Trends in dietary patterns and compliance with World Health Organization recommendations: a cross-country analysis.
To investigate time patterns of compliance with nutrient goals recommended by the World Health Organization (WHO). A single aggregated indicator of distance from the key WHO recommendations for a healthy diet is built using FAOSTAT intake data, bounded between 0 (maximum possible distance from goals) and 1 (perfect adherence). Two hypotheses are tested for different country groupings: (1) whether adherence has improved over time; and (2) whether cross-country disparities in terms of diet healthiness have decreased. One hundred and forty-nine countries, including 26 countries belonging to the Organisation for Economic Co-operation and Development (OECD) and 115 developing countries (including 43 least developed countries), with yearly data over the period 1961-2002. The Recommendation Compliance Index (RCI) shows significant improvements in adherence to WHO goals for both developing and especially OECD countries. The latter group of countries show the highest levels of the RCI and the largest increase over time, especially between 1981 and 2002. No improvement is detected for least developed countries. A reduction in disparities (convergence of the RCI) is observed only within the OECD grouping. Adherence to healthy eating guidelines depends on economic development. Diets are improving and converging in advanced economies, but developing and especially least developed countries are still far from meeting WHO nutrition goals. This confirms findings on the double burden of malnutrition and suggests that economic drivers are more relevant than socio-cultural factors in determining the healthiness of diets.


Ectopic expression of mucins in colorectal cancer metastasis.
Cancer metastasis is an ectopic growth of malignant cells. In human colorectal cancer, it is hypothesized that, during the progression of the disease to an advanced stage, highly malignant and metastatic tumor cells arise within primary tumors and become predominant. Based on this hypothesis, molecules associated with metastatic cells have been sought by the comparison of surgical specimens from patients at various clinical stages. Colorectal carcinomas with increased metastatic potential and with poor prognosis have been characterized by a loss of an organ-specific mucin determinant (sulfomucin), by an increased expression of non-intestinal sialomucins, and by an ectopic expression of adhesion ligands (sialyl-dimeric Lex antigens) on mucins.


RAD52 and ERCC6L/PICH have a compensatory relationship for genome stability in mitosis.
The mammalian RAD52 protein is a DNA repair factor that has both strand annealing and recombination mediator activities, yet is dispensable for cell viability. To characterize genetic contexts that reveal dependence on RAD52 to sustain cell viability (i.e., synthetic lethal relationships), we performed genome-wide CRISPR knock-out screens. Subsequent secondary screening found that depletion of ERCC6L in RAD52-deficient cells causes reduced viability and elevated genome instability, measured as accumulation of 53BP1 into nuclear foci. Furthermore, loss of RAD52 causes elevated levels of anaphase ultrafine bridges marked by ERCC6L, and conversely depletion of ERCC6L causes elevated RAD52 foci both in prometaphase and interphase cells. These effects were enhanced with combination treatments using hydroxyurea and the topoisomerase IIα inhibitor ICRF-193, and the timing of these treatments are consistent with defects in addressing such stress in mitosis. Thus, loss of RAD52 appears to cause an increased reliance on ERCC6L in mitosis, and vice versa. Consistent with this notion, combined depletion of ERCC6L and disrupting G2/M progression via CDK1 inhibition causes a marked loss of viability in RAD52-deficient cells. We suggest that RAD52 and ERCC6L play compensatory roles in protecting genome stability in mitosis.


Volvulus of the sigmoid colon.
A 30-year experience with sigmoid volvulus from the City of Memphis Hospital is presented with 121 cases. Differentiating viable from gangrenous sigmoid volvulus is difficult from history, physical examination, or laboratory data and one must rely on sigmoidoscopy. Sigmoidoscopy with insertion of a colon tube is the initial management with operative detorsion only if sigmoidoscopy fails. Elective sigmoid resection is advocated in view of the high recurrence rate. In gangrenous sigmoid volvulus, a Hartmann's procedure is preferred. There is a significant rate of "recurrent sigmoid volvulus" after elective resection.


Shape diagram of vesicles in Poiseuille flow.
Soft bodies flowing in a channel often exhibit parachutelike shapes usually attributed to an increase of hydrodynamic constraint (viscous stress and/or confinement). We show that the presence of a fluid membrane leads to the reverse phenomenon and build a phase diagram of shapes-which are classified as bullet, croissant, and parachute-in channels of varying aspect ratio. Unexpectedly, shapes are relatively wider in the narrowest direction of the channel. We highlight the role of flow patterns on the membrane in this response to the asymmetry of stress distribution.


Public health surveillance during Simhastha Kumbh, a religious mass gathering in Ujjain district, Madhya Pradesh, India, 2016.
A daily surveillance for disease detection and response at the Simhastha Kumbh Mela, in Ujjain, Madhya Pradesh, April-May 2016, was established. Existing weekly reporting of the Integrated Disease Surveillance Programme (IDSP) was modified to report 17 diseases or events from 22 public hospitals and three private hospitals in Ujjain. Water samples were also tested for fecal contamination in areas reporting diarrhea. We identified 56,600 ill persons (92% from government hospitals and 8% from private hospitals): 33% had fever, 28% acute respiratory infection, and 26% acute diarrheal diseases. There were 15 deaths (12 injury and 3 drowning). We detected two diarrhea outbreaks (Mahakaal Zone with 9 cases and Dutta Akhara Zone with 42 cases). Among 26 water samples, eight showed fecal contamination. This was a large implementation of daily disease surveillance in a religious mass gathering in India by IDSP. We recommended laboratory confirmation for diseases and similar daily surveillance in future mass gatherings in India.


Keys to success: pinpointing what works to improve hospital care.
In the quest to achieve better care, hospitals need to consider several factors that can mean the difference between success and failure. In a new report from the Commonwealth Fund, researchers sought to underscore these "ingredients for success" by studying what they considered four high-performing hospitals across the country: Beth Israel Deaconess Medical Center in Boston; El Camino Hospital in Mountain View, CA; Mission Hospitals in Asheville, NC; and Jefferson Regional Medical Center in Pittsburgh.


Occurrence and co-occurrence of hallucinations by modality in schizophrenia-spectrum disorders.
It is not only unclear why hallucinations in schizophrenia occur with different prevalence by modality, but also to what extent they do. Reliable prevalence estimates of hallucinations by modality in schizophrenia are currently lacking, particularly for non-auditory hallucinations. Studies have also tended to report lifetime, not point prevalence by modality. This study assessed the prevalence and co-occurrence of hallucinations, for both lifetime and point prevalence, across the auditory, visual, olfactory, and tactile modalities, in people diagnosed with chronic schizophrenia-spectrum disorders in Ireland (N=693) and Australia (N=218). Lifetime prevalence was 64-80% auditory, 23-31% visual, 9-19% tactile, and 6-10% olfactory. Past month prevalence was 23-27% auditory, 5-8% visual, 4-7% tactile, and 2% olfactory. The majority of participants had only hallucinated in one modality, with this nearly always being the auditory. Approximately one-third had hallucinated in two modalities, most commonly the auditory and visual. Most currently hallucinating patients also hallucinated in a single modality, again, nearly always the auditory. Whereas 30-37% of patients with lifetime auditory hallucinations had experienced visual hallucinations, 83-97% of patients with experience of visual hallucinations had experienced auditory hallucinations. These findings help delineate the modality distribution of hallucinations in schizophrenia, and provide an explanatory target for theoretical models.


The Impact of Social Media on Vaccination: A Narrative Review.
Vaccine hesitancy poses a significant global health challenge, fueled by misinformation and anti-vaccination campaigns on social media platforms (SMPs). This study examines the influence of social media on coronavirus disease 2019 (COVID-19) and non-COVID-19 vaccination in Asia during the peri-pandemic period. Through a comprehensive analysis of available literature, we aim to elucidate the role of SMPs in shaping vaccination attitudes and behaviors. The findings highlight the detrimental impact of social media on vaccination efforts and provide insights into addressing vaccine hesitancy during this critical period. A narrative review was conducted by searching the PubMed, Scopus, and Google Scholar databases from inception to May 26, 2022. Only English-language articles involving human participants from Asian countries were included in this review. Out of the 228 articles identified through the database search, 14 articles were included in the final analysis. The prevalence of COVID-19 vaccine hesitancy or negative attitudes towards COVID-19 vaccines in Asian countries was found to be high, ranging from 20% to 55% across countries. Notably, reliance on SMPs for vaccine-related information was associated with a higher likelihood of COVID-19 vaccine hesitancy. This trend coincided with the proliferation of misinformation and conspiracy theories that portrayed COVID-19 vaccines as harmful during the pandemic. Similar patterns were observed for other types of vaccines, including polio, measles mumps and rubella, and diphtheria-tetanus-pertussis vaccines. The use of SMPs was also found to be associated with increased fear among caregivers in Asian countries, as well as a 3-4 times higher likelihood of delayed immunization. SMPs negatively impact vaccine intent in Asia due to misinformation and anti-vaccination campaigns during the pandemic. However, they can be a powerful tool for healthcare providers and policymakers to promote informed decision-making. Efforts should focus on leveraging SMPs to disseminate reliable information and combat hesitancy, fostering a well-informed and vaccinated population in Asia.


Intracranial primary nonlymphomatous sarcomas in children: experience with eight cases and review of the literature.
Eight infants and children with intracranial primary nonlymphomatous sarcoma were studied clinically and histologically. Treatment consisted of surgical resection and postoperative radiation therapy. Only one patient received chemotherapy. Two patients are alive after 10 years, but the other six patients died 3 to 33 months after operation. Two illustrative cases with neuroradiological, light microscopic, and ultrastructural findings are presented; both cases showed radiological evidence of intracranial arterial encasement by sarcoma and computed tomographic evidence of multifocal lesions. The pertinent literature is reviewed to illuminate the more refined nature of primary sarcomas of the central nervous system. Irrespective of treatment, the majority of the patients had a limited survival and only a few lived longer than 5 years. Total resection seemed to afford the best prognosis, whereas the efficacy of radiation therapy and chemotherapy is indefinite.


Regulation of glucose-6-phosphate dehydrogenase in human erythrocytes.
Glucose-6-phosphate dehydrogenase catalyzes the initial and committed step of the pathway that is the principal source of NADPH in many cells. The intracellular rate of the enzyme in human erythrocytes was estimated from the rate at which the cells generated 14CO2 from 14C-labeled glucose in the presence of different amounts of methylene blue. This investigation differed from earlier studies in that: (a) accumulations of 6-phosphogluconate were considered in calculations of rate and (b) the cells were suspended in Krebs-Ringer bicarbonate buffer, which is the buffer system for erythrocytes in vivo. As with earlier studies, however, the intracellular enzyme was under unexplained inhibition or restraint relative to kinetic properties of the purified enzyme. Also, the intracellular enzyme exhibited sigmoid kinetics. In contrast, the isolated enzyme has been found to exhibit classical kinetics. In the course of dilution/ultrafiltration of the hemolysate a possible cause for the reduced activity of the enzyme was found: most of the NADP was bound to soluble macromolecules of the erythrocyte. The amount of NADP available to the enzyme was much less than the amount indicated by measurements of total (bound and unbound) NADP.


Evaluation of Quality Assessment Protocols for High Throughput Genome Resequencing Data.
Large-scale initiatives aiming to recover the complete sequence of thousands of human genomes are currently being undertaken worldwide, concurring to the generation of a comprehensive catalog of human genetic variation. The ultimate and most ambitious goal of human population scale genomics is the characterization of the so-called human "variome," through the identification of causal mutations or haplotypes. Several research institutions worldwide currently use genotyping assays based on Next-Generation Sequencing (NGS) for diagnostics and clinical screenings, and the widespread application of such technologies promises major revolutions in medical science. Bioinformatic analysis of human resequencing data is one of the main factors limiting the effectiveness and general applicability of NGS for clinical studies. The requirement for multiple tools, to be combined in dedicated protocols in order to accommodate different types of data (gene panels, exomes, or whole genomes) and the high variability of the data makes difficult the establishment of a ultimate strategy of general use. While there already exist several studies comparing sensitivity and accuracy of bioinformatic pipelines for the identification of single nucleotide variants from resequencing data, little is known about the impact of quality assessment and reads pre-processing strategies. In this work we discuss major strengths and limitations of the various genome resequencing protocols are currently used in molecular diagnostics and for the discovery of novel disease-causing mutations. By taking advantage of publicly available data we devise and suggest a series of best practices for the pre-processing of the data that consistently improve the outcome of genotyping with minimal impacts on computational costs.


[Preliminary aspects relating to the problem-solving process].
Certain theoretical and methodological aspects related to cognition and problem solving processes are reviewed in order to emphasize the inferencial procedures by which individuals overcome difficulties and limitations present in a problem situation and realize and overcome their own inferential limitations. The rôle that certain primary elements, like axioms, have in the process of making explicit and complete formal structures is also emphasized. Ability to demonstrate correctly and some limitations concerning the methalogic properties of axiomatic systems are also seen in relation to the inferential processes of cognition. Eliminatory inferential processes for adopting decisions are discussed and focused from opposite standpoints as those of associative learning theory and Gestalt theory. The inferential process is evaluated from the internal difficulty of a problem state of nature to the intellective resources available to the subject in order to validate the adopted decisions in problem solving. This comprises methods going from trial-and-error exploration to insight phenomena, through the formulation of all logical possibilities and the process of discarding them by means of experience or inference. According to the symbolic level that represents the problem state of nature formal structures are built up to the point by which they need to be gestallically closed by the inclusion of new primary terms or concepts that could be identified as axioms. This king of closure is postulated as a requirement of the aptitude for mathematics.


Efficacy of anti-TNFα drugs in patients with stricturing Crohn's disease.
Half of Crohn's disease patients develop stenosis around 20 years after the disease onset. For a long time, surgery has been the only therapeutic approach for strictures. The introduction of anti-TNFα could be revolutionary in the management of these patients due to their potential role in stenoses' treatment. The aim of our work was to summarize efficacy data of anti-TNFα drugs in stricturing CD patients. Several case series and observational studies have shown that infliximab and adalimumab are effective in determining improvement and remission of stenosis in CD patients in both clinical trials and clinical practice. The injection of intralesional infliximab could be a valid alternative in patients not responding to systemic therapy. Despite the promising literature data, the low level of evidence and the heterogeneity of the available studies do not allow to draw definitive conclusions on the use of TNFα inhibitors for the treatment of strictures. Further prospective randomized studies are needed to confirm and validate this therapeutic approach.


Safety of external fixation during postoperative chemotherapy.
We studied the safety of external fixation during post-operative chemotherapy in 28 patients who had undergone distraction osteogenesis (17, group A) or vascularised fibular grafting (11, group B) after resection of a tumour. Four cycles of multi-agent post-operative chemotherapy were administered over a mean period of 14 weeks (6 to 27). The mean duration of external fixation for all patients was 350 days (91 to 828). In total 204 wires and 240 half pins were used. During the period of post-operative chemotherapy, 14 patients (11 in group A, 3 in group B) developed wire- and pin-track infection. A total of ten wires (4.9%) and 11 half pins (4.6%) became infected. Seven of the ten infected wires were in periarticular locations. External fixation during post-operative chemotherapy was used safely and successfully for fixation of a vascularised fibular graft and distraction osteogenesis in 27 of 28 patients. Post-operative chemotherapy for malignant bone tumours did not adversely affect the ability to achieve union or cause hypertrophy of the vascularised fibular graft and had a minimal effect on distraction osteogenesis. Only one patient developed osteomyelitis which required further surgery.


[A woman with inguinal pain after a bone marrow biopsy].
Haemorrhaging after a bone marrow biopsy is a rare but possibly life-threatening event. We describe a case of a retroperitoneal haemorrhage after a routine bone marrow biopsy in a 77-year-old woman who presented the day after the procedure with inguinal pain.


Phase II open-label study investigating apalutamide in patients with biochemical progression after radical prostatectomy.
Apalutamide, a competent inhibitor of the androgen receptor, has shown promising clinical efficacy results for patients with advanced prostate cancer. Here, we describe the rationale and design for the SAVE trial, a multi-center, Phase II study, wherein 202 men with biochemical progression after radical prostatectomy are randomly assigned 1:1 to apalutamide plus salvage radiotherapy (SRT) or androgen-deprivation therapy with an luteinizing hormone-releasing hormone agonist or antagonist plus SRT. The primary objective is to compare sexual function between the two treatment arms based on the expanded prostate cancer index-26 sexual domain score at nine months after start of hormonal treatment. The key secondary objectives are to assess quality of life, to evaluate the safety profile and the short-term efficacy of apalutamide in combination with SRT. ClinicalTrials.gov identifier: NCT03899077.


Optimal hybrid sequencing and assembly: Feasibility conditions for accurate genome reconstruction and cost minimization strategy.
Recent advances in high-throughput genome sequencing technologies have enabled the systematic study of various genomes by making whole genome sequencing affordable. Modern sequencers generate a huge number of small sequence fragments called reads, where the read length and the per-base sequencing cost depend on the technology used. To date, many hybrid genome assembly algorithms have been developed that can take reads from multiple read sources to reconstruct the original genome. However, rigorous investigation of the feasibility conditions for complete genome reconstruction and the optimal sequencing strategy for minimizing the sequencing cost has been conspicuously missing. An important aspect of hybrid sequencing and assembly is that the feasibility conditions for genome reconstruction can be satisfied by different combinations of the available read sources, opening up the possibility of optimally combining the sources to minimize the sequencing cost while ensuring accurate genome reconstruction. In this paper, we derive the conditions for whole genome reconstruction from multiple read sources at a given confidence level and also introduce the optimal strategy for combining reads from different sources to minimize the overall sequencing cost. We show that the optimal read set, which simultaneously satisfies the feasibility conditions for genome reconstruction and minimizes the sequencing cost, can be effectively predicted through constrained discrete optimization. Through extensive evaluations based on several genomes and different read sets, we verify the derived feasibility conditions and demonstrate the performance of the proposed optimal hybrid sequencing and assembly strategy.


A role for the forebrain in mediating time-of-day differences in glucocorticoid counterregulatory responses to hypoglycemia in rats.
The time of day influences the magnitude of ACTH and corticosterone responses to hypoglycemia. However, little is known about the mechanisms that impart these time-of-day differences on neuroendocrine CRH neurons in the hypothalamic paraventricular nucleus (PVH). Rats received 0-3 U/kg insulin (or 0.9% saline) to achieve a range of glucose nadir concentrations. Brains were processed to identify phosphorylated ERK1/2 (phospho-ERK1/2)-immunoreactive cells in the PVH and hindbrain and CRH heteronuclear RNA in the PVH. Hypoglycemia did not stimulate ACTH and corticosterone responses in animals unless a glucose concentration of approximately 3.15 mM or below was reached. Critically the glycemic thresholds required to stimulate ACTH and corticosterone release in the morning and night were indistinguishable. Yet glucose concentrations below the estimated glycemic threshold correlated with a greater increase in corticosterone, ACTH, and phospho-ERK1/2-immunoreactive neurons in the PVH at night, compared with morning. In these same animals, the number of phospho-ERK1/2-immunoreactive neurons in the medial part of the nucleus of the solitary tract was unchanged at both times of day. These data collectively support a model whereby changes in forebrain mechanisms alter the sensitivity of neuroendocrine CRH to the hypoglycemia-related information conveyed by ascending catecholaminergic afferents. Circadian clock-driven processes together with glucose-sensing elements in the forebrain would seem to be strong contenders for mediating these effects.


Has social work met its commitment to Native Hawaiians and other Pacific Islanders? A review of the periodical literature.
Native Hawaiians and other Pacific Islanders (NHOPIs) were recognized in the 2000 U.S. census as a distinct racial minority group, with unique histories, values, and traditions. The profession of social work, with its historical commitment to social and cultural diversity, has begun to establish a knowledge base on this population in the periodical literature. In a review of literature published from 1995 to 2004, 32 articles were found in 23 journals. This represents 0.64 percent of the more than 5,000 articles published in these journals. Much of this literature, however, combined information on this population with that of Asian Americans, thereby masking the distinctiveness of Pacific Islanders. These results suggest that although social work has demonstrated a commitment to NHOPIs by beginning to establish a knowledge base, refinement and expansion of knowledge is still needed. The authors recommend three steps to refine this knowledge base: (1) increase the number of publications, (2) disaggregate data so that Asian Americans will be considered separately from NHOPIs, and (3) ensure that information on this population be anchored in cultural values and culturally based models of practice.


[Sequencing and analysis of N gene of street rabies virus isolated from different hosts in Zhejiang province].
To elucidate the characteristics of genetic variability and its relationship with prevalence, through sequencing and analysis of N gene among street rabies virus isolated from different hosts (homo sapiens, ferret badger, dog) in Zhejiang province. Samples were screened and confirmed by direct fluorescence assay and reverse transcript PCR. Sequences were analyzed using bio-information software. Eighteen street rabies virus strains were identified, including 2 from homo sapiens, 5 from ferret badger, and 11 from dog. Similarities of N gene and N protein were calculated to be 89.7%-100.0% and 98.4%-100.0% respectively. Mutations occurred in N gene were almost non-sense mutations. In addition,Data from phylogenetic analysis showed that all these strains could be classified into traditional genotype 1. The prevalence of rabies viruses among different hosts in Zhejiang province had certain regional properties. Rabies viruses isolated from the same kind of host or from the same/adjacent county/counties had the closest relationship. However, the characteristics of rabies virus prevalent in homo sapiens were somewhat complicated. In summary, the transmission of street rabies virus in Zhejiang province was from dogs to ferret badgers and homo sapiens, and the virus could circulate and cross-regional transmit among dogs and ferret badgers.


Primary disseminated form of Ewing sarcoma in association with hypercalcemia and acute renal failure.
We present a case of an extremely rare form of Ewing sarcoma--primary disseminated, with fulminating course, severe hypercalcemia, extensive calcium deposition in parenchymatous organs, including kidneys, and acute renal failure as a clinical consequence. Correction of hypercalcemia was followed by prompt restoration of the glomerular filtration rate (GFR), suggesting that hypercalcemia had a direct effect on its regulation independent of the renal tubular damage. The effectiveness of the treatment with indomethacin indirectly supports the possibility of prostaglandin-mediated humoral hypercalcemia of malignancy.


Directional bias during mating type switching in Saccharomyces is independent of chromosomal architecture.
Haploid Saccharomyces cells have the remarkable potential to change mating type as often as every generation, a process accomplished by an intrachromosomal gene conversion between an expressor locus MAT and one of two repositories of mating type information, HML or HMR. The particular locus selected as donor is dictated by the mating type of the cell, a bias that ensures productive mating type interconversion. Here we use green fluorescent protein tagging of the expressor and donor loci on chromosome III to show that this preference for donor locus does not result from a predetermined organization of chromosome III: HML and MAT as well as HMR and MAT remain separated in cells of both mating types. In fact, cells in which the inappropriate donor locus is artificially tethered to MAT still predominantly select the correct donor. We find, though, that initiation of switching leads to a rapid association of the correct donor locus with MAT. Thus, in mating type switching in Saccharomyces, donor preference is imposed at commitment to recombination rather than at physical contact of interacting DNA strands.


Temporomandibular joint dysfunction in various rheumatic diseases.
Temporomandibular disorder (TMD) is an inclusive term in which those conditions disturbing the masticatory function are embraced. It has been estimated that 33% of the population have signs of TMD, but less than 5% of the population will require treatment. The objective of this study was to measure the frequency of TMD in rheumatoid arthritis (RA), osteoarthrosis (OA), ankylosing spondylitis (AS) and systemic lupus erythematosus, and to define the limitations in everyday's life that patients perceive when present. A six-month survey of consecutive outpatients in a rheumatology clinic in a teaching hospital in Mexico was carried out. We defined TMD as: 1) the presence of pain; 2) difficulty on mouth opening, chewing or speaking; 3) the presence of non-harmonic movements of the temporomaxilar joints. All three characteristics had to be present. Z test was used to define differences between proportions. We present the results of 171 patients. Overall, 50 patients had TMD according to our operational definition (29.24%). Up to 76% of the sample had symptoms associated with the condition. TMD is more frequent in OA and in AS (29.24% vs 38% OA, P=0.009; 39% AS; P=0.005). We found no association between the severity of TMD and the request for specific attention for the discomfort produced by the condition. Only 8 of 50 (16%) patients with TMD had requested medical help for their symptoms, and they were not the most severe cases. TMD is more frequent in RA and OA. Although it may produce severe impairment, patients seem to adapt easily.


A Multidisciplinary Child Protection Team Improves the Care of Nonaccidental Trauma Patients.
We initiated a multidisciplinary Child Protection Team (CPT) as a subgroup of our pediatric multidisciplinary trauma peer review committee. Meetings are held monthly. Nonaccidental trauma (NAT) patients from the preceding month are reviewed. The meeting has two parts. During the open part, detectives and child protective services (CPS) workers are invited to discuss specific cases. The closed part focuses on improvement of specific processes and future outcomes. Attendance is recorded and minutes are kept. We sought to review accomplishments of this group. We retrospectively reviewed the minutes from our CPT meetings conducted between February 2014 and April 2015. We tracked attendance, cases reviewed, process improvement projects, and corrective action plans. Meeting attendance was very good-78 per cent. During the 15-month study period, we had 141 suspected NAT patients; 96 were reviewed at our meetings. CPS workers attended 53 per cent of the meetings; 13 investigations were discussed. We established a clinical practice guideline for the evaluation of NAT patients. We created a mechanism to improve compliance with follow-up skeletal surveys. Six corrective letters were sent to individuals notifying them of care concerns and opportunities for improvement. Equipment needs were identified, and we obtained a digital camera and speaker phone. We have conducted multiple educational sessions to increase awareness. Our CPT meeting has improved the care of our NAT patients and provided better communication between our hospital staff and CPS workers. We have improved inhospital processes for our NAT patients. We have provided educational opportunities to outside care providers.


Evidential meta-model for molecular property prediction.
The usefulness of supervised molecular property prediction (MPP) is well-recognized in many applications. However, the insufficiency and the imbalance of labeled data make the learning problem difficult. Moreover, the reliability of the predictions is also a huddle in the deployment of MPP models in safety-critical fields. We propose the Evidential Meta-model for Molecular Property Prediction (EM3P2) method that returns uncertainty estimates along with its predictions. Our EM3P2 trains an evidential graph isomorphism network classifier using multi-task molecular property datasets under the model-agnostic meta-learning (MAML) framework while addressing the problem of data imbalance. Our results showed better prediction performances compared to existing meta-MPP models. Furthermore, we showed that the uncertainty estimates returned by our EM3P2 can be used to reject uncertain predictions for applications that require higher confidence. Source code available for download at https://github.com/Ajou-DILab/EM3P2.


Precipitating Circumstances Associated With Intimate Partner Problem-Related Suicides.
In 2020, suicide was the 12th leading cause of death among adults in the U.S. Previous research has shown that one common precipitating circumstance among adult suicide decedents is experiencing intimate partner problems (IPPs), such as divorce, separation, romantic break-ups, arguments, conflicts, and intimate partner violence. This study examines how precipitating factors differ between IPP- and non-IPP-related suicides. In 2022, this study analyzed National Violent Death Reporting System data from adult suicide decedents in 48 states and 2 territories between 2003 and 2020. Multivariable logistic regression models were used to compare precipitating circumstances between IPP- and non-IPP-related suicides, controlling for sociodemographic characteristics. Of the 402,391 suicides, 20% (n=80,717) were known to be IPP-related. Circumstances that significantly increased the odds of IPP-related suicides included a history of suicidal thoughts and attempts and mental health problems (depressed mood, alcohol problem, mental health diagnosis), life stressors (interpersonal violence perpetration and victimization, arguments, financial problems, job problems, family problems), and recent legal problems. Non-IPP-related suicides were more likely to occur among older individuals and to be precipitated by a physical health problem or crime. The findings can inform prevention strategies that build resiliency and problem-solving skills, strengthen economic support, and identify and assist people at risk for IPP-related suicides. The Centers for Disease Control and Prevention's Suicide Resource for Action and Intimate Partner Violence Prevention resource packages highlight the best available evidence for policies, programs, and practices related to preventing suicides and IPP.


Clinical features and hospital management of bites by the white-lipped green pit viper (Trimeresurus albolabris).
The clinical features and hospital management of 31 patients who were bitten by the white-lipped green pit viper (Trimeresurus albolabris) in Hong Kong are reviewed. The cardinal features in these patients were local pain and swelling and mild coagulation abnormalities. Hospital management should include prophylaxis against tetanus, analgesics and measures to reduce local effects such as elevation of the limb. The benefits of the use of prophylactic antibiotics remain to be established. Severe coagulation disturbances were uncommon and responded to fresh frozen plasma and platelet transfusion.


Effects of N-acetyl cysteine on oxidative stress and TNF-α gene expression in diclofenac-induced hepatotoxicity in rats.
The consumption of non-steroidal anti-inflammatory drug, such as diclofenac, can lead to hepatotoxicity. In the present study, protective effect of N-acetyl cysteine (NAC) on diclofenac-induced hepatotoxicity was investigated. Thirty-two male rats were divided into four groups. Group 1 (control group) was treated with normal saline (1 ml/kg, i.p.) for 4 d. Group 2 (test without treatment) received diclofenac only (50 mg/kg, i.p.) for 4 d. Groups 3 and 4 received diclofenac (50 mg/kg, i.p.) plus NAC (150 mg/kg, p.o) and silymarin (100 mg/kg, p.o) for 4 d, respectively. At the end of experiment, serum glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), alkaline phosphatase (ALP), lipid profile, uric acid, protein carbonyl content, MDA, liver TNF-α, ferric-reducing antioxidant power, liver catalase, superoxide dismutase, vitamin C, and histopathological examination were done. In group 2, diclofenac caused a significant increase (p < .05) in the levels of serum ALP, GOT, GPT, TNF-α, uric acid, protein carbonyl content, MDA, and liver TNF-α gene expression as opposed to group 1. In treated groups with NAC and silymarin, a significant reduction (p < .05) was seen in all above mentioned parameters as well as improved liver histopathological changes compared with group 2. This study confirmed the protective effect of NAC on diclofenac-induced hepatotoxicity in rats due to not only reduces liver inflammatory cells, TNF-α, serum MDA, and PC but also through increases liver vitamin C, catalase, and superoxide dismutase activities.


Two new mutations in the MTATP6 gene associated with Leigh syndrome.
In this study we have analyzed the mtDNA encoded ATPase 6 and 8 genes ( MTATP6 and MTATP8) in two children with Leigh syndrome (LS) and reduced Mg (2+) ATPase activity in muscle mitochondria. In patient 1, with a mild and reversible phenotype, mutational analysis revealed a heteroplasmic T --> C mutation at nt position 9185 (T9185C) in the MTATP6. The mutation resulted in substitution of a highly conserved leucine to proline at codon 220. The proportion of the mutation was > 97 % in the patient's blood and muscle and 85 % in blood of his asymptomatic mother. Patient 2, with severe clinical phenotype and death at 2 years of age, exhibited a novel heteroplasmic T9191C missense mutation in the MTATP6, which converted a highly conserved leucine to a proline at position 222 of the polypeptide. The proportion of the mutation was 90 % in fibroblasts and 94 % muscle tissue. This mutation was absent in the patient's parents and sister suggesting that the mutation was de novo. Our findings expand the spectrum of mutations causing LS and emphasize the role of MTATP6 gene mutations in pathogenesis of LS.


Unique condensation patterns of triplex DNA: physical aspects and physiological implications.
Triple-stranded DNA structures can be formed in living cells, either by native DNA sequences or following the application of antigene strategies, in which triplex-forming oligonucleotides are targeted to the nucleus. Recent studies imply that triplex motifs may play a role in DNA transcription, recombination and condensation processes in vivo. Here we show that very short triple-stranded DNA motifs, but not double-stranded segments of a comparable length, self-assemble into highly condensed and ordered structures. The condensation process, studied by circular dichroism and polarized-light microscopy, occurs under conditions that mimic cellular environments in terms of ionic strength, ionic composition and crowding. We argue that the unique tendency of triplex DNA structures to self-assemble, a priori unexpected in light of the very short length and the large charge density of these motifs, reflects the presence of strong attractive interactions that result from enhanced ion correlations. The results provide, as such, a direct experimental link between charge density, attractive interactions between like-charge polymers and DNA packaging. Moreover, the observations strongly support the notion that triple-stranded DNA motifs may be involved in the regulation of chromosome organization in living cells.


Differential mRNA expression of seven genes involved in cholesterol metabolism and transport in the liver of atherosclerosis-susceptible and -resistant Japanese quail strains.
Two atherosclerosis-susceptible and -resistant Japanese quail (Coturnix japonica) strains obtained by divergent selection are commonly used as models to study atherosclerosis, but no genetic characterization of their phenotypic differences has been reported so far. Our objective was to examine possible differences in the expression of genes involved in cholesterol metabolism and transport in the liver between these two strains and to evaluate the value of this model to analyze the gene system affecting cholesterol metabolism and transport. A factorial study with both strains (atherosclerosis-susceptible versus atherosclerosis-resistant) and two diets (control versus cholesterol) was carried out. The mRNA concentrations of four genes involved in cholesterol biosynthesis (HMGCR, FDFT1, SQLE and DHCR7) and three genes in cholesterol transport (ABCG5, ABCG8 and APOA1) were assayed using real-time quantitative PCR. Plasma lipids were also assayed. Expression of ABCG5 (control diet) and ABCG8 (regardless of dietary treatment) and expression of HMGCR, FDFT1 and SQLE (regardless of dietary treatment) were significantly higher in the atherosclerosis-resistant than in the atherosclerosis-susceptible strain. Plasma triglyceride and LDL levels, and LDL/HDL ratio were significantly higher in the atherosclerosis-susceptible than in the atherosclerosis-resistant strain fed the cholesterol diet. In the atherosclerosis-susceptible strain, ABCG5 expression regressed significantly and positively on plasma LDL level, whereas DHCR7 and SQLE expression regressed significantly and negatively on plasma triglyceride level. Our results provide support for the hypothesis that the atherosclerosis-resistant strain metabolizes and excretes cholesterol faster than the atherosclerosis-susceptible strain. We have also demonstrated that these quail strains are a useful model to study cholesterol metabolism and transport in relation with atherosclerosis.


Role of phosphatidylserine and diacylglycerol in the fusion of chromaffin granules with target membranes.
The role of phosphatidylserine and diacylglycerol in the fusion of chromaffin granules with target membranes was investigated in vitro, monitoring the mixing of membrane lipids with the octadecyl rhodamine B fluorescence dequenching assay. Polylysine was able to induce fusion of chromaffin granule ghosts with plasma membrane vesicles in the absence of Ca2+. This fusion was maximal at 1.6 microM polylysine and the kinetics were dependent on the amount of plasma membrane added. Polylysine lowered the Ca2+ threshold concentration for inducing fusion, increased the extent of fusion at a given Ca2+ concentration and acted synergistically with Ca2+ when added prior to the cation. Removal of membrane proteins by trypsinization of chromaffin granule ghost and/or plasma membranes increased the extent of polylysine induced fusion. Incorporation of diacylglycerol into the plasma membrane promoted Ca(2+)-induced fusion. Chromaffin granule ghosts were induced to fuse with model membranes of different complexities from one resembling the inner monolayer of the erythrocyte membrane to one composed solely of pure phosphatidylserine. The characteristics of the fusion with model membranes were qualitatively similar to that observed with target plasma membrane, although differences in kinetics and stoichiometries were found. Interestingly, considerably low (microM) Ca2+ concentrations were able to induce fusion of chromaffin granule ghosts with diacylglycerol containing phosphatidylserine vesicles in the presence of polylysine. Our results indicate that acidic phospholipid-like phosphatidylserine may have an important role in the process of fusion and suggest that diacylglycerol, as a destabilizing lipid, may have a role by itself in promoting exocytosis in chromaffin cells.


Deep-Learning-Based Drug-Target Interaction Prediction.
Identifying interactions between known drugs and targets is a major challenge in drug repositioning. In silico prediction of drug-target interaction (DTI) can speed up the expensive and time-consuming experimental work by providing the most potent DTIs. In silico prediction of DTI can also provide insights about the potential drug-drug interaction and promote the exploration of drug side effects. Traditionally, the performance of DTI prediction depends heavily on the descriptors used to represent the drugs and the target proteins. In this paper, to accurately predict new DTIs between approved drugs and targets without separating the targets into different classes, we developed a deep-learning-based algorithmic framework named DeepDTIs. It first abstracts representations from raw input descriptors using unsupervised pretraining and then applies known label pairs of interaction to build a classification model. Compared with other methods, it is found that DeepDTIs reaches or outperforms other state-of-the-art methods. The DeepDTIs can be further used to predict whether a new drug targets to some existing targets or whether a new target interacts with some existing drugs.


The clinical pharmacology profile of the new antiepileptic drug perampanel: A novel noncompetitive AMPA receptor antagonist.
The clinical pharmacology profile of a drug critically determines its therapeutics, and this review summarizes the characteristics associated with the antiepileptic drug (AED) perampanel. A PubMed literature search was performed for perampanel. Congress abstract data are included where necessary and Eisai Ltd provided access to unpublished data on file. After oral ingestion, perampanel is rapidly absorbed and peak plasma concentrations occur 0.5-2.5 h later; its bioavailability is ~100%. Although the rate of perampanel absorption is slowed by food co-ingestion, the extent absorbed remains unchanged; therefore, perampanel can be administered without regard to meal times. The pharmacokinetics of perampanel are linear and predictable over the clinically relevant dose range (2-12 mg); perampanel is 95% protein-bound to albumin and α1-acid glycoprotein. Perampanel is extensively metabolized (>90%) in the liver, primarily by cytochrome P450 (CYP) 3A4, to various pharmacologically inactive metabolites. In healthy volunteers, the apparent terminal half-life is ~105 h, whereas the calculated effective half-life is 48 h. These half-life values allow for once-daily dosing, which will aid patient compliance and in the event of a missed dose, will have minimal impact on seizure control. In healthy volunteers prescribed carbamazepine, half-life decreases to 25 h. Clearance values are not significantly different in adolescents (~13.0 ml/min) and the elderly (~10.5 ml/min) compared with adults (10.9 ml/min). Perampanel has minimal propensity to cause pharmacokinetic interactions. However, it is the target of such interactions and CYP3A4-inducing AEDs enhance its clearance; this can be used to advantage because dose titration can be faster and thus optimum therapeutic outcome can be achieved sooner. Perampanel 12 mg, but not 4 or 8 mg, enhances the metabolism of the progesterone component of the oral contraceptive pill, necessitating the need for an additional reliable contraceptive method. Overall, perampanel has a favorable clinical pharmacology profile, which should aid its clinical use.


3D reconstruction of skin and spatial mapping of immune cell density, vascular distance and effects of sun exposure and aging.
Mapping the human body at single cell resolution in three dimensions (3D) is important for understanding cellular interactions in context of tissue and organ organization. 2D spatial cell analysis in a single tissue section may be limited by cell numbers and histology. Here we show a workflow for 3D reconstruction of multiplexed sequential tissue sections: MATRICS-A (Multiplexed Image Three-D Reconstruction and Integrated Cell Spatial - Analysis). We demonstrate MATRICS-A in 26 serial sections of fixed skin (stained with 18 biomarkers) from 12 donors aged between 32-72 years. Comparing the 3D reconstructed cellular data with the 2D data, we show significantly shorter distances between immune cells and vascular endothelial cells (56 µm in 3D vs 108 µm in 2D). We also show 10-70% more T cells (total) within 30 µm of a neighboring T helper cell in 3D vs 2D. Distances of p53, DDB2 and Ki67 positive cells to the skin surface were consistent across all ages/sun exposure and largely localized to the lower stratum basale layer of the epidermis. MATRICS-A provides a framework for analysis of 3D spatial cell relationships in healthy and aging organs and could be further extended to diseased organs.


Porous 3D columnar-sphere of NiO nanomaterials synthesized for supercapacitors via hydrothermal route: impact of thiourea concentration.
The charge storage application has witnessed a dramatic increase in terms of the short charge-discharge time of supercapacitors, specifically in highly active electrode materials. For charge storage supercapacitor applications, highly porous materials are preferable. In this research article, thiourea acts as a leaving agent in the preparation of the porous 3D spherical architecture of NiO nanomaterials. The influence of the molar concentration of thiourea on structural, morphological, and electrochemical charge storage applications has been studied. X-ray diffraction reveals a cubic structure with Fm3̄m space group for the NiO nanomaterials. The scanning electron microscopy (SEM) images show the porous 3D columnar spherical structure, and FTIR has been used for the optical analysis of the NiO materials. The 1D-3D columnar-spherical structure of the NiO flakes exhibits a high electrochemical charge storage pseudocapacitive nature. The optimized 0.40 M thiourea-NiO (Th-NiO) nanomaterial is highly hydrophilic, exhibiting a maximum specific capacity of 171.1 mA h g-1 at 5 mV s-1 by CV and 148.5 mA h g-1 at 0.2 mA cm-2 by GCD. The highest power, energy densities are 0.96 kW kg-1 and 6.66 W h kg-1 with the highest charge-discharge cycle rating of 92% up to 5000 cycles of the asymmetric NiO//rGO hybrid supercapacitor device.


The Quinlan case revisited.
... The point is that although physicians and hospitals (and their legal counsel) certainly feared in the 1970s and still fear prosecution and civil liability (and perhaps to an unreasonable degree), neither the complex psychosocial and economic nor the equally complex philosophical questions surrounding stopping artificial life support were settled at the time of the Quinlan case, and they are still not settled today. Perhaps our legal history does not need to be revised all that much.


Decidual/trophoblast prolactin-related protein: characterization of gene structure and cell-specific expression.
Decidual/trophoblast PRL-related protein (d/tPRP) is a member of the PRL gene family and is dually expressed in uterine and placental tissues in a highly coordinated pattern during pregnancy. In the present study, we describe the isolation and characterization of the d/tPRP gene. A lambda DASH II Wistar-Kyoto rat genomic library was screened with a labeled d/tPRP complementary DNA, resulting in the isolation of two phage clones, RGLd-41 [17.7 kilobases (kb)] and RGLd-42 (15.8 kb). RGLd-41 alone was found to contain the full-length d/tPRP gene and was used for subsequent analyses. The d/tPRP gene possesses a six-exon, five-intron organization. Relative to other highly conserved members of the PRL gene family, d/tPRP contains a single small additional exon (exon 3) situated between exons 2 and 3 of the prototypical PRL gene. The region corresponding to exon 3 of d/tPRP encodes for a unique amino acid region found in a subset of PRL family members. A reverse transcription-PCR (RT-PCR) tissue survey for d/tPRP messenger RNA revealed that d/tPRP expression was restricted to decidual and trophoblast tissues. A single transcription start site 65 bp upstream of the initiation codon was identified in decidual tissue, whereas multiple transcription start sites ranging from 61-66 bp upstream of the initiation codon were detected in placental tissue. Various tissue culture systems (primary cultures and cell lines) were evaluated for d/tPRP expression and activation of a 3.96-kb d/tPRP promoter-luciferase reporter construct. Decidual, spongiotrophoblast, and trophoblast giant cell populations expressed d/tPRP and were capable of activating the d/tPRP promoter-reporter construct, whereas other cell types were ineffective. Limited d/tPRP promoter activation was noted in uterine stromal cell lines. In summary, d/tPRP possesses a unique six-exon, five-intron gene structure and exhibits cell-specific expression that is regulated at least in part by a 3.96-kb 5'-flanking region.


Intention to quit among Indian tobacco users: findings from International Tobacco Control Policy evaluation India pilot survey.
Tobacco users face barriers not just in quitting, but also in thinking about quitting. The aim of this study was to understand factors encouraging intention to quit from the 2006 International Tobacco Control Policy (TCP) Evaluation India Pilot Study Survey. A total of 764 adult respondents from urban and rural areas of Maharashtra and Bihar were surveyed through face-to-face individual interviews, with a house-to-house approach. Dependent variable was "intention to quit tobacco." Independent variables were demographic variables, peer influence, damage perception, receiving advice to quit, and referral to cessation services by healthcare professionals and exposure to anti-tobacco messages. Logistic regression model was used with odds ratio adjusted for location, age, gender, and marital status for statistical analysis. Of 493 tobacco users, 32.5% intended to quit. More numbers of users who were unaware about their friends' tobacco use intended to quit compared to those who were aware (adjusted OR = 8.06, 95% CI = 4.58-14.19). Higher numbers of users who felt tobacco has damaged their health intended to quit compared to those who did not feel that way (adjusted OR = 5.62, 95% CI = 3.53-8.96). More numbers of users exposed to anti-tobacco messages in newspapers/magazines (adjusted OR = 1.76, 95% CI = 1.02-3.03), restaurants (adjusted OR = 2.47, 95% CI = 1.37-4.46), radio (adjusted OR=4.84, 95% CI = 3.01-7.78), cinema halls (adjusted OR = 9.22, 95% CI = 5.31-15.75), and public transportation (adjusted OR = 10.58, 95% = 5.90-18.98) intended to quit compared to unexposed users. Anti-tobacco messages have positive influence on user's intentions to quit.


Lipids of the ultra-thin square halophilic archaeon Haloquadratum walsbyi.
The lipid composition of the extremely halophilic archaeon Haloquadratum walsbyi was investigated by thin-layer chromatography and electrospray ionization-mass spectrometry. The analysis of neutral lipids showed the presence of vitamin MK-8, squalene, carotene, bacterioruberin and several retinal isomers. The major polar lipids were phosphatidylglycerophosphate methyl ester, phosphatidylglycerosulfate, phosphatidylglycerol and sulfated diglycosyl diether lipid. Among cardiolipins, the tetra-phytanyl or dimeric phospholipids, only traces of bisphosphatidylglycerol were detected. When the cells were exposed to hypotonic medium, no changes in the membrane lipid composition occurred. Distinguishing it from other extreme halophiles of the Halobacteriaceae family, the osmotic stress did not induce the neo-synthesis of cardiolipins in H. walsbyi. The difference may depend on the three-laminar structure of the cell wall, which differs significantly from that of other Haloarchaea.


Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study - PRIME study.
To assess the effectiveness, overall tolerability, and gastrointestinal (GI) tolerability of Durapain (fixed dose combination of tramadol hydrochloride immediate release [50 mg] and diclofenac sodium sustained release [75 mg]) in symptomatic treatment of severe acute pain in physician's routine clinical practice. In this prospective, multicenter, observational, post-marketing study, adult patients (aged 18-60 years) with severe acute pain were treated with tramadol hydrochloride/diclofenac sodium as per approved prescribing information. Evaluation was done at base-line, day 2, and day 5. Primary end point was pain intensity difference from baseline to day 5. A total of 351 patients (mean age 44.2 years; male 43%; female 57%) were included. The mean pain score was reduced from 9.2±1.09 at baseline to 2.8±1.73 at day 5 (p<0.0001). The number of patients with severe intensity of pain reduced from 100% at baseline to 18.3% at day 2 and 6.96% at day 5. According to the patient assessment, 68.36% of patients reported tolerability as "very good to good", whereas according to physician's assessment, "very good to good" tolerability was reported in 68.27% of patients. Five (1.43 %) patients discontinued the study because of adverse drug reaction. Five patients developed nine GI-related events of moderate intensity. Two patients developed three adverse reactions (burning sensation in urine, giddiness, and urine retention) other than GI events. No serious adverse drug reactions were reported during the study period. Tramadol hydrochloride/diclofenac sodium is an effective and well-tolerated treatment in Indian patients with severe acute pain. Treatment with tramadol hydrochloride/diclofenac sodium provides significant pain relief on day 2 and maintained until day 5 without any serious adverse reactions.


C-C bond formation with carbon dioxide promoted by a silver catalyst.
A catalytic amount of silver benzoate with 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD) was an effective catalytic system for the reaction of carbon dioxide with various ketones containing an alkyne group at an appropriate position. These reactions afforded the corresponding γ-lactone derivatives in good to high yields under mild conditions.


Education campaigns in coronary heart disease.
The key messages in health promotion materials have good short-term but poor long-term effects on health behaviour. An individual with risky health behaviour may increase their chances of developing heart disease. Understanding the psychosocial elements of behaviour may help health staff assist patients to adapt risky health behaviours. Nurses are in a prime position to ensure that the health promotion message is received and interpreted accurately by the patient.


The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation.
The short-chain fatty acid (SCFA) butyrate is produced via anaerobic bacterial fermentation within the colon and is thought to be protective in regard to colon carcinogenesis. Although butyrate (C4) is considered the most potent of the SCFA, a variety of other SCFA also exist in the colonic lumen. Butyrate is thought to exert its cellular effects through the induction of histone hyperacetylation. We sought to determine the effects of a variety of the SCFA on colon carcinoma cell growth, differentiation and apoptosis. HT-29 or HCT-116 (wild-type and p21-deleted) cells were treated with physiologically relevant concentrations of various SCFA, and histone acetylation state was assayed by acid-urea-triton-X gel electrophoresis and immunoblotting. Growth and apoptotic effects were studied by flow cytometry, and differentiation effects were assessed using transient transfections and Northern blotting. Propionate (C3) and valerate (C5) caused growth arrest and differentiation in human colon carcinoma cells. The magnitude of their effects was associated with a lesser degree of histone hyperacetylation compared with butyrate. Acetate (C2) and caproate (C6), in contrast, did not cause histone hyperacetylation and also had no appreciable effects on cell growth or differentiation. SCFA-induced transactivation of the differentiation marker gene, intestinal alkaline phosphatase (IAP), was blocked by histone deacetylase (HDAC), further supporting the critical link between SCFA and histones. Butyrate also significantly increased apoptosis, whereas the other SCFA studied did not. The growth arrest induced by the SCFA was characterized by an increase in the expression of the p21 cell-cycle inhibitor and down-regulation of cyclin B1 (CB1). In p21-deleted HCT-116 colon cancer cells, the SCFA did not alter the rate of proliferation. These data suggest that the antiproliferative, apoptotic and differentiating properties of the various SCFA are linked to the degree of induced histone hyperacetylation. Furthermore, SCFA-mediated growth arrest in colon carcinoma cells requires the p21 gene.


What the [beep]? Six-month-olds link novel communicative signals to meaning.
Over the first year, infants tune into the signals of their native language and begin to link them to meaning. Here, we ask whether infants, like adults, can also infer the communicative function of otherwise arbitrary signals (here, tone sequences) and link these to meaning as well. We examined 6-month-olds' object categorization in the context of sine-wave tones, a signal that fails to support categorization at any point during their first year. However, before the categorization task, we exposed infants to tones in one of two vignettes. In one, the tones were produced by an actor in a rich communicative exchange; in the other, infants heard the very same tones, but these were uncoupled from the actors' activity. Infants exposed to the communicative vignette successfully formed object categories in the subsequent test; those exposed to the non-communicative vignette failed, performing identically to infants with no prior exposure to this novel signal. This reveals in 6-month-old infants a remarkable flexibility in identifying which signals in the ambient environment are communicative and in linking these signals to core cognitive capacities including categorization.


Characterization of capillary inner surface conditions with streaming potential.
Streaming potential is created when an electrolyte solution is forced to flow pass a charged surface. For an uncoated fused silica capillary, the streaming potential is measured between the inlet and outlet vials while applying a pressure across the capillary. The changes in streaming potential can be used to characterize the properties of the capillary inner surface. In this work, HCl, NaCl, and NaOH solutions ranging from 0.4 to 6 mM were used as the background electrolyte (BGE) at temperatures of 15 to 35 °C for the mesurements. The streaming potential decreases with the increase in BGE concentration, and the trend is amplified at higher temperatures. When buffer solutions in the pH range of 1.5 to 12.7 were used as the BGE, streaming potential was shown to be sensitive to changes in pH but reaches a maximum at around 9.5. At pH < 3.3, no streaming potentials were observed. The pH of zero surface charge (streaming potential equals 0) changes with temperature, and is measured to be 3.3 to 3.1 when the temperature is changed from 15 to 35°C. Zeta potentials can be calculated from the measured streaming potential, conductivity, and the solution viscosity. Surface charge densities were calculated in this work using the zeta potentials obtained. We demonstrated that capillary surface conditions can significantly change the streaming potential, and with three different solutions, we showed that analyte-dependent adsorption can be monitored and mitigated to improve the peak symmetry and migration times reproducibility.


Varying effects of intravenous immunoglobulin on mononuclear cell proliferation in vitro.
Intravenous immunoglobulin (IVIG) is being increasingly used to treat numerous immune-mediated diseases. However, there is a paucity of knowledge on the specific mode of action of IVIG in vivo. In this study, the in vitro effects of IVIG on peripheral blood mononuclear cell (PBMC) proliferation using phytohemagglutinin (PHA), anti-CD3 monoclonal antibody (MAb), phorbol myristate acetate (PMA), or purified protein derivatives (PPD) have been analyzed. The PBMCs were obtained from more than 10 individual donors. In all cases, IVIG almost completely inhibited PBMC proliferation at concentration above 20 mg/mL except when used in conjunction with PMA. PHA-induced proliferation of PBMCs at concentrations ranging from 1 to 15 mg/mL did not show significant differences. Anti-CD3 MAb-induced proliferation showed dose-dependent inhibition at concentrations ranging from 1 to 10 mg/mL. Interestingly, PMA-induced proliferation of PBMCs showed a dose-dependent increase at the same concentration range. PPD-induced proliferation of PBMC at concentrations ranging from 1 to 10 mg/mL did not show any statistically significant differences. These results suggest that high dose IVIG may be necessary to immune modulation in vivo and IVIG has various effects on PBMCs proliferation in limited concentration in vitro.


[The incidence and predictors of atrial fibrillation in hypertrophic cardiomyopathy].
To observe the incidence and predictors of atrial fibrillation in hypertrophic cardiomyopathy (HCM). 612 HCM patients were analyzed prospectively from July 1990 to November 2007. The age, sex, height, weight, medical history, main symptoms and incidence of atrial fibrillation were recorded. The patients' mean age was (47.8 +/- 14.9). 414 patients (67.6%) were male. 377 patients (61.6%) had left ventricular outflow truct obstruction. 94 patients (15.4%) and atrial fibrillation. 43 patients (6.0%) had sustained and 51 patients (9.4%) had paroxysmal. The patients with atrial fibrillation were older in age and were predominantly female. Their medical history were longer, left atrial diameter (LAD) longer and plasma B-type natriuretic peptide (BNP) higher. logistic regression analysis indicated that the medical history (P = 0.012), LAD (P = 0.0001) and BNP (P = 0.017) were the independent predictors of atrial fibrillation in HCM. Atrial fibrillation was accompanied by a decrease in functional status and an increase in risk of stroke. The incidence of atrial fibrillation in HCM was high. The medical history, LAD and BNP were the independent predictors of its occurrence.


Increasing the field of view in grating based X-ray phase contrast imaging using stitched gratings.
Grating based X-ray differential phase contrast imaging (DPCI) allows for high contrast imaging of materials with similar absorption characteristics. In the last years' publications, small animals or parts of the human body like breast, hand, joints or blood vessels have been studied. Larger objects could not be investigated due to the restricted field of view limited by the available grating area. In this paper, we report on a new stitching method to increase the grating area significantly: individual gratings are merged on a carrier substrate. Whereas the grating fabrication process is based on the LIGA technology (X-ray lithography and electroplating) different cutting and joining methods have been evaluated. First imaging results using a 2×2 stitched analyzer grating in a Talbot-Lau interferometer have been generated using a conventional polychromatic X-ray source. The image quality and analysis confirm the high potential of the stitching method to increase the field of view considerably.


Note: A resonating reflector-based optical system for motion measurement in micro-cantilever arrays.
A robust, compact optical measurement unit for motion measurement in micro-cantilever arrays enables development of portable micro-cantilever sensors. This paper reports on an optical beam deflection-based system to measure the deflection of micro-cantilevers in an array that employs a single laser source, a single detector, and a resonating reflector to scan the measurement laser across the array. A strategy is also proposed to extract the deflection of individual cantilevers from the acquired data. The proposed system and measurement strategy are experimentally evaluated and demonstrated to measure motion of multiple cantilevers in an array.


Implications of a biphasic two-compartment model of constant flow ventilation for the clinical setting.
To investigate the theoretical effects of changing frequency (f), duty cycle (D), or end-inspiratory pause length on the distribution of ventilation and compartmental pressure in a heterogeneous, two compartment pulmonary model inflated by constant flow. Differential equations governing compartmental volume changes were derived and solved. Validation was conducted in a mechanical lung analogue with two mechanically independent compartments. Model predictions were then generated over wide ranges of f, D, or end-inspiratory pause. Disparity of compartmental end-expiratory pressure was identified as the primary mechanism by which changes in f, D, or pause alter the distribution of ventilation. Distribution of peak pressures was less sensitive to such changes. Compartmental ventilation was much less uniform than compartmental peak pressure. Ventilation could not be made entirely uniform by changes of f, D, or pause within the usual clinical range. In a linear, two compartment model of the respiratory system, disparity of compartmental end-expiratory pressures is the primary mechanism by which changes of f, D, or pause alter the distribution of ventilation during inflation with constant flow. Ventilation is less evenly distributed than peak alveolar pressure, and there are limits to the beneficial effects on the distribution of ventilation to be gained from manipulations of machine settings.


Electrical Characteristics of Metal-Oxide-Semiconductor Capacitor with High-κ/Metal Gate Using Oxygen Scavenging Process.
It has been widely accepted that the mismatch of lattice constants between HfO2 and Si generates interface traps at the HfO2-Si interface, which causes the degradation of device performances. For better interface quality, very thin SiO2 film (< 2 nm) has been inserted as an interlayer (IL) between HfO2 and Si despite of the increase of EOT. In order to obtain both the better interface quality and the reduction of EOT, we used Ti metal on HfO2/IL SiO2 stack as a scavenging layer to absorb oxygens in the SiO2 and various annealing conditions were applied to optimize the thickness of the SiO2. As a result, we can effectively shrink the EOT from 3.55 nm to 1.15 nm while maintaining the same physical thickness of gate stacks. Furthermore, the diffusion of oxygen was confirmed by high resolution transmission electron microscopy (HRTEM) and time-of-flight secondary ion mass Spectrometry (SIMS).


Recommendations for managing sexually transmitted infections: Incorporating the 2021 guidelines.
Sexually transmitted infections (STIs) are common and costly, with about 26 million STIs occurring each year in the US. Guidelines for the prevention and management of STIs are updated periodically. In 2021, the CDC updated its guidelines for the treatment of STIs. This article provides information on the most recent updates on managing STIs to help advanced practice nurses in their practice.


[Method of Calculating the Distance Between the Classes of the Structural Components of the Forebrain Birds].
The method of calculating the distance between the classes of the structural components of the brain of birds. Compared interclass distances of glia, neurons and neuroglial complexes in the forebrain hooded crow (Corvus cornix) (a bird with a highly rational activity) and common crossbill (Loxia curvirostra) (birds with a medium level of rational activity).


Impact of a long-term tobacco-free policy at a comprehensive cancer center: a series of cross-sectional surveys.
Spain has passed two smoke-free laws in the last years. In 2005, the law banned smoking in indoor places, and in 2010 the ban was extended to outdoor areas of certain premises such as hospitals. This study assesses the impact of smoking consumption among hospital workers at a comprehensive cancer center after the passage of two national smoke-free laws. Six cross-sectional surveys were conducted among a representative sample of hospital workers at a comprehensive cancer center in Barcelona (2001-2012) using a standardized questionnaire. Logistic regression was used to compare differences in the odds of smoking after the laws took effect (baseline vs. 1st law; 2nd law vs. 1st law). Baseline smoking prevalence was 33.1%. After passage of the 1st and 2nd laws, prevalence decreased, respectively, to 30.5% and 22.2% (p for trend =0.005). Prevalence ratios (PR) indicated a significant decrease in overall smoking after the 2nd law (PR = 0.65, 95% CI = 0.47-0-89). Smoking dropped in all professional groups, more prominently among those ≥35 years old, doctors, and women. Observed trends over the time included an increase in occasional smokers, a rise in abstinence during working hours but an increase in smoking dependence, and an increase in the employees' overall support for the smoke-free hospital project. A long-term tobacco control project combined with two smoke-free national laws reduced smoking rates among health workers and increased their support for tobacco control policies. The decrease was more significant after the passage of the outdoor smoke-free ban.


Structural and dynamic properties of concentrated alkali halide solutions: a molecular dynamics simulation study.
The physicochemical properties of alkali halide solutions have long been attributed to the collective interactions between ions and water molecules in the solution, yet the structure of water in these systems and its effect on the equilibrium and dynamic properties of these systems are not clearly understood. Here, we present a systematic view of water structure in concentrated alkali halide solutions using molecular dynamics simulations. The results of the simulations show that the size of univalent ions in the solution has a significant effect on the dynamics of ions and other transport properties such as the viscosity that are correlated with the structural properties of water in aqueous ionic solution. Small cations (e.g., Li+) form electrostatically stabilized hydrophilic hydration shells that are different from the hydration shells of large ions (e.g., Cs+) which behave more like neutral hydrophobic particles, encapsulated by hydrogen-bonded hydration cages. The properties of solutions with different types of ion solvation change in different ways as the ion concentration increases. Examples of this are the diffusion coefficients of the ions and the viscosities of solutions. In this paper we use molecular dynamics (MD) simulations to study the changes in the equilibrium and transport properties of LiCl, RbCl, and CsI solutions at concentrations from 0.22 to 3.97 M.


DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment.
MDSCs represent one of the key players mediating immunosuppression. These cells accumulate in the TME, lymphoid organs, and blood during tumor growth. Their mobilization was also reported after CY therapy. DNMTi 5AC has been intensively studied as an antitumor agent. In this study, we examined, using two different murine tumor models, the modulatory effects of 5AC on TU-MDSCs and CY-MDSCs tumor growth and CY therapy. Indeed, the percentage of MDSCs in the TME and spleens of 5AC-treated mice bearing TRAMP-C2 or TC-1/A9 tumors was found decreased. The changes in the MDSC percentage were accompanied by a decrease in the Arg-1 gene expression, both in the TME and spleens. CY treatment of the tumors resulted in additional MDSC accumulation in the TME and spleens. This accumulation was subsequently inhibited by 5AC treatment. A combination of CY with 5AC led to the highest tumor growth inhibition. Furthermore, in vitro cultivation of spleen MDSCs in the presence of 5AC reduced the percentage of MDSCs. This reduction was associated with an increased percentage of CD11c+ and CD86+/MHCII+ cells. The observed modulatory effect on MDSCs correlated with a reduction of the Arg-1 gene expression, VEGF production, and loss of suppressive capacity. Similar, albeit weaker effects were observed when MDSCs from the spleens of tumor-bearing animals were cultivated with 5AC. Our findings indicate that beside the direct antitumor effect, 5AC can reduce the percentage of MDSCs accumulating in the TME and spleens during tumor growth and CY chemotherapy, which can be beneficial for the outcome of cancer therapy.


Topography of the membrane domain of the liver Na+-dependent bile acid transporter.
The ileal apical and liver basolateral bile acid transporters catalyze the Na+-dependent uptake of these amphipathic molecules in the intestine and liver. They contain nine predicted helical hydrophobic sequences (H1-H9) between the exoplasmic N-glycosylated N terminus and the cytoplasmic C terminus. Previous in vitro translation and in vivo alanine insertion scanning studies gave evidence for either nine or seven transmembrane segments, with H3 and H8 noninserted in the latter model. N-terminal GFP constructs containing either successive predicted segments or only the last two domains of the liver transporter following a membrane anchor signal were expressed in HEK-293 cells, and a C-terminal glycosylation flag allowed detection of membrane insertion. Western blot analysis with anti-GFP antibody after alkali and PNGase treatment showed that H1, H2, H3 behaved as competent transmembrane (TM) sequences. Results from longer constructs were difficult to interpret. H9, however, but not H8 was membrane-inserted. To analyze the intact transporter, a C-terminal YFP fusion protein was expressed as a functionally active protein in the plasma membrane of HEK-293 cells as seen by confocal microscopy. After limited tryptic digestion to ensure the accessibility of only exoplasmic lysine or arginine residues, molecular weight (MW) analysis of the five cleavage products on SDS-PAGE predicted the presence of seven transmembrane segments, H1, H2, H3, H4, H5, H6, and H9, with H7 and H8 exoplasmic. This new method provided evidence for seven membrane segments giving a new model of the membrane domain of this protein and probably the homologous ileal transporter, with H7/H8 as the transport region.


Dietary sugar and artificial sweetener intake and chronic kidney disease: a review.
Sugar consumption, especially in the form of fructose, has been hypothesized to cause kidney disease. This review provides an overview of the epidemiologic evidence that sugar consumption increases CKD risk. Research supports a causal role of sugar in several kidney disease risk factors, including increasing serum uric acid levels, diabetes, and obesity. Sugar may also harm the kidney via other mechanisms. There is no evidence that sucrose is any safer for the kidney than high fructose corn syrup (HFCS) because both are similar in composition. To date, 5 epidemiologic studies have directly evaluated the relationship between sugar consumption (in the form of sugar-sweetened beverages) and CKD. Although most studies suggest that the risk of CKD is elevated among consumers of sugar-sweetened beverages, only 2 studies report statistically significant associations. Three studies have also examined diet soda consumption, with two reporting positive and significant associations. Confounding by unmeasured lifestyle factors may play a role in the positive results whereas poor measurement of sugar and artificial sweetener intake could explain null results. Nevertheless, the hypothesis that sugar causes kidney disease remains plausible, and alternative research designs may be needed.


Muscle growth mechanisms in response to isoenergetic changes in dietary non-protein energy source at low and high protein levels in juvenile rainbow trout.
This study investigates muscle growth mechanisms in juvenile rainbow trout in response to isoenergetic changes in dietary non-protein energy (NPE) source (F, fat vs. C, carbohydrates) at two levels of digestible protein to digestible energy (DP/DE) ratio. Fish (initial weight 32.4 g) were fed four diets having similar DE levels (~18 kJ g-1) with a high (HP/E~26 mg kJ-1) vs. low (LP/E~14 mg kJ-1) DP/DE ratio using F or C as major NPE source (7 week-experiment). The lowering of dietary DP/DE ratio increased myoblast determination protein 1a (myod1a) and decreased myostatin 1b (mstn1b) and cathepsin D (ctsd) muscle mRNA levels. The isoenergetic change in dietary NPE from F to C decreased myod1a and proliferative cell nuclear antigen (pcna) muscle mRNA levels. An interaction between DP/DE ratio and NPE source was observed in muscle transcript levels of myogenic factor 6 (mrf4/myf6), fast myosin heavy chain (fmhc) and fast myosin light chain 2 (fmlc2). White muscle total cross-sectional area decreased at low dietary DP/DE ratio and also when NPE source changed from F to C, linked i) to a decreased total number of white muscle fibres, indicating that low dietary DP/DE restricted muscle hyperplasia and that dietary carbohydrate were less efficiently used than fat to sustain muscle hyperplasia, and ii) to decreased percentage of large muscle fibres, indicating limited fibre hypertrophy. Not only the DP level or the DP/DE ratio, but also the isoenergetic change in dietary NPE source (fat vs carbohydrates) thus appears as a potent regulator of muscle hyperplasia and hypertrophy.


A Multilaboratory Commutability Evaluation of Proficiency Testing Material for Carbamazepine and Valproic Acid: A Study Within the Framework of the Dutch Calibration 2000 Project.
Medical laboratories are required to participate in interlaboratory comparisons of the analyses they perform. The materials used in these comparisons need to be of sufficient quality so that the comparison provides a picture of the performances. One of the main characteristics of the testing material is commutability, which is the ability of a material to yield the same numerical relationships between results of measurements as those relationships obtained when the same procedures are applied to patient samples. The aim of this study was to assess the commutability of 3 different matrices for the preparation of proficiency testing material (PTM) for the analysis of carbamazepine and valproic acid. Patient samples and PTM containing various concentrations of carbamazepine and valproic acid were collected, prepared, and shipped to different laboratories for analysis. Reported results for patient samples from each laboratory were plotted against results for patient samples of each of the other laboratories, and the corresponding regression line was calculated. The distance of results from PTM to the regression line is a measure for commutability. The distance is expressed as a multiple of the SDwl (average within-laboratory SD as calculated from external quality assessment scheme results) and referred to as relative residual. A commutability decision limit of 2 SDwl was set. For carbamazepine and valproic acid, a total of 78 and 105 laboratory couples respectively could be formed. The number of relative residuals for liquid human serum outside the commutability decision limit was 1, 4, and 0 for low, medium, and high concentrations of carbamazepine, respectively and 3, 1, and 0 for low, medium, and high concentrations of valproic acid, respectively. In both liquid and lyophilized bovine sera, the number of relative residuals outside the commutability decision limit was between 2 and 15 and between 6 and 21 for carbamazepine and valproic acid, respectively. Although not all results for PTM with carbamazepine and valproic acid are within the commutability decision limits, a preference for human serum can be seen.


Extensive Serological Survey of Multiple African Nonhuman Primate Species Reveals Low Prevalence of Immunoglobulin G Antibodies to 4 Ebola Virus Species.
Bats are considered a reservoir species for Ebola viruses, but nonhuman primates (NHPs) have represented a source of infection in several outbreaks in humans. Here we report serological screening of blood or fecal samples from monkeys (n = 2322) and apes (n = 2327). Thirty-six NHP species from Cameroon, Democratic Republic of the Congo, and Ivory Coast were tested with a sensitive and specific Luminex-based assay for immunoglobulin G antibodies to 4 Ebola virus species. Using the simultaneous presence of antibodies to nucleoproteins and glycoproteins to define positivity, we showed that specific Ebola virus antibodies are not widespread among NHPs. Only 1 mustached monkey (Cercopithecus cephus) from Cameroon was positive for Sudan ebolavirus. These observations support that NHPs are most likely intermediate hosts for Ebola viruses. With the increasing frequency of Ebola outbreaks, it is crucial to identify the animal reservoir and understand the ecology of Ebola viruses to inform disease control.


Novel isoforms of the transport regulator klar.
Klar is a regulator of microtubule-motor dependent transport processes in Drosophila, including nuclear migration, vesicle motility, and lipid-droplet transport. The single klar locus gives rise to multiple isoforms that presumably have unique functions. Up to now, three Klar isoforms (α, β, γ) were known. Here we describe two novel isoforms, δ and ε, whose expression depends on a previously uncharacterized promoter. Klar δ and/or ε are widely expressed during development, including in the embryonic and larval nervous system as well as in ovaries. When we specifically ablate Klar δ and ε expression genetically, no gross organismal phenotypes are apparent. However, ectopic expression of these isoforms causes nuclear mispositioning in developing photoreceptors and in oocytes, demonstrating their biological activity. Our analysis identifies novel forms of the Klar protein and provides new tools for functionally dissecting the complex klar locus.


Reduced efficacy of albendazole against Ascaris lumbricoides in Rwandan schoolchildren.
Control of human soil-transmitted helminths (STHs) relies on preventive chemotherapy of schoolchildren applying the benzimidazoles (BZ) albendazole or mebendazole. Anthelmintic resistance (AR) is a common problem in nematodes of veterinary importance but for human STHs, information on drug efficacy is limited and routine monitoring is rarely implemented. Herein, the efficacy of single dose albendazole (400 mg) was evaluated in 12 schools in the Huye district of Rwanda where Ascaris is the predominant STH. Ascaris eggs were detected by wet mount microscopy and the Mini-FLOTAC method to assess cure rate (CR) and faecal egg count reduction (FECR). Blood and faecal samples were analysed for co-infections with Plasmodium sp. and Giardia duodenalis, respectively. Ascaris positive samples collected before and after treatment were analysed for putatively BZ-resistance associated β-tubulin gene single nucleotide polymorphisms. The overall CR was 69.9% by Mini-FLOTAC and 88.6% by wet mount microscopy. The FECR was 75.4% and the 95% calculated confidence intervals were 50.4-87.8% using sample variance, 55.4-88.8% by bootstrapping, and 75.0-75.7% applying a Markov Chain Monte Carlo Bayesian approach. FECR varied widely between 0 and 96.8% for individual schools. No putative BZ-resistance associated polymorphisms were found in the four Ascaris β-tubulin isotype genes examined. Since FECRs <95% indicate reduced efficacy, these findings raise the suspicion of BZ resistance. In the absence of respective molecular evidence, heritable AR in the local Ascaris populations cannot be formally proven. However, since FECRs <95% indicate reduced efficacy, BZ resistance may be suspected which would be alarming and calls for further analyses and routine monitoring in preventive chemotherapy programs.


Prospective observational study of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck.
To evaluate the efficacy and safety of carbon-ion radiotherapy for non-squamous cell carcinoma of the head and neck, 35 patients were enrolled in this prospective study. The primary end-point was the 3-year local control rate, and the secondary end-points included the 3-year overall survival rate and adverse events. Acute and late adverse events were evaluated according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time for all patients was 39 months. Thirty-two and three patients received 64.0 Gy (relative biological effectiveness) and 57.6 Gy (relative biological effectiveness) in 16 fractions, respectively. Adenoid cystic carcinoma was dominant (60%). Four patients had local recurrence and five patients died. The 3-year local control and overall survival rates were 93% and 88%, respectively. Acute grade 2-3 radiation mucositis (65%) and dermatitis (31%) was common, which improved immediately with conservative therapy. Late mucositis of grade 2, grade 3, and grade 4 were observed in 11, one, and no patients, respectively. There were no adverse events of grade 5. Carbon-ion radiotherapy achieved excellent local control and overall survival rates for non-squamous cell carcinoma. However, the late mucosal adverse events were not rare, and meticulous treatment planning is required. Trial registration no. UMIN000007886.


Isolation of 2,5-diketopiperazines from Lysobacter capsici AZ78 with activity against Rhodococcus fascians.
Inhibitory activity of the biocontrol bacterial strain Lysobacter capsici AZ78 is related to the production of cyclo(l-Pro-l-Tyr), a 2,5-diketopiperazine with in vitro and in vivo toxic activity against Phytophthora infestans and Plasmopara viticola. Further investigation of culture filtrate organic extracts showed its ability to produce other 2,5-diketopiperazines. They were isolated and identified by spectroscopic (1H NMR and ESIMS) and physic (specific optical rotation) methods as cyclo(l-Pro-l-Val), cyclo(d-Pro-d-Phe), cyclo(l-Pro-l-Leu), and cyclo(d-Pro-l-Tyr). When tested against the phytopathogenic Gram-positive bacterium Rhodococcus fascians LMG 3605, cyclo(l-Pro-l-Val) showed a toxic activity similar to chloramphenicol at a comparable concentration. Overall, these data suggest that 2,5-diketopiperazines represent a class of metabolites characterizing the metabolome of L. capsici AZ78. Furthermore, the toxic activity showed by cyclo(l-Pro-l-Val) against R. fascians LMG 3605 broaden the spectrum activity of 2,5-diketopiperazines against phytopathogenic microorganisms enforcing their potential development as biopesticides.[Figure: see text].


Fabrication and evaluation of nanoparticle-assembled BSA microparticles for enhanced liver delivery of glycyrrhetinic acid.
The aim of the present study was to prepare and evaluate microparticle formulation encapsulated with glycyrrhetinic acid (GA) based on bovine serum albumin (BSA). The drug-loaded nanoparticles were firstly formed by a simple desolvation method, and were further assembled into microparticles using zinc chloride and glutaraldehyde as crosslinkers. The obtained microparticles contained approximately 30% (w/w) drug and showed as spherical particles with a size of about 2 μm. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) analysis indicated that GA lost its crystallinity during the nano/microencapsulation process. In vitro dissolution study demonstrated a typical sustained-release pattern for 24 h with a burst of 28.1% at the first 30 min, which fitted well by Higuchi model. After intravenous administration into mice, the microparticle formulation remained a higher drug level than the solution formulation in blood and liver for more than 18 h. These results suggested the potential benefit of using the prepared albumin microparticles as a promising vector for enhanced liver delivery of poorly water-soluble drug.


Review article: The prevention and reversal of hepatic fibrosis in autoimmune hepatitis.
Immunosuppressive treatment of autoimmune hepatitis can prevent or reverse hepatic fibrosis, but these anti-fibrotic effects are inconsistent secondary gains. To describe the anti-fibrotic effects of current therapies for autoimmune hepatitis, discuss the pathogenic mechanisms of hepatic fibrosis that might be targeted by anti-fibrotic interventions, indicate the non-invasive diagnostic tests of hepatic fibrosis that must be validated in autoimmune hepatitis and to suggest promising treatment opportunities. Studies cited in PubMed from 1972 to 2013 for autoimmune hepatitis, hepatic fibrosis, cirrhosis, anti-fibrotic therapy and non-invasive tests of hepatic fibrosis were selected. Hepatic fibrosis improves in 53-57% of corticosteroid-treated patients with autoimmune hepatitis; progressive fibrosis slows or is prevented in 79%; and cirrhosis may be reversed. Progressive hepatic fibrosis is associated with liver inflammation, and the inability to fully suppress inflammatory activity within 12 months is associated with progression to cirrhosis (54%) and death or need for liver transplantation (15%). Liver tissue examination remains the gold standard for assessing hepatic fibrosis, but laboratory and radiological tests may be useful non-invasive methods to measure the fibrotic response. Severe liver inflammation can confound radiological assessments, and the preferred non-invasive test in autoimmune hepatitis is uncertain. Individualised treatment adjustments and adjunctive anti-fibrotic therapies are poised for study in this disease. The prevention and reversal of hepatic fibrosis are achievable objectives in autoimmune hepatitis. Strategies that evaluate individualised therapies adjusted to the rapidity and completeness of the inflammatory response, and the use of adjunctive anti-fibrotic interventions, must be evaluated.


[On morphology of cerebral lesions in perinatal hypoxia (author's transl)].
From the autopsies of one year 47 brains (10 stillborns, 28 prematures and 9 newborns) were systematically examined for hypoxemic cerebral lesions. In contrast to literature findings in 75% of the cases not only veins but also arteries showed congestions and a cerebral edema due to disturbances of circulation and permeability, predominantly caused by hypoxia. Nearly half of the cases had primary leptomeningeal hemorrhages and hemorrhages in the germinal matrix tissue; stillborns had no hemorrhages in the germinal matrix. Encephalodystrophic foci were found in 17% of the cases examined. 41 of 47 brains showed single nerve cell damage with cytolysis and 8 ones a focal nerve cell decay, especially localized in the brain-stem. They were observed equally frequent in stillborne, newborns and prematures. The polyetiologic cerebral lesions point out that birth trauma does not play the dominating role in the etiology as hitherto supposed. Hypoxia gets an increasing importance. Frequently birth traumatic and hypoxemic cerebral lesions are associated.


[Detection and analysis of plasma VWF levels in healthy Chinese by automatic standardized assay].
Objective: To explore the normal range of plasma VWF levels of healthy Chinese and to analyze the influencing factors to VWF level. Methods: To detect the levels of von Willebrand factor antigen (VWF∶Ag) , von Willebrand factor ristocetin cofactor activity (VWF∶Rco) , von Willebrand factor collagen binding activity (VWF∶CB) , and the factor Ⅷ coagulation activity (FⅧ∶C) by using fully automatic and standardized testing instruments and matching reagent in 70 healthy Chinese. The effects of age, ABO blood type, gender and region were also analyzed. Meanwhile, 8 standard plasma samples (2 normal subjects, 6 cases of type 2 VWD) confirmed by NIBSC were tested for VWF values. Results: ① In 70 cases of healthy Chinese, the mean value of plasma VWF∶Ag, VWF∶Rco and VWF∶CB were (95.4±44.9) %, (105.9±35.4) % and (89.8±28.4) %, respectively; the ratio of VWF∶Rco/VWF∶Ag and VWF∶CB/VWF∶Ag was 1.18±0.25 and 1.03±0.29, respectively. ②There was no statistical significance in plasma VWF values between the age ≥30 years and <30 years group (P>0.05) . ③The VWF∶Rco, VWF∶CB of type O blood group were lower than that of non-O group (t=2.074, P=0.042; t=3.949, P=0.001) , but there was no statistical significance in VWF∶Ag, VWF∶Rco/VWF∶Ag, VWF∶CB/VWF∶Ag between the two groups (P>0.05) . ④There was no significant difference in VWF values between male and female groups (P>0.05) . ⑤The VWF∶Ag, VWF∶CB of the northern population (North area of Huaihe River) group were higher than that of southern population (Suzhou area) group (t=4.525, P=0.001; t=3.214, P=0.002) , but VWF∶Rco/VWF∶Ag, VWF∶CB/VWF∶Ag were lower than that of southern population group (t=6.373, P=0.001; t=2.902, P=0.005) , and there was no significant difference in VWF∶Rco between the two groups (t=1.598, P=0.115) . ⑥The VWF values of 8 standard plasma samples were in accordance with the known diagnosis. Conclusions: A more integrate plasma VWF levels of healthy Chinese people were obtained for the first time by using fully automatic and standardized testing instruments. It was also found that ABO blood group and region had a significant impact on the level of VWF, while the age and gender had no significant effect.


Leveraging the health equity implementation framework to foster an equity focus in medical education.
Teaching equitable clinical practice is of critical importance, yet how best to do so remains unknown. Educators utilize implementation science frameworks to disseminate clinical evidence-based practices (EBP). The Health Equity Implementation Framework (HEIF) is one of these frameworks, and it delineates how health equity may be concomitantly assessed and addressed in planning the implementation of an EBP. The HEIF therefore lays a strong foundation to understand and explain barriers and facilitators to implementation through an equity lens, making it well-suited for use by medical educators. Three equity-focused frames of reference within the model include (1) the clinical encounter, (2) societal context, and (3) culturally relevant factors, herein referred to as domains. The HEIF provides a structure for prospective and retrospective assessment of how EBP are taught and ultimately incorporated into clinical practice by trainees, with specific attention to delivering equitable care. We present three examples of common topics in internal medicine, contextualized by the three equity domains of the HEIF. We additionally acknowledge the limitations of this framework as a research tool with complex features that may not be suitable for brief teaching in the clinical environment. We propose a 360-degree learner assessment to ensure implementation of this framework is successful. By encouraging trainees to explore the narrative experiences of their patients and examine their own implicit biases, the HEIF provides a structure to address gaps in knowledge about delivering equitable care.