Attitudes towards polypharmacy and medication withdrawal among older inpatients in Italy.
From 20 to 65 % of older adults receiving polypharmacy take at least one potentially inappropriate medication (PIM), leading to a high risk of adverse drug reactions. The term deprescribing was coined to describe a process of optimization of drug regimens through the withdrawal of PIMs. There is a paucity of evidence on the attitudes, beliefs and willingness of hospitalized patients towards deprescribing. To measure at hospital discharge inpatients' attitudes and beliefs towards polypharmacy and the potential withdrawal of one or more of their medications using the PATD (Patients' Attitudes Towards Deprescribing) questionnaire and determine if they are associated with participant characteristics. Geriatric and internal medicine wards in an Italian teaching hospital. Administration of the PATD questionnaire (developed and validated in an Australian outpatient setting, translated and adapted to the Italian setting for this study) to a consecutive sample of 100 older (aged ≥65 years) inpatients with polypharmacy who were interviewed by a nurse or pharmacist at the time of hospital discharge. Older patients' attitudes and beliefs towards reducing medications and participant characteristics. Eighty-nine percent of patients surveyed would like to reduce the number of daily medications. The desire for deprescribing was not associated with age, sex or number of medications or medical conditions; older patients were less aware of the reasons for taking medications. The majority of hospitalized older adults with polypharmacy think they are taking a lot of drugs and would like to reduce this number. Older adults should not be considered a major limitation on deprescribing interventions. Future research should examine this issue with qualitative studies in order to gain a more in-depth understanding and explore how these findings can be translated into a multidisciplinary deprescribing process.


Surface-modified activated carbon for anaerobic digestion to optimize the microbe-material interaction.
The anaerobic digestion of organic materials produces biogas; however, optimizing methane (CH4) content within biogas plants by capturing carbon dioxide (CO2) is one of the challenges for sustainable biomethane production. CH4 is separated from biogas, which is called biogas upgrading for biomethane production. In this regard, in-situ CO2 capture and utilization could be an alternative approach that can be achieved using conductive particles, where the conductive particles support the direct intraspecific electron transfer (DIET) to promote CH4 production. In this investigation, a carbon nanotube (CNT) was grown over conductive activated carbon (AC). Then an iron (Fe) nanoparticle was anchored (AC/CNT/Fe), which ultimately supported microbes to build the biofilm matrix, thereby enhancing the DIET for CH4 formation. The biogas production and CH4 content increased by 17.57 % and 15.91 %, respectively, when AC/CNT/Fe was utilized. Additionally, 18S rRNA gene sequencing reveals that Methanosarcinaceae and Methanobacteriaceae families were the most dominant microbes in the reactor when conductive particles (AC/CNT/Fe) were applied. The proposed study supports the stable operation of biogas plants to utilize CO2 for CH4 production by using surface-modified material.


Prednisone in the treatment of tubulointerstitial nephritis in children.
Patients with tubulointerstitial nephritis (TIN) may develop permanent renal impairment. However, there are no prospective studies available on the treatment of TIN. The effect of prednisone in the treatment of TIN was evaluated in a total of 17 patients who received prednisone or who were followed up without medication. The patient group was subdivided based on the initial plasma creatinine (PCr), below or above 150 μmol/l. All prednisone-treated patients had normal plasma creatinine (PCr) after 1 month of treatment (median 59.1 [45-85] μmol/l) whereas only 50 % of patients in the non-treatment group had normal creatinine (median 81.0 [42-123] μmol/l) at the same time point (p = 0.025). During 6 months' follow-up, PCr decreased in all patient groups; however, it decreased significantly only in prednisone-treated patients with baseline PCr >150 μmol/l (p < 0.001). At the end of follow-up, no difference in PCr, glomerular filtration rate (GFR), or low molecular weight (LMW) proteinuria could be found between the study groups. A considerable number of patients in both groups had subnormal GFR and/or persistent LMW proteinuria at the 6-month follow-up visit. Eighty-two percent of the patients had uveitis. Prednisone speeds up the recovery from renal symptoms of TIN, especially in patients with severe nephritis. The renal function did not differ significantly between prednisone and control patients after 6 months' follow-up.


Activation of apoptotic pathways in the absence of cell death in an inner-ear immortomouse cell line.
Aminoglycoside antibiotics and cisplatin (CDDP) are the major ototoxins of clinical medicine due to their capacity to cause significant and permanent hearing loss by targeting the mammalian sensory cells. Understanding the pathogenesis of damage is the first step in designing effective prevention of drug-induced hearing loss. In-vitro systems greatly enhance the efficiency of biochemical and molecular investigations through ease of access and manipulation. HEI-OC1, an inner ear cell line derived from the immortomouse, expresses markers for auditory sensory cells and, therefore, is a potential tool to study the ototoxic mechanisms of drugs like aminoglycoside antibiotics and CDDP. HEI-OC1 cells (and also HeLa cells) efficiently take up fluorescently tagged gentamicin and respond to drug treatment with changes in cell death and survival signaling pathways. Within hours, the c-Jun N-terminal kinase pathway and the transcription factor AP-1 were activated and at later times, the "executioner caspase", caspase-3. These responses were robust and elicited by both gentamicin and kanamycin. However, despite the initiation of apoptotic pathways and transient changes in nuclear morphology, cell death was not observed following aminoglycoside treatment, while administration of CDDP led to significant cell death as determined by flow cytometric measurements; β-galactosidase analysis ruled out senescence in gentamicin-treated cells. The ability to withstand treatment with aminoglycosides but not with CDDP suggests that this cell line might be helpful in providing some insight into the differential actions of the two ototoxic drugs.


Multidetector row computed tomography quantification of bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation: a pilot study.
To evaluate multidetector row computed tomographic indexes to quantify bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplantation by correlation with pulmonary function tests (PFT). Eighteen patients with BOS after hematopoietic stem cell transplantation and 18 age-matched healthy volunteers were included. They underwent multidetector row computed tomography including inspiration and expiration scans. The patients also underwent PFTs. Mean lung density (MLD), relative areas (RAs) of lung with attenuation coefficients below specific thresholds, and 9 percentiles of the distribution of attenuation coefficients were computed. These parameters and PFT results were correlated. Mean MLD on inspiration (MLDin), MLD on expiration (MLDex), and the difference between the 2 (ΔMLD) were -858.5 HU, -788.6 HU, and 69.9, respectively, for the patients and -815.9 HU, -691.8 HU, and 124.1, respectively, for the volunteers. These parameters showed significant differences between the 2 groups (P<0.001) and strongly correlated with patients' residual forced expiratory volume in 1 second (FEV1) (r=0.71, 0.92, and 0.85, P≤0.001, respectively). RA with attenuation coefficients <-800 HU (RA800e) and the 80th percentile (80the) on expiration correlated most highly with the patients' residual FEV1 (r=-0.94, P<0.001). RA with attenuation coefficients <-800 HU (RA800e) and the 80th percentile (80the) on expiration are valid indexes of the patients' residual FEV1 in BOS.


Event-related potentials in response to 3-D auditory stimuli.
To evaluate auditory spatial cognitive function, age correlations for event-related potentials (ERPs) in response to auditory stimuli with a Doppler effect were studied in normal children. A sound with a Doppler effect is perceived as a moving audio image. A total of 99 normal subjects (age range, 4-21 years) were tested. In the task-relevant oddball paradigm, P300 and key-press reaction time were elicited using auditory stimuli (1000 Hz fixed and enlarged tones with a Doppler effect). From the age of 4 years, the P300 latency for the enlarged tone with a Doppler effect shortened more rapidly with age than did the P300 latency for tone-pips, and the latencies for the different conditions became similar towards the late teens. The P300 of auditory stimuli with a Doppler effect may be used to evaluate auditory spatial cognitive function in children.


Localization of calcium and phosphorus in early predentin-matrix components by electron spectroscopic imaging (ESI)-analysis in rat molars.
The subcellular distribution of the inorganic elements calcium (Ca) and phosphorus (P) was studied in the first-formed dentin matrix during initial mineralization in neonatal rat molars. This most peripheral matrix region is comprised of a proteoglycan-rich ground substance, interwoven by a collagenous network, matrix vesicles, aperiodic fibrils derived from the dental basal lamina, and apical odontoblastic cell processes. All matrix components may possibly serve as templets for mineral deposition during initial calcification of first-formed mantle dentin and predentin. By means of the very sensitive ESI-analysis we studied the subcellular localization of Ca and P and their possible association with distinct organic extracellular matrix components and odontoblasts. Ca-signals were found in the ground substance, at striated collagen fibrils and plasma membranes of odontoblasts in the cuspal early matrix region, but occurred only sparsely in the ground substance of the more distal matrix region where odontoblast processes attach to aperiodic fibrils of the dental basal lamina. Ca was generally absent in matrix vesicles. In contrast, P-signals were found in matrix vesicles, at aperiodic fibrils and at the plasma membranes of odontoblasts. Ca and P co-localized at striated collagen fibrils (type I or II). These results suggest that striated collagen fibrils might serve as primary deposition sites for calcium phosphate during early biological calcification of organic extracellular macromolecules.


Synthesis and evaluation of pharmacological properties of novel annelated 2,3-benzodiazepine derivatives.
New cyclofunctionalized 2,3-benzodiazepines characterized by a triazolone or triazindione ring fused on the "c" edge of the heptatomic nucleus have been prepared. These compounds were evaluated as potential anticonvulsant agents, and some of them proved to be more potent noncompetitive 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate (AMPA) receptor antagonists. In particular, 8,9-dimethoxy-6-(4-bromophenyl)-11H-[1,2,4]triazolo[4,5-c][2,3]benzodiazepin-3(2H)-one (5b) was almost 10-fold more active than GYKI-52466 and 3.5-fold more active than Talampanel. Furthermore, 5b potently reduced AMPA-evoked currents in electrophysiological experiments.


Acceptability of robotic manipulators in shared working environments through human-like redundancy resolution.
Next generation robotic manipulators are expected to resemble a human-like behavior at kinematic level, in order to reach the same level of dexterity of humans in operations like assembly of small pieces. These manipulators are also expected to share the same working environments with humans without artificial barriers. In this work we conjecture that making robots not only kinematically similar but also able to move and act in the same way as humans do, might facilitate their social acceptance. For this the kinematic redundancy of such new generation manipulators can be exploited. An experimental campaign has been organized to assess the physiological comfort/discomfort perceived by humans working side-by-side with robots. For comparison, a human-like and two alternative redundancy resolution strategies have been implemented. The analysis confirmed the hypothesis that a human-like motion of the robot helps in facilitating social acceptance, by reducing the perceived stress by humans in human-robot coexistence.


The first decade of oligotrophication of Lake Constance : II. The response of phytoplankton taxonomic composition.
In Lake Constance, after several decades of cutrophication, a decrease in phosphorus loading over the last decade has lead to a partial recovery from eutrophication. Here we analyse the shift in the taxonomic composition of phytoplankton during the first decade of oligotrophication in Lake Constance. During the 1980s, spring total P concentrations decreased from ca. 130 to less than 50 μ·l-1. This decrease was reflected by an approximately proportional decrease in summer phytoplankton biomass while spring phytoplankton biomass seemed unresponsive. Major taxonomic changes occured during both growth seasons. In spring, the proportion of diatoms, green algae and Chrysophyta increased while the proportion of Cryptophyta decreased. The summer trend was very different: the relative importance of diatoms decreased and Cryptophyta and Chrysophyta increased, while Chlorophyta reached their peak around 1985. These trends are also analysed at the genus level. Comparison with taxonomic trends during the eutrophication period shows the expected reversals in most cases. Comparison with other lakes shows general similarities, with the notable exception that Planktothrix rubescens has never been important in Lake Constance. The increase of diatoms during spring is attributed to their improved competitive performance with increasing Si:P ratios. Their decrease during summer is explained by the increasing silicate removal from the epilimnion by increasing spring populations.


The effects of hospice care on healthcare expenditure among cancer patients.
It is necessary to estimate the hospice usage and hospice-related cost for entire cancer patients using nationwide cohort data to establish a suitable ethical and cultural infrastructure. This study aims to show the effects of hospital hospice care on healthcare expenditure among South Korean cancer patients. This study is a retrospective cohort study using customized health information data provided by the National Health Insurance Service. Individuals who were diagnosed with stomach, colorectal, or lung cancer between 2003 and 2012 were defined as new cancer patients, which included 7,176 subjects. Patients who died under hospital-based hospice care during the follow-up period from January 2016 to December 2018 comprised the treatment group. Healthcare expenditure was the dependent variable. Generalized estimating equations was used. Among the subjects, 2,219 (30.9%) had used hospice care at an average total cost of 948,771 (± 3,417,384) won. Individuals who had used hospice care had a lower odds ratio (EXP(β)) of healthcare expenditure than those who did not (Total cost: EXP(β) = 0.27, 95% confidence intervals (CI) = 0.25-0.30; Hospitalization cost: EXP(β) = 0.32, 95% CI = 0.29-0.35; Outpatient cost: EXP(β) = 0.02, 95% CI = 0.02-0.02). Healthcare expenditure was reduced among those cancer patients in South Korea who used hospice care compared with among those who did not. This emphasizes the importance of using hospice care and encourages those hesitant to use hospice care. The results provide useful insights into both official policy and the existing practices of healthcare systems.


Evidence of symmetry lowering in antiferromagnetic metal TmB12with dynamic charge stripes.
Precise angle-resolved magnetoresistance (ARMR) and magnetization measurements have revealed (i) strong charge transport and magnetic anisotropy and (ii) emergence of a huge number of magnetic phases in the ground state of isotopically11B-enriched single crystals of TmB12antiferromagnetic (AF) metal with fcc crystal structure and dynamic charge stripes. We analyze for the first time the angularH-φphase diagrams of AF state of Tm11B12reconstructed from experimental ARMR and magnetization data arguing that the symmetry lowering leads to the appearance of several radial phase boundaries between different phases in the AF state. It is proposed that the suppression of the indirect Ruderman-Kittel-Kasuya-Yosida (RKKY) exchange along ⟨110⟩ directions between nearest neighboring magnetic moments of Tm3+ions and subsequent redistribution of conduction electrons to quantum fluctuations of the electron density (dynamic stripes) are the main factors responsible for the anisotropy. Essential (more than 25% atT= 2 K) anisotropy of the Neel field in the (110) plane was found in Tm11B12unlike to isotropic AF-P boundary in theH-φphase diagrams of Ho11B12. Magnetoresistance components are discussed in terms of charge carrier scattering on the spin density wave, itinerant ferromagnetic nano-domains and on-site Tm3+spin fluctuations.


Aristaless-related homeobox gene disruption leads to abnormal distribution of GABAergic interneurons in human neocortex: evidence based on a case of X-linked lissencephaly with abnormal genitalia (XLAG).
X-linked lissencephaly with abnormal genitalia (XLAG) is a rare disorder caused by mutations in the aristaless-related homeobox (ARX) gene, located on Xp22.13. Arx-null mice show loss of tangential migration of GABAergic interneurons, presumably being related to caudal ganglionic eminence tangential migration. In the present study, we investigated a subpopulation of GABAergic interneurons in the brain of an infant with XLAG, who had a novel nonsense mutation of the ARX gene, compared with those of age-matched normal controls and Miller-Dieker syndrome. We performed immunocytochemistry for interneuron and migration markers. We found that glutamic acid decarboxylase (GAD)- and calretinin (CR)-containing cells were significantly reduced in the neocortex and located in the white matter and neocortical subventricular zone, while neuropeptide Y- or cholecystokinin-containing cells were normally distributed. Moreover, in the neocortical subventricular region, the GAD- and CR-containing cells expressed the radial migration marker Mash-1 as well as nestin. Our findings suggest that ARX protein controls not only the tangential migration of GABAergic interneurons from the ganglionic eminence, but also may serve to induce radial migration from the neocortical subventricular zone.


Peripelvic Extravasation After Living Donor Kidney Transplant: A Case Report.
The patient was a 33-year-old man. A living donor kidney transplant from his father was performed, and a double-J ureteric stent was placed in the ureter of the transplanted kidney during surgery. Postoperatively, after the urethral catheter was removed, he presented with lower right abdominal pain when excessively strained during defecation. A computed tomography scan showed fluid retention in the retroperitoneal space around the transplanted kidney, and a drainage tube was placed. Urinary components were detected in the drainage, and the patient was diagnosed with peripelvic extravasation. Because the surgical wound opened during the course of treatment, debridement and wound treatment were performed. The patient underwent hyperbaric oxygen therapy, and peripelvic extravasation and wound dehiscence both improved.


Effect of atorvastatin on TH1 and TH2 cytokine secreting cells during T cell activation and differentiation.
Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are the most effective agents for the lowering of cholesterol in clinical practice. In addition to their lipid-lowering properties, statins also have immunomodulatory activities. Animal studies have shown that statins promote a T helper 2 (T(H)2) bias and suppress the secretion of T helper 1 (T(H)1) cytokines. We therefore examine whether atorvastatin modulates the T(H)1/T(H)2 responses in human T cells. Using primary T cells as well as differentiated T(H)1 and T(H)2 cells, the immunomodulatory effect of atorvastatin on cells secreting IFN-gamma (T(H)1 response) and IL-4 (T(H)2 response) was investigated. Atorvastatin had no effect on cells secreting IFN-gamma and IL-4 in primary T cells stimulated with anti-CD3 and -CD28 antibodies. Similarly, cells producing IFN-gamma and IL-4 in stable differentiated T(H)1 and T(H)2 cells were unaffected by atorvastatin. Furthermore, atorvastatin had no effect on the ratio of IFN-gamma+/IL-4+ cells during the differentiation of T(H)0 cells to T(H)1 and T(H)2 cells in long-term cultures. These data suggest that atorvastatin does not have any immunomodulatory effect on the T(H)1/T(H)2 balance in human T cells in vitro.


Back to the Future: A Glance Over Wolf Social Behavior to Understand Dog-Human Relationship.
This review focuses on wolf sociobiology to delineate the traits of cooperative baggage driven by natural selection (wolf-wolf cooperation) and better understand the changes obtained by artificial selection (dog-human cooperation). We selected some behaviors of the dog's ancestors that provide the basis for the expression of a cooperative society, such as dominance relationships, leverage power, post-aggressive strategies, and playful dynamics between pack members. When possible, we tried to compare the data on wolves with those coming from the dog literature. Wolves can negotiate commodities when the interacting subjects occupy different ranking positions by bargaining social tolerance with helping and support. They are able to manage group disruption by engaging in sophisticated post-conflict maneuvers, thus restoring the relationship between the opponents and reducing the spreading of aggression in the group. Wolves engage in social play also as adults to manipulate social relationships. They are able to flexibly adjust their playful interactions to minimize the risk of escalation. Complex cognitive abilities and communicative skills are probably the main proximate causes for the evolution of inter-specific cooperation in wolves.


Distributions and removal fluxes of trace metals in the water column of the Hung-Tsai Trough off southwestern Taiwan.
Vertical profiles of dissolved and particulate Mn, Fe, Ni, Cu, Zn, Cd, Pb, and (234)Th were determined in the Hung-Tsai Trough off southwestern Taiwan during 19-23 November, 2004. Except in the case of Cd, the distribution coefficient (K(d)) of the trace elements showed a negative correlation with the suspended particle concentration. Based on the average K(d) values, the general sequence of particle affinities for the eight trace elements is, from highest to lowest, Fe>Mn≈Pb>Zn≈Th>Cd≈Cu≈Ni. The trace metal data was coupled with the particle removal flux estimated from (234)Th/(238)U disequilibrium to investigate metal removal by particle sinking from the euphotic layer. The residence time of trace elements with respect to particle removal from the euphotic layer was estimated. A negative correlation between the residence time and the distribution coefficient for the trace metals was found.


Immunological properties of two related fragments from human and equine growth hormones.
The immunological properties of a synthetic human growth hormone fragment comprising the amino acids 73 through 128 and of the homologous natural horse growth fragment formed by amino acids 73 through 123, have been comparatively studied. Antisera obtained in rabbits inoculated with the native human hormone or with the fragments, were used. By hemagglutination experiments both fragments have the same reactivity toward the anti-human growth hormone serum, but complement fixation curves detect the existence of at least two populations of antibodies presumably originated against the sequence 73-128 of human growth hormone. Of these, only one of the corresponding antigenic areas is present in the homologous region of equine growth hormone. The known cross-reactivity detected between both hormones is thus partially explained.


Cerebral Microbleeds Remain for Nine Years: A Prospective Study with Yearly Magnetic Resonance Imaging.
Cerebral microbleeds (CMBs) are refined neuroimaging findings detected on T2*-weighted gradient echo (GRE) magnetic resonance imaging (MRI) and are widely accepted as an important marker of the vulnerability of cerebral small vessels. It is necessary to further clarify the natural history of CMBs by a longitudinal study. This study aimed to reveal the natural history of CMBs and find a better way to track CMBs by a prospective long-term observation. We performed yearly brain MRI assessments for 7 or more years in 8 nonvalvular atrial fibrillation Japanese outpatients with CMBs detected in the baseline MRI. We began to use a 3.0T MRI scanner from 2012 as well. We followed up 3 patients for 9 years, 2 for 8 years, and 3 for 7 years. In all patients, the CMBs at baseline did not disappear during the follow-up period. Importantly, the CMB in 1 patient seemed to disappear during the sixth imaging using 1.5T T2*-weighted GRE but was detected again during the seventh imaging with 3.0T susceptibility weighted imaging and ninth imaging with 3.0T T2* GRE. Moreover, in a patient implanted with a pacemaker, which is only applicable for 1.5T MRI at present, the CMB seemed to disappear and appeared once again with a 1.5T T2*-weighted GRE at a slice thickness of 2.5 mm instead of 5 mm. From this prospective study, we obtained 2 absolutely new findings that CMBs remained for as long as 9 years and a high-field or thin-slice MRI can detect concealed CMBs.


Formation of mutagens in boiled pork extract.
When boiled pork extract was heated under reflux at 102 degrees C for 4 hr mutagens, which were detected using Salmonella typhimurium strains TA98 and TA1538, were formed. The level of mutagenicity was dependent on the concentration of pork in the extract, the duration of boiling and on pH; the optimum pH for mutagen formation was found to be 9 to 11. Thin-layer chromatographic analysis showed that the mutagens formed in boiled pork extract were chromatographically distinguishable from benzo[a]pyrene and from the primary mutagenic pyrolysis products of tryptophan (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and of glutamic acid (2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole).


Iodine penetration and glycogen distribution in vital staining of oral mucosa with iodine solution.
To assess and compare iodine penetration and glycogen distribution in a vital staining of oral mucosa with iodine solution. Twenty samples were obtained including both iodine-stained and -unstained mucosa. Intraepithelial iodine was examined using frozen sections. Glycogen distribution was assessed by periodic acid-Schiff staining and transmission electron microscopy. Iodine accumulation was observed mainly superficially and in the upper and middle thirds of prickle cell layers, with glycogen in almost the whole epithelium except for the para- and basal cell layers. The pattern of iodine and glycogen distribution was classified into 3 types (full-, surround-, and scatter-type). The iodine color was mainly derived from the cells with full- and surround-type distributed glycogen in the upper half of the oral epithelium. The results of this study suggested that iodine penetrated into nonkeratinized oral epithelium and reacted mainly with intraepithelial glycogen homogeneously distributed in the cytoplasm.


Food-induced anaphylaxis.
Food-induced anaphylaxis (FIA) is a serious allergic reaction that may cause death rapidly in otherwise healthy individuals. There is no universal agreement on its definition or criteria for diagnosis. Hospital admissions for FIA have more than doubled in the last decade. Food is one of the most common causes of anaphylaxis, with most surveys indicating that food-induced reactions account for 30% to 50% of cases. The most commonly implicated foods are peanut, tree nuts, milk, eggs, sesame seeds, fish, and shellfish. The only life-saving treatment for anaphylaxis is allergen avoidance, and epinephrine injection if an anaphylactic event occurs.


Common complications in critically ill patients.
Patients in intensive care units (ICUs) are subject to many complications connected with the advanced therapy required for their serious illnesses. Complications of ventilatory support include problems associated with short-term and long-term intubation, barotrauma, gastrointestinal tract bleeding, and weaning errors. Cardiac tachyarrhythmias can arise from a patient's intrinsic cardiac disease, as well as from drug therapy itself. Hemodynamic monitoring is crucial to careful patient management, but it is associated with technical complications during insertion such as pneumothorax, as well as interpretive errors such as those caused by positive end-inspiratory pressure. Acute renal failure can develop as a result both of therapy with drugs such as aminoglycosides and hypotension of many etiologies, as well as the use of contrast media. Nosocomial infection, which is a dreaded complication in ICU patients, usually arises from sources in the urinary tract, bloodstream, or lung. Complications frequently can arise if the interactions of drugs commonly used in the ICU are not recognized. Further, the ICU patient is subject to nutritional complications, acid base problems, and psychological disturbances. This monograph deals with the frequency, etiology, and prevention of these common ICU complications.


From contemporary rehabilitation to restorative neurology.
Recent years have witnessed significant advances in the treatment of neurological injuries such as stroke, traumatic brain injuries (TBI), and spinal cord injuries (SCI). The current approach includes acute intervention to curb the primary insult, prevention of secondary complications and early rehabilitation to optimize residual function to ultimately enhance quality of life and independence. While this is effective in providing a degree of independence to many patients, we believe that further functional gains are possible for many patients who have plateaued followed a contemporary rehabilitation program. Complementary methods are available today that are not widely used, but have demonstrated great promise in augmenting function and quality of life in patients who cannot benefit further from currently available treatment options.


MicroRNA Expression Profiles in Response to Phytophthora infestans and Oidium neolycopersici and Functional Identification of sly-miR397 in Tomato.
Late blight and powdery mildew are two widespread tomato diseases caused by Phytophthora infestans and Oidium neolycopersici, respectively, which reduce the quantity and quality of tomato. MicroRNAs (miRNAs) play critical roles in tomato resistance to various pathogens. Investigating the function of miRNAs is of great significance in controlling tomato diseases. To identify potential miRNAs involved in the interaction of tomato with P. infestans or O. neolycopersici, we analyzed the expression profiles of small RNAs in tomato leaves infected with these two pathogens using RNA-seq technology. A total of 330 and 288 miRNAs exhibited differences in expression levels after exposure to P. infestans and O. neolycopersici, respectively. One hundred and forty-six commonly differentially expressed (DE) miRNAs responsive to P. infestans and O. neolycopersici infestation were detected, including 10 commonly known conserved DE miRNAs and 136 novel miRNAs. Among these known DE miRNAs, sly-miR397 was strongly downregulated in response to P. infestans or O. neolycopersici infection. Silencing of sly-miR397 resulted in enhanced tolerance to the pathogens, whereas overexpression of sly-miR397 showed increased susceptibility. Furthermore, changes in sly-miR397 expression could also affect expression levels of pathogenesis-related genes and reactive oxygen species-scavenging genes, leading to altered necrotic cells and H2O2 levels. In addition, the number of lateral branches significantly changed in transgenic plants. Taken together, our results provide potential miRNA resources for further research of miRNA-disease associations and indicates that sly-miR397 acts as a negative regulator of disease resistance and influences lateral branch development in tomato.


An adipose-specific control of thermogenesis in body weight regulation.
Much of our understanding about 'adaptive thermogenesis' as a control system in mammalian weight regulation derives from studies of experimental starvation and overfeeding, and these have served to characterize its functional role as an 'attenuator' of energy imbalance. By applying a system-analysis approach in evaluating data on the energetics of starvation and refeeding, evidence is presented here in support of the hypothesis that there are in fact two distinct control systems underlying adaptive thermogenesis. In one of them, the efferent limb is primarily under the control of the sympathetic nervous system (SNS), whose functional state is dictated by overlapping or interacting signals arising from a variety of environmental stresses, including food deprivation, deficiency of essential nutrients, excess energy intake and exposure to cold or to infections; it is hence referred to as the non-specific control of thermogenesis, and is likely to occur primarily in organs/tissues with a high specific metabolic rate (eg liver, kidneys, brown fat). The other is independent of the functional state of the SNS and is dictated solely by signals arising from the state of depletion of the adipose tissue fat stores; it is hence referred to as the adipose-specific control of thermogenesis, and is postulated to occur primarily in the skeletal muscle. While suppression of this adipose-specific thermogenesis during both starvation and refeeding leads to energy conservation, the energy spared during refeeding is directed specifically at the replenishment of the fat stores, so that it functions as an 'accelerator' of fat recovery. These two distinct control systems for adaptive thermogenesis have been incorporated in a compartmental model of body weight and body composition regulation. This is used to provide a mechanistic explanation as to how, during weight recovery, they can operate simultaneously but in opposite directions--with activation of thermogenesis under non-specific control being energy-dissipating, while suppression of thermogenesis under adipose-specific control being energy-conserving--and could hence explain the paradox of a high efficiency of fat recovery co-existing with an overall state of enhanced thermogenesis and hypermetabolism. Elucidating the components of the adipose-specific control of thermogenesis (ie its sensors, signals and effector mechanisms) will have important implications for our understanding of body composition regulation, and hence for the development of more effective strategies in the management of cachexia and obesity.


Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury.
Fractalkine (FKN), also known as neurotactin, is a CX(3)C chemokine that exists in both secreted and neuronal membrane-bound forms and is upregulated during brain inflammation. There is accumulating evidence that FKN induces chemotaxis by binding to its receptor CX(3)CR1 on leukocytes and microglia. We generated FKN-deficient mice to study the role of FKN in postischemic brain injury. After transient focal cerebral ischemia, FKN-deficient mice had a 28% reduction in infarction size and lower mortality rate, when compared to wild-type littermates. The findings of this study indicate a possible role for FKN in augmenting postischemic injury and mortality after transient focal cerebral ischemia.


Mental health outcome and resilience among aiding Wuhan nurses: One year after the COVID-19 outbreak in China.
This study aimed to explore whether aiding Wuhan experience of nurses was associated with adverse mental health outcome one year after the COVID-19 outbreak in China. In this study, 100 nurses with and 100 nurses without aiding Wuhan experience a year ago were enrolled from February 1, 2021 to March 31, 2021 in Zhejiang Province, China. Depression, anxiety, insomnia, distress and psychological resilience of participants was assessed and analyzed. A total of 100 participants from 112 aiding Wuhan nurses completed the survey, with a response rate of 89.3%. Another 100 nurses from the same hospitals without aiding Wuhan experience were enrolled as controls. In both groups, a considerable proportion of participants reported symptoms of depression (46.0% for the aiding Wuhan group vs. 49.0% for the controls, similarly hereinafter), anxiety (40.0% vs. 38.0%), and PTSD (61.0% vs. 56.0%). Aiding Wuhan nurses were more likely to suffer from insomnia (41.0% vs. 29.0%, P = 0.041). Multivariable logistic regression analysis showed that aiding Wuhan experience was not associated with depression (adjusted OR (AOR) 0.22; 95%CI, 0.05-1.01), anxiety (AOR 0.53; 95%CI, 0.12-2.43), insomnia (AOR 1.52; 95%CI, 0.76-3.02), PTSD (AOR 0.50; 95%CI, 0.19-1.34), or resilience (AOR 1.59; 95%CI, 0.78-3.26). Resilience was negatively correlated with depression, anxiety, insomnia, and PTSD. This survey indicated that aiding Wuhan experience a year ago did not cause additional adverse mental health outcomes in nurses, expect for insomnia. The psychological status of nurses in general calls for more attention.


Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study.
To assess the efficacy of an original DAC-7 regimen: daunorubicine (DNR) 60 mg/m2/day, days 1-3; cytarabine (AraC) 200 mg/m2/day, days 1-7; cladribine (2-CdA) 5 mg/m2/day, days 1-5, 400 untreated adult acute myeloid leukemia patients (including 63 with preceding myelodysplastic syndrome), aged 45 (16-60) years were randomized to either DAC-7 (n=200) or DA-7 (without 2-CdA, n=200). The overall CR rate equaled 72% for DAC-7 and 69% for DA-7 arm (P=NS). After a single course of DAC-7 induction, the CR rate equaled 64% and was significantly higher compared to 47% in the DA-7 arm (P=0.0009). Median hospitalization time during the induction was 7 days shorter for DAC-7 compared to the DA-7 group (33 vs 40 days, P=0.002). Toxicity was comparable in both groups. The probability of 3-year leukemia-free survival (LFS) for DAC-7 and DA-7 group equaled 43 and 34%, respectively (P=NS). There was a trend toward higher LFS rate for patients aged >40 years receiving DAC-7 compared with DA-7 regimen (44 vs 28%, P=0.05). This study proves that addition of 2-CdA increases antileukemic potency of DNR+AraC regimen, thus resulting in a higher CR rate after one induction cycle when compared to DA-7, without additional toxicity. It shortens hospitalization time and may improve long-term survival in patients aged >40 years.


A replication competent lentivirus (RCL) assay for equine infectious anaemia virus (EIAV)-based lentiviral vectors.
Lentiviral vectors are being developed to satisfy a wide range of currently unmet medical needs. Vectors destined for clinical evaluation have been rendered multiply defective by deletion of all viral coding sequences and nonessential cis-acting sequences from the transfer genome. The viral envelope and accessory proteins are excluded from the production system. The vectors are produced from separate expression plasmids that are designed to minimize the potential for homologous recombination. These features ensure that the regeneration of the starting virus is impossible. It is a regulatory requirement to confirm the absence of any replication competent virus, so we describe here the development and validation of a replication competent lentivirus (RCL) assay for equine infectious anaemia virus (EIAV)-based vectors. The assay is based on the guidelines developed for testing retroviral vectors, and uses the F-PERT (fluorescent-product enhanced reverse transcriptase) assay to test for the presence of a transmissible reverse transcriptase. We have empirically modelled the replication kinetics of an EIAV-like entity in human cells and devised an amplification protocol by comparison with a replication competent MLV. The RCL assay has been validated at the 20 litre manufacturing scale, during which no RCL was detected. The assay is theoretically applicable to any lentiviral vector and pseudotype combination.


Hypoxic pulmonary vascular response can screen subclinical lifestyle disease in healthy population.
Subclinical life style disease can cause endothelial dysfunction associated with perfusion abnormalities and reduced vascular compliance. Subclinical elevated beta type natriuretic peptide (BNP) has been associated with altered fluid shift from extra to intracellular space during acute hypoxia. Therefore we measured vascular response and BNP levels during acute hypoxia to study endothelial functions among healthy individuals. Individuals were exposed to acute normobaric hypoxia of FiO2 = 0.15 for one hour in supine position and their pulmonary and systemic vascular response to hypoxia was compared. Individuals were divided into two groups based on either no response (Group 1) or rise in systolic pulmonary artery pressure to hypoxia (Group 2) and their BNP levels were compared. BNP was raised after hypoxia exposure in group 2 only from 18.52 ± 7 to 21.56 ± 10.82 picogram/ml, p < 0.05. Group 2 also showed an increase in mean arterial pressure and no fall in total body water in response to acute hypoxia indicating decreased endothelial function compared to Group 1. Rise in pulmonary artery pressure and BNP level in response to acute normobaric hypoxia indicates reduced endothelial function and can be used to screen subclinical lifestyle disease among healthy population.


Complications of extracorporeal shock-wave lithotripsy and percutaneous nephrolithotomy.
The serious complications of ESWL associated with the Dornier HM-3 lithotripter are well known. It is incumbent on operators to recognize these problems and, when possible, to anticipate them and utilize a treatment plan that will minimize their occurrence. Appropriate use of percutaneous techniques, double-J stents, and ureteroscopy and aggressive use of antibiotics can minimize the serious complications associated with ESWL. It will be of interest to see whether newer generation lithotripters will produce an incidence of complications similar to that of the Dornier HM-3 or whether unique problems will call for new strategies. We have described the clinically important complications of ESWL and percutaneous nephrolithotomy. At this time, these modalities should be looked on as complementary procedures. Each has specific indications, and, when used appropriately, often in concert, both will provide safe, effective treatment for patients with renal calculus disease.


Rapid and sensitive detection of norovirus genomes in oysters by a two-step isothermal amplification assay system combining nucleic acid sequence-based amplification and reverse transcription-loop-mediated isothermal amplification assays.
We developed a two-step isothermal amplification assay system, which achieved the detection of norovirus (NoV) genomes in oysters with a sensitivity similar to that of reverse transcription-seminested PCR. The time taken for the amplification of NoV genomes from RNA extracts was shortened to about 3 h.


13.7% Efficiency Small-Molecule Solar Cells Enabled by a Combination of Material and Morphology Optimization.
Compared with the quick development of polymer solar cells, achieving high-efficiency small-molecule solar cells (SMSCs) remains highly challenging, as they are limited by the lack of matched materials and morphology control to a great extent. Herein, two small molecules, BSFTR and Y6, which possess broad as well as matched absorption and energy levels, are applied in SMSCs. Morphology optimization with sequential solvent vapor and thermal annealing makes their blend films show proper crystallinity, balanced and high mobilities, and favorable phase separation, which is conducive for exciton dissociation, charge transport, and extraction. These contribute to a remarkable power conversion efficiency up to 13.69% with an open-circuit voltage of 0.85 V, a high short-circuit current of 23.16 mA cm-2 and a fill factor of 69.66%, which is the highest value among binary SMSCs ever reported. This result indicates that a combination of materials with matched photoelectric properties and subtle morphology control is the inevitable route to high-performance SMSCs.


Gata3 is required in late proneurosensory development for proper sensory cell formation and organization.
It has previously been shown that the zinc-finger transcription factor Gata3 has dynamic expression within the inner ear throughout embryonic development and is essential for cochlear neurosensory development. However, the temporal window for which Gata3 is required for proper formation of the cochlear neurosensory epithelia remains unclear. To investigate the role of Gata3 in cochlear neurosensory development in the late prosensory stages, we used the Sox2-creERT2 mouse line to target and conditionally delete Gata3 at E11.5, a timepoint before cells have fully committed to a neurosensory fate. While the inner ears of Sox2-creERT2: Gata3 f/f mice appear normal with no gross structural defects, the sensory cells in the organ of Corti are partially lost and disorganized in an increasing severity from base to apex. Additionally, spiral ganglion neurons display aberrant peripheral projections, including increased distances between radial bundles and disorganization upon reaching the organ of Corti. Furthermore, heterozygous Sox2-creERT2: Gata3 f/+ mice show a reduced aberrant phenotype in comparison to the homozygous mutant, supporting the hypothesis that Gata3 is not only required for proper formation at the later proneurosensory stage, but also that a specific expression level of Gata3 is required. Therefore, this study provides evidence that Gata3 plays a time-sensitive and dose-dependent role in the development of sensory and neuronal cells in late proneurosensory stages.


Perceptions of research capacity in public health organisations: comparison of NSW metropolitan and non-metropolitan Local Health Districts.
Objective The aims of this study were to explore and compare the perceptions of research capacity and culture (RCC) in metropolitan and non-metropolitan New South Wales (NSW) Local Health Districts (LHDs). Methods The Research Capacity and Culture Tool was delivered online to clinicians and health managers. A 10-point Likert scale of success or skill at organisational, team and individual level of research capacity was used. An independent t -test assessed differences in domain means between non-metropolitan and metropolitan LHDs. Results A total of 1243 participants responded. Responses to the survey indicated the perception of individual's research skills were greater than the perception of RCC at both the team and organisational levels. Participants from metropolitan locations had significantly higher mean scores across all three domains compared with non-metropolitan locations (P Conclusion Results indicated the perception of individual's research skills were greater than the team and organisational levels. Participants from metropolitan locations had significantly higher perceptions of RCC across all three domains compared with non-metropolitan locations. This was the largest study to date in Australia investigating RCC in NSW LHDs, and the first study to explore multiple professions across multiple organisations while comparing metropolitan and non-metropolitan settings. This research may inform targeted strategies for building research capacity in NSW LHDs.


Immunohistochemical study of myelin sheaths formed by oligodendrocytes interacting with dissociated dorsal root ganglion neurons in culture.
The addition of central nervous system (CNS) glial cells to dissociated networks of rat dorsal root ganglion neurons in tissue culture provided a useful system for the study of CNS myelin sheath formation. The CNS myelin basic proteins (BP) and proteolipid protein (PLP) were demonstrable in these cultures by immunoperoxidase techniques. Both BP and PLP were detectable in myelinating oligodendrocytes and CNS myelin sheaths. Anti-BP serum and anti-PLP serum were useful immunohistochemical staining reagents for the identification of myelinating oligodendrocytes and CNS myelin sheaths in tissue culture.


Use of exercise challenge to investigate possible tolerance to beta-adrenoceptor stimulation in asthma.
The effect of prolonged salbutamol administration on beta-adrenoceptor function in asthma has been examined. Six adult patients received salbutamol tablets (16 mg daily) for between 4 and 20 weeks and six adolescents received salbutamol aerosol (800 microgram daily) for 2--5 weeks. Before and after the treatment period the acute bronchodilator response to inhaled salbutamol and the ability of inhaled salbutamol to protect against exercise-induced asthma were examined. Lymphocyte beta-adrenoceptor function was also measured in the patients on tablet therapy. Inhaled salbutamol was less effective in protecting against exercise-induced asthma at the end of the treatment period in the patients who had received tablet therapy, but otherwise there was no significant change in beta-receptor function of either airways or lymphocytes. This apparent loss of efficacy of inhaled salbutamol in the prevention of exercise-induced asthma in some subjects, even when its acute bronchodilator effect is preserved, might reflect differences in the susceptibility of different beta-adrenoceptors to desensitization after prolonged stimulation: its clinical importance remains uncertain.


Modeling and source localization of MEG activities.
During the past decade, substantial advances in the understanding of the functional organization of the human brain have been made through the technique of MEG topographic mapping. Most of these investigations were concerned with the estimation and localization of sources which were modeled as single current dipoles positioned in a semi-infinite volume conductor with homogeneous conductivity. However, the sources in the brain are complex, and the head as a volume conductor consists of different materials with different electrical conductivities. The influence of these inhomogeneities on the MEG topography is studied by a computer simulation, modeling the sources as single or multiple dipoles located in inhomogeneous volume conductors. The computer simulation suggests some important aspects in estimation of source localization. The sources of MEG activities in human subject during sleep are also studied. A comparison of simulated MEG topographic patterns with measured data suggests that the sources of K-complexes can be modeled by two current dipoles. Sources for delta waves are analyzed by the FFT technique. The results show that the frequency distributions are different for delta waves measured by MEG and EEG techniques, leading us to conclude that at least two different sources are present. The MEG measurements have an advantage to provide important information concerning brain function which cannot be obtained using the EEG measurements.


A murine coronavirus MHV-S isolate from persistently infected cells has a leader and two consensus sequences between the M and N genes.
A plaque-cloned mouse hepatitis virus mutant, MHV-S No. 8, was isolated from Ki-BALB cells persistently infected with MHV-S. The mRNAs 1 to 6 were larger in the mutant, whereas there was no difference between the two viruses in the size of the smallest mRNA, mRNA 7. Sequence analyses of the genomic RNA, mRNA 6, and mRNA 7 of the two viruses revealed that an additional 111 nt were inserted just upstream of the intergenic consensus sequence preceding the N gene in MHV-S No. 8. The inserted region consisted of two different parts; the 3'-most 30 nt corresponded to nucleotides 28 to 57 of the leader sequence and the 5'-most 81 nt corresponded to nucleotides 58 to 138 of mRNA 7. This structure of No. 8 was most likely generated by RNA-RNA recombination between genomic RNA and subgenomic RNA species. The nucleotide insertion in the intergenic sequence between genes M and N resulted in two consensus sequences separated by 111 nt. Primer extension analysis revealed that the amount of a slightly larger, subgenomic mRNA resulting from initiation of synthesis at the upstream consensus sequence was only 5% of the usual sized mRNA 7 initiated from the downstream consensus sequence.


Intubated COVID-19 predictive (ICOP) score for early mortality after intubation in patients with COVID-19.
Patients with coronavirus disease 2019 (COVID-19) can have increased risk of mortality shortly after intubation. The aim of this study is to develop a model using predictors of early mortality after intubation from COVID-19. A retrospective study of 1945 intubated patients with COVID-19 admitted to 12 Northwell hospitals in the greater New York City area was performed. Logistic regression model using backward selection was applied. This study evaluated predictors of 14-day mortality after intubation for COVID-19 patients. The predictors of mortality within 14 days after intubation included older age, history of chronic kidney disease, lower mean arterial pressure or increased dose of required vasopressors, higher urea nitrogen level, higher ferritin, higher oxygen index, and abnormal pH levels. We developed and externally validated an intubated COVID-19 predictive score (ICOP). The area under the receiver operating characteristic curve was 0.75 (95% CI 0.73-0.78) in the derivation cohort and 0.71 (95% CI 0.67-0.75) in the validation cohort; both were significantly greater than corresponding values for sequential organ failure assessment (SOFA) or CURB-65 scores. The externally validated predictive score may help clinicians estimate early mortality risk after intubation and provide guidance for deciding the most effective patient therapies.


Promoting blood donation through social media: Evidence from Brazil, India and the USA.
Social media has the potential to encourage prosocial behaviors at scale, yet very little causal evidence exists on the impact of related efforts. Blood donation is a particularly difficult, but essential prosocial behavior that is often critically undersupplied. We examine the effect of Facebook's blood donation tool on voluntary blood donation. We partnered with four major blood banks in the United States covering 363 collection facilities in 46 states and Washington, D.C. We tracked the tool's impact on blood donations during its staggered rollout on a sample of more than 47,000 facility-date observations from March 2019 to September 2019. The tool caused an increase of 0.55 total donations per facility per day (+4.0% [95% CI: 0.04%-8.0%]), and an increase of 0.15 donations from first-time donors per facility per day (+18.9% [95% CI: 4.7%-33.1%]). Longitudinal evidence from Brazil and India suggests the share of donors who both received a message from the tool and stated they were influenced by Facebook to donate increased from 0% to 14.1% [95% CI: 12.1%-16.2%] in the first year of the tool's deployment (i.e., September 2018 to August 2019). These meaningful increases, especially from first-time donors, demonstrate that social media platforms can play an important role in fostering offline prosocial behaviors that benefit the health and well-being of societies around the world.


Acute renal proximal tubule alterations during induced metabolic crises in a mouse model of glutaric aciduria type 1.
The metabolic disorder glutaric aciduria type 1 (GA1) is caused by deficiency of the mitochondrial glutaryl-CoA dehydrogenase (GCDH), leading to accumulation of the pathologic metabolites glutaric acid (GA) and 3-hydroxyglutaric acid (3OHGA) in blood, urine and tissues. Affected patients are prone to metabolic crises developing during catabolic conditions, with an irreversible destruction of striatal neurons and a subsequent dystonic-dyskinetic movement disorder. The pathogenetic mechanisms mediated by GA and 3OHGA have not been fully characterized. Recently, we have shown that GA and 3OHGA are translocated through membranes via sodium-dependent dicarboxylate cotransporter (NaC) 3, and organic anion transporters (OATs) 1 and 4. Here, we show that induced metabolic crises in Gcdh(-/-) mice lead to an altered renal expression pattern of NaC3 and OATs, and the subsequent intracellular GA and 3OHGA accumulation. Furthermore, OAT1 transporters are mislocalized to the apical membrane during metabolic crises accompanied by a pronounced thinning of proximal tubule brush border membranes. Moreover, mitochondrial swelling and increased excretion of low molecular weight proteins indicate functional tubulopathy. As the data clearly demonstrate renal proximal tubule alterations in this GA1 mouse model during induced metabolic crises, we propose careful evaluation of renal function in GA1 patients, particularly during acute crises. Further studies are needed to investigate if these findings can be confirmed in humans, especially in the long-term outcome of affected patients.


Action of some pancreatic enzymes on Vibrio cholerae.
The action of pancreatic amylase, trypsin, lipase, and whole pancreatin was tested on five strains of Bibrio cholerae. Amylase did not act on any strain in concentrations to 10,000 IU/ml whereas trypsin increased vacuolization and lipase enhanced retraction of the protoplasm particularly in 2 of the 5 tested vibrio strains. Pancreatin caused damage hoth of the cell wall and the cytoplasm. It is suggested that these enzymes may play a role in the defense of the body against cholera vibrios.


Animal nutrition and lipids in animal products and their contribution to human intake and health.
Few EU countries meet targets for saturated fatty acid (SFA) intake. Dairy products usually represent the single largest source of SFA, yet evidence indicates that milk has cardioprotective properties. Options for replacing some of the SFA in milk fat with cis-monounsaturated fatty acids (MUFA) through alteration of the cow's diet are examined. Also, few people achieve minimum recommended intakes (~450-500 mg/d) of the long chain n-3 polyunsaturated fatty acids (PUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Enrichment of EPA+DHA in poultry meat via bird nutrition is described and how this would impact on habitual intake is discussed.


Resistance of gram-negative bacilli and staphylococci from blood cultures to aminoglycoside antibiotics. Comparison of 3 in vitro investigations from Austria 1982-1988.
A total of 790 blood culture isolates was collected during 3 study periods in 1982/83, 1984/85 and 1987/88. Staphylococci were the most frequent bacteria in the first two periods (56.5% and 63%, respectively). During the last period, E. coli was the most frequent of all species (27%). Differences in the distribution of bacteria between the laboratories were considerable. In one laboratory in Vienna, coagulase-negative staphylococci dominated in all 3 study periods (32%, 33% and 47%). Susceptibility against gentamicin, tobramycin and netilmicin (MIC less than or equal to 4 mg/l), as well as against amikacin (MIC less than or equal to 8 mg/l) were determined by a microdilution method. The resistance rates against gentamicin (G) were 25%, 21% and 25%, against tobramycin (T) 27%, 19% and 25%, against netilmicin (N) 6%, 4% and 19%, and against amikacin (A), 5%, 2% and 19%. Most resistant strains were staphylococci (G 26%-41%, T 26%-46%, N 3%-31%, A 3%-36%), whereas gram-negative bacilli were more susceptible (G 12%-14%, T 7%-11%, N 7%-9%, A 1%-7.5%). The increase of resistance against netilmicin and amikacin in staphylococci was most striking. Nearly all those strain could be attributed to one laboratory in Vienna. Most of them were coagulase-negative staphylococci. In the first study period, the most frequent pattern was resistance against gentamicin and tobramycin, whereas in the last period resistance to all 4 aminoglycosides dominated. The study demonstrates considerable local differences in antibiotic resistance. Monitoring of antibiotic resistance in collaborative studies using standardized methods should be a valuable tool in planning strategies for controlling an epidemic spread of resistance.


Cellular delivery of peptide nucleic acid by cell-penetrating peptides.
Peptide nucleic acid (PNA) is a promising tool in biomedical research. PNA oligomers can be synthesized according to peptide synthesis protocols, but they hybridize to complementary RNA and DNA strands like oligonucleotides. The main hindrance to the use of PNA oligomers has been their poor uptake by cells. Fortunately, this limitation can be overcome by the application of peptide vectors. Different strategies are used to conjugate peptide vectors and PNA oligomers. In this chapter we discuss different types of delivery vectors (receptor ligands and cell-penetrating peptides) and strategies for the design and synthesis of PNA-vector conjugates. A protocol for the delivery of antisense PNA oligomer-cell-penetrating peptide conjugates is also described.


Insufficient pain control for patients with cancer and dementia during terminal cancer stages.
To estimate differences in pain control between patients with cancer and with or without dementia during terminal cancer stages 3 months or 1 month before cancer death. We conducted frequency matching cohort for age, sex, and year of death for both groups at a 1:4 ratio. The prescription prevalence, total cumulative dose, and average daily dose of opioids during the terminal cancer stages 3 months and 1 month before cancer death were estimated. Patients with cancer and dementia were prescribed lower amounts of opioids 3 months before death (57.5% vs. 73.9%, respectively; adjusted odds ratio [OR] 0.46; 95% confidence interval [CI] 0.44-0.49) and 1 month before death (54.4% vs. 70.3%, respectively; adjusted OR 0.50; 95% CI 0.47-0.53). The total cumulative dose of opioids (mg) was lower in patients with cancer and dementia 3 and 1 month(s) before death (3 months: 1,578 mg vs. 2,666 mg, respectively; β=-1,125.9, P<0.001; 1 month: 921 mg vs. 1,533 mg, respectively; β=-622.1, P<0.001). The average daily opioid dose (mg/day), patients with cancer and dementia received a lower dose 3 months before death (31 mg vs. 48 mg; β=-22.6, P<0.001) and 1 month before death (38 mg vs. 60 mg; β=-17.1, P<0.001). The prevalence of opioid prescription was significantly lower in patients with both cancer and dementia during their terminal cancer stages 3 months and 1 month before death.


Variations in CRHR1 are associated with persistent pulmonary hypertension of the newborn.
Persistent pulmonary hypertension of the newborn (PPHN) is associated with substantial infant morbidity and mortality. Recently, genetic associations have been found in idiopathic pulmonary arterial hypertension. PPHN was significantly (P < 0.05) associated with genetic variants in corticotropin-releasing hormone (CRH) receptor 1, CRHR1 and CRH-binding protein, CRHBP. Association with CRHR1 rs4458044 passed the Bonferroni threshold for significance. No mutations were found in the bone morphogenetic protein receptor type II (BMPR2) gene. We describe previously unreported genetic associations between PPHN and CRHR1 and CRHBP. These findings may have implications for further understanding the pathophysiology of PPHN and treatment. We performed a family-based candidate gene study to examine a genetic association with PPHN and sequenced the BMPR2 gene in 72 individuals. We enrolled 110 families with infants diagnosed with PPHN based on inclusion criteria. After medical chart review, 22 subjects were excluded based on predefined criteria, and DNA samples from 88 affected infants and at least one parent per infant were collected and genotyped. Thirty-two single-nucleotide polymorphisms in 12 genes involved in vasoconstriction/vasodilation, lung development, surfactant regulation, or vascular endothelial cell function were investigated using family-based association tests.


Inferior vena cava to aorta ratio in dehydrated pediatric patients: a systematic review and meta-analysis.
Dehydration due to acute diarrhea is among the leading causes of mortality. However, advancements in management and technology do not help clinicians differentiate dehydration degrees. Ultrasound using the inferior vena cava to aorta (IVC/ Ao) ratio is a promising noninvasive technique to identify significant pediatric dehydration. Therefore, this systematic review and meta-analysis aimed to examine the diagnostic parameters of the IVC/Ao ratio for predicting clinically significant dehydration in pediatric patients. We searched the MEDLINE, PubMed, Cochrane Library, ScienceDirect, and Google Scholar databases for studies of pediatric patients (≤18 years old) who presented with signs and symptoms of dehydration due to acute diarrhea, gastroenteritis, or vomiting. The inclusion criteria were cross-sectional, case-control, cohort, and randomized controlled trial study design and publication in any language. We then conducted a meta-analysis using the midas and metandi commands from Stata software. Five studies of 461 patients were included. The combined sensitivity was 86% (95% confidence interval [CI], 79%-91%), while the specificity was 73% (95% CI, 59%-84%). The area under the curve was 0.89 (95% CI, 0.86-0.91). The positive likelihood ratio (LR+) was 3.2 (95% CI, 2.1-5.1) with a 76% posttest probability, while the negative likelihood ratio (LR-) was 0.18 (95% CI, 0.12-0.28) with a 16% posttest probability. The combined negative predictive value was 0.83 (95% CI, 0.75-0.91), while the positive predictive value was 0.75 (95% CI, 0.68-0.82). The IVC/Ao ratio was insufficient to exclude or confirm significant dehydration in pediatric patients. More studies are needed, especially multicenter, adequately powered diagnostic research, to will help establish the usefulness of the IVC/Ao ratio.


Exenatide plus metformin compared with metformin alone on β-cell function in patients with Type 2 diabetes.
To quantify how much exenatide added to metformin improves β-cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone. A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to exenatide (5 μg twice a day for the first 4 weeks and forced titration to 10 μg twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and β-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-α. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation. Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment β-cell function index (HOMA-β) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity-C reactive protein and tumour necrosis factor-α. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin. Exenatide is effective not only on glycaemic control, but also in protecting β-cells and in reducing inflammation.


Hydroxyglutaric aciduria and malignant brain tumor: a case report and literature review.
L -2-Hydroxyglutaric aciduria (L -2-OHGA) is a rare autosomal recessive inherited encephalopathy. This inborn error, characterized by psychomotor retardation, progressive ataxia and typical magnetic resonance imaging findings, presents in early infancy. To make a definitive diagnosis, an anomalous accumulation of L -2-hydroxyglutaric acid must be detected in body fluids. Here, we present a 17-year-old boy with L: -2-OHGA who developed an anaplastic ependymoma during the course of this disease. We also present a literature review including seven other patients who developed malignant brain tumors during the course of L -2-OHGA. This correlation may indicate a possible increased risk of brain tumors among patients with L -2-hydroxyglutaric aciduria.


Patient comfort and surgeon satisfaction during cataract surgery using topical anesthesia with or without dexmedetomidine sedation.
To determine the safety and efficacy of perioperative dexmedetomidine (Dex) sedation on patient comfort and surgeon satisfaction during cataract surgery under topical anesthesia. Forty-four patients having routine clear corneal phacoemulsification surgery under topical anesthesia were included in the study. Patients were randomly divided into two groups: Dex group (n=22) and control group (n=22). Patients in the Dex group were to receive intravenous Dex using an infusion pump and those in the control group were to receive 0.9% saline infusion. Primary outcome measures were patient comfort, surgeon satisfaction, and patient pain perception. There was no significant difference between the groups in terms of baseline characteristics including age, sex, eye side, pupil diameter, and vital signs (p>0.05 for all). Patient comfort and surgeon satisfaction in Dex group was better than in control group (p=0.042 and p=0.003, respectively). The mean pain perception score was lesser in the Dex group (1.23+-.72) than control group (3.64+/-1.43), (p<0.001). The mean surgical time and intraoperative complications were similar in both groups (p>0.05). There was no significant effect of the Dex sedation on vital signs perioperatively (p>0.05 for all). Dex sedation improved patient and surgeon satisfaction and decreased patients' pain perception while undergoing cataract surgery under topical anesthesia. It appears to be a safe and suitable choice of sedation for cataract surgery.


Disparities in refusal of surgery for gynecologic cancer.
To identify sociodemographic and clinical factors associated with refusal of gynecologic cancer surgery and to estimate its effect on overall survival. The National Cancer Database was surveyed for patients with uterine, cervical or ovarian/fallopian tube/primary peritoneal cancer treated between 2004 and 2017. Univariate and multivariate logistic regression were used to assess associations between clinico-demographic variables and refusal of surgery. Overall survival was estimated using the Kaplan-Meier method. Trends in refusal over time were evaluated using joinpoint regression. Of 788,164 women included in our analysis, 5875 (0.75%) patients refused surgery recommended by their treating oncologist. Patients who refused surgery were older at diagnosis (72.4 vs 60.3 years, p < 0.001) and more likely Black (OR 1.77 95% CI 1.62-1.92). Refusal of surgery was associated with uninsured status (OR 2.94 95% CI 2.49-3.46), Medicaid coverage (OR 2.79 95% CI 2.46-3.18), low regional high school graduation (OR 1.18 95% CI 1.05-1.33) and treatment at a community hospital (OR 1.59 95% CI 1.42-1.78). Patients who refused surgery had lower median overall survival (1.0 vs 14.0 years, p < 0.01) and this difference persisted across disease sites. Between 2008 and 2017, there was a significant increase in refusal of surgery annually (annual percent change +1.41%, p < 0.05). Multiple social determinants of health are independently associated with refusal of surgery for gynecologic cancer. Given that patients who refuse surgery are more likely from vulnerable, underserved populations and have inferior survival, refusal of surgery should be considered a surgical healthcare disparity and tackled as such.


Subcutaneous endoscopically assisted ligation (SEAL) of the internal ring for repair of inguinal hernias in children: a novel technique.
Subcutaneous endoscopically assisted ligation (SEAL) is a technique for high ligation of the patent processus at the internal ring without a groin incision or dissection of the vas and vessels. Under endoscopic visualization through a single umbilical port, a suture is guided extraperitoneally around the internal ring, avoiding the vas and vessels. The safety, efficacy (recurrence risk), and cost-effectiveness of this unproven procedure must be tested against standard open repair in a trial.


Leveraging species richness and ecological condition indices to guide systematic conservation planning.
The global crises of biodiversity loss and climate change are interconnected in root cause and solutions. Targeted land conservation has emerged as a leading strategy to protect vulnerable species and buffer climate impacts, however, consistent methods to assess biodiversity and prioritize areas for protection have not yet been established. Recent landscape-scale planning initiatives in California present an opportunity to conserve biodiversity, but to enhance their effectiveness, assessment approaches should move beyond commonly used measures of terrestrial species richness. In this study, we compile publicly available datasets and explore how distinct biodiversity conservation indices - including indicators of terrestrial and aquatic species richness and of biotic and physical ecosystem condition - are represented in watersheds of the northern Sierra Nevada mountain region of California (n = 253). We also evaluate the extent to which the existing protected area network covers watersheds that support high species richness and intact ecosystems. Terrestrial and aquatic species richness showed unique spatial patterns (Spearman R = 0.27), with highest richness of aquatic species in the low-elevation watersheds of the study area and highest richness of terrestrial species in mid- and high-elevation watersheds. Watersheds with the highest ecosystem condition were concentrated in upper-elevations and were poorly correlated with those with the highest species richness (Spearman R = -0.34). We found that 28% of watersheds in the study area are conserved by the existing protected area network. Protected watersheds had higher ecosystem condition (mean rank-normalized score = 0.71) than unprotected areas (0.42), but species richness was generally lower (0.33 in protected versus 0.57 in unprotected watersheds). We illustrate how the complementary measures of species richness and ecosystem condition can be used to guide strategies for landscape-scale ecosystem management, including prioritization of watersheds for targeted protection, restoration, monitoring, and multi-benefit management. Though designed for California, application of these indices to guide conservation planning, design monitoring networks, and implement landscape-scale management interventions provides a model for other regions of the world.


Enhancing mixed toluene and formaldehyde pollutant removal by Zamioculcas zamiifolia combined with Sansevieria trifasciata and its CO2 emission.
Indoor air pollutants comprise both polar and non-polar volatile organic compounds (VOCs). Indoor potted plants are well known for their innate ability to improve indoor air quality (IAQ) by detoxification of indoor air pollutants. In this study, a combination of two different plant species comprising a C3 plant (Zamioculcas zamiifolia) and a crassulacean acid metabolism (CAM) plant (Sansevieria trifasciata) was used to remove polar and non-polar VOCs and minimize CO2 emission from the chamber. Z. zamiifolia and S. trifasciata, when combined, were able to remove more than 95% of pollutants within 48 h and could do so for six consecutive pollutant's exposure cycles. The CO2 concentration was reduced from 410 down to 160 ppm inside the chamber. Our results showed that using plant growth medium rather than soil had a positive effect on decreasing CO2. We also re-affirmed the role of formaldehyde dehydrogenase in the detoxification and metabolism of formaldehyde and that exposure of plants to pollutants enhances the activity of this enzyme in the shoots of both Z. zamiifolia and S. trifasciata. Overall, a mixed plant of Z. zamiifolia and S. trifasciata was more efficient at removing mixed pollutants and reducing CO2 than individual plants.


[Intelligence evaluation of 22 patients with congenital velopharyngeal incompetence].
To study the intelligence of 22 patients with CVPI. We examined the IQ of 22 patients with CVPI by Wechsler Primary Preschool Scale of Intelligence (WPSSI) and Wechsler Intelligence Scale for Children-Revised (WISC-R). The IQ of patients with CVPI was 44-109. The mean value and SD were 67.46+/-19.29. Patients with normal IQ accounted for 45.5%. 54.5% of patients with CVPI had mental retardation (MR), most of which were mild. More than half of the patients with CVPI showed MR. It's necessary to evaluate the intelligence in patients with CVPI, and give treatment as early as possible.


Electrografting of thionine diazonium cation onto the graphene edges and decorating with Au nano-dendrites or glucose oxidase: Characterization and electrocatalytic applications.
Thionine (Th) diazonium cation is covalently attached onto the glassy carbon (GC) electrode via graphene nanosheets (GNs) (GC-GNs-Th). The GC-GNs-Th electrode is subjected to further modifications to fabricate (i) glucose and (ii) nitrite sensors. Further modifications include: (i) direct immobilization of glucose oxidase (GOx) and (ii) electrodeposition of gold dendrite-like nanostructures (DGNs) on the GC-GNs-Th surface, constructing GC-GNs-Th-GOx and GC-GNs-Th-DGNs modified electrodes, respectively. The GC-GNs-Th-GOx biosensor exhibited a linear response range to glucose, from 0.5 to 6.0mM, with a limit of detection (LOD) of 9.6 μM and high sensitivity of 43.2 µAcm(-2)mM(-1). Also, the GC-GNs-Th-DGNs sensor showed a wide dynamic response range for NO2(-) ion with two linear parts, from 0.05 μM to 1.0 μM and 30.0 μM to 1.0mM, a sensitivity of 263.2 μAmM(-1) and a LOD of 0.01 μM. Applicability of the modified electrodes was successfully tested by determination of glucose in human blood serum and nitrite in water based on addition/recovery tests.


Synthesis of functionalized dioxa-aza[7]helicenes using palladium catalyzed arylations.
Despite the recent reports on transition-metal catalyzed cycloisomerization strategies toward helicenes, the amount of palladium catalyzed routes remains rather scarce. Within this letter the successful preparation and characterization of novel dioxa-aza[7]helicenes using palladium mediated coupling reactions is presented.


Common sports injuries to the knee.
The evaluation and treatment of knee injuries is common in the practice of sports medicine. The knee is the most commonly injured joint of the lower extremity. Therefore, the podiatrist should have an adequate knowledge and skill in the knee examination, anatomy, pathology, and biomechanics to properly diagnose and treat disorders of the joint. The etiologies of knee pain can be divided into five categories: (1) anterior, (2) posterior, (3) medial, (4) lateral, and (5) general for simplicity of description. The doctor can easily evaluate the painful knee in the athlete by remembering the major pathologies within each anatomic quadrant. Attention should be directed at those deformities of the knee that have biomechanical origins in the foot, in part or in toto. This biomechanical relationship when balanced into the treatment plan will increase the success of the management of the patient.


Effects of opioid peptides and naloxone on nervous tissue in culture.
It was shown that opioid peptides stimulate nervous tissue growth in culture in the rat, which manifests itself in augmented outgrowth of neurites from explants and in an increase in the number of glial and fibroblast-like cells in the growth zone. The effects of opioid peptides ([Leu]- and [Met]-enkephalins, beta- and gamma-endorphins and some synthetic analogues of [Leu]-enkephalin) on the growth of organotypic cultures of rat sympathetic and dorsal root ganglia and spinal cord were investigated. Neurite outgrowth, cell composition, and size of the growth zone as well as the dynamics of its formation were estimated. Changes in the survival of neurons in dorsal root ganglion cultures were determined. The experiments were performed with living cultures as well as with fixed preparations. In experiments with sympathetic ganglia, it was demonstrated that a significant growth-promoting effect is exerted by peptides taken at concentrations of 10(-8) M to 10(-14) M. Naloxone does not eliminate the effects of peptides, but stimulates the growth at 10(-5) M to 10(-7) M. Studies with spinal cord revealed that naloxone (10(-6) M) enhances the response to [Leu]-enkephalin (10(-9) M). The survival of dorsal root ganglion neurons under the influence of a [leu]-enkephalin analog (10(-9) M) exceeds control values by approximately two to four times. Thus, opioid peptides were shown to exert a strong growth-promoting effect on nervous tissue in culture. This effect is dual: in neurons the peptides stimulate the outgrowth of neurites and their survival, while in glial cells they change the rate of their migration and, probably, their proliferation. It is suggested that opioid peptides, besides their already established functions, may play a role in the development and regeneration of nervous tissue.


A distance metric for a class of tree-sibling phylogenetic networks.
The presence of reticulate evolutionary events in phylogenies turn phylogenetic trees into phylogenetic networks. These events imply in particular that there may exist multiple evolutionary paths from a non-extant species to an extant one, and this multiplicity makes the comparison of phylogenetic networks much more difficult than the comparison of phylogenetic trees. In fact, all attempts to define a sound distance measure on the class of all phylogenetic networks have failed so far. Thus, the only practical solutions have been either the use of rough estimates of similarity (based on comparison of the trees embedded in the networks), or narrowing the class of phylogenetic networks to a certain class where such a distance is known and can be efficiently computed. The first approach has the problem that one may identify two networks as equivalent, when they are not; the second one has the drawback that there may not exist algorithms to reconstruct such networks from biological sequences. We present in this article a distance measure on the class of semi-binary tree-sibling time consistent phylogenetic networks, which generalize tree-child time consistent phylogenetic networks, and thus also galled-trees. The practical interest of this distance measure is 2-fold: it can be computed in polynomial time by means of simple algorithms, and there also exist polynomial-time algorithms for reconstructing networks of this class from DNA sequence data. The Perl package Bio::PhyloNetwork, included in the BioPerl bundle, implements many algorithms on phylogenetic networks, including the computation of the distance presented in this article. Some counterexamples, proofs of the results not included in this article, and some computational experiments are available at Bioinformatics online.


Soil high Cd exacerbates the adverse impact of elevated O3 on Populus alba 'Berolinensis' L.
Pollution with both heavy metal and ground-level ozone (O3) has been steadily increasing, especially in the cities with heavy industry. Little information is known about their combined impacts on urban tree. This study was aimed at characterizing the interactive effects of soil cadmium (Cd) addition and O3 fumigation on visible injury and growth, photosynthesis, oxidative stress, antioxidant enzyme activities, abscisic acid (ABA) content and bioaccumulation of Cd in one-year-old Populus alba 'Berolinensis' saplings by using open top chambers in Shenyang city with developed heavy industry, Northeast China. In this study, poplar saplings were grown in the pots containing soil with different concentrations of Cd (0, 100 and 500 mg kg-1) under ambient air (40 µg L-1) and elevated O3 (120 µg L-1). The results showed that EO and its combination with high Cd (500 mg kg-1) induced significant foliar injury symptoms, decreased root weight (by 41.6%) and total biomass (by 17.4%), inhibited net photosynthetic rate and stomatal conductance, and increased malondialdehyde and ABA contents after 4 weeks of O3 exposure. Elevated O3 exacerbated the accumulation of Cd in leaves and stems of poplar plants grown in the pots with high Cd-polluted soil. Our results also indicated that high Cd pollution in soil increased the susceptibility of plants to O3 and exacerbated the adverse impact of elevated O3 on physiological metabolisms of poplar species, which implied that it was very necessary to take into consideration for O3-tolerance of tree species during phytoremediation of Cd-polluted soil in heavy industrial areas.


Direct Sibling Influence on Eating Behavior in Early Childhood: Siblings as Role Models and Caregivers.
Despite the majority of US children having at least 1 sibling, little is known about how siblings influence eating behavior and obesity risk. This qualitative study explored mothers' perceptions of older siblings' influences on younger siblings' eating behavior in the context of mealtimes in early childhood. A purposive subsample of mothers (n = 30) who participated in the Intervention Nurses Start Infants Growing on Healthy Trajectories and SIBSIGHT studies completed retrospective semi-structured interviews designed to explore the implications of sibling influences on maternal feeding practices during infancy and toddlerhood. Interviews were conducted by video conference with mothers between January and March 2021. All interviews were audio-recorded, transcribed, and a qualitative content analysis approach was used to code and identify themes. Two main themes were identified related to the influence of older siblings on younger siblings during feeding interactions: 1) Older siblings as positive role models for younger siblings and 2) Older siblings acted as caregivers for younger siblings. Younger siblings received encouragement at mealtimes to try new foods. Older siblings assisted their mothers in caregiving and feeding tasks in developmentally appropriate ways. Findings may help to elucidate the role of older siblings in shaping eating behavior and obesity risk of siblings in early childhood. Better understanding the role of siblings can aid in the development of novel interventions and anticipatory nutrition guidance in family-based clinical and community care.


New concepts in HIV-1 vaccine development.
With 2 million people newly infected with HIV-1 in 2014, an effective HIV-1 vaccine remains a major public health priority. HIV-1 vaccine efficacy trials in humans, complemented by active and passive immunization studies in non-human primates, have identified several key vaccine-induced immunological responses that may correlate with protection against HIV-1 infection. Potential correlates of protection in these studies include V2-specific, polyfunctional, and broadly neutralizing antibody responses, as well as effector memory T cell responses. Here we review how these correlates of protection are guiding current approaches to HIV-1 vaccine development. These approaches include improvements on the ALVAC-HIV/AIDSVAX B/E vaccine regimen used in the RV144 clinical trial in Thailand, adenovirus serotype 26 vectors with gp140 boosting, intravenous infusions of bNAbs, and replicating viral vectors.


[Two unusual bone tumours of the hand (author's transl)].
Two unusual cases of bone tumours of the fingers are described: an isolated metastasis of the bronchial carcinoma and an ossifying osteofibroma. Brief review of the literature, clinical picture and histological findings.


Early changes in the adaptation to a low calcium diet in the chick.
Twelve hours after the diet of 3-week-old chicks was changed from a 1% to a 0.1% concentration of calcium (Ca), the growth rate and circulating levels of growth hormone had fallen while renal 25-hydroxecholecalciferol-24-hydroxylase had risen. The amount of 47Ca incorporated into bone from an injection given 18 h previously was lower than in the control birds. Over the following 2 1/2 days on the low Ca diet, the renal 1-hydroxylase activity rose and the plasma prolactin level fell, but the other parameters moved back toward the control level. It was concluded that early adjustments in hormonal and mineral metabolism counteract the acute effects of a dietary Ca shortage until longer-term adaptive changes begin to compensate for a continuing Ca deficiency. The renal hydroxylase activities were not directly influenced by the level of circulating growth hormone or prolactin.


Structural bases that underline Trypanosoma cruzi calreticulin proinfective, antiangiogenic and antitumor properties.
Microbes have developed mechanisms to resist the host immune defenses and some elicit antitumor immune responses. About 6 million people are infected with Trypanosoma cruzi, the protozoan agent of Chagas' disease, the sixth neglected tropical disease worldwide. Eighty years ago, G. Roskin and N. Klyuyeva proposed that T. cruzi infection mediates an anti-cancer activity. This observation has been reproduced by several other laboratories, but no molecular basis has been proposed. We have shown that the highly pleiotropic chaperone calreticulin (TcCalr, formerly known as TcCRT), translocates from the parasite ER to the exterior, where it mediates infection. Similar to its human counterpart HuCALR (formerly known as HuCRT), TcCalr inhibits C1 in its capacity to initiate the classical pathway of complement activation. We have also proposed that TcCalr inhibits angiogenesis and it is a likely mediator of antitumor effects. We have generated several in silico structural TcCalr models to delimit a peptide (VC-TcCalr) at the TcCalr N-domain. Chemically synthesized VC-TcCalr did bind to C1q and was anti-angiogenic in Gallus gallus chorioallantoic membrane assays. These properties were associated with structural features, as determined in silico. VC-TcCalr, a strong dipole, interacts with charged proteins such as collagen-like tails and scavenger receptors. Comparatively, HuCALR has less polarity and spatial stability, probably due to at least substitutions of Gln for Gly, Arg for Lys, Arg for Asp and Ser for Arg that hinder protein-protein interactions. These differences can explain, at least in part, how TcCalr inhibits the complement activation pathway and has higher efficiency as an antiangiogenic and antitumor agent than HuCALR.


Biomolecular condensates tunes immune signaling at the Host-Pathogen interface.
Membraneless organelles participate in diverse spatiotemporal regulation of cellular signal transduction by recruiting necessary signaling factors. During host-pathogen interactions, the plasma membrane (PM) at the interface between the plant and microbes serves as a central platform for forming multicomponent immune signaling hubs. The macromolecular condensation of the immune complex and regulators is important in regulating immune signaling outputs regarding strength, timing, and crosstalk between signaling pathways. This review discusses mechanisms that regulate specific and crosstalk of plant immune signal transduction pathways through macromolecular assembly and condensation.


Introduction of a tryptophan reporter group into loop 1 of the recA protein. Examination of the conformational states of the recA-ssDNA complex by fluorescence spectroscopy.
Site-directed mutagenesis was used to replace His-163 in the Loop 1 region of the recA protein with a tryptophan residue. The [H163W]recA protein binds single-stranded DNA (ssDNA), catalyzes ssDNA-dependent ATP hydrolysis, and is fully active in the three-strand exchange reaction. In addition, the fluorescence properties of the Trp-163 reporter group are very sensitive to the binding of nucleotide cofactors to the H163W]recA-ssDNA complex. The fluorescence of Trp-163 is modestly quenched by the binding of ADP (21%) and strongly quenched by the nonhydrolyzable ATP analog, ATP gamma S (70%); since ADP and ATP gamma S stabilize the closed and open conformations of the recA-ssDNA complex, respectively, the quenched states observed with these nucleotides likely reflect differences in the fluorescence properties of tryptophan 163 in these two states. ATP has a more complex time-dependent effect on Trp-163 fluorescence. When ATP is added to [H163W]recA-ssDNA complexes, there is an immediate quenching of Trp-163 fluorescence (44%) which is intermediate in intensity between that observed with ADP and ATP gamma S. The ATP-induced quenching gradually decreases with time as the pool of ATP is converted to ADP by the ATP hydrolysis activity of the [H163W]recA protein. These results are discussed with regard to the nucleotide cofactor-dependent conformational transitions of the recA-ssDNA complex.


The NuroSleeve, a user-centered 3D printed hybrid orthosis for individuals with upper extremity impairment.
Active upper extremity (UE) assistive devices have the potential to restore independent functional movement in individuals with UE impairment due to neuromuscular diseases or injury-induced chronic weakness. Academically fabricated UE assistive devices are not usually optimized for activities of daily living (ADLs), whereas commercially available alternatives tend to lack flexibility in control and activation methods. Both options are typically difficult to don and doff and may be uncomfortable for extensive daily use due to their lack of personalization. To overcome these limitations, we have designed, developed, and clinically evaluated the NuroSleeve, an innovative user-centered UE hybrid orthosis. This study introduces the design, implementation, and clinical evaluation of the NuroSleeve, a user-centered hybrid device that incorporates a lightweight, easy to don and doff 3D-printed motorized UE orthosis and a functional electrical stimulation (FES) component. Our primary goals are to develop a customized hybrid device that individuals with UE neuromuscular impairment can use to perform ADLs and to evaluate the benefits of incorporating the device into occupational therapy sessions. The trial is designed as a prospective, open-label, single-cohort feasibility study of eight-week sessions combined with at-home use of the device and implements an iterative device design process where feedback from participants and therapists informs design improvement cycles. All participants learned how to independently don, doff, and use the NuroSleeve in ADLs, both in clinical therapy and in their home environments. All participants showed improvements in their Canadian Occupational Performance Measure (COPM), which was the primary clinical trial outcome measure. Furthermore, participants and therapists provided valuable feedback to guide further development. Our results from non-clinical testing and clinical evaluation demonstrate that the NuroSleeve has met feasibility and safety goals and effectively improved independent voluntary function during ADLs. The study's encouraging preliminary findings indicate that the NuroSleeve has met its technical and clinical objectives while improving upon the limitations of the existing UE orthoses owing to its personalized and flexible approach to hardware and firmware design. ClinicalTrials.gov identifier: NCT04798378, https://clinicaltrials.gov/ct2/show/NCT04798378 , date of registration: March 15, 2021.


Clinical Effectiveness of Family Therapeutic Interventions Embedded in General Pediatric Primary Care Settings for Parental Mental Health: A Systematic Review and Meta-analysis.
The aim of this systematic review and meta-analysis was to synthesize the available evidence on embedded family therapy interventions in pediatrics and impacts on parental mental health and family functioning outcomes. The Cochrane Collaboration guidelines for systematic reviews and meta-analysis were used for this study. Six electronic databases were searched for randomized controlled trials and cluster randomized trials. The Cochrane Collaboration's Risk of Bias Tool and GRADE system were used to rate the quality of evidence of the included studies. The primary outcomes included parental distress, parental depressive symptoms, and dysfunctional parent-child interaction. Fixed effects models showed statistically significant reductions in parental distress at 6-month and 12-month post-intervention in favor of the intervention group. Family therapy model, intervention level, delivery modality, and dosage moderated intervention impacts on parental distress. Fixed effects models showed statistically significant reductions in parental depressive symptoms and in dysfunctional parent-child interaction in favor of the intervention group. Family therapy interventions can be successfully embedded in general pediatric primary care, and intended outcomes are achieved in this setting. Recommendations for future research and implications for policy development are discussed.


An alternative method for the evaluation of organ weight experiments.
Previous work has suggested that the use of relative organ weights can lead to erroneous conclusions in toxicological experiments. A method of analysis involving very little extra experimentation is suggested and evaluated. Simulated results from rat organ weights indicate that the method is superior to the use of relative organ weights and leads to reliable conclusions being drawn about the treatment effects.