Evaluation of the Quality, Accuracy, and Readability of Online Patient Resources for the Management of Articular Cartilage Defects.
Objective Patients commonly use the Internet to obtain their health-related information. The purpose of this study was to investigate the quality, accuracy, and readability of online patient resources for the management of articular cartilage defects. Design Three search terms ("cartilage defect," "cartilage damage," "cartilage injury") were entered into 3 Internet search engines (Google, Bing, Yahoo). The first 25 websites from each search were collected and reviewed. The quality and accuracy of online information were independently evaluated by 3 reviewers using predetermined scoring criteria. The readability was evaluated using the Flesch-Kincaid (FK) grade score. Results Fifty-three unique websites were evaluated. Quality ratings were significantly higher in websites with a FK score >11 compared to those with a score of ≤11 ( P = 0.021). Only 10 websites (19%) differentiated between focal cartilage defects and diffuse osteoarthritis. Of these, 7 (70%) were elicited using the search term "cartilage defect" ( P = 0.038). The average accuracy of the websites was high (11.7 out of maximum 12), and the average FK grade level (13.4) was several grades higher than the recommended level for readable patient education material (eighth grade level). Conclusions The quality and readability of online patient resources for articular cartilage defects favor those with a higher level of education. Additionally, the majority of these websites do not distinguish between focal chondral defects and diffuse osteoarthritis, which can fail to provide appropriate patient education and guidance for available treatment. Clinicians should help guide patients toward high-quality, accurate, and readable online patient education material.


[Loss of function and morphological changes in subfoveolar choroidal neovascularisations and various beginnings of photodynamic therapies].
In the year 2000, the photodynamic therapy (PDT) was introduced as a new option for the treatment of exudative choroidal neovascularisation (CNV). Since this kind of therapy required the health insurance company's consent, the waiting period for the first therapy varied considerably. Between July 2000 and September 2004, 133 eyes were treated via PDT. In this study, 59 courses were analysed retrospectively, all of them within the frame of a classic or predominantly classic exudative CNV. At the time of indication for the therapy, 38.46 % of the eyes of patients under the age of 65 and 73.91 % of the eyes of patients over the age of 65 showed a visual acuity (VA) of less than 0.3. Nine eyes lost the VA needed to drive a car (> or = 0.6), eight eyes lost the reading ability (< 0.4) before the first PDT. One eye lost its reading ability, one eye reached the classification of "visually handicapped & blindness" (< or = 0.3) and one eye went blind (< or = 0.02) within 7 days of waiting time. Elderly people showed less VA at first investigations by ophthalmologists, which underscores the necessity of an intensive campaign about the classic symptoms of AMD. The results of this study confirm that loss of VA can be caused by CNV progression within seven days. Whether or not rapid treatment with PDT influences the visual and morphological outcome, has to be proven by more extensive studies.


Stereotactic radiosurgery for patients with recurrent intracranial ependymomas.
The objective of the study is to define the tumor control rate and complications associated with stereotactic radiosurgery (SRS) for patients with recurrent intracranial ependymoma. Retrospective review of 26 patients (49 tumors) having SRS between 1990 and 2008. Twenty-five patients (96 %) had undergone one or more craniotomies; one patient underwent SRS for a metastatic tumor after resection of a spinal ependymoma. Nineteen patients (73 %) had received cranial external beam radiotherapy (median dose, 54 Gy). Eight patients (31 %) were less than 18 years old. The median target volume was 2.2 cm(3) (range, 0.3-66.6); the median tumor margin dose was 18 Gy (range, 12-24). The median follow-up after SRS was 3.1 years (range, 3 months-13.1 years). The median overall survival after SRS was 5.5 years. The 1-year and 3-year survival rates were 96 and 69 %, respectively. Local tumor control (LC) was achieved in 33 of 49 lesions (67 %) with a median time to progression of 14.7 months (range, 2.9 months-11.2 years). The 1-year and 3-year progression-free survival rates were 80 and 66 %, respectively. The 1-year and 3-year LC rate was 85 and 72 %, respectively. On univariate analysis, higher tumor grade was associated with worse OS (grade 3-4, 27 % vs grade 2, 82 %, p = 0.04). Seven patients (27 %) had distant tumor progression and two patients (8 %) had symptomatic radiation necrosis after SRS. SRS for recurrent intracranial ependymoma provided good LC and may improve survival for patients with limited recurrent disease after prior treatment.


Distal ulnar translocation in the treatment of giant-cell tumors of the distal end of the radius.
Two patients with a giant-cell tumor of the distal end of the radius were treated by en bloc resection of the distal part of the radius and by replacement of the resected segment with the translocated distal portion of the ipsilateral ulna. The blood supply to the ulna without detaching its soft-tissue attachments. The distal articular surface of the ulna was resected and the ulna was fused to the lunate and the scaphoid. The ulnar segment was internally fixed to the proximal segment of the radius and to the carpus with an intramedullary Steinmann pin. Both patients obtained a useful, pain-free extremity with more than 85 per cent of forearm rotation and 10 to 15 degrees of flexion-extension at the wrist.


Subperiosteal and full-thickness skin rhytidectomy.
Subperiosteal lateral brow and midface elevation, upper lid blepharoplasty, transconjunctival retroseptal fat removal, lower lid skin excision, and full-thickness skin rhytidectomy are combined in one operation to rejuvenate the entire face. This combination of procedures is designed to restore both anthropometric and subjective attributes of youth. The attributes of a youthful face may be summarized as brows with an apex lateral slant, eyes that are narrow, lower lids that are short, cheeks that are full, and necks that are well defined. In addition to restoring a youthful appearance, the techniques described avoid some common iatrogenic sequelae of facial rejuvenative surgery. In a clinical experience with 28 patients over 3 years, this combination of procedures has proved to be safe and predictable.


L-Methionine-gamma-lyase, as a target to inhibit malodorous bacterial growth by trifluoromethionine.
Methyl mercaptan is a major component responsible for oral malodor. This compound arises from the bacterial metabolism of methionine. Here we show that the growth of Porphyromonas gingivalis, a periodontal microorganism that produces large amounts of methyl mercaptan, was strongly inhibited by l-trifluoromethionine (TFM), a fluorinated derivative of methionine. In contrast, TFM had no effect on the growth of bacteria which do not produce methyl mercaptan. In addition, the survival rate of P. gingivalis-infected mice was remarkably increased by the co-injection of TFM. These results suggest that TFM is a promising antibacterial agent specific to the malodorous oral bacteria.


The development of intelligent healthcare in China.
Intelligent healthcare (IH) is proposed with the fast application of Internet of Things technology in the healthcare area in recent years. It is considered as an expansion of e-health and telemedicine. As the largest developing country, China is investing large amounts of resources to push forward the development of IH. It is one of the centerpieces of the country's New Healthcare Reform, and great expectation is placed on it to help solve the conflict between limited healthcare resources and the large patient population. Essential policies, milestones, standards, and specifications from the Chinese government since the 1990s were reviewed to show the brief development history of IH in China. Some typical cases and products have been analyzed to present the current situation. The main problems and future development directions have been summarized. The IH industry in China has great potential and is growing very fast, but a lot of challenges also exist. In the future both government support and the active participation of nongovernmental capital are needed to push forward the whole industry.


The current situation in education and training of health-care professionals across Africa to optimise the delivery of palliative care for cancer patients.
The need for palliative care education remains vital to contribute to the quality of life of patients, both adults and children, with cancer in Africa. The number of patients with cancer continues to rise, and with them the burden of palliative care needs. Palliative care has been present in Africa for nearly four decades, and a number of services are developing in response to the HIV/AIDS epidemic. However, the needs of cancer patients remain a challenge. Education and training initiatives have developed throughout this time, using a combination of educational methods, including, more recently, e-learning initiatives. The role of international and national organisations in supporting education has been pivotal in developing models of education and training that are robust, sustainable, and affordable. Developing a material for education and professional development needs to continue in close collaboration with that already in production in order to optimise available resources. Seeking ways to evaluate programmes in terms of their impact on patient care remains an important part of programme delivery. This article reviews the current situation.


Effects of the peripherally acting μ-opioid receptor antagonist methylnaltrexone on acute pancreatitis severity: study protocol for a multicentre double-blind randomised placebo-controlled interventional trial, the PAMORA-AP trial.
Moderate to severe acute pancreatitis (AP) is associated with a high rate of complications and increased mortality, yet no targeted pharmacologic treatment currently exists. As pain is a dominant symptom in AP, patients are exposed to excess levels of both endo- and exogenous opioids, which may have harmful effects on the course of AP. This trial investigates the effects of the peripherally acting μ-opioid receptor antagonist (PAMORA) methylnaltrexone on disease severity and clinical outcomes in patients with moderate to severe AP. PAMORA-AP is a multicentre, investigator-initiated, double-blind, randomised, placebo-controlled, interventional trial, which will be conducted at four referral centres for acute pancreatitis in Denmark. Ninety patients with early-onset AP (pain onset within 48 h) as well as predicted moderate to severe disease (two or more systemic inflammatory response syndrome criteria upon admission) will be prospectively included. Subsequently, participants will be randomised (1:1) to intravenous treatment with either methylnaltrexone or matching placebo (Ringer's lactate) during 5 days of admission. The primary endpoint will be the group difference in disease severity as defined and measured by the Pancreatitis Activity Scoring System (PASS) score 48 h after randomisation. Secondary endpoints include daily PASS scores; disease severity according to the Atlanta classification; quantification of need for analgesics, nutritional support, intravenous fluid resuscitation and antibiotics; duration of hospital admissions, readmission rates and mortality. Pain intensity and gut function will be self-reported using validated questionnaires. Exploratory endpoints include circulating levels of pro-and anti-inflammatory markers, polyethylene glycol recovery from the urine, circulating levels of blood markers of intestinal permeability, the prevalence of pancreatic complications on computed tomography (CT) scans, and colon transit time assessed using a CT-based radiopaque marker method. This trial aims to evaluate the PAMORA methylnaltrexone as a novel targeted pharmacotherapy in patients with moderate to severe AP with the potential benefit of improved patient outcomes. ClinicalTrials.gov NCT04743570 . Registered on 28 January 2021. EudraCT 2020-002313-18.


Did the Great Recession affect mortality rates in the metropolitan United States? Effects on mortality by age, gender and cause of death.
Mortality rates generally decline during economic recessions in high-income countries, however gaps remain in our understanding of the underlying mechanisms. This study estimates the impacts of increases in unemployment rates on both all-cause and cause-specific mortality across U.S. metropolitan regions during the Great Recession. We estimate the effects of economic conditions during the recent and severe recessionary period on mortality, including differences by age and gender subgroups, using fixed effects regression models. We identify a plausibly causal effect by isolating the impacts of within-metropolitan area changes in unemployment rates and controlling for common temporal trends. We aggregated vital statistics, population, and unemployment data at the area-month-year-age-gender-race level, yielding 527,040 observations across 366 metropolitan areas, 2005-2010. We estimate that a one percentage point increase in the metropolitan area unemployment rate was associated with a decrease in all-cause mortality of 3.95 deaths per 100,000 person years (95%CI -6.80 to -1.10), or 0.5%. Estimated reductions in cardiovascular disease mortality contributed 60% of the overall effect and were more pronounced among women. Motor vehicle accident mortality declined with unemployment increases, especially for men and those under age 65, as did legal intervention and homicide mortality, particularly for men and adults ages 25-64. We find suggestive evidence that increases in metropolitan area unemployment increased accidental drug poisoning deaths for both men and women ages 25-64. Our finding that all-cause mortality decreased during the Great Recession is consistent with previous studies. Some categories of cause-specific mortality, notably cardiovascular disease, also follow this pattern, and are more pronounced for certain gender and age groups. Our study also suggests that the recent recession contributed to the growth in deaths from overdoses of prescription drugs in working-age adults in metropolitan areas. Additional research investigating the mechanisms underlying the health consequences of macroeconomic conditions is warranted.


Fluorescent 2D metal-organic framework nanosheets (MONs): design, synthesis and sensing of explosive nitroaromatic compounds (NACs).
2D metal-organic framework nanosheets (MONs) lie at the heart of contemporary research on metal-organic materials. We have rationally designed and synthesized a fluorescent 6-connecting hexaacid linker H6TPA based on the 1,3,5-triphenylbenzene core to access layered MOFs by metal-assisted self-assembly. Treatment of H6TPA with In3+ salt does indeed lead to a layered porous MOF, i.e.In-TPA. It is shown that the ultrasonication-induced liquid phase of exfoliation (UILPE) of the latter in a top-down fashion affords few-layer 2D metal-organic nanosheets (MONs). The delamination of 2D MONs in ethanol occurs with 'turn-on' fluorescence, which is otherwise suppressed in the bulk material. The exfoliated MONs in ethanol exhibit blue fluorescence with a respectable quantum yield of 0.15 and serve as efficient sensory materials for 'turn-off' fluorescence detection of explosive nitroaromatic compounds (NACs). While all nitroaromatics are found to quench the fluorescence of MONs, the most electron-deficient trinitrotoluene (TNT) exhibited the highest efficiency; at 2 mM concentration of TNT, the fluorescence of 2D MONs was found to be quenched with an efficiency of 80% (permitting the detection of TNT at ca. 11 ppm level), while that of the unmetallated linker, i.e.H6TPA, was quenched with only 5% efficiency. The unique attributes of MONs, namely the rigidity of the linker upon metallation and porosity that facilitates guest confinement within the pores, for efficient sensing of nitroaromatics are thus demonstrated for the first time.


SMART: identification and annotation of domains from signalling and extracellular protein sequences.
SMART is a simple modular architecture research tool and database that provides domain identification and annotation on the WWW (http://coot.embl-heidelberg.de/SMART). The tool compares query sequences with its databases of domain sequences and multiple alignments whilst concurrently identifying compositionally biased regions such as signal peptide, transmembrane and coiled coil segments. Annotated and unannotated regions of the sequence can be used as queries in searches of sequence databases. The SMART alignment collection represents more than 250 signalling and extracellular domains. Each alignment is curated to assign appropriate domain boundaries and to ensure its quality. In addition, each domain is annotated extensively with respect to cellular localisation, species distribution, functional class, tertiary structure and functionally important residues.


Acrocyanosis: an overview.
It is a functional peripheral vascular disorder characterized by bluish discoloration of skin and mucous membrane due to diminished oxyhemoglobin. It may be due to central or local tissue oxygenation defects. It is a painful episodic disorder, where trophic changes and ulceration are very rare except in necrotizing variant. By definition, it refers to persistent abnormally deep blue or cyanotic discoloration of skin over extremities (hand and feet most commonly) due to decreased oxyhemoglobin. It can be both primary and secondary to psychiatric, neurologic, autoimmune, infective, metabolic and other causes. The existing hypothesis suggests the prevailing role of vasospastic reaction over possible blood rheology impairment.[1] As per the current line of thinking, it is due to chronic vasospasm of small cutaneous arteries, and arterioles along with compensatory dilatation in the capillary and post capillary venules causes cyanosis and sweating. Acrocyanosis is an uncommon condition. It usually presents with coolness and violaceous dusky discolorations of hands and less frequently the feet. Other peripheral part like ear, nose, lips and nipple can also be affected.[2] The changes may be transient after cold exposure but frequently persist during winter and even in summer. There is no standard and curative medical or surgical treatment of acrocyanosis. In mild cases, it is unnecessary to give any drug treatment. Life style modification, dietary and hygiene counseling, avoidance of cold and reassurance that the bluish skin discoloration does not indicate any serious illness is all that is necessary.


Nutrient intake of physically fit and unfit men and women.
Participation in physical activity and following a diet low in fat, saturated fat, and cholesterol and high in fiber are important in the prevention and treatment of cardiovascular disease and other health problems. Despite the importance of both behaviors, little is known about the interactive role of diet and physical activity. The association between physical activity and diet has been studied, but data on the association between cardiorespiratory fitness (CRF), which is an objective measure of habitual physical activity, and diet are lacking in adults. This report examines nutrient intakes of men and women across low, moderate, and high fitness categories and compares the intakes to national dietary recommendations. It is the first step in examining the relationship between diet, CRF, and morbidity and mortality endpoints in the Aerobics Center Longitudinal Study (ACLS). Between 1987 and 1995, 7959 men and 2453 women participating in the ACLS provided 3-d diet records and completed a preventive medical examination. CRF was measured using a maximal exercise test, anthropometric and other clinical variables were measured following a standardized protocol, and lifestyle factors were assessed with a medical history questionnaire. After adjusting for potential confounders, there was a significantly lower percent of energy from fat and saturated fat across low, moderate, and high CRF categories. With additional adjustment for total energy intake, there was a significantly higher dietary fiber intake and a significantly lower cholesterol intake across CRF categories. The percentage of men and women meeting national dietary recommendations was higher at higher CRF levels. Men and women with higher fitness levels consumed diets that more closely approached national dietary recommendations than their lower fit peers.


Trichuris muris egg-hatching assay for anthelminthic drug discovery and characterization.
Trichuriasis is a neglected tropical disease widely distributed among tropical and sub-tropical areas and associated with poverty and lack of access to safe drinking water, sanitation and hygiene. Existing drugs have limited efficacy and face a constant risk of developing resistance, necessitating the search for alternative treatments. However, drug discovery efforts are sparse and little research has been performed on anthelminthic effects on embryonated eggs, the infectious life stage of Trichuris spp. We examined bacterial species dependent egg hatching of the murine model parasite Trichuris muris and identified Escherichia coli, Pseudomonas aeruginosa and Enterobacter hormaechei effective as hatching inducers, resulting in hatching yields of 50-70%. Streptococcus salivarius, reported to be associated with reduced drug efficacy of ivermectin-albendazole coadministration in Trichuris trichiura infected patients, did not promote egg hatching in vitro. We optimized hatching conditions using E. coli grown in luria broth or brain-heart infusion media to reach consistently high hatching yields to provide a sensitive, robust and simple egg-hatching assay. Oxantel pamoate demonstrated the strongest potency in preventing hatching, with an EC50 value of 2-4 μM after 24 h, while pyrantel pamoate, levamisole and tribendimidine exhibited only moderate to weak inhibitory effects. Conversely, all tested benzimidazoles and macrolide anthelminthics as well as emodepside failed to prevent hatching (EC50 > 100 μM). Our study demonstrates that egg-hatching assays complement larval and adult stage drug sensitivity assays, to expand knowledge about effects of current anthelminthics on Trichuris spp. Further, the developed T. muris egg-hatching assay provides a simple and cheap screening tool that could potentially lead to the discovery of novel anthelminthic compounds.


Splenic injury during colonoscopy: modern treatment approach and splenic salvage.
Splenic injury is a rare complication of colonoscopy, estimated to occur in 0.020 to 0.034% of procedures, with a 30-day mortality of 3.6% (1-3). Of the three major severe adverse events during colonoscopy (perforation, bleeding, and splenic injury), splenic injury has the highest mortality but is rarest (1). The spleen is attached to the colonic splenic flexure by the splenocolic ligament, suggesting that manipulation of the colon during colonoscopy may cause direct tension or impaction on the spleen and splenic hilum as the mechanism of injury (2,3). Patients typically present within 24 hours of colonoscopy with severe abdominal pain and peritonism, and may be haemodynamically unstable (2). The majority of published cases of high-grade splenic injury due to colonoscopy have been managed with splenectomy (2,3), however smaller numbers have been managed with embolization and conservative measures (3). Modern treatment options for splenic injury due to colonoscopy can be classified into con- servative, endovascular, and surgical management (3). Conservative management involves inpatient moni- toring, with analgesia, intravenous fluids, and blood transfusion (2,3). Endovascular treatment is splenic artery embolization, typically with deployment of coils into the splenic artery proximal to the splenic hilum or into a single splenic artery branch in cases with an isolated focal injury (2-4). Surgical management is principally laparotomic splenectomy (2,3). In modern treatment protocols, splenectomy is usually reserved for unstable patients who require emergent laparotomy (4). Given the similarity in mechanism between splenic injuries due to blunt trauma and those due to colonoscopy, it may be helpful to conceptualize splenic injuries due to colonoscopy according to the American Association for the Surgery of Trauma (AAST) grading system (5). After institutional ethical approval, electronic medical records over a 10-year period (2012-2022) were searched to identify all patients treated for splenic injury due to colonoscopy, with the following inclusion criteria: • Splenic laceration diagnosed on computed tomography (CT). Colonoscopy within 72 hours of CT diagnosis. • Absence of blunt external traumatic incident between colonoscopy and diagnosis. Patient demographic information, past surgical history, colonoscopy indication, splenic injury grading, treatment and outcome data were analysed. Two males and 3 females were included, with median age of 63 years (range: 40-72), and four had undergone previous abdominal surgery (Table 1) (Figure 1). AAST injury grades were II to V. One patient with an AAST II injury was treated conservatively without requiring embolization or splenectomy. Three patients with AAST III-V injuries were treated primarily with splenic artery embolization, with one patient undergoing splenectomy 2 weeks later due to increased haematoma on CT. One patient with AAST III injury was treated conservatively but then underwent splenectomy 6 days later due to clinical rebleeding. All patients in the cohort survived, and 3 of 5 achieved splenic salvage. The spleen has important immune and non-immune functions, as the main filter of blood-borne pathogens, antigens, and red blood cells and patients post- splenectomy have increased life-long risk of infection(6). Embolization preserves splenic function via collateral arterial supply and splenectomy may therefore be best reserved for patients who require emergent laparotomy or where conservative and endovascular management have failed. In the present cohort, 3 of 5 patients were able to avoid splenectomy, higher than in previous published reports (47-69% splenectomy rate) (2,3). The higher splenectomy and mortality rates in previous reports may be due to publication bias favouring severe cases. As a rare complication of colonoscopy, splenic injury requires prompt diagnosis and management to minimize mortality. All patients in the present cohort survived, 3 of 5 with splenic salvage. A treatment protocol utilizing conservative management for low-grade injuries and embolization for high-grade injuries may optimise rates of splenic salvage with long-term public health benefits. This paper has not been presented previously at a conference and is not under consideration by any other journal for publication. The authors have no conflicts of interest to declare. This research was not supported by any funding.


CACNA1I gain-of-function mutations differentially affect channel gating and cause neurodevelopmental disorders.
T-type calcium channels (Cav3.1 to Cav3.3) regulate low-threshold calcium spikes, burst firing and rhythmic oscillations of neurons and are involved in sensory processing, sleep, and hormone and neurotransmitter release. Here, we examined four heterozygous missense variants in CACNA1I, encoding the Cav3.3 channel, in patients with variable neurodevelopmental phenotypes. The p.(Ile860Met) variant, affecting a residue in the putative channel gate at the cytoplasmic end of the IIS6 segment, was identified in three family members with variable cognitive impairment. The de novo p.(Ile860Asn) variant, changing the same amino acid residue, was detected in a patient with severe developmental delay and seizures. In two additional individuals with global developmental delay, hypotonia, and epilepsy, the variants p.(Ile1306Thr) and p.(Met1425Ile), substituting residues at the cytoplasmic ends of IIIS5 and IIIS6, respectively, were found. Because structure modelling indicated that the amino acid substitutions differentially affect the mobility of the channel gate, we analysed possible effects on Cav3.3 channel function using patch-clamp analysis in HEK293T cells. The mutations resulted in slowed kinetics of current activation, inactivation, and deactivation, and in hyperpolarizing shifts of the voltage-dependence of activation and inactivation, with Cav3.3-I860N showing the strongest and Cav3.3-I860M the weakest effect. Structure modelling suggests that by introducing stabilizing hydrogen bonds the mutations slow the kinetics of the channel gate and cause the gain-of-function effect in Cav3.3 channels. The gating defects left-shifted and increased the window currents, resulting in increased calcium influx during repetitive action potentials and even at resting membrane potentials. Thus, calcium toxicity in neurons expressing the Cav3.3 variants is one likely cause of the neurodevelopmental phenotype. Computer modelling of thalamic reticular nuclei neurons indicated that the altered gating properties of the Cav3.3 disease variants lower the threshold and increase the duration and frequency of action potential firing. Expressing the Cav3.3-I860N/M mutants in mouse chromaffin cells shifted the mode of firing from low-threshold spikes and rebound burst firing with wild-type Cav3.3 to slow oscillations with Cav3.3-I860N and an intermediate firing mode with Cav3.3-I860M, respectively. Such neuronal hyper-excitability could explain seizures in the patient with the p.(Ile860Asn) mutation. Thus, our study implicates CACNA1I gain-of-function mutations in neurodevelopmental disorders, with a phenotypic spectrum ranging from borderline intellectual functioning to a severe neurodevelopmental disorder with epilepsy.


Characterizing the Structures, Spectra, and Energy Landscapes Involved in the Excited-State Proton Transfer Process of Red Fluorescent Protein LSSmKate1.
By applying molecular dynamics (MD) simulations and quantum chemical calculations, we have characterized the states and processes involved in the excited-state proton transfer (ESPT) of LSSmKate1. MD simulations identify two stable structures in the electronic ground state of LSSmKate1, one with a protonated chromophore and the other with a deprotonated chromophore, thus leading to two separate low-energy absorption maxima with a large energy spacing, as observed in the calculated and experimentally measured absorption spectra. Proton transfer is induced by electronic excitation. When LSSmKate1 is excited, the electrons in the chromophore are transferred from the phenol ring to the N-acylimine moiety; the acidity of a phenolic hydroxyl group is thus enhanced. The calculated potential energy curves (PECs) exhibit energetic feasibility in the generation of the fluorescent species in LSSmKate1, and the exact agreement between the calculated and experimentally measured values of the large Stokes shift further provides solid theoretical evidence for the ESPT process taking place in photoexcited LSSmKate1. The molecular environments play a significant role in the geometries and absorption/emission energies of the chromophores. Overall, TD-ωB97X-D/molecular mechanics (MM) provides a better description of the optical properties of LSSmKate1 than TD-B3LYP/MM, although it always overestimates the excitation energies.


Intrarectal immunization with rotavirus 2/6 virus-like particles induces an antirotavirus immune response localized in the intestinal mucosa and protects against rotavirus infection in mice.
Rotavirus (RV) is the main etiological agent of severe gastroenteritis in infants, and vaccination seems the most effective way to control the disease. Recombinant rotavirus-like particles composed of the viral protein 6 (VP6) and VP2 (2/6-VLPs) have been reported to induce protective immunity in mice when administered by the intranasal (i.n.) route. In this study, we show that administration of 2/6-VLPs by the intrarectal (i.r.) route together with either cholera toxin (CT) or a CpG-containing oligodeoxynucleotide as the adjuvant protects adult mice against RV infection. Moreover, when CT is used, RV shedding in animals immunized by the i.r. route is even reduced in comparison with that in animals immunized by the i.n. route. Humoral and cellular immune responses induced by these immunization protocols were analyzed. We found that although i.r. immunization with 2/6-VLPs induces lower RV-specific immunoglobulin G (IgG) and IgA levels in serum, intestinal anti-RV IgA production is higher in mice immunized by the i.r. route. Cellular immune response has been evaluated by measuring cytokine production by spleen and Peyer's patch cells (PPs) after ex vivo restimulation with RV. Mice immunized by the i.n. and i.r. routes display higher gamma interferon production in spleen and PPs, respectively. In conclusion, we demonstrate that i.r. immunization with 2/6-VLPs protects against RV infection in mice and is more efficient than i.n. immunization in inducing an anti-RV immune response in intestinal mucosa.


Can zinc supplementation ameliorate cadmium-induced alterations in the bioelement content in rabbits?
The study was designed to investigate the influence of zinc (Zn) supplementation on cadmium-induced alterations in zinc, copper (Cu), and magnesium (Mg) status in rabbits. For this purpose, the concentrations of cadmium (Cd), Zn, Cu, and Mg were estimated in the blood, liver, kidney, and bone. The rabbits were divided in a control group, a Cd group-animals intoxicated orally with Cd (10 mg kg-1 bw, as aqueous solution of Cd-chloride), and a Cd+Zn group-animals intoxicated with the same dose of Cd and co-treated with Zn (20 mg kg-1 bw, as aqueous solution of Zn-sulphate). Solutions were administered orally, every day for 28 days. Sample mineralisation was performed with concentrated nitric acid (HNO3) and perchloric acid (HClO4) (4:1) and metal concentrations were determined by atomic absorption spectrophotometry (AAS). Zinc supplementation improved some of Cd-induced disturbances in bioelement levels in the investigated tissues. Beneficial effects of Zn on Zn and Cu levels were observed in blood, as well as on the Cu kidney level. The calculated values for Cu/Zn, Mg/Zn, and Mg/Cu ratios in blood suggest that Zn co-treatment reduces Cd-induced changes in bioelement ratios in blood.


Effect of crystallization rate and colloidal stability on structural rearrangements during growth of colloidal monolayers.
The structural rearrangements during growth of colloidal crystals were investigated using a combination of light microscopy and image analysis based on a Delaunay triangulation procedure. We followed the creation and disappearance of square lattice domains during the convection-promoted formation of colloidal monolayers by drying. We found that the concentration of square lattice domains increased with the crystal growth rate and that there is a direct relation between the concentration of square lattice domains formed at the crystal-suspension interface and the lower concentration of these domains in the colloidal monolayer; hence, the degree of rearrangement from square lattice domains to a close-packed triangular structure is not significantly affected by the crystal growth rate for colloidally stable suspensions. The colloidal stability, manipulated by the addition of salt, has a profound influence on the structural features of the growing monolayers. Particles that adhere strongly to each other, and to the substrate, tend to resist rearrangement; hence, the defect density is high in the colloidal monolayers and the structural reorganization of the square lattice domains to the more stable close-packed triangular structure occurred gradually over large distances from the crystal-suspension interface.


Anaerobic co-digestion of the organic fraction of municipal solid waste with FOG waste from a sewage treatment plant: recovering a wasted methane potential and enhancing the biogas yield.
Anaerobic digestion is applied widely to treat the source collected organic fraction of municipal solid wastes (SC-OFMSW). Lipid-rich wastes are a valuable substrate for anaerobic digestion due to their high theoretical methane potential. Nevertheless, although fat, oil and grease waste from sewage treatment plants (STP-FOGW) are commonly disposed of in landfill, European legislation is aimed at encouraging more effective forms of treatment. Co-digestion of the above wastes may enhance valorisation of STP-FOGW and lead to a higher biogas yield throughout the anaerobic digestion process. In the present study, STP-FOGW was evaluated as a co-substrate in wet anaerobic digestion of SC-OFMSW under mesophilic conditions (37 degrees C). Batch experiments carried out at different co-digestion ratios showed an improvement in methane production related to STP-FOGW addition. A 1:7 (VS/VS) STP-FOGW:SC-OFMSW feed ratio was selected for use in performing further lab-scale studies in a 5L continuous reactor. Biogas yield increased from 0.38+/-0.02 L g VS(feed)(-1) to 0.55+/-0.05 L g VS(feed)(-1) as a result of adding STP-FOGW to reactor feed. Both VS reduction values and biogas methane content were maintained and inhibition produced by long chain fatty acid (LCFA) accumulation was not observed. Recovery of a currently wasted methane potential from STP-FOGW was achieved in a co-digestion process with SC-OFMSW.


Amygdala but not hippocampal lesions impair olfactory memory for mate in prairie voles (Microtus ochrogaster).
Exposure to an unfamiliar male conspecific results in pregnancy interruption (i.e., the Bruce effect) in rodents. Unlike most laboratory rodents, female prairie voles (Microtus ochrogaster) are induced into estrus by chemosensory stimuli contained in the urine of male conspecifics while grooming the anogenital (A-G) region of unfamiliar males. Female prairie voles maintain a brief "memory" for the stud male for 8-10 days after mating. Subsequent exposure to the same mate within this 8- to 10-day window does not elicit A-G investigation by the female and pregnancy block does not result. However, exposure to the original male after 10 days evokes A-G investigation and pregnancy block. To determine the neuroanatomic area(s) involved in olfactory memory for mate, female voles received bilateral electrolytic lesions of either the amygdala or hippocampus. Females were subsequently exposed to males for 48 h, separated for 3 days, then reintroduced to their original mate for 24 h. Although pregnancy rate did not differ among the experimental groups, a greater proportion of amygdala-lesioned females displayed pregnancy block when reexposed to their previous mates compared with hippocampal- or sham-lesioned voles. Amygdala-lesioned voles also displayed a greater number of A-G investigations compared with the other groups. Performance on olfactory tests was not impaired. Taken together, these results suggest that the amygdala plays an important role in olfactory memory for mate in prairie voles.


Clinical and prognostic significance of eosinophilia and inv(16)/t(16;16) in pediatric acute myelomonocytic leukemia (AML-M4).
The cytogenetic aberrations inv(16)(p13.1q22)/t(16;16)(p13.1;q22), frequently detected in acute myelomonocytic leukemia with eosinophilia (FAB type M4eo), are generally considered a prognostically favorable subgroup. M4eo comprises a distinct morphology compared to M4 without eosinophilia (M4eo-) and therefore may be indicative for a different pathogenesis. Morphology and cytogenetic/molecular analyses of a Dutch cohort of pediatric acute myelomonocytic leukemia (AML-M4) patients were performed and studied in order to analyze the association between the presence of eosinophilia morphology (M4eo+), inv(16)/t(16;16) (inv(16)+), clinical features, and outcome. Of the 119 included patients with available combined morphological and cytogenetic results, 60% had M4eo- without inv(16) (inv(16)-), 10% had M4eo-/inv(16)+, 13% had M4eo+/inv(16)-, and 17% had M4eo+/inv(16)+. M4eo+ was significantly associated with the presence of inv(16)/t(16;16) (P < 0.001). Patients with M4eo+ had no significantly superior outcome compared with patients with M4eo-, whereas patients with inv(16)+ had significantly superior probabilities of event-free survival and probabilities of overall survival compared with patients without inv(16)-. Patients with M4eo+/inv(16)+ had no significantly better outcome than those with M4eo-/inv(16)+. The prognostically favorable impact of distinct morphology with eosinophilia probably relies on its association with inv(16)/t(16;16). Simultaneous presence of both eosinophilia and inv(16) was not associated with superior outcome in our study. These results may be relevant for risk-group classification and risk-group adapted treatment and underline the importance of accurate cytogenetic analysis.


Suspension syndrome: a scoping review and recommendations from the International Commission for Mountain Emergency Medicine (ICAR MEDCOM).
Suspension syndrome describes a multifactorial cardio-circulatory collapse during passive hanging on a rope or in a harness system in a vertical or near-vertical position. The pathophysiology is still debated controversially. The International Commission for Mountain Emergency Medicine (ICAR MedCom) performed a scoping review to identify all articles with original epidemiological and medical data to understand the pathophysiology of suspension syndrome and develop updated recommendations for the definition, prevention, and management of suspension syndrome. A literature search was performed in PubMed, Embase, Web of Science and the Cochrane library. The bibliographies of the eligible articles for this review were additionally screened. The online literature search yielded 210 articles, scanning of the references yielded another 30 articles. Finally, 23 articles were included into this work. Suspension Syndrome is a rare entity. A neurocardiogenic reflex may lead to bradycardia, arterial hypotension, loss of consciousness and cardiac arrest. Concomitant causes, such as pain from being suspended, traumatic injuries and accidental hypothermia may contribute to the development of the Suspension Syndrome. Preventive factors include using a well-fitting sit harness, which does not cause discomfort while being suspended, and activating the muscle pump of the legs. Expediting help to extricate the suspended person is key. In a peri-arrest situation, the person should be positioned supine and standard advanced life support should be initiated immediately. Reversible causes of cardiac arrest caused or aggravated by suspension syndrome, e.g., hyperkalaemia, pulmonary embolism, hypoxia, and hypothermia, should be considered. In the hospital, blood and further exams should assess organ injuries caused by suspension syndrome.


The antiproliferative effect of trans-retinoic acid is associated with selective induction of interleukin-1 beta, a cytokine that directly inhibits growth of lung cancer cells.
Retinoids show promise for prevention and treatment of cancers. In most cases, the mechanisms of their anticancer effects are poorly defined, but interactions with cytokine genes have been postulated in several systems. The effects of trans-retinoic acid (RA) on proliferation and cytokine gene expression in the human lung carcinoma Lu-CSF-1 are reported. RA exhibited cell-cycle independent inhibition of Lu-CSF-1 growth while stimulating endogenous interleukin-1 beta and suppressing granulocyte-macrophage colony-stimulating factor and IL-6 mRNAs. Reduction in granulocyte-macrophage colony-stimulating factor and IL-6 message was associated with reduced RNA stability and was translated into reduced protein levels. IL-1 beta mRNA stability was not decreased, and elevation in IL-1 beta protein levels was of a comparable magnitude to the increased amounts of its RNA. Growth inhibition similar to that following RA treatment could be reproduced by exposing cells to exogeneous IL-1 beta alone. These data suggest that changes in autologous cytokine gene expression might contribute to growth inhibition of lung cancer cells by RA.


Arbuscular mycorrhizal fungi induce the non-mevalonate methylerythritol phosphate pathway of isoprenoid biosynthesis correlated with accumulation of the 'yellow pigment' and other apocarotenoids.
Plants and certain bacteria use a non-mevalonate alternative route for the biosynthesis of many isoprenoids, including carotenoids. This route has been discovered only recently and has been designated the deoxyxylulose phosphate pathway or methylerythritol phosphate (MEP) pathway. We report here that colonisation of roots from wheat, maize, rice and barley by the arbuscular mycorrhizal fungal symbiont Glomus intraradices involves strong induction of transcript levels of two of the pivotal enzymes of the MEP pathway, 1-deoxy-D-xylulose 5-phosphate synthase (DXS) and 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR). This induction is temporarily and spatially correlated with specific and concomitant accumulation of two classes of apocarotenoids, namely glycosylated C13 cyclohexenone derivatives and mycorradicin (C14) conjugates, the latter being a major component of the long-known 'yellow pigment'. A total of six cyclohexenone derivatives were characterised from mycorrhizal wheat and maize roots. Furthermore, the acyclic structure of mycorradicin described previously only from maize has been identified from mycorrhizal wheat roots after alkaline treatment of an 'apocarotenoid complex' of yellow root constituents. We propose a hypothetical scheme for biogenesis of both types of apocarotenoids from a common oxocarotenoid (xanthophyll) precursor. This is the first report demonstrating (i) that the plastidic MEP pathway is active in plant roots and (ii) that it can be induced by a fungus.


Cobalt ion-coordinated self-assembly synthesis of nitrogen-doped ordered mesoporous carbon nanosheets for efficiently catalyzing oxygen reduction.
The design and synthesis of a promising porous carbon-based electrocatalyst with an ordered and uninterrupted porous structure for oxygen reduction reaction (ORR) is still a significant challenge. Herein, an efficient catalyst based on cobalt-embedded nitrogen-doped ordered mesoporous carbon nanosheets (Co/N-OMCNS) is successfully prepared through a two-step procedure (cobalt ion-coordinated self-assembly and carbonization process) using 3-aminophenol as a nitrogen source, cobalt acetate as a cobalt source and Pluronic F127 as a mesoporous template. This work indicates that the formation of a two dimensional nanosheet structure is directly related to the extent of the cobalt ion coordination interaction. Moreover, the critical roles of pyrolysis temperature in nitrogen doping and ORR catalytic activity are also investigated. Benefiting from the high surface area and graphitic degree, high contents of graphitic N and pyridinic N, ordered interconnected mesoporous carbon framework, as well as synergetic interaction between the cobalt nanoparticles and protective nitrogen doped graphitic carbon layer, the resultant optimal catalyst Co/N-OMCNS-800 (pyrolyzed at 800 °C) exhibits comparable ORR catalytic activity to Pt/C, superior tolerance to methanol crossover and stability.


Socioeconomic Burden of Bloodstream Infections Caused by Carbapenem-Resistant Enterobacteriaceae.
Although infection with carbapenem-resistant Enterobacteriaceae (CRE) has become an urgent public health threat worldwide, the socioeconomic burden of CRE bloodstream infection (BSI) remains to be clarified. This retrospective study included all patients infected with Escherichia coli or Klebsiella pneumoniae who were hospitalized for BSI from 2013 to 2015. Socioeconomic burden, including direct and indirect economic burden, was compared in patients infected with carbapenem-sensitive Enterobacteriaceae (CSE) and CRE following 1:1 propensity score matching (PSM) to control for confounding variables. Data from 879 patients with Enterobacteriaceae BSI were evaluated, including 152 (17.3%) patients infected with CRE and 727 (82.7%) infected with CSE. PSM yielded 112 pairs of 224 patients. Median hospital length of stay did not differ significantly in the CRE and CSE groups (35 vs 29 days, P = 0.089), but in-hospital 28-day mortality rate was significantly higher in patients infected with CRE than with CSE (45.5% vs 32.1%, P = 0.040). Median direct economic burden was significantly greater in patients with CRE-BSI than with CSE-BSI during hospitalization ($24,940.1 vs 16,864.0, P = 0.017) but not during the period after infection ($10,403.4 vs 8498.0, P = 0.178). Drug expenditure accounted for the largest proportion of costs in both groups. The median disability-adjusted life year (DALY) was higher in CRE-BSI than in CSE-BSI patients, but the difference was not statistically significant (7.9 vs 6.7 years, P = 0.190). Median indirect economic burden did not differ significantly in these two groups ($3848.5 vs 1139.9, P = 0.304), although indirect economic burden increased significantly from 2013 to 2015 in patients with CRE-BSI. Carbapenem resistance had a major impact on the clinical and socioeconomic burden of patients with Enterobacteriaceae BSI. The higher mortality rate in patients with CRE-BSI was associated with increased direct healthcare burden and indirect socioeconomic loss.


[Genetic constitution analysis of idiopathic sudden hearing loss].
The purpose of this research is to understand the etiology of sudden hearing loss due to genetic factors in Turkish people. Determination of these genetic factors and better understanding of molecular pathogenesis may guide more realistic planning and treatment recommendations. Forty patients (Group 1; 19 males, 21 females; mean age 37.9+/-15.6 years; range 9 to 76 years) who presented with sudden hearing loss to the Ear, Nose and Throat Clinic of Medical Faculty Hospital of Cumhuriyet University between January 2008 and June 2009, and were diagnosed with sudden hearing loss through history, physical examination and review of audiometric findings, and 20 healthy volunteers (Group 2; 14 males, 6 females; mean age 31.7+/-4.4 years; range 24 to 43 years) for the control group were included in this study. All Patients were evaluated by the genetic clinic for the GJB2, GJB3, GJB6 and WFS1 gene using multiplex ligation-dependent probe amplification (MLPA) method mutation analysis. No difference was found in the peripheral blood sample analyses of the two groups at WFS1 exon 8 and connexin 26, 30 and 31 gene zones using the MLPA method with respect to heterozygous mutation (p=0.291, p>0.05). In four patients in group 1 heterozygous mutation was detected at the target gene zone. Heterozygous mutation was in the WFS1 exon 8 zone in two patients; and in the WFS1 exon 1 zone in other two patients. Sudden hearing loss studies in the future should include connexin 26, connexin 30 and other gene mutations that may affect the function of the gap-junction located in the region of the cochlea stria vascularis (stV), basal membrane (BM), spiral limbus (Li) and spiral ligament (SL). These studies should be performed on larger series, and should include family members of patients with sudden hearing loss.


Effect of disease duration and prior disease-modifying antirheumatic drug use on treatment outcomes in patients with rheumatoid arthritis.
To determine if disease duration and number of prior disease-modifying antirheumatic drugs (DMARDs) affect response to therapy in patients with established rheumatoid arthritis (RA). Associations between disease duration or number of prior DMARDs and response to therapy were assessed using data from two randomised controlled trials in patients with established RA (mean duration, 11 years) receiving adalimumab+methotrexate. Response to therapy was assessed at week 24 using disease activity outcomes, including 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)), Simplified Disease Activity Index (SDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI), and proportions of patients with 20%/50%/70% improvement in American College of Rheumatology (ACR) responses. In the larger study (N=207), a greater number of prior DMARDs (>2 vs 0-1) was associated with smaller improvements in DAS28(CRP) (-1.8 vs -2.2), SDAI (-22.1 vs -26.9) and HAQ-DI (-0.43 vs -0.64) from baseline to week 24. RA duration of >10 years versus <1 year was associated with higher HAQ-DI scores (1.1 vs 0.7) at week 24, but results on DAS28(CRP) and SDAI were mixed. A greater number of prior DMARDs and longer RA duration were associated with lower ACR response rates at week 24. Data from the second trial (N=67) generally confirmed these findings. Number of prior DMARDs and disease duration affect responses to therapy in patients with established RA. Furthermore, number of prior DMARDs, regardless of disease duration, has a limiting effect on the potential response to adalimumab therapy.


BAG3 increases the invasiveness of uterine corpus carcinoma cells by suppressing miR-29b and enhancing MMP2 expression.
Approximately 30% of uterine corpus carcinomas are diagnosed at an advanced stage and have a poor prognosis. Our previous study indicated that BCL2-associated athanogene 3 (BAG3) enhances matrix metalloproteinase-2 (MMP2) expression and binds to MMP2 to positively regulate the process of cell invasion in ovarian cancer cells. Recently, altered miRNA expression patterns were observed in several groups of patients with endometrial cancers. One of the altered miRNAs, miR-29b, reportedly reduces tumor invasiveness by suppressing MMP2 expression. Our aim in the present study was to examine the relationships among BAG3, miR-29b and MMP2 in endometrioid adenocarcinoma cells. We found that BAG3 suppresses miR-29b expression and enhances MMP2 expression, which in turn increases cell motility and invasiveness. Moreover, restoration of miR-29b through BAG3 knockdown reduced MMP2 expression, as well as cell motility and invasiveness. Collectively, our findings indicate that BAG3 enhances MMP2 expression by suppressing miR-29b, thereby increasing the metastatic potential of endometrioid adenocarcinomas.


Predictors of catheter-related gram-negative bacilli bacteraemia among cancer patients.
Gram-negative bacillary bacteraemia (GNB) is associated with high morbidity and mortality among cancer patients. We conducted this study to determine the risk factors that may predict the catheter as the source of GNB in cancer patients. From July 2005 to December 2006 all 266 cancer patients with GNB and central venous catheters (CVCs) at The University of Texas M. D. Anderson Cancer Centre in Houston, were classified as catheter-related bloodstream infection (CRBSI) according to Infectious Diseases Society of America criteria. We compared clinical and microbiological features of CRBSIs and non-CRBSIs. We identified 78 CRBSIs and 126 non-CRBSIs. On univariate analysis, polymicrobial bacteraemia, Stenotrophomonas maltophilia bacteraemia, and more than 1000 CFUs in CVC blood cultures, were more common among CRBSI cases. Escherichia coli bacteraemia, haematologic cancer, neutropenia and prior antibiotic use were more common among non-CRBSI cases. On multivariate analysis, S. maltophilia bacteraemia (odds ratio (OR), 5.78; 95% confidence interval (CI), 1.47-22.78; p 0.045), polymicrobial bacteraemia (OR, 4.04; 95% CI, 1.56-10.44; p 0.042), and more than 1000 CFUs from CVC blood cultures (OR, 4.39; 95% CI, 2.02-9.27; p <0.01), were associated with CRBSI. Neutropenia was associated with non-CRBSI (OR, 0.26; 95% CI, 0.13-0.53; p <0.01). Several factors such as S. maltophilia bacteraemia, polymicrobial bacteraemia and more than 1000 CFUs from a blood culture drawn through the CVC may assist the clinicians in assessing whether an indwelling catheter is the source of a GNB and hence CVC removal may be considered.


Azide Ionic Liquids for Safe, Green, and Highly-Efficient Azidation Reactions to Produce Azide Polymers.
Azide compounds are widely used and especially, polymers bearing pendant azide groups are highly desired in numerous fields. However, harsh reaction conditions are always mandatory to achieve full azidation, causing severe side reactions and degradation of the polymers. Herein, we report the design and preparation of two azide ionic liquids (AILs) with azide anion and triethylene glycol (E3 )-containing cation, [P444E3 ][N3 ] and [MIME3 ][N3 ]. Compared with the traditional sodium azide (NaN3 ) approach, both AILs showed much higher reaction rates and functional-group tolerance. More importantly, they could act as both reagents and solvents for the quantitative azidation of various polymeric precursors under mild conditions. Theoretical simulations suggested that the outstanding performance of AILs originated from the existence of ion pairs during the reaction, and the E3 moieties played a crucial role. Lastly, after the reaction, the AILs could be easily regenerated, presenting a safer, greener, and highly efficient synthesis route for azide polymers.


A novel liver stiffness measurement-based prediction model for cirrhosis in hepatitis B patients.
While liver stiffness measurement (LSM) predicts histological cirrhosis accurately, complementary methods are needed for better performance. Furthermore, alanine aminotransferase (ALT) influences LSM, making it necessary to modify its use in patients with high ALT levels. We developed a new LSM-based prediction model for cirrhosis and estimated the thresholds for different ALT levels. From 2008 to 2009, we prospectively enrolled 330 consecutive patients who were diagnosed with chronic hepatitis B (CHB) and underwent a liver biopsy and LSM on the same day. For detection of cirrhosis, we performed univariate and multivariate analyses, using the chi(2)-test/t-test and logistic regression respectively. Thereafter, a prediction model was derived from multivariate predictors. In multivariate analyses of patients with and without cirrhosis, we found significant differences in the LSM, spleen diameter and platelet count. Then, we developed an LSM-spleen diameter to platelet ratio index (LSPI): (LSM x spleen diameter/platelet count) x 100. The area under the receiver operating curve was 0.956, significantly higher than LSM alone (0.919, P=0.032). We suggested different thresholds in patients with ALT< or = upper limit of normal (ULN) (normal-ALT group, 164 patients) and ALT>ULN (high-ALT group, 166 patients). In the normal-ALT group, LSPI thresholds of 38 and 62 provided 95.7% negative predictive value (NPV) and a 95.5% PPV (positive predictive value), while in the high-ALT group, thresholds of 42 and 94 yielded 95.1% NPV and 96.4% PPV respectively. Therefore, liver biopsy could be avoided in 76.7% of the subjects. LSPI is a useful, non-invasive tool that can replace liver biopsy in the assessment of liver fibrosis in the majority of CHB patients.


Pancreaticobiliary maljunction: retrospective and nationwide survey in Japan.
Pancreaticobiliary maljunction (PBM) is a congenital anomaly defined as a union of the pancreatic and biliary duct that is located outside the duodenal wall. The Japanese Study Group on Pancreaticobiliary Maljunction and the Committee for Registration enrolled and analyzed 1627 patients with PBM who had been diagnosed and treated from January 1, 1990 to December 31, 1999 at 141 hospitals throughout the country. There were 1239 patients with dilatation of the bile duct (group A) and 388 patients without dilatation (group B). The average age was 24 years in group A and 47 years in group B; the age was significantly higher in group B. The type of confluence between the terminal choledochus and the pancreatic duct has been classified into three types (type a, right-angle type; type b, acute-angle type; and type c, complex type). In group A, type a accounted for 57.9% and was significantly more frequent compared with the other types (type b, 32.4%; type c, 5.6%). In group B, type b accounted for 60.8%, being significantly more frequent compared with the other types (type a, 29.4%; type c, 7.2%). Subjective symptoms, preoperative complications (e.g., liver dysfunction and acute pancreatitis), pancreatic stone, and pancreatic duct morphological abnormality were significantly more frequent in group A. However, the amylase levels in the bile and gallbladder were significantly higher in group B, and the presence of gallstone and morphological abnormality of the gallbladder was significantly more frequent in group B. The occurrence rate of cancer in the biliary tract was 10.6% in group A and 37.9% in group B, being significantly higher in group B. In group A, cancer of the extrahepatic bile duct was seen in 33.6% and cancer of the gallbladder was seen in 64.9%, but gallbladder cancer was present significantly more frequently in the patients with diffuse or cylindrical dilatation, and bile duct cancer was present significantly more frequently in the patients with cystic dilatation. In group B, 93.2% of the patients had gallbladder cancer, and bile duct cancer was found in as few as 6.8%. Against this background Japanese surgeons regard cholecystectomy, resection of the extrahepatic bile duct, and hepaticojejunostomy as standard operations for PBM with dilatation of the bile duct. However, opinion on whether or not the bile duct should be removed in the treatment of PBM without dilatation of the bile duct has been divided among Japanese surgeons. A randomized controlled trial is necessary.


The Effect of Splenic Irradiation on Mean Fluorescence Intensity Values of HLA Antibody in Presensitized Patients Waiting for Kidney Transplantation.
To explore the desensitization treatment of patients waiting for kidney transplantation, this article comparative analysis of the effect of splenic irradiation on mean fluorescence intensity (MFI) values of HLA antibodies of 4 presensitized patients. After splenic irradiation, the mean MFI values of HLA-I antibody in 4 patients all decreased (P ≤ .001, P ≤ .001, P ≤ .001, P ≤ .001), and 3 patients had a decrease in intensity level (P ≤ .001, P = .001, P ≤ .001); as for HLA-II antibody, the mean MFI values in 3 patients also decreased (P ≤ .001, P = .025, P = .016), 1 patient had a decrease in intensity level (P ≤ .001) and the other 2 cases had no significant changes (P = 1.000, P = .564). On the other hand, splenic irradiation reduces MFI values in different levels of HLA antibody. So, splenic irradiation can reduce the MFI values of HLA antibodies.


Prevalence of mild cognitive impairment in community-dwelling Chinese populations aged over 55 years: a meta-analysis and systematic review.
Mild cognitive impairment (MCI) is an intermediate phase between normal cognitive ageing and overt dementia, with amnesic MCI (aMCI) being the dominant subtype. This study aims to synthesise the prevalence results of MCI and aMCI in community-dwelling populations in China through a meta-analysis and systematic review. The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol. English and Chinese studies published before 1 March 2020 were searched from ten electronic bibliographic databases. Two reviewers screened for relevance of the studies against the pre-defined inclusion and exclusion criteria and assessed the quality of the included studies using the Risk of Bias Tool independently. A random-effect model was adopted to estimate the prevalence of MCI and aMCI, followed by sub-group analyses and meta-regression. Sensitivity and publication bias tests were performed to verify the robustness of the meta-analyses. A total of 41 studies with 112,632 participants were included in the meta-analyses. The Chinese community-dwelling populations over 55 years old had a pooled prevalence of 12.2% [95% confidence interval (CI): 10.6, 14.2%] for MCI and 10.9% [95% CI, 7.7, 15.4%] for aMCI, respectively. The prevalence of MCI increased with age. The American Psychiatric Association's Diagnostic tool (DSM-IV) generated the highest MCI prevalence (13.5%), followed by the Petersen criteria (12.9%), and the National Institute on Aging Alzheimer's Association (NIA-AA) criteria (10.3%). Women, rural residents, and those who lived alone and had low levels of education had higher MCI prevalence than others. Higher MCI prevalence was identified in community-dwelling older adult populations in China compared with some other countries, possibly due to more broadened criteria being adopted for confirming the diagnosis. The study shows that aMCI accounts for 66.5% of MCI, which is consistent with findings of studies undertaken elsewhere. PROSPERO CRD42019134686.


An imbalanced ratio between PC(16:0/16:0) and LPC(16:0) revealed by lipidomics supports the role of the Lands cycle in ischemic brain injury.
Promoting brain recovery after stroke is challenging as a plethora of inhibitory molecules are produced in the brain preventing it from full healing. Moreover, the full scope of inhibitory molecules produced is not well understood. Here, using a high-sensitivity UPLC-MS-based shotgun lipidomics strategy, we semiquantitively measured the differential lipid contents in the mouse cerebral cortex recovering from a transient middle cerebral artery occlusion (MCAO). The lipidomic data were interrogated using the soft independent modeling of class analogy (SIMCA) method involving principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Statistics of the 578 confirmed lipids revealed 84 species were differentially changed during MCAO/reperfusion. The most dynamic changes in lipids occurred between 1 and 7 days post-MCAO, whereas concentrations had subsided to the Sham group level at 14 and 28 days post-MCAO. Quantitative analyses revealed a strong monotonic relationship between the reduction in phosphatidylcholine (PC)(16:0/16:0) and the increase in lysophosphatidylcholine (LPC)(16:0) levels (Spearman's Rs = -0.86) during the 1 to 7 days reperfusion period. Inhibition of cPLA2 prevented changes in the ratio between PC(16:0/16:0) and LPC(16:0), indicating altered Land's cycle of PC. A series of in vitro studies showed that LPC(16:0), but not PC(16:0/16:0), was detrimental to the integrity of neuronal growth cones and neuronal viability through evoking intracellular calcium influx. In contrast, PC(16:0/16:0) significantly suppressed microglial secretion of IL-1β and TNF-α, limiting neuroinflammation pathways. Together, these data support the role of the imbalanced ratio between PC(16:0/16:0) and LPC(16:0), maintained by Lands' cycle, in neuronal damage and microglia-mediated inflammatory response during ischemic recovery.


Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-to-plasma-membrane recycling.
Retromer is a protein assembly that orchestrates the sorting of transmembrane cargo proteins into endosome-to-Golgi and endosome-to-plasma-membrane transport pathways. Here, we have employed quantitative proteomics to define the interactome of human VPS35, the core retromer component. This has identified a number of new interacting proteins, including ankyrin-repeat domain 50 (ANKRD50), seriologically defined colon cancer antigen 3 (SDCCAG3) and VPS9-ankyrin-repeat protein (VARP, also known as ANKRD27). Depletion of these proteins resulted in trafficking defects of retromer-dependent cargo, but differential and cargo-specific effects suggested a surprising degree of functional heterogeneity in retromer-mediated endosome-to-plasma-membrane sorting. Extending this, suppression of the retromer-associated WASH complex did not uniformly affect retromer cargo, thereby confirming cargo-specific functions for retromer-interacting proteins. Further analysis of the retromer-VARP interaction identified a role for retromer in endosome-to-melanosome transport. Suppression of VPS35 led to mistrafficking of the melanogenic enzymes, tyrosinase and tryrosine-related protein 1 (Tyrp1), establishing that retromer acts in concert with VARP in this trafficking pathway. Overall, these data reveal hidden complexities in retromer-mediated sorting and open up new directions in our molecular understanding of this essential sorting complex.


One-trocar-assisted pyeloplasty: An attractive alternative to open pyeloplasty.
To survey the effects of one-trocar-assisted pyeloplasty (OTAP) in the treatment of ureteropelvic junction obstruction (UPJO) in kids. Forty-four children (±3.5 years) were submitted to OTAP procedure. A flank incision under the XII rib was made, the Gerota's fascia was achieved and a balloon Hasson trocar with an operative telescope inserted for retroperitoneal access. The renal pelvis and ureter were isolated and exteriorised. Forty-two patients underwent Anderson-Hynes dismembered and one Fenger pyeloplasty . One patient was converted to an open procedure. Two patients presented an aberrant crossing vessel. In all patients, a double J stent was positioned. The operative time and length of stay (LOS) were evaluated. Renal scan and ultrasound (US) were utilised to evaluate the results from 6 to 12 months. OTAP was successful in all but 1 patient. Mean operative time and LOS were 128 min and 3,5 days. We had four operative complications (9.09%). The US and a nuclear scan confirmed the resolution of the UPJO in all patients except one with the Fenger pyeloplasty who had an open Anderson-Hynes. The combination of retroperitoneoscopic and open procedures for dismembered pyeloplasty offers a simple, time-saving method in a minimally invasive fashion with low morbidity for patients with UPJO.


Outcomes in patients visiting hospital emergency departments in the United States because of periodontal conditions.
The chances of presenting to hospital emergency departments (EDs) are significantly higher in individuals who ignore regular dental care and in those with medical conditions. Little is known about nationwide estimates of hospital-based ED visits caused by periodontal conditions in the United States. The objective of this study is to determine the incidence of ED visits caused by periodontal conditions that occurred in a 2006 nationwide sample and to identify the risk factors for hospitalization during the ED visits. The Nationwide Emergency Department Sample (NEDS) for 2006 was used for this study. Patients who visited the ED with a primary diagnosis of acute gingivitis, chronic gingivitis, gingival recession, aggressive or acute periodontitis, chronic periodontitis, periodontosis, accretions, other specified periodontal disease, or unspecified gingival and periodontal disease were selected for this study. Estimates were projected to the national levels using the discharge weights. The association between patient characteristics and the odds of being hospitalized was examined using a multivariable logistic regression analysis. A total of 85,039 visits to hospital-based EDs with a mean charge per visit of $456.31 and total charges close to $33.3 million were primarily attributed to gingival and periodontal conditions in the United States. Close to 36% and 33% of all visits occurred among the lowest income group and uninsured population, respectively. The total ED charges for those covered by Medicare, Medicaid, private insurance, and other insurance plans were close to $4.95 million, $9.14 million, $8.01 million, and $0.92 million, respectively. The uninsured were charged a total of $10.06 million. Inpatient admission to the same hospital was required for 1,167 visits. The total hospitalization charge for this group was $17.51 million. Patients with comorbid conditions (congestive heart failure, valvular disease, hypertension, paralysis, neurologic disorders, chronic pulmonary disease, hypothyroidism, liver disease, AIDS, coagulopathy, deficiency anemia, obesity, alcohol abuse, or drug abuse) were associated with higher odds for hospitalization during an ED visit for periodontal conditions compared to those without comorbid conditions (P <0.05). Patients who had a primary diagnosis of acute or aggressive periodontitis were associated with significantly higher odds of being hospitalized during ED visits. Estimates from the NEDS suggest that a total of 85,039 hospital-based ED visits had a primary diagnosis for periodontal conditions. Close to $33.3 million was charged by hospitals for treating these conditions on an emergency basis. ED visits with a primary diagnosis for acute and aggressive periodontitis, covered by Medicare insurance, and comorbid conditions were more likely to result in hospitalization based on the analysis of the NEDS. However, when interpreting these conclusions, one should keep the limitations inherent to hospital discharge datasets in perspective.


Lymphocytes and urine in ceroid lipofuscinosis.
Pathognomonic ultrastructural inclusions were found in the lymphocytes of 16 patients with neuronal ceroid lipofuscinosis (Batten's disease) and in the urine of three of four of such patients. These inclusions remained type specific for each patient and were identical with deposits in nerve cells and other body tissues. They persisted in lymphocytes in short-term tissue culture, but disappeared with stimulation by phytohemagglutinin. Siblings had identical inclusions. None were present in heterozygotes. Examination of lymphocytes in the peripheral blood cells is an easy method to use in the diagnosis of ceroid lipofuscinosis, but it cannot be used to detect carriers.


Sporadic hemiplegic migraine.
Sporadic hemiplegic migraine (SHM) is defined as migraine attacks associated with some degree of motor weakness/hemiparesis during the aura phase and where no first degree relative (parent, sibling or child) has identical attacks. The present review deals with recent scientific studies according to which: The SHM prevalence is estimated to be 0.005%; SHM patients have clinical symptoms identical to patients with familial hemiplegic migraine (FHM) and significantly different from patients with migraine with typical aura (typical MA); SHM affected had no increased risk of migraine without aura (MO), but a highly increased risk of typical MA compared to the general population; SHM patients only rarely have mutations in the FHM gene CACNA1A; SHM attacks in some cases can be treated with Verapamil. The reviewed data underlie the change in the International Classification of Headache Disorders 2nd edition where SHM became separated from migraine with typical aura or migraine with prolonged aura. All cases with motor weakness should be classified as either FHM or SHM.


Movement behaviors and mental health of caregivers of preschoolers in China during the COVID-19 pandemic.
This study aimed to examine the associations between physical activity (PA), sedentary behavior (SB), sleep, and the mental health of caregivers of preschool children following the COVID-19 outbreak. From 5 October to 16 December 2020, responses from 2476 respondents in China were collated through an online survey or a written questionnaire. Movement behaviors (PA, SB, screen time, and sleep), mental health (depression, anxiety, and stress), and demographic information were self-reported by the respondents. Linear mixed models were used for data analysis. Valid responses were received from 2002 caregivers (35.5 ± 4.9 years old, 76.3% females) of children between 3 and 6 years old in China (Hong Kong 3.2%, Shanghai 20.6%, Guangzhou 34.1%, Guiyang 26.7%, Xuzhou 11.3%, Xi'an 4.1%). A higher level of PA was associated with a lower score of depression, while lower SB and longer sleep duration were associated with lower scores of depression, anxiety, and stress. Meeting the Canadian 24-h movement guidelines was associated with less symptoms of depression, anxiety, and stress. Higher PA was associated with lower levels of depression, while longer sleep and lower SB were associated with better scores of depression, anxiety, and stress. Meeting the Canadian 24-h movement guidelines has been associated with better mental health during the COVID-19 pandemic. Interventions to improve mental health among caregivers should involve enhancing their overall movement behaviors.


[The 13C-methacetin breath test for quantitative noninvasive liver function analysis with an isotope-specific nondispersive infrared spectrometer in liver cirrhosis].
Cytochrome-P450-dependent liver function can be measured with the 13C-methacetin breath test (MBT). This has heretofore been done with the use of a mass-spectrometer. This study was undertaken to evaluate the MBT (NDIRS) done with the isotope-selective nondispersive infrared spectrometer. 20 healthy volunteers (ten women, ten men, aged 22-76 years) and 16 patients (ten women, six men, aged 48-71 years) with histologically confirmed liver cirrhosis (Child-Pugh stage A [n = 7], B [n = 5] or C [n = 4]) were given 13C-methacetin in 100 ml of tea after a 12-hour fasting period. Breath tests were performed before the test drink and 5, 10, 15, 20, 30, 40, 50, 60, 80, 100, 120, 150 and 180 min thereafter. The ratio of 13C to 12C was determined, as delta (/1000), and from it the maximal percentage rate (PDRmax) calculated, as well as the cumulative rate (cPDRmax) after 30, 60, 120 and 180 min (Median and 5th and 95th percentiles). For patients with liver cirrhosis there were significantly lower values for cPDRmax and cPDR after 30, 60, 120 and 180 min than in the healthy subjects (P < 0.002): PDR [%]/h: 3.9 (0.7-15.9) vs. 36.5 (23.1-50.0); cDPR 30 min [%]: 1.1 (-0.2-6.0) vs. 12.4 (7.6-17.1); cDPR 3 h [%]: 9.8 (-2.3-27.5) vs. 36.0 (29.9-45.1). There were significant differences among the patients, depending on their Child-Pugh staging. The MBT with the cost-effective NDIRS can reliably and noninvasively distinguish between healthy subjects and patients with liver cirrhosis. The test is therefore suitable for the quantitative analysis of liver functions.


Does spinal anesthesia for total hip or knee arthroplasty entail longer operating room occupancy compared to general anesthesia? Case-control study of 337 spinal versus 243 general anesthesias.
Treatment protocols, including anesthesia, are constantly progressing to improve rapid early postoperative recovery in lower-limb arthroplasty. To the best of our knowledge, however, no studies compared general versus spinal anesthesia (GA vs. SA) in the surgical pathway of patients undergoing total knee or hip arthroplasty (TKA, THA). Better knowledge of the processes should improve efficacy in theater and optimize surgical planning. The present study comparing GA and SA in the operating room aimed to assess 1) theater occupancy times, and 2) times for each step in a surgery day according to type of anesthesia. SA leads to longer theater occupancy than GA in TKA and THA. A single-center retrospective case-control study analyzed data for the period January 2019 to December 2020 in 303 TKAs (100 GA, 203 SA) and 277 THAs (143 GA, 134 SA), comparing times for all perioperative steps and particularly theater occupancy. In TKA, occupancy did not differ between GA and SA: 98 ± 16 min versus 98 ± 14 min respectively; Δ = 0 min (p = 0.78). In THA, occupancy was shorter with SA than GA: 117 ± 23 min versus 123 ± 26 min respectively; Δ = - 6 min (p = 0.02). In THA, time to perform SA was longer than induction of GA: 28 ± 13 min versus 23 ± 12 min respectively; Δ = + 5 min (p<0.001). In TKA, time to leaving the operating room was shorter with SA than GA: 8 ± 5 min versus 14 ± 7 min respectively; Δ = - 6 min (p<0.001). Discussion / Conclusion: SA did not involve longer mean theater occupancy than GA for TKA, and reduced it by 6 minutes for THA. III; case-control study.


Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism.
Genes encoded on chromosome 6 within the major histocompatibility complex region are thought to play an important role in the pathogenesis of psoriasis. A potential candidate gene is tumor necrosis factor alpha. The tumor necrosis factor alpha promoter contains several polymorphisms including two G-->A transitions at position -308 and -238, which are the most common in Caucasian populations. The TNF238.2 (-238A) allele has been strongly associated with psoriasis. We have investigated the effect of the -238 and -308 variants on transcription of the tumor necrosis factor alpha gene in luciferase reporter gene assays. In addition, peripheral blood mononuclear cells of 47 patients with psoriasis and 43 controls were stimulated with different antigens and mitogens (streptococcal sonicate and superantigen, lipopolysaccharide, phorbol-12-myristate, phytohemagglutinin, CD3 antibodies) and tumor necrosis factor alpha production was measured in supernatants by enzyme-linked immunosorbent assay. The psoriasis-associated tumor necrosis factor alpha promoter allele TNF238.2 showed a significantly decreased transcriptional activity. Peripheral blood mononuclear cells carrying this allele produced significantly less tumor necrosis factor alpha after stimulation with T cell mitogens and streptococcal antigens in comparison to controls. The promoter allele TNF238.2 seems to influence tumor necrosis factor alpha production; a possible role in the pathogenesis of psoriasis has to be further evaluated.


A pro-inflammatory role of lymphoid cells in acute pleurisy in rats.
The effect of viable splenic lymphoid cells and their constituents (filtrate) on carrageenan-induced acute pleurisy was investigated in rats. Suspensions of lymphoid cells administered intravenously to recipients just prior to initiation of pleurisy enhance both the volume of exudate and cell accumulation in the pleural cavity 3 h after the irritation. Similar results were observed when filtrate of disrupted lymphoid cells was injected either 30 or 5 min before the carrageenan, but not when administered 30 min afterwards. Suspensions of bone marrow cells, on the contrary, were ineffective in producing an enhancement of the parameters studied. When administered into the pleural cavity together with carrageenan, the lymphoid cell filtrate augmented the inflammatory response to the irritant. Nevertheless, it was ineffective, per se, to elicit any local change. It is suggested that lymphoid cells may play a pro-inflammatory role in the initiation of the process by enhancing both the fluid and the cellular components of inflammation.


The entry-exit method of shadow boundary segmentation.
A new method has been developed for interpreting the shadows of arbitrarily shaped surfaces by segmenting and labeling the shadow boundary. The method is based on the fact that a linear projection of any light ray (the ray is assumed to originate at a single, distant source) across a shadow either enters or exits the shadow at its boundary. Hence, junctures of entry and exit segments form vertices that can be found directly for any given direction of illumination and view. Entry-exit vertices that are extremes of the boundary (which is normal to the axis of light) can be identified as junctures of specific profiles of the shadow-making object. These junctures, in turn identify the segments connected to them. The method assumes successful lower level extraction of shadow boundaries. When one object occludes part of another object's shadow, critical junctures occur, but these sometimes are not entry-exit vertices. These hidden junctures create ambiguities that must be dealt with in the context of neighboring segments. Certain a priori knowledge is helpful in this situation. The method may require knowledge of the surface or the object. The entry-exit method also provides a new link between the tasks of shadow boundary extraction and shape inference in the overall process of shadow interpretation. In conjunction with existing methods for the other tasks, the entry-exit method makes it possible to interpret arbitrarily shaped shadows.


Restoration of decayed primary incisors using strip crowns.
Caries of the primary incisors is a common problem that can be arrested if recognized early enough. However, the arrested decay is unsightly. Celluloid 'strip' crown forms, used with composite resin, now allow the restoration of even the most badly decayed primary incisors. The authors describe this quick and efficient technique.


Where bio meets nano: the many uses for nanoporous aluminum oxide in biotechnology.
Porous aluminum oxide (PAO) is a ceramic formed by an anodization process of pure aluminum that enables the controllable assembly of exceptionally dense and regular nanopores in a planar membrane. As a consequence, PAO has a high porosity, nanopores with high aspect ratio, biocompatibility and the potential for high sensitivity imaging and diverse surface modifications. These properties have made this unusual material attractive to a disparate set of applications. This review examines how the structure and properties of PAO connect with its present and potential uses within research and biotechnology. The role of PAO is covered in areas including microbiology, mammalian cell culture, sensitive detection methods, microarrays and other molecular assays, and in creating new nanostructures with further uses within biology.


Oxygen vacancy-enhanced photothermal performance and reactive oxygen species generation for synergistic tumour therapy.
Vacancy engineering is a robust strategy to tune nanomaterials' electronic structures for physicochemical properties regulation. Here, we report and realize the first oxygen vacancy-enhanced photothermal and oxidation dual-induced synergistic tumour therapy using oxygen vacancies enriched MnO2@Au nanoconstructs as the therapeutic agent with a high photothermal effect, enhanced highly-toxic superoxide radical generation, good biocompatibility and tumour microenvironment regulation capacity. Our work opens up a new route for cancer nanotheranostics by regulating the electronic structure of nanomaterials resulting in enhanced efficacy.


[Lesions of the lungs in children with acute leukemia].
Investigation of the lungs of 65 children who died of acute leukemia, revealed pathological alterations in 39 of them. Specific leukemic infiltration of the lung parenchyma was found in 29.3%, but it did not play an important role in tanathogenesis. Pneumonias were diagnosed in 46.1% of the observations being the main cause of death in 23%. The inflammatory processes showed a marked tendency for spread because of low immunologic responsiveness of the patients and poor neutrophil reaction. Because of this, segmental pneumonias predominated in our observations, and in 5 cases total bilateral interstitial pneumonias had developed. Three of them were due to Pneumocystis carinii and two were drug pulmonitis.


[Antibiotic-resistant coliforms in a purification station on a pig-breeding farm].
The survival of antibiotic-resistant enteric bacteria in the effluent treatment plant of a pig farm was studied by quantitative determinations of resistant and sensitive populations at different sites of the effluent purification process. The effluent treatment system, combining storage and aeration tanks, reduced the concentration of enteric organisms in the output of the plant to about one-tenth of the concentration found in the incoming untreated slurry. This reduction occurred mainly at the level of the aerated tank and was observed for the total population of enteric organisms as well as for the various populations resistant to ampicillin, chloramphenicol, kanamycin, streptomycin and tetracycline respectively. Moreover, no particular sequence of resistances seems to have been selected during treatment. Storage and aeration of pig slurry before disposal reduces the risk of dissemination of antibiotic-resistant bacteria of animal origin in the environment, as compared to the frequent direct spreading of untreated effluents.


Management of colonic injuries in the combat theater.
Combat injuries are more often associated with blast, penetrating, and high-energy mechanisms than civilian trauma, generating controversy about the management of combat colonic injury. Despite implementation of mandatory colostomy in World War II, recent civilian data suggest that primary repair without diversion is safe and feasible. This study describes the modern management of battle-related colonic injuries and seeks to determine whether management strategy affects early complications. Records from the combat theater (downrange) and tertiary referral center in Germany were retrospectively reviewed from 2005 to 2006. Patient characteristics, management strategy, treatment course, and early complications were recorded. Comparison groups by management strategy were as follows: primary repair, diversion, and damage control. A total of 133 (97% male) patients sustained colonic injuries from penetrating (71%), blunt (5%), and blast (23%) mechanisms. Average injury severity score was 21 and length of stay in the referral center was 7.1 days. Injury distribution was 21% ascending, 21% descending, 15% transverse, 27% sigmoid, and 25% rectum. Downrange complications for primary repair, initial ostomy, and damage control groups were 14%, 15%, and 30%, respectively. On discharge from the center, 62% of patients had undergone a diversion. The complication rate was 18% overall and was unrelated to management strategy (P = .16). Multivariate analysis did not identify independent predictors of complications. Early complications were similar by mechanism, anatomic location, severity of injury, and management strategy. More diversions were performed for rectosigmoid injury. Good surgical judgment allows for low morbidity and supports primary repair in selected cases. Damage control surgery is effective in a multinational theater of operations.


Cigarette smoking and drug use among a nationally representative sample of HIV-positive individuals.
Among HIV-positive populations, the prevalence of cigarette smoking remains disproportionately high and is associated with significant morbidity and mortality. Little is known about this topic among HIV-positive persons in the general population. Data came from the 2005 to 2011 National Survey on Drug Use and Health (NSDUH) public use data files. Unadjusted and adjusted multinomial logistic regression analyses explored the associations between socio-demographic, drug and alcohol use, and drug and/or alcohol treatment characteristics with smoking status among HIV-positive individuals (n = 349). More than 40% of the sample was current smokers. In adjusted analyses, females (aRRR = .11, 95% CI = .03-.41) and participants who had never been married (aRRR = .19, 95% CI = .05-.58), were more likely to be former smokers than never smokers. Females (aRRR = .37, 95% CI = .14-.96) and individuals older than age 35 (aRRR = .37, 95% CI = .16-.89) were less likely to be current smokers than never smokers. Conversely, previously married persons (aRRR = 5.72, 95% CI = 1.40-23.31), participants reporting binge drinking (aRRR = 5.96, 95% CI = 2.27-15.64), and lifetime drug or alcohol treatment (aRRR = 5.12, 95% CI = 2.09-12.55) were more likely to be current smokers than never smokers. Findings help confirm the high prevalence of smoking among HIV-positive persons suggesting the need for integrated substance use and smoking cessation treatment among HIV-positives. The present findings have implications for the development and implementation of targeted smoking cessation programs for HIV-positive smokers.


Closed-loop cavitation control for focused ultrasound-mediated blood-brain barrier opening by long-circulating microbubbles.
Focused ultrasound (FUS) exposure in the presence of microbubbles (MBs) has been successfully used in the delivery of various sizes of therapeutic molecules across the blood-brain barrier (BBB). While acoustic pressure is correlated with the BBB opening size, real-time control of BBB opening to avoid vascular and neural damage is still a challenge. This arises mainly from the variability of FUS-MB interactions due to the variations of animal-specific metabolic environment and specific experimental setup. In this study, we demonstrate a closed-loop cavitation control framework to induce BBB opening for delivering large therapeutic molecules without causing macro tissue damages. To this end, we performed in mice long-term (5 min) cavitation monitoring facilitated by using long-circulating MBs. Monitoring the long-term temporal kinetics of the MBs under varying level of FUS pressure allowed to identify in situ, animal specific activity regimes forming pressure-dependent activity bands. This enables to determine the boundaries of each activity band (i.e. steady oscillation, transition, inertial cavitation) independent from the physical and physiological dynamics of the experiment. However, such a calibration approach is time consuming and to speed up characterization of the in situ, animal specific FUS-MB dynamics, we tested a novel method called 'pre-calibration' that closely reproduces the results of long-term monitoring but with a much shorter duration. Once the activity bands are determined from the pre-calibration method, an operation band can be selected around the desired cavitation dose. To drive cavitation in the selected operation band, we developed an adaptive, closed-loop controller that updates the acoustic pressure between each sonication based on measured cavitation dose. Finally, we quantitatively assessed the safety of different activity bands and validated the proposed methods and controller framework. The proposed framework serves to optimize the FUS pressure instantly to maintain the targeted cavitation level while improving safety control.


Characterization of a novel sucrose phosphorylase from Paenibacillus elgii and its use in biosynthesis of α-arbutin.
α-Arbutin, a naturally occurring glycosylated derivative of hydroquinone (HQ), effectively inhibits melanin biosynthesis in epidermal cells. It is widely recognized as a fourth-generation whitening agent within the cosmetic industry. Currently, enzymatic catalysis is universally deemed the safest and most efficient method for α-arbutin synthesis. Sucrose phosphorylase (SPase), one of the most frequently employed glycosyltransferases, has been extensively reported for α-arbutin synthesis. In this study, a previously reported SPase known for its effectiveness in synthesizing α-arbutin, was used as a probe sequence to identify a novel SPase from Paenibacillus elgii (PeSP) in the protein database. The sequence similarity between PeSP and the probe was 39.71%, indicating a degree of novelty. Subsequently, the gene encoding PeSP was coexpressed with the molecular chaperone pG-Tf2 in Escherichia coli, significantly improving PeSP's solubility. Following this, PeSP was characterized and employed for α-arbutin biosynthesis. The specific activity of co-expressed PeSP reached 169.72 U/mg, exhibited optimal activity at 35℃ and pH 7.0, with a half-life of 3.6 h under the condition of 35℃. PeSP demonstrated excellent stability at pH 6.5-8.5 and sensitivity to high concentrations of metal ions. The kinetic parameters Km and kcat/Km were determined to be 14.50 mM and 9.79 min- 1·mM- 1, respectively.The reaction conditions for α-arbutin biosynthesis using recombinant PeSP were optimized, resulting in a maximum α-arbutin concentration of 52.60 g/L and a HQ conversion rate of 60.9%. The optimal conditions were achieved at 30℃ and pH 7.0 with 200 U/mL of PeSP, and by combining sucrose and hydroquinone at a molar ratio of 5:1 for a duration of 25 h.


Genome-wide association study reveals new loci for yield-related traits in Sichuan wheat germplasm under stripe rust stress.
As one of the most important food crops in the world, increasing wheat (Triticum aestivum L.) yield is an urgent task for global food security under the continuous threat of stripe rust (caused by Puccinia striiformis f. sp. tritici) in many regions of the world. Molecular marker-assisted breeding is one of the most efficient ways to increase yield. Here, we identified loci associated to multi-environmental yield-related traits under stripe rust stress in 244 wheat accessions from Sichuan Province through genome-wide association study (GWAS) using 44,059 polymorphic markers from the 55 K single nucleotide polymorphism (SNP) chip. A total of 13 stable quantitative trait loci (QTLs) were found to be highly associating to yield-related traits, including 6 for spike length (SL), 3 for thousand-kernel weight (TKW), 2 for kernel weight per spike (KWPS), and 2 for both TKW and KWPS, in at least two test environments under stripe rust stress conditions. Of them, ten QTLs were overlapped or very close to the reported QTLs, three QTLs, QSL.sicau-1AL, QTKW.sicau-4AL, and QKWPS.sicau-4AL.1, were potentially novel through the physical location comparison with previous QTLs. Further, 21 candidate genes within three potentially novel QTLs were identified, they were mainly involved in the regulation of phytohormone, cell division and proliferation, meristem development, plant or organ development, and carbohydrate transport. QTLs and candidate genes detected in our study for yield-related traits under stripe rust stress will facilitate elucidating genetic basis of yield-related trait and could be used in marker-assisted selection in wheat yield breeding.


SNF1/AMPK pathways in yeast.
The SNF1/AMPK family of protein kinases is highly conserved in eukaryotes and is required for energy homeostasis in mammals, plants, and fungi. SNF1 protein kinase was initially identified by genetic analysis in the budding yeast Saccharomyces cerevisiae. SNF1 is required primarily for the adaptation of yeast cells to glucose limitation and for growth on carbon sources that are less preferred than glucose, but is also involved in responses to other environmental stresses. SNF1 regulates transcription of a large set of genes, modifies the activity of metabolic enzymes, and controls various nutrient-responsive cellular developmental processes. Like AMPK, SNF1 protein kinase is heterotrimeric. It is phosphorylated and activated by the upstream kinases Sak1, Tos3, and Elm1 and is inactivated by the Reg1-Glc7 protein phosphatase 1. Further regulation of SNF1 is achieved through autoinhibition and through control of its subcellular localization. Here we review the current understanding of SNF1 protein kinase pathways in Saccharomyces cerevisiae and other yeasts.