response in the context of SCI/D. Semi-structured interviews were conducted with providers and Veterans recruited through seven VHA facilities that had sustained a disaster since 2003. Audio recordings of the interviews were transcribed; transcripts were analyzed using constant comparative techniques. Forty participants completed an interview, including 21 VHA SCI/D providers and 19 Veterans with SCI/D. Disasters experienced by participants were weather related. While many Veterans were evacuated or admitted to nearby VHA facilities, others chose to stay in their communities. All facilities had formal disaster plans and engaged in related training; however, participants explained that many aspects of a response take shape 'in the moment,' and must address both provider and Veteran needs. Dispersion of resources hindered well-coordinated care, but effective communication, teamwork, advanced warnings, and VHA's electronic medical record facilitated efforts. Even in the case of thorough planning, Veterans with SCI/D and their healthcare providers are faced with pressing needs during disasters, and identifying strategies to coordinate care is critical. The lessons learned are intended to inform the efforts of healthcare providers who may be involved in the care of individuals with SCI/D in future disasters.


Selected CC and CXC chemokines in children with atopic asthma.
There are only limited data on CC and CXC chemokines regulation in children with asthma. We compared the serum profile of selected CC and CXC chemokines in patients with atopic asthma and healthy children. Serum concentration of CC chemokines RANTES, MCP-1, and CXC chemokines IP-10, MIG, IL-8, RANTES was measured using cytometric bead array in 44 children with atopic asthma and 17 healthy subjects. The concentration of RANTES was significantly higher and the MIG level was lower in all children with asthma as compared to their control counterparts. We observed increased RANTES and decreased MIG levels also in patients with stable asthma when compared with children in the control group. The IP-10 concentration was similar between the whole asthma group and healthy controls, while significantly increased levels of this chemokine in acute asthma have been observed when compared to stable asthma. For MCP-1 and IL-8, the serum concentration was similar in all compared groups. The MIG concentration correlated positively with IP-10, IL-8, and CRP levels and negatively with the eosinophil count. A negative correlation between the IP-10 and eosinophil count and a negative correlation between FEV1 and IP-10 were found. An increased serum RANTES level in children with asthma may result in enhancement of Th2 lymphocyte recruitment into the airway. A decreased expression of Th1 chemokine MIG in children with stable asthma may contribute to a diminished antagonizing effect on Th2 cytokine production and hence intensify Th2 predominance. An increased IP-10 level in children during an asthma attack suggest that this chemokine is a serological marker of disease exacerbation.


Challenges to detect glaucomatous visual field loss with pupil perimetry.
We evaluated the pattern deviation of pupil fields to differentiate a glaucomatous damage using the head-mounted perimeter "imo". Thirty-four eyes of 26 glaucoma patients (mean age, 55.1 years) were examined. The pattern deviation (85th percentile) of pupil fields was calculated from the difference between age-matched normal and abnormal percentage pupil constriction. Consequently, glaucomatous damages were remarkably distinguished from the normal pupil fields using the pattern deviation of the imo.


Mitochondria, telomeres and cell senescence: Implications for lung ageing and disease.
Cellular senescence, the irreversible loss of replicative capacity in somatic cells, plays a causal role in the development of age-related pathology and in a number of age-related chronic inflammatory diseases. The ageing lung is marked by an increasing number of senescent cells, and evidence is mounting that senescence may directly contribute to a number of age-related respiratory diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). Telomere dysfunction and alterations in mitochondrial homeostasis frequently occur in cellular senescence and are important to the development of the often detrimental senescence-associated secretory phenotype (SASP). The roles of telomeres, the mitochondria and cellular senescence in lung ageing and disease are discussed. Therapeutic interventions targeting cellular senescence are considered for delaying or potentially reversing age-related respiratory disease.


Sensorimotor or Balance Training to Increase Knee-Extensor and Knee-Flexor Maximal Strength in Patients With Knee Osteoarthritis: A Critically Appraised Topic.
Knee osteoarthritis (KOA) is a complex progressive synovial joint disease that results in impaired muscle function, including a considerable loss of maximal strength and power. Exercise therapies, such as sensorimotor or balance training and resistance training, are frequently used to improve muscle function, mobility, and quality of life, but their impact on maximal muscle strength in patients with KOA is not well understood. Does sensorimotor or balance training improve knee-extensor and knee-flexor maximal muscle strength compared with strength training or no intervention in patients with KOA? Results from 4 fair- to good-quality randomized controlled/clinical trials (level 1b) revealed inconsistent grade B evidence regarding the effect of sensorimotor or balance training to improve knee-extensor and knee-flexor maximal muscle strength in patients with KOA. Two studies, one good-quality study and one fair-quality study, showed significant strength improvements, and 2 good-quality studies demonstrated no significant strength enhancements. Sensorimotor or balance training may be useful to improve maximal strength of quadriceps and hamstring muscle groups in patients with KOA; however, it seems that this depends on a training duration of at least 8 weeks and the use of unstable devices to induce destabilization of patients' balance, initiating neuromuscular adaptations. Due to inconsistent evidence (grade B), the true effect of sensorimotor or balance training to improve knee-extensor and knee-flexor maximal muscle strength in patients with KOA remains unclear and needs to be further investigated.


Prior experience with flavored alcohol increases preference for flavored alcohol but flavor does not influence binge-like drinking behavior in mice.
Binge drinking can lead to various negative consequences and in non-experimental settings, alcohol usually contains flavoring, which may promote increased binge drinking. Preclinical models of binge-like drinking have been well established, however, the influence of flavor on alcohol preference and binge-like drinking has not been fully explored. Male and female C57BL/6 J mice were tested via two-bottle choice with alcohol flavored with different concentrations of unsweetened Cherry flavor Kool-Aid and water. Next, mice were tested for preference for flavored alcohol over plain alcohol. Consumption of flavored alcohol versus water was examined over 48 h. Binge-like drinking with flavored alcohol was validated via drinking in the dark (DID). A separate cohort of mice underwent chronic DID for 6 weeks with either flavored or plain alcohol. After chronic DID, mice were then tested for preference for flavored versus plain alcohol and then alcohol consumption despite adverse effects was examined using the quinine adulteration test. The 0.1% Kool-Aid concentration was chosen to use for further testing based on intake. Mice preferred Kool-Aid flavored alcohol over plain alcohol after the concentration test, but mice with no prior exposure to plain or flavored alcohol preferred plain over flavored alcohol. Throughout all initial testing, female mice showed increased alcohol intake compared to male mice. Both male and female mice showed binge-like drinking of flavored alcohol, with females having higher intake and blood alcohol levels. Kool-Aid flavor did not increase alcohol intake during chronic binge-like drinking. Previous exposure to flavored alcohol during DID increased the preference for flavored alcohol over plain alcohol but did not influence alcohol consumption despite adverse effects. The present study indicates that prior experience with flavored alcohol increases preference and intake, suggesting an effect of learned safety from neophobia. However, flavor does not impact binge-like alcohol consumption or alcohol drinking despite negative consequences. Additionally, the current study shows that female mice will consume more flavored alcohol than males, similar to findings from other alcohol studies.


[Life as a process of existence, reproduction and aging of polyhierarchical systems].
Comments on the definitions of life as a process of functioning polyhierarchic biological structures in the conditions of flow of energy to systems and existence of liquid water are presented. The phenomenon of life can be considered as a complex process of repeated cycles of origin, reproduction, aging, and death of polyhierarchical systems. Laws of thermodynamics and the principle of substance stability «are the driving forces» of this process. Life is a set of non-spontaneous and spontaneous processes of transformation and exchange of structures of different hierarchies in spatially isolated biological systems.


Will population decreases in caffeine consumption unveil attention deficit disorders in adults?
Attention deficit disorders (ADD) represent the commonest behavior disorder observed in children but only recently has the persistence of these disorders into adulthood been acknowledged. As individuals with ADD enter adolescence and then adulthood some behavioral symptoms appear to cease, others become muted. This change has usually been attributed to physiological maturation. One environmental factor which may also contribute to the altered clinical picture is the regular ingestion of caffeine beginning in late adolescence. Caffeine has been found to alter the behavior of ADD children in a manner resembling more widely prescribed stimulant medications. If some adults with ADD have responded positively to caffeine ingestion then it would be predicted that increases in reports of ADD symptoms will escalate with the rapid decline in caffeine consumption in North America.


Current and potential new treatment strategies for creatine deficiency syndromes.
Creatine deficiency syndromes (CDS) are inherited metabolic disorders caused by mutations in GATM, GAMT and SLC6A8 and mainly affect central nervous system (CNS). AGAT- and GAMT-deficient patients lack the functional brain endogenous creatine (Cr) synthesis pathway but express the Cr transporter SLC6A8 at blood-brain barrier (BBB), and can thus be treated by oral supplementation of high doses of Cr. For Cr transporter deficiency (SLC6A8 deficiency or CTD), current treatment strategies benefit one-third of patients. However, as their phenotype is not completely reversed, and for the other two-thirds of CTD patients, the development of novel more effective therapies is needed. This article aims to review the current knowledge on Cr metabolism and CDS clinical aspects, highlighting their current treatment possibilities and the most recent research perspectives on CDS potential therapeutics designed, in particular, to bring new options for the treatment of CTD.


Emerging opportunities in bioconjugates of Elastin-like polypeptides with synthetic or natural polymers.
Nature is an everlasting source of inspiration for chemical and polymer scientists seeking to develop ever more innovative materials with greater performances. Natural structural proteins are particularly scrutinized to design biomimetic materials. Often characterized by repeat peptide sequences, that together interact by inter- and intramolecular interactions and form a 3D skeleton, they contribute to the mechanical properties of individual cells, tissues, organs, and whole organisms. (Numata, K. Polymer Journal 2020, 52, 1043-1056) Among them elastin, and its main repeat sequences, have been a source of intense studies for more than 50 years resulting in the specific research field dedicated to elastin-like polypeptides (ELPs). These are currently widely investigated in different applications, namely protein purification, tissue engineering, and drug delivery, and some technologies based on ELPs are currently explored by several start-up companies. In the present review, we have summarized pioneering contributions on ELPs, progress made in their genetic engineering, and understanding of their thermal behavior and self-assembly properties. Considered as intrinsically disordered protein polymers, we have finally focused on the works where ELPs have been conjugated to other synthetic macromolecules as covalent hybrid, statistical, graft, or block copolymers, highlighting the huge opportunities that have still not been explored so far.


Bacterial and fungal biodeterioration of discolored building paints in Lagos, Nigeria.
Microbial induced discolorations are an unsightly feature occurring on painted walls in Lagos, the commercial hub of Nigeria. Very few studies have been carried out conventionally about the microbial community structure of discolored painted walls in Nigeria therefore, knowledge of the true microbial diversity is elusive. To further our understanding of the phylogenetic diversity of representative microbial community on 40 discolored and three clean-looking buildings, a comparative DNA sequence analysis of 16S rDNA genes was undertaken. Following DNA extraction, portions of the rDNA genes were amplified by PCR and sequenced. Resulting sequences were compared with GenBank data base sequences. Fifteen unique fungal sequences and one bacterial sequence were obtained. Majority (37.50%) of rDNA sequences analyzed, represent the genus Meyerozyma of which the novel fungus Meyerozyma guilliermondii, which to our knowledge, has not yet been implicated in painted walls was detected. Clones from the discolored painted wall isolates also produced a data set in which 31.25% of sequences were related to Fusarium proliferatum and 6.25% were Pseudomonas aeruginosa. The remaining sequences clustered with members of the genera Candida (6.25%), Aspergillus (12.5%) and Cerrena (6.25%). The study provides reliable data on microbial communities on painted walls and information for paint biocide formulation.


Timing and implications for immune response to vaccine in SARS-CoV-2 breakthrough infections.
COVID-19 vaccines elicit a strong anti-S antibodies response. We aim to describe antibody titers in peri-vaccination SARS-CoV-2 infections. This is a retrospective longitudinal single-cohort study. Serological tests were performed at the time of the first SARS-CoV-2 vaccine dose (T0) and 60 (T1), 120 (T2), and 240 (T3) days after. The study included 4,682 subjects. Group A had the infection without an anti-S Ig response. Group B and C seroconverted for anti-N Ig between T0 and T1 and between T1 and T2, respectively. Group D was persistently anti-N Ig negative. Group B showed an initial sub-optimal response, reaching the highest titer at T3. Those who received the second dose 120 days after the infection had higher titers compared to those who received it 21 days after the first dose. The immune response depends on the number and the timing of vaccine doses, highlighting the need for a more personalized approach to vaccination.


Two-dimensional mapping of three phenotype-associated isoforms of the prion protein in sporadic Creutzfeldt-Jakob disease.
Transmissible spongiform encephalopathies (TSE), or prion diseases, are mammalian neurodegenerative disorders characterized by a conformational modification of the host-encoded prion protein (PrP(C)) into an isoform which is detergent-insoluble and partially resistant to protease treatment (PrP(Sc)). Distinct types of PrP(Sc), differing in conformation and variation in the relative amount of their glycoforms, have been associated with different phenotypes of TSE. In sporadic Creutzfeldt-Jakob disease (sCJD), two major types of PrP(Sc), with proteinase K (PK)-resistant fragments of 21 and 19 kDa, have been described. No consensus exists, however, on the molecular classification of PrP(Sc) in sCJD, since further heterogeneity within PrPSc conformers has been reported. We studied 19 subjects with dementia or dementia/ataxia at onset and 12 subjects with ataxia at onset. Following two-dimensional gel electrophoresis, we characterized PrP(C) and PrP(Sc) species in normal and sCJD brains by immunoblotting with antibodies recognizing N-terminal and C-terminal PrP regions. Three types of PrP(Sc) were detected in detergent-insoluble fractions from sCJD brains, mainly consisting of full-length PrP(Sc) in subjects with rapidly progressive dementia, and two different sets of amino-truncated PrP(Sc) glycoforms in subjects with dementia/ataxia and ataxia at onset. Examination of the PrP(Sc) core fragment, following PK treatment and deglycosylation, confirmed the existence of three distinctive patterns. These findings have immediate implications for the molecular classification of sCJD.


Double color-opponent receptive fields of carp bipolar cells.
Bipolar cells with double color-opponent receptive fields were found in the carp retina. They were classified into two types depending on their response polarity. In the receptive field center, type I cells showed hyperpolarization to a long wavelength spot (R-) and depolarization to a short wavelength spot (G+), while in the surround they showed R+, G- responses. Type II cells showed responses of opposite polarities to those of type I cells, namely R + G- in the center, and R - G+ in the surround. From their spectral sensitivity, R components were identified as coming from red-sensitive cones, and G components from green-sensitive cones. These bipolar cells are thought to be the origin of double color-opponent receptive fields of retinal ganglion cells.


Effect of ethanol administration on activities of some lysosomal hydrolases in the mouse.
1. The studies were carried on 98 random 6-week-old male mice. The mice were divided into control and experimental groups. The experimental animals were given 10% and 20% ethanol solution daily for 7, 14 and 28 days. 2. In the lysosomal fractions of the liver, kidneys, muscle and brain, the activities of beta-galactosidase, beta-glucuronidase, N-acetyl-beta-glucosaminidase, alanyl-aminopeptidase, leucyl-aminopeptidase, lysosomal esterase and lysosomal lipase were affected. 3. The changes in enzyme activities in the investigated tissue were related to the time and concentration of the administered ethanol.


The evolving role of commutability in metrological traceability.
Commutability is a property of a reference material (RM) which denotes that the analytical response in measurement procedures (MPs) observed for the measurand is the same for the RM as for clinical samples that contain the same amount of the measurand. Matrix-based secondary calibrators are required to be commutable with clinical samples to achieve metrological traceability of results from a clinical laboratory MP to higher order references. Results for clinical samples may not agree among different end-user MPs if a noncommutable RM is used in the calibration hierarchy for one or more of the MPs. Consequently, a useful RM is one that is commutable with clinical samples for all or most MPs in common use. If a matrix-based RM is noncommutable for one or a few MPs, a correction for the noncommutability bias may be added in the calibration hierarchy to enable the results for clinical samples to be metrologically traceable to the RM. Producing a large batch of matrix-based RM requires pooling single donations and making various modifications of the matrix such as spiking with exogenous substances, freezing or lyophilization. These modifications could potentially affect commutability of the RM and compromise its suitability. Documentation of commutability of matrix-based RMs used as calibrators is required by the International Organization for Standardization and the Joint Committee for Traceability in Laboratory Medicine. We describe how commutability was recognized as a critical requirement for metrological traceability and we present recommendations from the IFCC Working Groups on Commutability and on Commutability in Metrological Traceability.


Electroacupuncture effects in a rat model of complete Freund's adjuvant-induced inflammatory pain: antinociceptive effects enhanced and tolerance development accelerated.
We have previously shown that electroacupuncture (EA) produced antinociception through the release of endogenous opioid peptides to activate opioid receptors during acute nociception. EA produced tolerance after its prolonged application. It has reported that 100 Hz EA could reduce mechanical hyperalgesia in complete Freund's adjuvant (CFA)-induced inflammatory nociception rats. The present study aims to investigate the antinociceptive effect of EA and the development of EA tolerance in chronic inflammatory nociception rats with CFA injection into the hind paw plantar. The results showed that the antinociceptive effect of 100 Hz EA was significantly enhanced in CFA-induced inflammatory nociception rats. Naloxone at 20 mg/kg could significantly block this antinociceptive effect. Chronic tolerance to EA was developed faster in CFA-induced inflammatory nociception rats than in normal rats. Therefore, 100 Hz EA could enhance antinociceptive effects and accelerate tolerance development in CFA-induced inflammatory nociception rats. The enhancement of EA antinociceptive effect in CFA-induced inflammatory nociception rats might involve the endogenous opioid peptides such as dynorphin.