Interaction of time-varying albumin and phosphorus on mortality in incident dialysis patients.
Hypoalbuminemia and hyperphosphatemia have been shown to be strong predictors of mortality in dialysis patients that might not be independent from each other. We prospectively investigated the relationship and interaction between serum albumin and phosphorus with all-cause mortality in an inception cohort of incident dialysis patients. We followed 235 incident dialysis patients in a prospective single-center cohort study (INVOR study) applying a time-dependent Cox proportional hazards model using all measured laboratory values (2887 albumin and 10306 phosphorus values). Eighty-two patients (35%) died during a median follow-up of 35.1 months. Albumin was inversely associated with mortality (hazard ratio [95% confidence interval]: 0.23 [0.14 to 0.36]; P < 0.001), whereas higher phosphorus concentrations showed a trend to an increasing risk for mortality (hazard ratio 1.57 [95% confidence interval 0.97 to 2.54]; P = 0.07). Importantly, we observed a significant interaction between albumin and phosphorus (P = 0.01). The lowest risk was found with concurrent low phosphorus and high albumin values, whereas risk was increased with either concurrent low phosphorus and low albumin values or high phosphorus and high albumin values. In incident dialysis patients the associations of serum phosphorus and albumin concentrations with mortality are modified by each other over time. Phosphorus-lowering interventions that concomitantly can cause a fall in serum albumin level may be harmful and warrant additional studies. If confirmed, epidemiologic studies and therapeutic guidelines aiming for target values should consider this interplay.


Reduced smooth muscle-fibroblasts transformation potentially decreases intestinal wound healing and colitis-associated cancer in ageing mice.
Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population. Given the increased incidence of cancer and the population ageing trend globally, it is very important to explore how ageing impairs tissue wound healing and spontaneous cancer. In a murine model of DSS-induced acute colitis and AOM/DSS-induced colitis-associated cancer (CAC), we found ageing significantly decreases intestinal wound healing and simultaneous CAC initiation, although ageing does not affect the incidence of AOM-induced, sporadic non-inflammatory CRC. Mechanistically, reduced fibroblasts were observed in the colitis microenvironment of ageing mice. Through conditional lineage tracing, an important source of fibroblasts potentially derived from intestinal smooth muscle cells (ISMCs) was identified orchestrating intestinal wound healing and CAC initiation in young mice. However, the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice, accompanied by decreased intestinal wound healing and decreased CAC initiation. ISMCs-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture experiments. We further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into fibroblasts. Meanwhile, the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing mice. Conditional knockdown of YAP/TAZ in ISMCs of young mice results in reduced fibroblasts in the colitis microenvironment, decreased intestinal wound healing and decreased CAC initiation, similar to the phenotype of ageing mice. In addition, the data from intestine samples derived from inflammatory bowel disease (IBD) patients show that activation of YAP/TAZ also occurs in ISMCs from these patients. Collectively, our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC initiation. Furthermore, our work also identified a potential source of fibroblasts involved in colitis and CAC.


CH3NH3Br solution as a novel platform for the selective fluorescence detection of Pb2+ ions.
The development of a simple fluorescent sensor for detecting the Pb2+ heavy metal is fundamentally important. The CH3NH3PbBr3 perovskite material exhibits excellent photoluminescence properties that are related to Pb2+. Based on the effects of Pb2+ on the luminescent properties of CH3NH3PbBr3, we design a novel platform for the selective fluorescence detection of Pb2+ ions. Herein, we use a CH3NH3Br solution at a high concentration as the fluorescent probe. Incorporation of PbBr2 into the CH3NH3Br solution results in a rapid chemical reaction to form CH3NH3PbBr3. Hence, the nonfluorescent CH3NH3Br material displays a sensitive and selective luminescent response to Pb2+ under UV light illumination. Moreover, the reaction between CH3NH3Br and PbBr2 could transform Pb2+ into CH3NH3PbBr3, and therefore, CH3NH3Br may also be used to extract Pb2+ from liquid waste in recycling applications.


Task-related MEG source localization via discriminant analysis.
To investigate the neural activity corresponding to different cognitive states, it is of great importance to localize the cortical areas that are associated with task-related modulation. In this paper, we propose a novel discriminant pattern source localization (DPSL) method to analyze MEG data. Unlike most traditional source localization methods that aim to find "dominant" sources, DPSL is developed to capture the "differential" sources that distinguish different cognitive states. As will be demonstrated by the experimental results in this paper, the proposed DPSL method offers superior accuracy to identify the spatial locations of task-related sources.


Exogenous epibrassinolide application improves essential oil biosynthesis and trichome development in peppermint via modulating growth and physicochemical processes.
Peppermint has gained a promising status due to the presence of a high proportion of bioactive compounds, especially menthol. Due to its pharmacological efficacy, the demand for its plant-based bioactive compounds necessitates its cultivation worldwide. Brassinosteroids are polyhydroxylated sterol derivatives that regulate diverse processes and control many agronomic traits during plant growth and development. A factorial randomised pot experiment was performed in the net house to investigate the effect of 24-Epibrassinolide (EBL) on the growth, physiology, essential oil content, stomatal behaviour and trichome development of the three cultivars of peppermint. Four levels of foliage-applied EBL, viz. 0, 10-5, 10-6 and 10-7 M were applied to the three cultivars of peppermint (Kukrail, Pranjal and Tushar). Among the different treatments of EBL, the application of 10-6 M increased shoot length by 38.84, 37.59 and 36.91%, root length by 36.73, 29.44 and 33.47%, chlorophyll content by 24.20, 22.48 and 23.32%, PN by 32.88, 32.61 and 33.61%, EO content by 32.72, 30.00 and 28.84%, EO yield per plant by 66.66, 77.77 and 73.33% and menthol yield per plant by 127.27, 110 and 118.18% in Kukrail, Tushar and Pranjal respectively, compared with their respective control plants. Further, the 10-6 M EBL exhibited improved trichome size and density, cellular viability and menthol content of the oil analysed from scanning electron microscopy, confocal laser scanning microscopy and GC-MS respectively as compared to the control. In conclusion, out of different levels of EBL, two sprays of 10-6 M EBL proved effective in enhancing the morphophysiological features and productivity of mint plants, particularly for cultivar Kukrail.


Plant soaking decomposition as well as nitrogen and phosphorous release in the water-level fluctuation zone of the Three Gorges Reservoir.
The operating scheme of the Three Gorges Reservoir results in a summer drought in the water-level fluctuation zone during which plants grow vigorously. In the winter inundation season, soaking plants may decompose and release nutrients resulting in water quality deterioration. This study quantifies the contributions of the underwater decomposition of nine dominant plant species in the water-level fluctuation zone to nutrient release. The in-situ litterbag technique was used to study for soaking decomposition over 200days. All soaking plant species decomposed rapidly at an average rate of 1.99±0.33%d-1 in the early stage of soaking (0 to 30days) and at an average rate of only 0.07±0.04%d-1 in the later stage (30 to 200days). After 200days of soaking, the nine plant species released an average of 312.40±39.97gkg-1 organic carbon, 6.71±4.29gkg-1 of nitrogen and 2.25±1.25gkg-1 of phosphorus. A positive relationship was found between soaking plant decomposition rates and initial C/N ratios of 25 to 50, and a negative relationship where the C/N ratios were between 50 and 100. The amounts of total nitrogen or total phosphorus released were significantly negatively correlated with the initial C/N or C/P ratios of the plants. Among the studied plant species, Xanthium sibiricum Patr ex Widder showed high level of nutrient release via soaking decomposition. In contrast, Cynodon dactylon (Linn.) Pers. and Polygonum hydropiper exhibited low levels of nutrient release and are recommended as suitable species for the ecological restoration of the water-level fluctuation zone. Our results demonstrate that after 200days of soaking plant decomposition, the loadings of total organic carbon, nitrogen, and phosphorus in the water-level fluctuation zone of the Three Gorges Reservoir were 2942.1, 81.1, and 24.7kgha-1, respectively and therefore could potentially damage the aquatic environment of the reservoir.


Europium functionalized black phosphorus quantum dots as a CRET platform for synergistically enhanced chemiluminescence.
In this work, we synthesize stable europium ion modified black phosphorus quantum dots (Eu-BPQDs) using a microwave irradiation technique, which can react with organic amines exhibiting unique chemiluminescence (CL). The mechanism of the Eu-BPQDs/organic amines CL system accounting for the efficient CRET is induced by the chelation of organic amines with the surface functionalized europium.


Selenium losses in 10 burned patients.
To determine the selenium (Se) losses and balances, 10 patients with burns of 32 +/- 9% (mean +/- SD) of total body surface and aged 36 +/- 9 years were studied from D1 (first post-injury) unitl D7. Cutaneous losses were extracted from the textiles surrounding the patients. Serum and urine were collected until D20. Exudative losses of nitrogen decreased progressively (mean 8.7 +/- 3.8 g/24H). Se was detectable in wound seepage only during excision-grafting: mean operative loss was 342 +/- 191 mug. Mean urinary Se excretion was 41 +/- 13 mug/24H. Operative cutaneous losses led to some negative balances. Serum Se and glutathione peroxydase (GSHPx) were depressed until D20. Serum Se was related to N intake (p < 0.001). The decreased Se and GSHPx levels reflect a deficiency state, which measured losses did not explain, but limitations of the measurement methods prevented detection of Se cutaneous losses 100 mug/24H.


Worldwide access to evidence-based mental health literature: how useful is PubMed in Anglo-Saxon and non-Anglo-Saxon countries?
The aim of this study was to verify the presence of cultural variety among the psychiatric journals available on PubMed, the major online tool for accessing literature. Data for analysis were taken from a survey of the world psychiatric journals indexed in Index Medicus 1999 (IM), the alphabetical list used by PubMed, and from the mean impact factor (IF) values of the journals. Approximately 80% of international psychiatric literature available on PubMed is published in Anglo-Saxon countries, especially in the USA (59.8% of the total). The widespread use of the English language (94.9% of all the journals) further stresses the dominance of the Anglo-Saxon cultural model, as do the mean IF values of Anglo-Saxon journals compared to non-Anglo-Saxon publications (3.252 vs. 1.693; P=0.0079). The under-representation of non-Anglo-Saxon cultural models on PubMed plays a negative role for bringing about a truly multicultural literature in psychiatry.


Impacts of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 variants Alpha and Delta on Coronavirus Disease 2019 transmission dynamics in four metropolitan areas of the United States.
To characterize Coronavirus Disease 2019 (COVID-19) transmission dynamics in each of the metropolitan statistical areas (MSAs) surrounding Dallas, Houston, New York City, and Phoenix in 2020 and 2021, we extended a previously reported compartmental model accounting for effects of multiple distinct periods of non-pharmaceutical interventions by adding consideration of vaccination and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants Alpha (lineage B.1.1.7) and Delta (lineage B.1.617.2). For each MSA, we found region-specific parameterizations of the model using daily reports of new COVID-19 cases available from January 21, 2020 to October 31, 2021. In the process, we obtained estimates of the relative infectiousness of Alpha and Delta as well as their takeoff times in each MSA (the times at which sustained transmission began). The estimated infectiousness of Alpha ranged from 1.1x to 1.4x that of viral strains circulating in 2020 and early 2021. The estimated relative infectiousness of Delta was higher in all cases, ranging from 1.5x to 2.4x. The estimated Alpha takeoff times ranged from February 10 (for New York City, which was evidently impacted much earlier than the other regions) to March 23, 2021. The estimated Delta takeoff times were more tightly clustered, ranging from June 8 to June 24, 2021. Estimated takeoff times are consistent with genomic surveillance data.


Hodgkin lymphoma in Africa: present and future.
Hodgkin lymphoma (HL) was described for the first time in 1832 by Sir Thomas Hodgkin, who is considered the father of the disease. This lymphoma occupies a special place among childhood malignancies, due to its high rate of cure. HL is described as one of the most common haematological malignancies in African children. Despite high rates of survival achieved in resource rich countries, the outcome in Africa is not as rewarding as many challenges are encountered. This paper reviews published African studies on childhood HL in order to delineate the amplitude of this health problem and its African specifics, in the quest for effective ways to improve the outcome of the children diagnosed with this disease.


Mixed acenannellated metallotetraazaporphins: a new class of amphiphilic photosensitizers for the photodynamic therapy of cancer.
The first synthesis of amphiphilic mixed acenannellated metallotetraazaporphins compounds, designed with the aim of improving cell membrane penetration, is described and the preliminary results on their photocytotoxicity are presented.


Comparison of the Ames assay and the induction of sister chromatid exchanges: results with ten pharmaceuticals and five selected agents.
Seven antischistosomal drugs, two antimalarial drugs, and one antiamoebic drug were tested in all five Ames strains for induction of mutation, as well as for induction of cytotoxicity, inhibition of cellular progression, and the induction of sister chromatid exchanges in two cultured mammalian cell lines. We found that two agents shown to be negative in the Ames test were positive for sister chromatid exchange induction. Based on qualitative and quantitative evaluation, we find that all but three of the pharmaceuticals should be considered to be potential human carcinogens.


Mechanism of proton transfer in [FeFe]-hydrogenase from Clostridium pasteurianum.
[FeFe]-Hydrogenases are complex metalloproteins that catalyze the reversible reduction of protons to molecular hydrogen utilizing a unique diiron subcluster bridged to a [4Fe4S] subcluster. Extensive studies have concentrated on the nature and catalytic activity of the active site, yet relatively little information is available concerning the mechanism of proton transport that is required for this activity. Previously, structural characterization of [FeFe]-hydrogenase from Clostridium pasteurianum indicated a potential proton transport pathway involving four residues (Cys-299, Glu-279, Ser-319, and Glu-282) that connect the active site to the enzyme surface. Here, we demonstrate that substitution of any of these residues resulted in a drastic reduction in hydrogenase activity relative to the native enzyme, supporting the importance of these residues in catalysis. Inhibition studies of native and amino acid-substituted enzymes revealed that Zn(2+) specifically blocked proton transfer by binding to Glu-282, confirming the role of this residue in the identified pathway. In addition, all four of these residues are strictly conserved, suggesting that they may form a proton transport pathway that is common to all [FeFe]-hydrogenases.


Laparoscopic Microwave Liver Ablation and Portal Vein Ligation: An Alternative Approach to the Conventional ALPPS Procedure in Hilar Cholangiocarcinoma.
Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a new procedure aimed at promoting the overgrowth of small future liver remnants (FLR). The role of ALPPS in hilar cholangiocarcinoma (h-CCA) is currently considered marginal because liver split in the presence of bile duct obstruction increases postoperative morbidity and mortality (Schadde et al. in Ann Surg 260:829-836,2014; Nadalin et al. in Z Gastroenterol 52:35-42,2014). Virtual liver split (Gall et al. in Ann Surg 261:e45-e46,2015) could improve the outcome of ALPPS in h-CCA. A 64-year-old woman with a type IIIA h-CCA without evidence of vascular involvement had a small FLR (FLR/body weight: 0.47 cm3/kg). After bilateral percutaneous biliary drainage (PBD) and bilirubin normalization, the patient was planned for laparoscopic step 1 ALPPS using microwave ablation (MWA). Because of possible challenge in hilar dissection in this tumor type, robotic assistance was preferred to conventional laparoscopy for step 1. The patient recovered promptly from step 1, with a 68 % increase in the volume of FLR by postoperative day (POD) 10 (FLR/body weight of 0.79 cm3/kg). On POD 15, the patient underwent open right hepatectomy with en bloc resection of the caudate lobe, bile duct bifurcation, and extrahepatic biliary duct (T2N1M0R0). Estimated blood loss was negligible during step 1 and 150 mL during step 2. The patient recovered well. Chemotherapy was started 6 weeks after ALPPS stage 2, and was well tolerated and full course. Twenty months after resection the patient is alive, well, and disease-free. Laparoscopic ALPPS (Machado et al. in Ann Surg 256:e13,2012) and MWA on the intended split line (Gringeri and Boetto in Ann Surg 261:e42-e43,2015) have been recently described. The combination of these techniques with PBD allowed successful ALPPS in a patient with h-CCA.


Resource-stratified implementation of a community-based breast cancer management programme in Peru.
Breast cancer incidence and mortality rates continue to rise in Peru, with related deaths projected to increase from 1208 in 2012, to 2054 in 2030. Despite improvements in national cancer control plans, various barriers to positive breast cancer outcomes remain. Multiorganisational stakeholder collaboration is needed for the development of functional, sustainable early diagnosis, treatment and supportive care programmes with the potential to achieve measurable outcomes. In 2011, PATH, the Peruvian Ministry of Health, the National Cancer Institute in Lima, and the Regional Cancer Institute in Trujillo collaborated to establish the Community-based Program for Breast Health, the aim of which was to improve breast health-care delivery in Peru. A four-step, resource-stratified implementation strategy was used to establish an effective community-based triage programme and a practical early diagnosis scheme within existing multilevel health-care infrastructure. The phased implementation model was initially developed by the Breast Cancer Initiative 2·5: a group of health and non-governmental organisations who collaborate to improve breast cancer outcomes. To date, the Community-based Program for Breast Health has successfully implemented steps 1, 2, and 3 of the Breast Cancer Initiative 2·5 model in Peru, with reports of increased awareness of breast cancer among women, improved capacity for early diagnosis among health workers, and the creation of stronger and more functional linkages between the primary levels (ie, local or community) and higher levels (ie, district, region, and national) of health care. The Community-based Program for Breast Health is a successful example of stakeholder and collaborator involvement-both internal and external to Peru-in the design and implementation of resource-appropriate interventions to increase breast health-care capacity in a middle-income Latin American country.


Development and evaluation of classifiers.
Diagnostic tests, medical tests, screening tests, biomarkers, and prediction rules are all types of classifiers. This chapter introduces methods for classifier development and evaluation. We first introduce measures of classification performance including sensitivity, specificity, and receiver operating characteristic (ROC) curves. We then review some issues in the design of studies to assess and compare the performance of classifiers. Approaches for using the data to estimate and compare classifier accuracy are then introduced. Next, methods for combining multiple classifiers into a single classifier are presented. Lastly, we discuss other important aspects of classifier development and evaluation. The methods presented are illustrated with real data.


Treatment of pulmonary aspergilloma by endoscopic intracavitary instillation of ketoconazole.
The authors report a case of pulmonary aspergilloma in which a fungus ball was visualized and a biopsy specimen was obtained at fiberoptic bronchoscopy. The fungus ball was successfully treated with bronchoscopic instillation of ketoconazole. It appears that this approach can be useful in the treatment of patients who are high-risk candidates for pulmonary resection.


Analysis of the effect of immunization in rabies time series.
The authors analysed time series of rabies cases diagnosed in Hungary between 1967 and 2001. In Transdanubia (West Hungary), an oral immunization program started in 1992 and in East Hungary in 2001. Both long term and seasonal trends were identified in the time series of rabies cases. In order to characterize the underlying processes governing the behaviour of the epidemic, the fluctuations around the trend were analysed before and after immunization separately. It turned out that the tail of the complementary cumulative distribution functions differ. The tail of the distribution follows an inverse power law (IPL) function and describes the distribution of extreme events. The significant difference in the IPL exponents before and after immunization can be explained by the theory of Highly Optimized Tolerance (HOT).


Low-intensity ultrasound adjuvant therapy: enhancement of doxorubicin-induced cytotoxicity and the acoustic mechanisms involved.
In this study, the effects of low-intensity pulsed ultrasound (LIU) as an adjuvant to doxorubicin (DOX) treatment was further investigated in comparison to hyperthermia as another widely used adjuvant. The effects were compared with respect to cell killing and apoptosis induction in U937 cells. Human primary liver cancer (PLC) cells were also used to evaluate the effects of the combinations. The use of an echo contrast agent was investigated for further enhancement of cytotoxicity. Finally, the acoustic mechanisms involved were investigated. The effects of different treatment regimens on cell viability were determined using the Trypan blue dye-exclusion test. Apoptosis induction was detected by flow cytometry using fluorescein isothiocyanate-annexin V and propidium iodide staining. The mechanistic study involved electron paramagnetic spin trapping for detecting free radical formation as an indicator of the occurrence of inertial cavitation and spectrophotometry for sucrose hydrolysis as an indicator for noncavitational effects. The combination treatments exerted synergistic effects on cytotoxicity depending on the acoustic conditions used. The use of LIU as an adjuvant to DOX treatment was shown to be superior to the use of hyperthermia as an adjuvant. Moreover, the combination seems to be promising for other cancer types provided that the acoustic conditions are properly selected with respect to drug concentration. The key ultrasound mechanism responsible for the synergism observed was shown to be the production of free radicals by inertial cavitation. Non-cavitational forces were also shown to contribute to the effect. This study is motivating to engage in in vivo research with various cancer types as a step toward clinical applicability and is emphasizing on the importance of developing therapeutic protocols for setting LIU parameters with respect to other therapeutic conditions.


Microcephalin 1/BRIT1-TRF2 interaction promotes telomere replication and repair, linking telomere dysfunction to primary microcephaly.
Telomeres protect chromosome ends from inappropriately activating the DNA damage and repair responses. Primary microcephaly is a key clinical feature of several human telomere disorder syndromes, but how microcephaly is linked to dysfunctional telomeres is not known. Here, we show that the microcephalin 1/BRCT-repeats inhibitor of hTERT (MCPH1/BRIT1) protein, mutated in primary microcephaly, specifically interacts with the TRFH domain of the telomere binding protein TRF2. The crystal structure of the MCPH1-TRF2 complex reveals that this interaction is mediated by the MCPH1 330YRLSP334 motif. TRF2-dependent recruitment of MCPH1 promotes localization of DNA damage factors and homology directed repair of dysfunctional telomeres lacking POT1-TPP1. Additionally, MCPH1 is involved in the replication stress response, promoting telomere replication fork progression and restart of stalled telomere replication forks. Our work uncovers a previously unrecognized role for MCPH1 in promoting telomere replication, providing evidence that telomere replication defects may contribute to the onset of microcephaly.


Pars plana vitrectomy for posteriorly dislocated intraocular lenses: risk factors and surgical approach.
To present updated risk factors, anatomical and visual outcomes and a surgical approach to posteriorly dislocated intraocular lenses (IOL). A retrospective case series review of patients presenting with posteriorly dislocated IOL to the vitreous was performed. All cases were managed surgically with pars plana vitrectomy (PPV) followed by IOL repositioning and refixation or IOL exchange. Clinical characteristics, risk factors for IOL dislocation, visual outcomes and intraoperative and postoperative complications were investigated. Forty patients with posteriorly dislocated IOL underwent 3-port PPV and lens retrieval at an average of 6.5 years after cataract surgery. The main causes of IOL dislocation were previous PPV, myopia, pseudoexfoliation syndrome, ocular trauma and recurrent intravitreal injections. The existing IOL was repositioned and secured in 90% of the cases. Visual acuity improved in 34 patients, maintained in 5 and deteriorated in 1. All IOLs were central and stable at final follow-up. Posterior intraocular lens dislocation is becoming more prevalent. The main underlying causes found in this series were previous vitrectomy, myopia and recurrent intra-vitreal substance injections. Visual acuity improved in most cases after lens repositioning; however visual outcome is often limited due to associated ocular co-morbidities despite adequate lens position. Despite complete lack of zonular support, a posteriorly dislocated IOL can often be preserved by repositioning and fixation of the lens in the posterior chamber. Pathologies primarily associated with this type of lens malposition include history of vitrectomy, high myopia and multiple intravitreal substance injections.


Small incision clear lens extraction for correction of high myopia.
To evaluate the effectiveness, predictability, and safety of clear lens extraction in the correction of high myopia. Kartal Education and Research Hospital, Istanbul, Turkey. This retrospective study comprised 56 eyes of 30 patients who had clear lens extraction to correct myopia of 12.00 diopters (D) or more. Small incision clear lens extraction using an anterior chamber maintainer was performed and low-power posterior chamber intraocular lens (IOL) was implanted. The mean postoperative follow-up was 40.2 +/- 11.9 months. Uncorrected visual acuity improved in 94.6% of eyes. Best-corrected visual acuity (BCVA) improved in 37 eyes (66%); 27 (48.2%) gained two or more lines. The percentage of eyes achieving a BCVA of 20/40 or better increased from 26.7% preoperatively to 58.9% postoperatively. Of the eyes, 38 (67.8%) were within +/- 1.00 D of targeted refractive error and 52 (92.8%) were within +/- 2.00 D. Posterior capsule tear with vitreous loss occurred in one eye (1.7%). During the follow-up, retinal detachment (RD) occurred in 2 eyes (3.5%). Clear lens extraction and IOL implantation was effective and had an acceptable predictability and a low morbidity in correcting high myopia. Regular retinal examination is necessary to prevent postoperative RD.


A rare case of combined small-cell lung cancer with unusual soft tissue metastasis.
Combined small-cell lung carcinoma (SCLC) is a rare tumor. We report a case of combined SCLC of the lung, including adenocarcinoma and spindle-shaped cell tumor, with an unusual initial presentation. The patient suffered from a right shoulder mass, subsequently undergoing biopsy. A lung nodule was noted later after complete examination. The diagnosis turned out to be combined cell carcinoma with three different components (small-cell carcinoma, adenocarcinoma, and spindle-shaped cell tumor) after examination upon total removal of the lung nodule by lobectomy. In addition to the rarity of the three components in such a tumor, soft tissue metastasis also made it an unusual case.


Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial.
Several lines of evidence suggest that classic psychedelics (5-HT2A receptor agonists or partial agonists) such as psilocybin might facilitate behavior change in individuals with substance use disorders. We conducted a multi-site, double-blind, randomized controlled trial (RCT) to assess the effects of psilocybin-assisted psychotherapy in alcohol-dependent volunteers. In addition to a structured 12-week psychotherapy platform, participants (n = 96) were randomly assigned (1:1) to receive either oral psilocybin or an active placebo (oral diphenhydramine) in each of two dosing sessions (at weeks 4 and 8). Initial doses were 25 mg/70 kg psilocybin or 50 mg diphenhydramine, which could be increased in the second session depending on initial response. The psychotherapy platform combined evidence-based, manualized therapy for alcohol dependence with a supportive context for the dosing sessions. All participants were followed in the RCT through week 36. At the end of the RCT, participants who still met safety criteria were offered an open-label psilocybin session. Data collected at screening, baseline and throughout the study included: demographics, measures of alcohol use, subjective response to psilocybin and diphenhydramine, and safety measures. The primary outcome was the proportion of heavy drinking days during the 32 weeks after the first dosing session (i.e., between week 4 and week 36). Secondary outcomes included safety, additional measures of drinking (e.g., abstinence, drinking days, etc.), craving, self-efficacy, and acute effects. We will also explore moderators and mediators of the primary outcome. The primary outcomes will be published elsewhere. In this paper, we describe the protocol and rationale for our design decisions.


Advice of General Practitioner, of Surgeon, of Endocrinologist, and Self-determination: the Italian Road to Bariatric Surgery.
Bariatric surgery (BS) is considered the most efficient treatment for severe obesity. International guidelines recommend multidisciplinary approach to BS (general practitioners, endocrinologists, surgeons, psychologists, or psychiatrists), and access to BS should be the final part of a protocol of treatment of obesity. However, there are indications that general practitioners (GPs) are not fully aware of the possible benefits of BS, that specialty physicians are reluctant to refer their patients to surgeons, and that patients with obesity choose self-management of their own obesity, including internet-based choices. There are no data on the pathways chosen by physicians and patients to undergo BS in the real world in Italy. An exploratory exam was performed for 6 months in three pilot regions (Lombardy, Lazio, Campania) in twenty-three tertiary centers for the treatment of morbid obesity, to describe the real pathways to BS in Italy. Charts of 2686 patients (788 men and 1895 women, 75.5% in the age range 30-59 years) were evaluated by physicians and surgeons of the participating centers. A chronic condition of obesity was evident for the majority of patients, as indicated by duration of obesity, by presence of several associated medical problems, and by frequency of previous dietary attempts to weight loss. The vast majority (75.8%) patients were self-presenting or referred by bariatric surgeons, 24.2% patients referred by GPs and other specialists. Self-presenting patients were younger, more educated, more professional, and more mobile than patients referred by other physicians. Patients above the age of 40 years or with a duration of obesity greater than 10 years had a higher prevalence of all associated medical problems. The majority of patients referred to a tertiary center for the treatment of morbid obesity have a valid indication for BS. Most patients self-refer to the centers, with a minority referred by a GP or by specialists. Self-presenting patients are younger, more educated, more professional, and more mobile than patients referred by other physicians. Older patients and with a longer duration of obesity are probably representative of the conservative approach to BS, often regarded as the last resort in an endless story.


Quantitative determination of anti-tumor agent bis(4-fluorobenzyl)trisulfide, fluorapacin and its pharmaceutical preparation by high-performance liquid chromatography.
A simple isocratic and stability-indicating HPLC method was developed and validated for the quantitative determination of anti-tumor agent fluorapacin and its pharmaceutical preparation. A Spherisorb ODS II C(18) (250 mm x 4.6 mm, 5 microm) column was eluted with a mobile phase consisting of acetonitrile/water (85:15, v/v). The analyses were performed at 40+/-1 degrees C with a flow rate of 1.0 mL/min and UV detection at 218 nm. The calibration curve was linear over a concentration range of 160-240 microg/mL with the correlation coefficient of 0.9997. The LOD and LOQ were determined to be 1.4 and 7.0 ng/mL, respectively. Average recoveries were 98.27% and 100.40% for fluorapacin API and its drug product with corresponding relative standard deviations (R.S.D.) of 0.41% and 0.30%, respectively. Good repeatability (precision and intermediate precision), accuracy and tolerability were obtained with R.S.D. of <1.0%. This specific and reliable method has been successfully applied for quality control of fluorapacin API and drug product.


The association of circulating endotoxaemia with the development of multiple organ failure in burned patients.
In this study, we examined the relationship of plasma endotoxin levels to the development of multiple organ failure (MOF), and the outcome in patients with thermal injury. A prospective cohort study of 17 patients admitted with burns covering more than 70 per cent of body surface area was undertaken. Circulating endotoxin concentrations were measured by modified limulus amoebocyte lysate assay in serial samples of plasma. Seven out of 17 burned patients developed MOF according to multiple criteria. The plasma endotoxin concentrations of patients with MOF were 0.512-1.127 EU/ml, which were significantly higher than that of 10 patients without MOF (0.216-0.553 EU/ml), on 3, 14, 21 and 28 days postburn (p < 0.05-0.01). A significantly higher incidence of positive endotoxin tests (> or = 0.120 EU/ml) was found in patients who developed MOF as compared to those patients who did not develop MOF during the observation period (p < 0.05). As the mean endotoxin levels increased, the incidence of MOF and death rate also increased, and persistent endotoxemia carried a poor prognosis. The present investigation provides further evidence that endotoxemia in severely burned patients commonly occurs. Circulating endotoxin has also been found to be strongly associated with the development of MOF and mortality following major burn injury.


A conservative strategy in non-ST-segment elevation myocardial infarction - constraints and prognosis: The situation in Portugal.
The aim of this study was to assess the impact of a conservative strategy in non-ST-segment elevation myocardial infarction in patients in the Portuguese Registry of Acute Coronary Syndromes. The 3780 patients included in the study over a three-year period were divided into three groups: group 1, patients treated by a conservative strategy during hospitalization; group 2, patients who underwent coronary angiography without percutaneous coronary intervention (PCI); and group 3, patients who underwent PCI. Clinical and procedural data and in-hospital complications were compared. The primary endpoint was defined as in-hospital or one-year mortality and the secondary endpoint as the presence of at least one of the following in-hospital complications: major bleeding according to the GUSTO criteria, need for blood transfusion, invasive ventilation, heart failure or reinfarction. Of the patients analyzed, 16.5% were treated by a conservative strategy. Patients in this group were older, more often women, and had more high-risk factors. A conservative strategy was associated with a higher rate of the primary endpoint - in-hospital mortality (10.6% vs. 1.1% vs. 0.6% in groups 1, 2 and 3, respectively, p<0.001, odds ratio (OR) 6.974, 95% confidence interval [CI]: 2.775-17.527) and one-year mortality (26.1% vs. 6.8% vs. 4.1%, p<0.001, hazard ratio (HR) 2.925, 95% CI: 1.433 -5.974) - and of the secondary endpoint - 37.2% vs. 18.9% vs. 14.6%, p<0.001; OR 1.471 95% CI: 1.043 -2.076. In this patient population, a conservative strategy is an independent predictor of in-hospital mortality, in-hospital complications and one-year mortality.


Carboxylic acid reductase: Structure and mechanism.
Carboxylic acid reductase (CAR) enzymes are large multi-domain proteins that catalyse the ATP- and NADPH-dependent reduction of wide range of acids to the corresponding aldehydes. This particular reaction is of considerable biotechnological interest. Recent advances in the structural and solution studies of isolated domain, di-domain and full-length CAR enzymes revealed valuable insights into the mechanism of carboxylic acid reduction activity. This review features the phylogenetic, sequence and structural insight into the CAR and implications of these observations in order to improve carboxylic acid reduction activity to develop CAR as robust biocatalyst.


Generalized attention-weighted reinforcement learning.
In neuroscience, attention has been shown to bidirectionally interact with reinforcement learning (RL) to reduce the dimensionality of task representations, restricting computations to relevant features. In machine learning, despite their popularity, attention mechanisms have seldom been administered to decision-making problems. Here, we leverage a theoretical model from computational neuroscience - the attention-weighted RL (AWRL), defining how humans identify task-relevant features (i.e., that allow value predictions) - to design an applied deep RL paradigm. We formally demonstrate that the conjunction of the self-attention mechanism, widely employed in machine learning, with value function approximation is a general formulation of the AWRL model. To evaluate our agent, we train it on three Atari tasks at different complexity levels, incorporating both task-relevant and irrelevant features. Because the model uses semantic observations, we can uncover not only which features the agent elects to base decisions on, but also how it chooses to compile more complex, relational features from simpler ones. We first show that performance depends in large part on the ability to compile new compound features, rather than mere focus on individual features. In line with neuroscience predictions, self-attention leads to high resiliency to noise (irrelevant features) compared to other benchmark models. Finally, we highlight the importance and separate contributions of both bottom-up and top-down attention in the learning process. Together, these results demonstrate the broader validity of the AWRL framework in complex task scenarios, and illustrate the benefits of a deeper integration between neuroscience-derived models and RL for decision making in machine learning.


Whole-genome sequencing of Mycobacterium tuberculosis from Cambodia.
Cambodia has one of the highest tuberculosis (TB) incidence rates in the WHO Western Pacific region. Remarkably though, the prevalence of multidrug-resistant TB (MDR-TB) remains low. We explored the genetic diversity of Mycobacterium tuberculosis (MTB) circulating in this unique setting using whole-genome sequencing (WGS). From October 2017 until January 2018, we collected one hundred sputum specimens from consenting adults older than 21 years of age, newly diagnosed with bacteriologically confirmed TB in 3 districts of Phnom Penh and Takeo provinces of Cambodia before they commence on their TB treatment, where eighty MTB isolates were successfully cultured and sequenced. Majority of the isolates belonged to Lineage 1 (Indo-Oceanic) (69/80, 86.25%), followed by Lineage 2 (East Asian) (10/80, 12.5%) and Lineage 4 (Euro-American) (1/80, 1.25%). Phenotypic resistance to both streptomycin and isoniazid was found in 3 isolates (3/80, 3.75%), while mono-resistance to streptomycin and isoniazid was identical at 2.5% (N = 2 each). None of the isolates tested was resistant to either rifampicin or ethambutol. The specificities of genotypic prediction for resistance to all drugs tested were 100%, while the sensitivities of genotypic resistance predictions to isoniazid and streptomycin were lower at 40% (2/5) and 80% (4/5) respectively. We identified 8 clusters each comprising of two to five individuals all residing in the Takeo province, making up half (28/56, 50%) of all individuals sampled in the province, indicating the presence of multiple ongoing transmission events. All clustered isolates were of Lineage 1 and none are resistant to any of the drugs tested. This study while demonstrating the relevance and utility of WGS in predicting drug resistance and inference of disease transmission, highlights the need to increase the representation of genotype-phenotype TB data from low and middle income countries in Asia and Africa to improve the accuracies for prediction of drug resistance.


Revaccination with 23-valent pneumococcal polysaccharide vaccine in the Japanese elderly is well tolerated and elicits immune responses.
Following primary vaccination of adults ⩾65years of age with 23-valent pneumococcal polysaccharide vaccine (PPSV23), immune responses increase and thereafter appear to decrease over time. With increased life expectancy worldwide, revaccination with PPSV23 may be required for continued protection of the elderly population against pneumococcal disease. The present study evaluated the immunogenicity and safety of revaccination with PPSV23 in the Japanese elderly. Depending on prior history of PPSV23 vaccination, adults aged ⩾70years were given a first dose (primary group; N=81) or second dose (revaccination group; N=161, at least 5years after first dose) of PPSV23 intramuscularly. Subjects were matched for gender, age, and number and type of comorbidity across both groups. Blood samples were collected before and 4weeks postvaccination to measure serotype-specific immunoglobulin G (IgG) concentrations and opsonophagocytic killing activity (OPA) antibody titers to serotypes included in the vaccine. Injection-site and systemic adverse events (AEs) were collected for 14days postvaccination. Baseline serotype-specific IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) were generally higher in subjects with a prior history of PPSV23 vaccination than in PPSV23-naïve subjects. The levels of IgG GMCs and OPA GMTs after revaccination were generally comparable to those observed after primary vaccination. Incidences of systemic AEs were comparable between the 2 groups. Although incidences of injection-site AEs were higher following revaccination than primary vaccination, the difference was not clinically significant as most AEs were mild to moderate in intensity and resolved within 5days after revaccination without treatment. Revaccination with PPSV23 was well tolerated and associated with increases in serotype-specific IgG concentrations and OPA titers in the elderly who received a prior PPSV23 dose at least 5years before. Revaccination with PPSV23 can be safely implemented in the elderly for continued prevention against pneumococcal disease. NCT02260882.


A phase I safety study of topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia.
Chemotherapy-induced alopecia (CIA) negatively affects psychosocial health and quality of life (QoL). Currently, there are no approved pharmacologic agents to prevent CIA. Here, we evaluated the safety, tolerability, and potential signal of efficacy of topical calcitriol (BPM31543) on CIA prevention. This Phase 1 trial included 23 female patients with breast cancer, gynecologic cancer, or sarcomas receiving a taxane-based chemotherapy. Patients received a 3 + 3 dose-escalation regimen at 5, 10, 20, 40, 60, and 80 μg/mL, with 3-6 patients per group. Patients applied topical BPM31543 to the scalp twice a day for 2 weeks prior to chemotherapy and continued until chemotherapy treatment was completed. The maximum tolerated dose (MTD) during first 28 day application was determined. Adverse event (AE) monitoring, pharmacokinetics, blinded photographic assessments, and patient self-assessment were evaluated. Out of 23 patients treated with BPM31543, 8 patients experienced at least 1 treatment-related adverse event (AE). The majority of AEs were mild to moderate in severity. Only 1 patient experienced SAEs (vomiting, nausea, fever, and flank pain) considered treatment related. Alopecia < 50% from baseline was observed in 8 patients at Week 7, and, of which 2 patients had < 50% alopecia maintained at Week 15. There were no detectable effects of topical BPM31543 on serum levels of calcitriol. BPM31543 applied topically twice daily to the scalp is safe and well tolerated in patients receiving taxane-based chemotherapy. No DLT was observed at up to 80 µg/mL, and MTD was not reached. Based on the data from this trial, BPM31543 represents a promising therapy and warrants further investigation in Phase 2/3 trials.


Multiwell in-gel protein digestion and microscale sample preparation for protein identification by mass spectrometry.
In-gel peptide digestion has become a widely used technique for characterizing proteins resolved by two-dimensional gel electrophoresis. Peptides generated from gel pieces are frequently contaminated with detergent and salts. Prior to matrix-assisted laser desorption/ionization-time of flight mass spectrometry analysis, these contaminants are removed using micro scale C18 sample preparation columns. In this paper, data are presented to demonstrate the application of a solvent resistant MultiScreen 96-well plate with a low peptide binding membrane and ZipTip micropipette based sample preparation. Recoveries of peptides (m/z of 1000 to 5000 Da) derived from standard protein protease digests, were estimated at various stages of the analytical process. An optimized protocol has been established and all the reagents and consumables have been packaged in a ready to use commercial kit. Data will be presented to show the application of this technology package to accelerate the throughput of protein characterization by protease fragmentation.


Molecular identification and antiviral function of the guanylate-binding protein (GBP) genes in the Chinese tree shrew (Tupaia belangeri chinesis).
Following viral detection and interferons (IFNs) production, several hundreds of IFN-stimulated genes (ISGs) are subsequently induced to act as direct antiviral effectors or regulators of the IFN signaling. The guanylate-binding protein (GBP) family belongs to IFN-inducible GTPases defending the host against a diverse group of invading pathogens such as parasites, bacteria and viruses. The Chinese tree shrew (Tupaia belangeri chinese) has been increasingly used as an alternative experimental animal to primates in studying viral infectious diseases. Hitherto, the tree shrew GBP family has not been characterized. In this study, we identified five tree shrew GBP genes (tGBP1, tGBP2, tGBP4, tGBP5 and tGBP7) and characterized their antiviral activities. All these tGBPs were ubiquitously expressed in heart, spleen, intestines, kidney, liver, lung and brain tissues of the tree shrew. IFN-γ treatment of tree shrew primary renal cells (TSPRCs) significantly induced the mRNA expression of tGBPs. Infections with Newcastle disease virus (NDV), encephalomyocarditis virus (EMCV) and type 1 herpes simplex virus (HSV-1) enhanced tGBPs mRNA expression in TSPRCs, but had no effect on the localization of tGBP proteins in the cytoplasm. tGBP1, but not the other four tGBPs, showed antiviral activity against vesicular stomatitis virus (VSV) and HSV-1 infections. Taken together, this study provided the first-hand information of the GBP family members in the Chinese tree shrew, which might assist the development of tree shrew animal model for infectious diseases.


Increase in intracellular free/bound NAD[P]H as a cause of Cd-induced oxidative stress in the HepG(2) cells.
The present study shows the use of confocal autofluorescence spectroscopy coupled with the time-resolved fluorescence decay analysis to measure changes in FAD/NAD[P]H and free/bound NAD[P]H in HepG(2) cells at 0.5, 1.5, 3 and 4.5h after exposure to cadmium chloride (Cd). These changes were compared to changes in GSSG/GSH and production of reactive oxygen radicals (ROS) production. The results demonstrated that both FAD/NAD[P]H and GSSG/GSH increased significantly upon exposure to Cd. The change in GSSG/GSH occurred as early as 1.5h after treatment while the change in FAD/NAD[P]H did not occur until 3h after exposure. Production of ROS was also increased at 1.5h. The ratio of free/bound NAD[P]H was studied. It was demonstrated that free/bound NAD[P]H increased significantly as early as 0.5h and remained elevated until 4.5h after treatment with Cd. The present study provides novel data to show that changes in NAD[P]H metabolism precedes the increase in ROS production and cellular oxidative stress (increase GSSG/GSH, FAD/NAD[P]H). It is suggested that Cd causes a release of NAD[P]H, an important cofactor for electron transfer, from its normal protein binding sites. This may result in a disruption of the activity of the enzyme and proteins, and may lead to the subsequent toxic events.


Metabolism of diethylstilbestrol in hamster hepatocytes.
Under certain modulating conditions the liver of the male Syrian golden hamster is a target organ for the carcinogenic effect of the synthetic estrogen diethylstilbestrol (DES). As a basis for mechanistic studies aimed at elucidating the role of metabolic activation in the process of DES-induced neoplasia, the metabolism of 14C-DES was investigated in freshly isolated hamster hepatocytes. These oxidative metabolites of DES, viz. Z,Z-dienestrol,3'-hydroxy-DES and 1-hydroxy-E-DES, were formed in 14.2, 9.1, and 0.3% yield, respectively, when hepatocytes were incubated with 50 nmol DES/mg cellular protein for 60 min. Glucuronides (4.0%) and sulfates (2.8%) of DES and of the oxidative metabolites were also found, and non-extractable binding of radioactivity to cellular protein was observed indicating the formation of reactive intermediates. The capability of hamster hepatocytes to oxidize and conjugate DES should allow the investigation of the effects of modulators on the metabolic activation of DES in this cellular system in order to help clarify the mechanisms of DES-induced hepatocarcinogenesis.


The Effect of a Higher Bias Gas Flow on Imposed T-Piece Resistance and Breathing in Preterm Infants at Birth.
The resistance created by the PEEP-valve of a T-piece resuscitator is bias gas flow dependent and might affect breathing in preterm infants. In this study we investigated the effect of a higher bias gas flow on the imposed inspiratory and expiratory T-piece resistance and expiratory breaking manoeuvres (EBM) in preterm infants during spontaneous breathing on CPAP at birth. In a retrospective pre-post implementation study of preterm infants <32 weeks gestation, who were stabilised with a T-piece resuscitator, a bias gas flow of 12 L/min was compared to 8 L/min. All spontaneous breaths on CPAP within the first 10 min of starting respiratory support were analysed on a breath-by-breath basis to determine the breathing pattern of each breath and to calculate the imposed inspiratory and expiratory T-piece resistance (Ri, Re), flow rates and tidal volume. In total, 54 infants were included (bias gas flow 12 L/min: n = 27, 8 L/min: n = 27) with a median GA of 29+6 (28+4-30+3) and 28+5 (25+6-30+3), respectively (p = 0.182). Ri and Re were significantly lower in the 12 L/min compared to 8 L/min bias flow group [Ri: 29.6 (26.1-33.6) vs. 46.4 (43.0-54.1) cm H2O/L/s, p < 0.001; Re: 32.0 (30.0-35.1) vs. 48.0 (46.3-53.9) cm H2O/L/s, p < 0.001], while the incidence of EBM [77% (53-88) vs. 77% (58-90), p = 0.586] was similar. During stabilisation of preterm infants at birth with a T-piece resuscitator, the use of a higher bias gas flow reduced both the imposed inspiratory and expiratory T-piece resistance for the infant, but this did not influence the incidence of EBMs.


Inhibition of the human tissue plasminogen activator in plasma from different species.
The rate and extent of complex formation between protease inhibitors present in plasma from different species and a human plasminogen activator purified to homogeneity from the supernatant of a human melanoma cell line was studied in vitro. The fibrinolytic activity of the one-chain plasminogen activator disappeared form human, cat and rabbit plasma with a half-life of 100 minutes. By means of antibodies directed against purified protease inhibitors the main inhibitor in human, cat, dog and rabbit plasma was identified as alpha 2-antiplasmin. Alpha 2-macroglobulin and C1-esterase-inhibitor functioned as inhibitors to a lesser extent. The main inhibitor in rat plasma was alpha 2-macroglobulin. The plasma half-life was 3 (rabbit and human) to 10 (dog and rat) times shorter for the two-chain form than for the one-chain form of the plasminogen activator molecule. It is also concluded that, with respect to plasma elimination of the fibrinolytic activity, among the common laboratory animals, the rabbit is the most suitable animal available for the study of fibrinolysis.


Unusual pseudocapacitive lithium-ion storage on defective Co3O4nanosheets.
Secondary lithium-ion batteries are restricted in large-scale applications including power grids and long driving electric vehicles owing to the low specific capacity of conventional intercalation anodes possessing sluggish Li-ion diffusion kinetics. Herein, we demonstrate an unusual pseudocapacitive lithium-ion storage on defective Co3O4nanosheet anodes for high-performance rechargeable batteries. Cobalt-oxide nanosheets presented here composed of various defects including vacancies, dislocations and grain boundaries. Unique 2D holey microstructure enabled efficient charge transport as well as provided room for volume expansions associated with lithiation-delithiation process. These defective anodes exhibited outstanding pseudocapacitance (up to 87%), reversible capacities (1490 mAh g-1@ 25 mA g-1), rate capability (592 mAh g-1@ 30 A g-1), stable cycling (85% after 500 cycles @ 1 A g-1) and columbic efficiency (∼100%). Exceptional Li-ion storage phenomena in defective Co3O4nanosheets is accredited to the pseudocapacitive nature of conversion reaction resulting from ultrafast Li-ion diffusion through various crystal defects. The demonstrated approach of defect-induced pseudocapacitance can also be protracted for various low-cost and/or eco-friendly transition metal-oxides for next-generation rechargeable batteries.


Evaluation of a charcoal-sorbitol mixture as an antidote for oral aspirin overdose.
The preparation of charcoal in a 70% sorbitol solution results in a suspension that is more palatable and less gritty than an aqueous slurry of charcoal. Although the charcoal-sorbitol mixture may be slightly less effective in reducing the extent of aspirin absorption compared with a charcoal slurry, it may prove to be of particular value in those cases where acceptance of a charcoal slurry presents a problem.


Leucaena species valoration for biomass and paper production in 1 and 2 year harvest.
In order to identify faster-growing non-woody species usable for biomass and paper production, four Leucaena species (L.diversifolia, L. colinsii, L. salvadorensis and three varieties of L. leucocephala) were tested. All the Leucaena species showed a good soil and climatic adaptation to Spain Southwest except for L. salvadorensis. Studied Leucaena species showed biomass productivity ranges from 67.14 to 9.44 t ha(-1) (o.d.b.) and 43.6 to 11.4 t ha(-1) under Mediterranean conditions for the first and second year sprouts, respectively. The quantity of solubles and extractives shows similar values when compared with wood materials. Relatively lower lignin content in Leucaena (from 15.7% to 21.4%) species has been found with respect to other vegetal species. The alpha-cellulose contents (39.4-45.3%) are in the range of the normal values expected for the other non-wood raw materials. The study confirms the feasibility of organocell yield pulping process to Leucaena species. Organocell process provides an efficient delignification (kappa number 12.4 and pulp yield 42.2%) for L. leucocephala and suitably physical characteristics of paper sheet (tensile index 20.3 kNm/kg for L. diversifolia).


Benefit of ultrasonography in the detection of clinically and mammographically occult breast cancer.
The purpose of this study was to evaluate the performance of high-resolution ultrasonography in the detection of clinically and mammographically occult breast cancer. From September 2003 to November 2006, a total of 1485 patients were confirmed to have in situ or invasive breast cancer in Hong Kong Sanatorium and Hospital Breast Care Centre. All patients underwent mammography (MMG) and/ or sonography (USG) evaluation. Patients' age and size of tumor detected by USG alone were compared with those detected by MMG. Altogether, 222 patients (17%) had positive imaging findings on USG only, among which 22 (13%) patients had nonpalpable tumors. Performing USG increased the cancer detection rate among clinically and mammographically occult breast lesions by 14.3%. The mean size of the tumors detected only by USG was 1.98 cm, which was not significantly different from the mean size of tumor detected by MMG (1.46) (p = 0.23). This remains true in the group of patients with nonpalpable tumors (1.36 vs. 1.46 cm, p = 0.88). The sensitivity of USG is 91%, which is significantly higher than that of MMG (78%) (p = 0.001). This remains true in patients age <40 or > or = 40, tumor grading I toIII, and LVI +/- cases. However, MMG had higher sensitivity in the group of patients with nonpalpable tumors (73% vs. 62%, p = 0.01) and noninvasive cancers (72% vs. 69%, p = 0.01). The use of high-resolution USG may lead to detection of a significant number of occult cancers that are no different in size from nonpalpable mammographically detected lesions.


A single Cu(II) catalyst for the three-component coupling of diverse nitrogen sources with aldehydes and alkynes.
A single Cu(II) catalyst without the addition of ligand or base couples a diverse range of nitrogen sources with alkynes and aldehydes bearing alkyl, halogenated, silyl, aryl, and heteroaryl groups. The first example of a copper-catalyzed alkynylation involving p-toluenesulfonamide provides high yields of N-Ts-protected propargylamines. The superior activity of copper(II) triflate also allows this three-component alkynylation to incorporate a ketone.


Enhanced ordering reduces electric susceptibility of liquids confined to graphene slit pores.
The behaviours of a range of polar and non-polar organic liquids (acetone, ethanol, methanol, N-methyl-2-pyrrolidone (NMP), carbon tetrachloride and water) confined to 2D graphene nanochannels with thicknesses in the range of 4.5 Å to 40 Å were studied using classical molecular dynamics and hybrid density functional theory. All liquids were found to organise spontaneously into ordered layers parallel to the confining surfaces, with those containing polar molecules having their electric dipoles aligned parallel to such surfaces. In particular, monolayers of NMP showed remarkable in-plane ordering and low molecular mobility, suggesting the existence of a previously unknown 2D solid-like phase. Calculations for polar liquids showed dramatically reduced static permittivities normal to the confining surfaces; these changes are expected to improve electron tunnelling across the liquid films, modifying the DC electrical properties of immersed assemblies of carbon nanomaterials.


Children with autism spectrum disorder perform comparably to their peers in a parent-child cooperation task.
This study investigates whether and how parent's cooperation affects child's cooperation, and whether that differs between children with/without autism spectrum disorder (ASD). The experiment involved a cooperative key-pressing task completed first by parent-parent dyads and then by parent-child dyads, meanwhile brain activity in the right frontal-parietal cortex of dyad partners was measured synchronously. The results showed the following: ASD children exhibited performance comparable to those of their peers, as was the level of brain synchronization with their parents, which was mainly due to parents with ASD children tending to adjust their own response patterns to match those of their children. These findings suggest that parents can somewhat actively mitigate the lower interpersonal synchronization ability of ASD children, in behavioral or/and neural level.


Depletion of CD8+ T cells increases susceptibility and reverses vaccine-induced immunity in mice infected with Trypanosoma cruzi.
The role of CD8+ T cells in immune control of Trypanosoma cruzi infection in mice was examined by using in vivo depletion of CD8+ T cells with antibodies. Both the resistant C57BL/6J and the highly susceptible C3H/HeSnJ developed higher parasitemias and increased or earlier mortality when depleted of CD8+ T cells before infection with the Brazil strain of T. cruzi. CD8 depletion also affected the induction and expression of immunity to T. cruzi after vaccination with the avirulent Corpus Christi strain of T. cruzi. C57BL/6J mice depleted of CD8+ T cells either before or after vaccination showed a near total loss of vaccine induced protection. C3H mice were only partially protected by the vaccination procedure but the protection was totally reversed by anti-CD8 treatment. Chronically infected mice that had survived the acute infection were unaffected by CD8 depletion and showed neither a recrudescence of parasitemia nor an increased susceptibility to reinfection. These results suggest that CD8+ T cells play a role in immunity to T. cruzi in the acute phase but possibly not during the chronic phase of infection. Also, immunization with Corpus Christi strain T. cruzi induces an immunity that is distinct from that induced by survival of the acute phase of infection. The mechanism by which CD8+ T cells contribute to control of T. cruzi infection is not known. However, CD8 depletion had no effect on suppressed immune responses, suggesting their function in T. cruzi-infected mice is related more to the cytotoxic activity or cytokine-producing capacity of this subpopulation of T cells.


Pattern of meningitis in Al-Ain medical district, United Arab Emirates--a decadal experience (1990-99).
Haemophilus influenzae vaccine was introduced in the United Arab Emirates in 1999. Our objective was to describe the pattern of meningitis in a health district in the decade before the introduction of the vaccine and compare it with the data from elsewhere. For this retrospective study we included 128 meningitis cases reported from 1990 to 1999. Information on the cases was abstracted from the case notification forms and clinical and laboratory data from the hospital case notes. H. influenzae was the most common cause of bacterial meningitis (n=59, 46.1%) followed by Streptococcus pneumoniae (n=20, 15.6%). Meningitis was a disease primarily of infants and children and the median age was 15 months. One fifth of the patients (n=27) had neurological sequelae of which 33.3% had seizures and 25.9% developed deafness. 18.9% (10 out of 53) of H. influenzae isolates were resistant to ampicillin compared with 5.9% (3 out of 51) to chloramphenicol. 78.9% (15 out of 19) of S. pneumoniae isolates were susceptible to penicillin. The epidemiology of meningitis in our health district is similar to the epidemiology of meningitis during the pre-vaccine era in other countries.


Aplastic anemia: a new complication in the recent mysterious hepatitis outbreak among children worldwide: two case reports.
Recently, an unknown hepatitis outbreak among children has concerned many individuals worldwide. These cases are frequently reported, mainly from Europe and other countries. In this study, we present two similar patients, who, to the best of our knowledge, are the first cases reported in the Middle East (Shiraz, Fars Province, Iran). Unlike in similar cases reported up until 30 April 2022, our patients' hepatitis eventually resulted in aplastic anemia. In this study, we present cases of two Iranian boys aged 13 and 8 years with hepatitis of unknown origin who developed aplastic anemia in the course of hospitalization. Hepatitis-associated aplastic anemia is a well-known immune-mediated form of aplastic anemia that we detected in our patients and treated with immunosuppressive therapy. One patient established a satisfactory response to the treatment, but unfortunately, the other was declared brain dead.


Circulating vitamin D binding protein levels are not associated with relapses or with vitamin D status in multiple sclerosis.
A low vitamin D status has been associated with multiple sclerosis (MS). Most circulating vitamin D metabolites are bound to vitamin D binding protein (DBP). The purpose of this study was to explore whether there is an association between MS and DBP. We compared DBP concentrations in blood samples of controls (n = 30) and subjects with relapsing-remitting MS (RRMS) during remission (n = 29) and relapse (n = 15). Furthermore, we explored correlations of DBP with 25- hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D levels (1,25(OH)2D), and the effect of high-dose vitamin D3 supplementation on DBP levels in RRMS patients (n = 15). DBP-concentration did not differ between the sub-groups measured, and there was no correlation between DBP and vitamin D metabolite concentration within the physiological range. Upon supplementation of high doses vitamin D3, DBP concentration remained unaltered. After supplementation, serum 1,25(OH)2D(R = 0.517, p = 0.049), but not 25(OH)D, correlated positively with DBP. We found no association between DBP, MS, and vitamin D status within the physiological range. After high-dose vitamin D supplementation, DBP concentrations may be relevant for vitamin D metabolism.


How to study proteins by circular dichroism.
Circular dichroism (CD) is being increasingly recognised as a valuable technique for examining the structure of proteins in solution. However, the value of many studies using CD is compromised either by inappropriate experimental design or by lack of attention to key aspects of instrument calibration or sample characterisation. In this article, we summarise the basis of the CD approach and its application to the study of proteins, and then present clear guidelines on how reliable data can be obtained and analysed.


Promoting the use of crumb rubber concrete in developing countries.
The use of accumulated waste materials in third world countries is still in its early phases. It will take courage for contractors and others in the construction industry to recycle selected types of waste materials in the concrete mixes. This paper addresses the recycling of rubber tires accumulated every year in Jordan to be used in concrete mixes. The main objectives of this research were to provide more scientific evidence to support the use of legislation or incentive-based schemes to promote the reuse of accumulated waste tires. This research focused on using crumb tires as a replacement for a percentage of the local fine aggregates used in the concrete mixes in Jordan. Different concrete specimens were prepared and tested in terms of uniaxial compression and splitting tension. The main variable in the mixture was the volumetric percentage of crumb tires used in the mix. The test results showed that even though the compressive strength is reduced when using the crumb tires, it can meet the strength requirements of light weight concrete. In addition, test results and observations indicated that the addition of crumb rubber to the mix has a limited effect toward reducing the workability of the mixtures. The mechanical test results demonstrated that the tested specimens of the crumb rubber concrete remained relatively intact after failure compared to the conventional concrete specimens. It is also concluded that modified concrete would contribute to the disposal of the non-decaying scrap tires, since the amount being accumulated in third world countries is creating a challenge for proper disposal. Thus, obliging authorities to invest in facilitating the use of waste tires in concrete, a fundamental material to the booming construction industry in theses countries, serves two purposes.


Pulmonary function testing of animals chronically exposed to diluted diesel exhaust.
The purpose of this work was to assess the potential effect that chronic inhalation of diesel exhaust may have on lung mechanics and lung volume. Noninvasive pulmonary function tests that produced data on lung air flows and volumes have been conducted repeatedly on 25 male Fischer-344 rats exposed to diesel exhaust at a particulate concentration of 1500 micrograms m-3, 20 h per day, 5 1/2 days per week, for 612 days. The same tests were conducted on 25 clean air control animals. When the data were normalized, the majority of tests did not reveal any significant deviation from the norm for the first year of exposure. In the second year, the functional residual capacity and its component volumes - expiratory reserve and residual volume, maximum expiratory flow at 40% of vital capacity, maximum expiratory flow at 20% of vital capacity and the forced expiratory volume in 0.1 s - were significantly greater in the diesel exposed animals. The data are inconsistent with known clinically significant adverse health effects. Although the lung volume changes in the diesel exposed animals could be indicative of emphysema or other forms of chronic obstructive lung disease, this interpretation is contradicted by the air flow data which suggest simultaneous lowering of the resistance of the smaller airways. The observations are not consistent with documented clinical lung disease in man.


A novel 2-(2-Formyl-4-methyl-phenoxy)-N-phenyl-acetamide-based fluorescence turn-on chemosensor for selenium determination with high selectivity and sensitivity.
A novel turn-on fluorescent chemosensor, 2-(2-Formyl-4-methyl-phenoxy)-N-phenyl-acetamide (FMPPA) was designed and synthesized, and its photophysical properties were characterized. Upon coordination with Se (IV), the chemosensor showed incredible fluorescence enhancement (turn-on), other alkali, alkaline earth, transitional metal ions, and common anions including Li(+), Na(+), K(+), Rb(+), Cs(+), Be(2+), Mg(2+), Ca(2+), Sr(2+), Ba(2+), Ni(2+), Cu(2+), Cd(2+), Zn(2+), Mn(2+), As(3+), Pt(4+), V(5+), Fe(3+), Mo(6+), Al(3+), CO3(2-), Cl(-), SCN(-), AC(-), NO3(-), F(-), SO4(2-) had no significant interference on Se (IV) determination. The chemosensor exhibits a dynamic response range for Se (IV) from 3.32 × 10(-7) to 2.63 × 10(-6)M, with a detection limit of 9.38 × 10(-9)M (3σ).


Disposition of fluoride in a fatal case of unsuspected sodium fluoride poisoning.
A case of suicidal ingestion of sodium fluoride roach powder by a 33-year-old black woman is presented. Disposition of fluoride (mg/l or mg/kg) was: bile, 3.4; gastric content, 225; kidney, 16; liver, 8.6 and urine, 295. No history of roach powder ingestion was available at autopsy. This case illustrates the need for extensive toxicological screening to determine if fatal poisoning has occurred when histopathological findings are unremarkable.


Tomato yellow vein streak virus and Tomato golden vein virus: a reappraisal of the classification status of two South American Begomovirus species based upon genome-wide pairwise identity of multiple isolates.
Tomato yellow vein streak virus (ToYVSV) and tomato golden vein virus (TGVV) are begomoviruses reported infecting tomatoes and other hosts across South America. However, their close phylogenetic relationship has generated uncertainties about their taxonomic status and nomenclature. In fact, genomic DNA-A identity levels of isolates reported with an identical virus name may range from 89-100%. In view of the potential inaccuracy regarding the classification status of these viruses (strains vs. distinct species), we carried out a comprehensive set of analyses employing all 45 available isolates with complete DNA-A sequences with either ToYVSV or TGVV designation. Two clear-cut clusters were identified and they were consistent with the current criteria for Begomovirus species demarcation. Moreover, our reappraisal confirmed a large array of misnamed isolates and recognized a distinctive set of virus species-specific genomic, biological, and ecological features. Hence, the present work gives support to the notion that these viruses are closely-related, but they are distinct and valid Begomovirus species. From the breeding standpoint, this information will be useful in guiding germplasm screening strategies searching for sources of large-spectrum resistance to isolates of both viruses.


[Is surgical education associated with additional costs? A controlled economic study on the German DRG System for primary TKA].
Total knee arthroplasty (TKA) is one of the most common procedures in orthopaedic surgery, the cost of surgical training has as yet not been quantified. In a pilot study, we investigated the economic impact of surgical training under DRG system influences, analysing the cost-proceeds structure in surgical training for orthopaedic residents. Consecutive TKAs were performed by the most educated surgeon (Group A) having implanted ≥ 1000 TKAs, another attending (Group B) with ≥ 200 TKAs and a resident (Group C) having assisted in 25 TKAs (n = 30 patients per Group A-C). All patients were embedded in a standardised clinical pathway. By analysing the costs parameters such as numbers of blood transfusions, the operating time and the length of stay in the hospital we investigated the health care-related costs matched to the DRG-based financial refunding. Data were analysed after undergoing a analysis of variance followed by a post-hoc Scheffé procedure. On the one hand the resident generated additional costs of 1111,7 ± 97 € in comparison to the Group A surgeon and 1729,8 ± 152 € compared to the attending Group B (p > 0,05), these were generated by longer stay in hospital, longer operation time and higher need of resources. On the other hand there were significantly higher proceeds of the Group C in comparison to the attending Group B and also to Group A: 474,78 ± 82 € vs. A and 150,54 ± 52 € vs. Group B (p < 0,05). This was generated both by a higher patient clinical level of complexity (PCCL) and increased complication rates resulting in a consecutively augmented profit by grouping these patients to a more lucrative DRG. Overall the deficit per patient treated by the resident is 637 ± 77 € vs. Group A and 1579,3 ± 137 € vs. Group B (p > 0,05). The German DRG matrix results in higher profits accounted to the learning surgeon by increased PCCL relevant status and grouping the case to a more profitable DRG. Hereby, the additional costs are only partly redeemed. Surgical education of residents is associated with additional costs for the hospital. These costs have to be redeemed to allow good surgical training for hospitals having good teaching conditions.


Survival From Pediatric Out-of-Hospital Cardiac Arrest During Nights and Weekends: An Updated Japanese Registry-Based Study.
Disparities in survival after pediatric out-of-hospital cardiac arrest (OHCA) between on-duty hours and off-duty hours have previously been reported. However, little is known about whether these disparities have remained in recent years. This study aimed to examine the association of outcomes after pediatric OHCA with time of day and day of week. This observational study analyzed the Japanese government-led nationwide population-based registry data of OHCA patients. Pediatric (<18 years) patients who experienced OHCA between 2012 and 2017 were included. A multivariable logistic regression model was used to examine the association of both time of day (day/evening vs night) and day of week (weekday vs weekend) with outcomes after OHCA. The primary outcome was 1-month survival. A total of 7,106 patients (mean age, 5.7 ± 6.5 years; 60.9% male) were included. 1,897 events (26.7%) occurred during night hours, and 2,096 events (29.5%) occurred on weekends. Overall, 1,192 (16.8%) survived 1 month after OHCA. After adjusting for potential confounders, 1-month survival during day/evening (1,047/5,209 [20.1%]) was significantly higher than that at night (145/1,897 [7.6%]) (adjusted odds ratio: 2.31 [95% CI: 1.87-2.86]), whereas there was no significant difference in 1-month survival between weekdays (845/5,010 [16.9%]) and weekends (347/2,096 [16.6%]) (adjusted odds ratio: 1.04 [95% CI: 0.88-1.23]). One-month survival after pediatric OHCA remained significantly lower during night than during day/evening, although disparities in 1-month survival between weekdays and weekends have been eliminated over time. Further studies are warranted to investigate the mechanisms underlying decreased survival at night.


Detection of phosphatidylcholine oxidation products in rat heart using quadrupole time-of-flight mass spectrometry.
An improved technique for the analysis of phosphatidylcholine (PC) and lyso-phosphatidylcholine (lyso-PC) oxidation products was developed using quadrupole time of flight (Q-TOF) mass spectrometry with electrospray ionization. We separated these products using an HPLC C(8) column with a gradient of methanol and 10mM aqueous ammonium acetate. Monohydroxides, oxo derivatives, and trihydroxides of palmitoyl-linoleoyl (C16:0/C18:2) PC, stearoyl-linoleoyl (C18:0/C18:2) PC, and oleoyl-linoleoyl (C18:1/C18:2) PC were detected mainly as MH(+) and [M+Na](+) ions in the heart of the intact rat. Using standard synthetic PC-OH (C16:0/C18:2-OH), the lipid extract component was identified as (C16:0/C18:2-OH) PC based on the product ions of ESI-MS-MS and, the PC-OH concentration was quantitated. Four oxidatively modified 1-lyso-phosphatidylcholines (lyso-PCs) were also detected. This is the first report showing the presence of monohydroxides, oxo derivatives, and trihydroxides of (C16:0/C18:2)PC, (C18:0/C18:2)PC, and (C18:1/C18:2) PC in the rat heart.


Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data.
To present efficacy and cycle control data pooled from three pivotal studies of the contraceptive patch (Ortho Evra/Evra). Three multicenter, open-label, contraceptive studies that included up to 13 treatment cycles. 183 centers. 3,319 women. Three consecutive 7-day patches (21 days) with 1 patch-free week per cycle. Contraceptive efficacy and cycle control. Overall and method failure life-table estimates of contraceptive failure through 13 cycles were 0.8% (95% CI, 0.3%-1.3%) and 0.6% (95% CI, 0.2%-0.9%), respectively. Corresponding Pearl indices were 0.88 (95% CI, 0.44-1.33) and 0.7 (95% CI, 0.31-1.10). Contraceptive failure among women with a body weight < 90 kg (<198 lb) was low and uniformly distributed across the weight range. A subgroup of women with body weight > or = 90 kg (> or = 198 lb) may have increased risk of pregnancy. The incidence of breakthrough bleeding was low and decreased over time. In contraceptive patch users, the overall annual probability of pregnancy was 0.8% and the method failure probability was 0.6%. The efficacy of the patch was high and similar across age and racial groups. Among women < 90 kg (<198 lb), contraceptive failure was low and uniformly distributed across the range of body weights. In women > or = 90 kg (> or = 198 lb), contraceptive failures may be increased. Efficacy and cycle control have been shown to be comparable to an established oral contraceptive.


Build It and They Shall Come: Medical Education Communities of Practice.
Producing scholarship in education is essential to the career development of a clinician-educator. Challenges to scholarly production include a lack of resources, time, expertise, and collaborators. To develop communities of practice for education scholarship through an international society to increase community and academic productivity. We developed multi-institutional scholarship pods within the American Thoracic Society through the creation of a working group (2017-2019). Pods met virtually, and meetings were goal focused to advance education scholarship within their area of interest. To understand the impact of these scholarship pods, we surveyed pod leaders and members in 2021 and analyzed the academic productivity of each pod via a survey of pod leaders and a review of the PubMed index. Nine pods were created, each with an assigned educational topic. The survey had a response rate of 76.6%. The perceived benefits were the opportunity to meet colleagues with similar interests at other institutions, production of scholarly work, and engagement in new experiences. The main challenges were difficulty finding times to meet because of competing clinical demands and aligning times among pod members. Regarding academic productivity, eight publications, four conference presentations, and one webinar/podcast were produced by six of the nine pods. The development of communities of practice resulted in increased multi-site collaboration, with boosted academic productivity as well as an enhanced sense of belonging. Multiple challenges remain but can likely be overcome with accountability, early discussion of roles and expectations, and clear delegation of tasks and authorship.


Haemocompatibility of amorphous hydrogenated carbon thin films, optical properties and adsorption mechanisms of blood plasma proteins.
Haemocompatibility is one of the most important properties, together with the tissue compatibility and corrosion and wear resistance that determine the biocompatibility of the artificial implants. Carbon-based thin films, such as amorphous carbon (a-C) and amorphous hydrogenated diamond-like carbon (a-C:H or DLC) are considered as excellent candidates for use as biocompatible coatings on biomedical implants. The aim of this work is the comparative study of the haemocompatibility of the a-C:H thin films developed by magnetron sputtering under various deposition conditions, the development of a methodology in order to study the haemocompatibility of thin films, the optical properties of the adsorbed proteins (human serum albumin and fibrinogen) and their adsorption mechanisms. Haemocompatibility and the optical properties of a-C:H thin films and the adsorbed proteins were studied by spectroscopic ellipsometry (SE). The films grown under floating conditions performed better haemocompatibility compared with those deposited under application of bias voltage. In the range of vis-UV, proteins are transparent, while they present an absorption peak at higher energies, but except these characteristics, their optical functions are rather featureless. Adsorption mechanisms were studied through AFM technique too. AFM results are in accordance with those derived by SE. Combination of the two techniques gives us a more accurate description of protein adsorption mechanisms.


Validation of an assessment, medical problem-oriented plan, and care plan tools for demonstrating the clinical pharmacist's activities.
Identifying, preventing, and resolving medical problems are some of the most central functions of clinical pharmacy (CP) and pharmaceutical care (PC) practitioners. Usually, the practitioners and researchers find a challenging to link the problem and the appropriate intervention to be included in the care plan. A comprehensive, well-structured, validated, simple use and standardized tool, which fulfill these requirements in daily clinical practice, are currently rare. To design and validate a comprehensive medical problem-oriented plan (MPOP) classification system in addition to assessment and care plan tools for use in practicing, researching, and teaching CP and PC. The methodology was composed of five steps: literature searching and classification of the problems; developing the assessment of treatments and care plan templates; implementing the tutorial; validation; completion and evaluation of the final version. The classification system (MPOP tool) is an open hierarchical structure, where higher levels are broadly defined, consisting of 5 main categories, and lower levels become more specific. In the MPOP tool's final version, a total of 24 major subcategories were distributed to the major five categories as 4 (Indication), 5 (Effectiveness), 7 (Safety), 3 (Patient), and 5 (Miscellaneous). Different minor subcategories (subcategory 2, n = 62) and 95 plans (interventions) were determined. Each of the subcategories and plans includes a notes section that represents a specific detail. There was strong agreement on using the MPOP tool between the two authors (κ = 1.000, p < 0.0005) and between three random clinical pharmacists out of 17 (κ = 0.947, 95% CI, 0.840 to 1.055, p < 0.0005). The validity and reliability statistics demonstrate that the Alsayed_v1 tools are extremely appropriate. The majority of users expressed high satisfaction with all the assessment, MPOP, and care plan tools. The Alsayed_v1 tools introduced in this paper were applied to actual patient cases and were validated. These tools include: assessment of treatments, MPOP, and care plan. Including the interventions in the classification system is important especially in PC research where the type of recommendations should be documented to assess the value and impact of the service and saves the time of practitioners in typing the appropriate interventions. By applying the steps within these Alsayed tools, the clinical pharmacists can actively provide the best practice to achieve the optimal patient outcome.


The evolution of selective primary health care.
This paper traces the evolution of the selective primary health care (SPHC) concept, from its presentation at a meeting in Bellagio, Italy, and its subsequent publication in the New England Journal of Medicine in 1979. It reviews the early debate between those in favor of selectivity and those in favor of comprehensive primary health care (CPHC). While this debate was going on, a breakthrough in terms of implementation came with UNICEF's launching of its Children's Revolution in 1982/83, promoting four specific 'social and scientific advances' for improving the health and nutrition of the world's children. They were growth monitoring, oral rehydration therapy, breastfeeding and immunization. Meanwhile the interest of a number of people for achieving 'Health For All' by targeting for action an essential short list of diseases was the impetus for another conference in 1985, Good Health at Low Cost. Through analysis of the achievements of four societies (Cost Rica, China, Kerala and Sri Lanka) efforts were made to define further a prioritized health development strategy, and a number of measures were identified as helping countries achieve good health. While some have argued that SPCH and CPHC are irreconcilable and diametrically opposed, this paper suggests that both SPCH and CPHC are both acceptable. Technology has its place. The field of view of SPHC has enlarged drastically, from individual diseases to the role of other sectors such as education and agriculture. The concept of SPHC has broadened to accept Rifkin's and Walt's assertion that "developmental processes need further exploration and research strengthening capabilities within countries".(ABSTRACT TRUNCATED AT 250 WORDS)


Chemical, Microbiological, and Functional Characterization of Kefir Produced from Cow's Milk and Soy Milk.
Kefir is a functional beverage that contains lactic and acetic acid bacteria (LAB, AAB) and yeasts. This work's aim was to study the chemical, microbial, and functional characteristics of kefir produced from cow's milk and soy milk. After fermentation, free amino acids were 20.92 mg 100 mL-1 and 36.20 mg 100 mL-1 for cow's milk and soy milk kefir, respectively. Glutamic acid was majority in both, suggesting that microbial proteolysis leads to an increase in free amino acids including glutamic acid. 108-109 CFU mL-1 LAB, 106-107 CFU mL-1 AAB, and 106-107 CFU mL-1 yeasts were counted in cow's milk kefir, whereas soy milk kefir contained greatly lower yeasts and AAB. Lactococcus lactis, Kazachstania unispora, and Saccharomyces cerevisiae were isolated as major microorganisms in both kefirs. Acetobacter orientalis only existed in cow's milk kefir. Cow's milk and soy milk showed ACE inhibitory activity, which significantly increased after fermentation. Both kefirs also exhibited antioxidant activity and bactericidal activity against Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus.


Radiotherapy in the age of cancer immunology: Current concepts and future developments.
Major advances in the knowledge of cancer biology and its interactions with tumor immune environment led to the emergence, in the last five years of new immunotherapy-based treatment strategies in cancer patients. At the same time, improvement in radiation technique and progress in radiobiology allowed in the last decade to expand the applications of radiotherapy in a growing number of settings. At present, there are strong theoretical basis to propose immune-enhanced radiation therapy that may represent in the future a new paradigm of treatment, combining the intrinsic power of radiotherapy to elicit a specific, systemic, tumor-directed immune response with modern highly conformal and precise dose delivery, in order to maximize response at the major site of disease and obtain durable disease control. The aim of this review is to describe the principal mechanisms of immune modulation of response to radiation and investigational strategies to harness the potential of radiation-inducible immune response: radiation therapy is expected to be not just a local treatment but the cornerstone of a multimodal strategy that might achieve long-lasting tumor remission at the primary site and systemic efficacy metastatic lesions.


Immune response of porcine alveolar macrophages to a concurrent infection with porcine reproductive and respiratory syndrome virus and Haemophilus parasuis in vitro.
Porcine reproductive and respiratory syndrome virus (PRRSV) can predispose pigs to secondary respiratory infection with bacteria such as Haemophilus parasuis. Animals infected with both pathogens develop more severe clinical disease. The immune response of porcine alveolar macrophages (PAMs) to simultaneous infection with PRRSV and H. parasuis was analysed in vitro, describing cytokine production, expression of cell surface molecules, and production of reactive oxygen species (ROS). Concurrent infection with PRRSV and H. parasuis increased gene expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) in PAMs in comparison with PAMs infected with PRRSV or H. parasuis alone. An additive effect of dual infection on IL-1β production was confirmed at the protein level. PAMs infected with PRRSV showed increased production of ROS compared to controls. Conversely, simultaneous infection of PAMs with PRRSV and H. parasuis decreased production of ROS, indicating the presence of an H. parasuis defence mechanism against respiratory burst. Concurrent infection of PAMs with PRRSV and H. parasuis was shown to elicit a pro-inflammatory immune response represented by significant IL-1β production. Severe multifactorial respiratory disease in natural conditions caused by both pathogens could be the consequence of pro-inflammatory mediated immunopathology.


Study on physicochemical, structural, and functional properties of Zhengdan958 and Xianyu335 cornstarch from newly harvested corn under postharvest ripening conditions at ambient temperature.
The importance of starch in nutrition and industry is unquestionable. This study investigated the changes in physicochemical, structural, and functional properties of cornstarch from newly harvested Zhengdan958 (Zd958) and Xianyu335 (Xy335) corn during for 0, 20, 40, and 60 d at ambient temperature. The results showed no significant changes in the proximate components and apparent structure of Zd958 and Xy335 cornstarch under postharvest ripening conditions. Compared with 0 d, the molecular weight distribution and mass fraction of Zd958 and Xy335 cornstarch have changed significantly, the relative crystallinity (RC) has significantly increased from 26.4% to 26.5%-28.8% and 28.4%, and R1045/1022 has significantly increased from 0.828 to 0.826 to 0.843 and 0.883, respectively. The changes in structure indicated that the synthesis and rearrangement of cornstarch molecules formed highly ordered crystalline structures, and the ordered structures of long-range and short-range molecules increased. Moreover, the changes in structure affected the pasting characteristics and texture profiles of cornstarch, therefore, affecting the final food quality.


Thumb reconstruction by the posterior interosseous osteocutaneous flap.
An island osteo-fasciocutaneous flap, based on the posterior interosseous vessels, is described for thumb reconstruction. The artery supplies the fascial plexus of the posterior forearm as well as the superficial and deep extensor muscles. A vascularised bone segment of the upper third of the ulna can be harvested, including a cuff of the extensor pollicis longus muscle. The flap was used successfully in two clinical cases.


Characterization of C30 carotenoid and identification of its biosynthetic gene cluster in Methylobacterium extorquens AM1.
Methylobacterium species, the representative bacteria distributed in phyllosphere region of plants, often synthesize carotenoids to resist harmful UV radiations. Methylobacterium extorquens is known to produce a carotenoid pigment and recent research revealed that this carotenoid has a C30 backbone. However, its exact structure remains unknown. In the present study, the carotenoid produced by M. extorquens AM1 was isolated and its structure was determined as 4-[2-O-11Z-octadecenoyl-β-glucopyranosyl]-4,4'-diapolycopenedioc acid (1), a glycosylated C30 carotenoid. Furthermore, the genes related to the C30 carotenoid synthesis were investigated. Squalene, the precursor of the C30 carotenoid, is synthesized by the co-occurrence of META1p1815, META1p1816 and META1p1817. Further overexpression of the genes related to squalene synthesis improved the titer of carotenoid 1. By using gene deletion and gene complementation experiments, the glycosyltransferase META1p3663 and acyltransferase META1p3664 were firstly confirmed to catalyze the tailoring steps from 4,4'-diapolycopene-4,4'-dioic acid to carotenoid 1. In conclusion, the structure and biosynthetic genes of carotenoid 1 produced by M. extorquens AM1 were firstly characterized in this work, which shed lights on engineering M. extorquens AM1 for producing carotenoid 1 in high yield.


Association between miRNA-145 and miRNA-155 expression in peripheral blood mononuclear cells of patients with multiple sclerosis: a case-control study.
MicroRNAs (miR or miRNA) are short regulatory RNAs, which modulate post-transcriptional gene expression. Dysregulation of these molecules contributes to pathogenicity of autoimmune disorders, such as multiple sclerosis (MS). This study was conducted to investigate changed expression pattern of miRNA-145 and miRNA-155 in MS. We collected blood samples of 75 patients with relapsing-remitting MS patients and 75 healthy controls. Ficoll-Hypaque density gradient method was used to isolate peripheral blood mononuclear cells. Also, total RNA was extracted and subjected to RT-PCR analysis. We used the Mann-Whitney U test to evaluate the differences in expression levels of target miRNAs between the groups. We found that expression of miRNA-145 (P = 0.012) and miRNA-155 (P = 0.005) were partly reduced in patients with relapse-remitting MS in comparison with healthy controls. The miRNA-145 had an area under curve (AUC) of 0.621 (P = 0.01) and miRNA-155 levels had an AUC of 0.625 (P = 0.008). Decreased expression of miRNA-145 and miRNA-155 contributes to development of relapse-remitting MS, while further large scale observational studies and meta-analyses are required.