Colon interposition in the treatment of carcinoma of the esophagus and gastric cardia.
The stomach is the organ most used for restoring esophageal continuity after esophageal resection for malignancy. In the present series, we report our experience over a 20-year period (1965 through 1984) with an alternative method, colon interposition. Two hundred forty-eight patients (124 men and 124 women) underwent colon interposition. Seventy-one percent (175) of the tumors were squamous cell carcinomas, and 23% (58) were adenocarcinomas in the gastric cardia and lower esophagus. The left colon was the substitute of first choice and was used in 54% of the patients. Of the interpositions, 59% were antiperistaltic. Esophagectomy without thoracotomy was the method in 146 patients. The operative mortality was 16% (40 patients), and 3% (8 patients) sustained colon graft necrosis. Leakage in the upper anastomosis occurred in 4% (10). No dysphagia was experienced by 85%, 80%, and 76% of the patients during reexaminations 3, 6, and 12 months, respectively, after operation. The 1-year and 5-year survival for patients with squamous cell carcinoma was 40% and 10%, respectively, and for patients with adenocarcinoma, 50% and 12%, respectively. The data from this study suggest that colon interposition offers a good alternative for long-term relief of dysphagia in patients with carcinoma of the esophagus. The rate of complications is acceptable.


Interventions to improve human papillomavirus vaccination among Chinese female college students: study protocol for a randomized controlled trial.
While the HPV vaccines have been approved by the US FDA since 2006, in recent years an increasing number of women are living with cervical cancer globally. Among them, Chinese women have a higher cervical cancer incidence and mortality rate than the global average, with mortality rates being almost twice the global average. However, the current approach of HPV vaccination in China is not satisfactory given the high disease burden of cervical cancer. The current study is a randomized controlled trial designed to identify the barriers and facilitators of HPV vaccination among Chinese female students. This study will also test a health intervention measure via a popular form of new media in order to improve the HPV vaccine uptake under the framework of Information-Motivation-Behavioral skill Model (IMB). This investigation is a multicenter, school-based, prospective, randomized, parallel group, double-blind, blank-controlled trial involving a 7-day education intervention with a further 6-month follow-up. We will enroll at least 3360 participants older than 18 years. The enrolled participants will be randomly divided into two groups (1:1 ratio). The intervention group will be offered a 7-day mobile health education, and participants in both groups will fill out 4 questionnaires at the baseline, 1 month, 3 months and 6 months after the intervention. The primary outcome is the difference in HPV vaccination or reservation for the HPV vaccine between the intervention and control groups. Secondary outcomes will include the comparison of (1) knowledge, attitudes, motivation, beliefs and behavioral skill about HPV and cervical cancer prevention, and (2) the willingness to uptake HPV vaccination. This study will examine the theory-based intervention in improving HPV vaccination among Chinese female college students. We will conduct the randomized controlled trial to provide scientific evidence on the potential effect of the IMB theory-based intervention. Findings from this study will contribute to a growing research field which assesses the effectiveness of mobile-based, school-targeted and theoretically guided interventions for promoting HPV vaccination in adolescents. Chinese Clinical Trial Registry (ChiCTR), ChiCTR1900025476; Registered on 27 August 2019.


RNA-Sequencing Analysis Pipeline for Prognostic Marker Identification in Cancer.
Sequencing analysis finds many applications in various fields of biology from comparative genomics to clinical research. Recent studies, using high-throughput sequencing method, has generated terabytes of data. It is challenging to interpret and draw a meaningful conclusion without the proper understanding of various steps involved in the analysis of such data. This chapter deals with the pipeline to be followed to process the raw RNA sequencing (RNA-Seq) reads, align, assemble, and quantify them in order to draw significant clinical conclusions from them.


Local injection of amphotericin B: novel use in the treatment of fungal maxillary sinusitis.
This report highlights the role of local amphotericin B (AMB) injection in cases of maxillary mucormycosis. The COVID-19 pandemic has resulted in a dramatic rise in the number of rhino-orbital mucormycosis cases. Although extensive surgical debridement remains the gold standard treatment, tissue salvage is desirable. The cases of two patients treated with local AMB are reported here, indicating that early intervention for maxillary fungal sinusitis in the form of local AMB may avoid the need for more invasive treatment.


[A study on expression of CD44V6 and PCNA in squamous cell carcinomas].
To investigate the expression of cluster of differentiation 44 variant 6 (CD44V6) and proliferating cell nuclear antigen (PCNA) in squamous cell carcinomas (SCC) in eyes. Streptavidinbiotin peroxidase complex (SABC) immunohistochemical method was used to study the expression of CD44V6 and PCNA in 35 cases with squamous cell carcinoma in eyes, 20 cases with papilloma, 11 cases with normal eyelid tissue. The CD44V6 positive rate was 62.9% (22/35) in squamous cell carcinomas in eyes, 15.0% (3/20) in papillomas, none in 11 cases with normal eyelid tissue. The positive expression rate of CD44V6 in the malignant group was significantly higher than that in the benign and control group, and the positive expression rate of CD44V6 in cases with metastasis was significantly higher than that without metastasis. PCNA labeling index (PI) in the CD44V6 positive expression of tumors was significantly higher than that in the CD44V6 negative expression of tumors (t = 20.21, P < 0.01). The over-expression of CD44V6 is correlated with the progress and metastasis of SCC. CD44V6 protein expression is correlated positively with PCNA expression, and the evaluation of both CD44V6 and PCNA is useful for predicting the prognosis.


Clinical characteristics of adult inpatients with Measles in Beijing from 2010 to 2021: a retrospective analysis.
With the measles vaccine coverage rate gradually increasing, adult patients' epidemiological and clinical characteristics have changed. To analyze the clinical characteristics of adult measles patients in Beijing Youan Hospital. We retrospectively reviewed the electronic medical records of 818 patients diagnosed with measles at Beijing Youan Hospital between June 2010 and October 2021. We divided all hospitalized patients into two demographics groups, using 14 years of age as the cut-off. Of the adult inpatients, 110 (74.83%) were aged 20-40. There was an overall peak incidence in 2014, and yearly peaks came in April. Fever, cough, erythema, and Koplik's spots were present in 79.59%, 82.1%, 99.3%, and 59.8% of the adult group, respectively, compared to 75.26%, 92.0%, 99.9%, and 39.0% of the pediatric group. Decreased lymphocytes and hepatic impairment were common in adults. The adult group's median level of C-reactive protein was higher than that of the pediatric group (p < 0.05). The positive rate of measles antibody (IgM) detection was 64.6% in the adults and 78.8% in the pediatric group (p < 0.05). Of the adults, 46.9%, 8.8%, and 66% had pneumonia, gastroenteritis, and antibiotic use, compared to 89.6%, 2.7%, and 83.2% of the pediatric patients. The duration of symptoms before admission and the average length of hospital stay was approximately six days in both groups. Koplik's spots are more likely to be detected by clinicians in adult patients admitted to the hospital. Active surveillance is helpful for adults who are negative for IgM on admission. Although the proportion of adult measles patients with liver injury is high, the disease is generally mild. Measles significantly impacts peripheral blood lymphocytes in adults, but adults are at lower risk of concurrent pneumonia than the pediatric group. Clinicians need to pay attention to the appropriate use of antibiotics. Expanding the coverage of the measles vaccination in high-risk areas is beneficial for preventing measles in adults.


Madura foot and a continued diagnostic enigma: Dot-in-circle sign on magnetic resonance imaging and ultrasound.
Madura foot is a chronic granulomatous disease of the skin and underlying tissues caused by fungi or bacteria. Early diagnosis is important to avoid disfiguring limb deformities. Low clinical suspicion, limited availability of diagnostic tools, and infection with fastidious organisms may lead to misdiagnosis and delayed treatment. Imaging tests can help to make a timely diagnosis in a non-invasive manner. Here we report two patients with a non-classical clinical presentation and a more favorable differential diagnoses who were correctly diagnosed as cases of Madura foot based on the ''dot-in-circle sign'', a specific finding on magnetic resonance imaging and ultrasound.


Predictors of in-hospital Outcomes in Patients With Cirrhosis and Coronavirus Disease-2019.
Coronavirus disease-2019 (COVID-19) cases continue to increase globally. Poor outcomes in patients with COVID-19 and cirrhosis have been reported; predictors of outcome are unclear. The existing data is from the early part of the pandemic when variants of concern (VOC) were not reported. We aimed to assess the outcomes and predictors in patients with cirrhosis and COVID-19. We also compared the differences in outcomes between the first wave of pandemic and the second wave. In this retrospective analysis of a prospectively maintained database, data on consecutive cirrhosis patients (n = 221) admitted to the COVID-19 care facility of a tertiary care center in India were evaluated for presentation, the severity of liver disease, the severity of COVID-19, and outcomes. The clinical presentation included: 18 (8.1%) patients had compensated cirrhosis, 139 (62.9%) acute decompensation (AD), and 64 (29.0%) had an acute-on-chronic liver failure (ACLF). Patients with ACLF had more severe COVID-19 infection than those with compensated cirrhosis and AD (54.7% vs. 16.5% and 33.3%, P < 0.001). The overall mortality was 90 (40.7%), the highest among ACLF (72.0%). On multivariate analysis, independent predictors of mortality were high leukocyte count, alkaline phosphatase, creatinine, child class, model for end-stage liver disease (MELD) score, and COVID-19 severity. The second wave had more cases of severe COVID-19 as compared to the first wave, with a similar MELD score and Child score. The overall mortality was similar between the two waves. Patients with COVID-19 and cirrhosis have high mortality (40%), particularly those with ACLF (72%). A higher leukocyte count, creatinine, alkaline phosphatase, Child class, and MELD score are predictors of mortality.


Serum and local IL-4, IL-5, IL-13 and immunoglobulin E in allergic rhinitis.
Allergic rhinosinusitis (AR) is a clinical manifestation of a type 1 hypersensitive reaction. A complex of reactions involving components of the immune system - cells, mediators, cytokines, neuropeptides, adhesion molecules etc., are involved in the manifestation of the disease symptoms. To evaluate the role of some serum and local cytokines and IgE molecules in the pathogenesis of AR comparing results in patients and healthy controls. The study was conducted at the Prof. Dr. St. Kirkovich University Hospital and Medical University, Stara Zagora, Bulgaria. A trend towards higher serum levels in patients with AR compared to controls was found for IL-4, but with no significant difference. In the group of AR patients, those with the intermittent form had higher, although with no significance, interleukin 4 (IL-4) levels in the lavage compared to those with the persistent form. In nasal lavage fluids a tendency towards higher IL-5 levels was found in intermittent AR patients compared to those with persistent AR. A slight trend towards significantly higher serum levels of IL-13 in overweight patients compared to those with normal weight was found. Regardless of the obvious differences of the concentrations of the cytokines studied in our groups, oftentimes no significant difference is observed. More studies should be conducted in order to show the role of IL-4, -5, -13, and IgE in the pathogenesis and severity of the disease.


Endothelial Gata5 transcription factor regulates blood pressure.
Despite its high prevalence and economic burden, the aetiology of human hypertension remains incompletely understood. Here we identify the transcription factor GATA5, as a new regulator of blood pressure (BP). GATA5 is expressed in microvascular endothelial cells and its genetic inactivation in mice (Gata5-null) leads to vascular endothelial dysfunction and hypertension. Endothelial-specific inactivation of Gata5 mimics the hypertensive phenotype of the Gata5-null mice, suggestive of an important role for GATA5 in endothelial homeostasis. Transcriptomic analysis of human microvascular endothelial cells with GATA5 knockdown reveals that GATA5 affects several genes and pathways critical for proper endothelial function, such as PKA and nitric oxide pathways. Consistent with a role in human hypertension, we report genetic association of variants at the GATA5 locus with hypertension traits in two large independent cohorts. Our results unveil an unsuspected link between GATA5 and a prominent human condition, and provide a new animal model for hypertension.


Harnessing adaptive novelty for automated generation of cancer treatments.
Nanoparticles have the potential to modulate both the pharmacokinetic and pharmacodynamic profiles of drugs, thereby enhancing their therapeutic effect. The versatility of nanoparticles allows for a wide range of customization possibilities. However, it also leads to a rich design space which is difficult to investigate and optimize. An additional problem emerges when they are applied to cancer treatment. A heterogeneous and highly adaptable tumour can quickly become resistant to primary therapy, making it inefficient. To automate the design of potential therapies for such complex cases, we propose a computational model for fast, novelty-based machine learning exploration of the nanoparticle design space. In this paper, we present an evolvable, open-ended agent-based model, where the exploration of an initially small portion of the given state space can be expanded by an ongoing generation of adaptive novelties, whenever the simulated tumour makes an adaptive leap. We demonstrate that the nano-agents can continuously reshape themselves and create a heterogeneous population of specialized groups of individuals optimized for tracking and killing different phenotypes of cancer cells. In the conclusion, we outline further development steps so this model could be used in real-world research and clinical practice.


Preparation of a diphtheria toxin-pullulan conjugate that elicits good IgG antibody production with poor IgE synthesis.
Diphtheria toxin is detoxified through conjugation with pullulan. The toxin-pullulan conjugate is easily purified by DEAE-Sephacel chromatography. The conjugate forms a transparent 'clear line' with anti-toxin antibodies on agarose plate, which offers a good indicator of conjugate formation. The toxin-pullulan conjugate induces both IgG1 and IgG2b antibody production with diminished IgE response, while the alum-precipitated conventional toxoid causes mainly increases in IgE as well as IgG1 antibody formation. The anti-toxin HA titre (IgG antibody) induced by the toxin-pullulan conjugate parallels the neutralizing activity of the immune-sera. These results suggest that the conjugation of toxin to pullulan is a very powerful method by which to develop a vaccine that induces neutralizing antibody with diminished IgE antibody synthesis.


Arterial PaO2 and PaCO2 influence seizure duration in dogs receiving electroconvulsive therapy.
The influence of arterial O2 and CO2 tensions on electroconvulsive seizure duration was investigated in five mongrel dogs under consistent anaesthetic conditions. Seizure durations were measured in a randomized protocol of nine possible combinations of arterial gas tension spanning increased, normal or decreased levels of PaO2 and PaCO2. Seizure duration was directly related to PaO2 (p less than 0.00001) and inversely related to PaCO2 (p less than 0.0001). A significant synergism was evident at the extremes of PaO2 and PaCO2, with seizure duration being greater than predicted for hyperoxia-hypocapnia and hypoxia-hypercapnia and shorter than predicted for hypoxia-hypocapnia and hyperoxia-hypercapnia. We conclude that arterial gas tensions strongly influence ECT-induced seizure duration and through this may influence the therapeutic efficacy of electroconvulsive therapy.


Evaluating Survival After Hospitalization Due to Immune-Related Adverse Events From Checkpoint Inhibitors.
As immune checkpoint inhibitors (CPI) are increasingly approved for cancer treatment, hospitalizations related to severe immune-related adverse events (irAE) will increase. Here, we identify patients hospitalized due to irAEs and describe survival outcomes across irAE, CPI, and cancer type. We identified patients hospitalized at our institution from January 2012 to December 2020 due to irAEs. Survival was analyzed using Kaplan-Meier survival curves with log-rank tests. Of 3137 patients treated with CPIs, 114 (3.6%) were hospitalized for irAEs, resulting in 124 hospitalizations. Gastrointestinal (GI)/hepatic, endocrine, and pulmonary irAEs were the most common causes of irAE-related hospitalization. After CPI initiation, the average time to hospitalization was 141 days. Median survival from hospital admission was 980 days. Patients hospitalized due to GI/hepatic and endocrine irAEs had longer median survival than patients with pulmonary irAEs (795 and 949 days vs. 83 days [P < .001]). Patients with melanoma and renal cell carcinoma had longer median survival than patients with lung cancer (2792 days and not reached vs. 159 days [P < .001]). There was longer median survival in the combination group compared to the PD-(L)1 group (1471 vs. 529 days [P = .04]). As CPI use increases, irAE-related hospitalizations will as well. These findings suggest that among patients hospitalized for irAEs, survival differs by irAE and cancer type, with worse survival for patients with irAE pneumonitis or lung cancer. This real-world data contributes to research pertaining to hospitalization due to severe irAEs, which may inform patient counseling and treatment decision-making.


Effect of warming on the rectal motile activity: identification of rectal warming reflex.
The identification in the rectal wall of warm receptors sensitive to warm temperature has not been found in the literature. Therefore, we investigated the hypothesis that rectal warming effects rectal dilation, which seems to indicate the existence of warm receptors. The rectal wall tone was studied in 24 healthy volunteers (14 men, 10 women, mean age 36.7+/-10.4 years). It was assessed by a barostat system during rectal infusion with normal saline at 30 degrees C, 40 degrees C, 45 degrees C, and 50 degrees C. The test was repeated after rectal anesthetization with lidocaine. The rectal tone on rectal saline infusion at a temperature of 30 degrees C showed no response (P>0.05), whereas at a temperature of 40 degrees C, 45 degrees C, and 50 degrees C, it exhibited a significant decrease (P<0.05, <0.01, <0.001, respectively), which was proportional to the rising degree of temperature. Warm saline infusion into the anesthetized rectum resulted in no significant change in the rectal wall tone. Rectal infusion with warm saline produced rectal dilation that increased with temperature elevation. This effect is suggested to be mediated through a reflex called "rectal warming reflex: and advances the possibility of the existence of warm receptors in the rectal wall; however, further studies are needed to confirm the issue.


Adult-onset primary focal foot dystonia.
Although primary focal hand dystonia has been well characterized, primary focal foot dystonia in adults has rarely been reported. Our objective was to describe the clinical phenotype and treatment outcomes in patients with primary, adult-onset focal foot dystonia. To this end we conducted a retrospective study of four consecutive patients (59.5+/-13.5 years, range 44-67) diagnosed over a period of 6 years and followed-up for at least 5 years. Focal foot dystonia resulted in variable physical impairment. Anti-dystonic agents were mildly effective whereas botulinum toxin injections provided substantial benefit when used. Focal primary focal foot dystonia seems to be a rare form of focal dystonia with distinct clinical features that may benefit from treatment with botulinum toxin.


Directionally selective response of cells in the middle temporal area (MT) of the macaque monkey to the movement of equiluminous opponent color stimuli.
Based on the fact that a great majority of cells in the middle temporal (MT) area of the macaque respond to movement of luminance contours with directional selectivity, this area has been thought to be concerned with the analysis of visual motion. However, objects can be discriminated from the background not only by differences in luminance but also by differences in color. It is possible that color signals are also used for motion analysis in MT. In the present study, we examined whether MT cells respond to movement of a pattern composed of pure color-contours. Using a color TV system, a moving color bar was displayed on a uniform background whose color was opponent with that of the bar. The main bar/background color combination we examined was magenta/cyan. Yellow/blue and cyan/magenta combinations were also examined for some cells. The response of MT cells to movements of opponent-color stimuli was recorded while the bar/background luminance ratio was changed from 1/10 to 10/1. In half of 89 cells tested in 3 monkeys, the response decreased considerably (disappeared completely in some cells) at a luminance ratio close to the human equiluminous condition. In the other half, a directional response persisted at any bar/background luminance ratio, though the response decreased to a varied extent (30-90% of the maximum response) near the ratio 1 (human equiluminous condition). The average magnitude of the equiluminous response to the magenta/cyan stimulus for the overall population was about 35% of the maximal response when the length of the bar (0.5 degrees in width) and the movement amplitude were set to be optimal for individual cells, i.e. smaller than 15 degrees and 10 degrees of visual angle, respectively. This fall to 23% when the bar length and movement amplitude were limited to 2 degrees. The same cell responded to pure color-contours of yellow/blue as well as of cyan/magenta combinations. Thus, MT can detect the direction of movement of pure color-contours, although the sensitivity is less than for luminance contours.


Immediate return of nerve function following microsurgical repair.
The conduction of motor nerve impulses across the suture line of microsurgically repaired peripheral nerves has previously been demonstrated. The present study was undertaken to test the hypothesis that such conducted impulses would produce physiological responses in the limb distally. Studies of nerve conduction, muscle motor unit activity and paw tremor were carried out before and after division and repair of the sciatic nerves of nine New Zealand white rabbits. The results indicated that immediately after nerve repair stimulation of the proximal nerve can result in physiological neuromuscular responses distally.


How to narrow down chromosomal breakpoints in small and large derivative chromosomes--a new probe set.
Here a new fluorescence in situ hybridization (FISH-) based probe set is presented and its possible applications are highlighted in 34 exemplary clinical cases. The so-called pericentric-ladder-FISH (PCL-FISH) probe set enables a characterization of chromosomal breakpoints especially in small supernumerary marker chromosomes (sSMC), but can also be applied successfully in large inborn or acquired derivative chromosomes. PCL-FISH was established as 24 different chromosome-specific probe sets and can be used in two- up multicolor-FISH approaches. PCL-FISH enables the determination of a chromosomal breakpoint with a resolution between 1 and ∼10 megabasepairs and is based on locus-specific bacterial artificial chromosome (BAC) probes. Results obtained on 29 sSMC cases and five larger derivative chromosomes are presented and discussed. To confirm the reliability of PCL-FISH, eight of the 29 sSMC cases were studied by array-comparative genomic hybridization (aCGH); the used sSMC-specific DNA was obtained by glass-needle based microdissection and DOP-PCR-amplification. Overall, PCL-FISH leads to a better resolution than most FISH-banding approaches and is a good tool to narrow down chromosomal breakpoints.


The Meaning of Spirituality and Spiritual Well-Being among Thai Breast Cancer Patients: A Qualitative Study.
Spirituality is the essence of a human being. Patients who have good spiritual well-being (SWB) will also have better quality of life. However, health-care providers usually under-assess this aspect due to lack of practical guideline. In Thailand, the validated survey came from a different cultural background and was heavily based on Buddhism approach. The aim of the study is to assess the meaning of spirituality and SWB in Thai breast cancer patients in Southern Thailand where people have more diverse cultural and religious background. Descriptive qualitative phenomenology design. In-depth interview with stratified purposive sampling method. The interviews took place in the oncology outpatient unit department and participants' home. Inclusion criteria were being diagnosed with breast cancer, age over 18 years old, able to communicate in Thai, has a Palliative Performance Scale more than 50, and was not diagnosed with any psychological disorder. Descriptive statistic. From October 2016 to February 2018, 16 women joined the study. Three themes emerged with five subthemes: (1) feeling life worthwhile, (2) sense of belonging in the community, and (3) feeling connected to the nature. For Thai women, who have breast cancer, their spirituality focuses on family, mainly their children. They also have better SWB if they have good family relationship, social support, or feeling connected with nature or higher being in a religious or nonreligious way. Future survey design needs to be broader in a secular view and on another perspective rather than the religious approach.


The role of spatial frequency in the processing of hierarchically organized stimuli.
Can spatial frequency differences between local and global forms account for differences in the way different levels of structure are analyzed? We examined this question by having subjects identify local or global forms of hierarchical stimuli that had been contrast balanced. Contrast balancing eliminates low spatial frequencies, so that both local and global forms must be identified on the basis of high spatial frequency information. Response times (RTs) to global (but not local) forms were slowed for contrast-balanced stimuli, suggesting that low spatial frequencies mediate the global RT advantage typically found. In contrast, interference between local and global forms was little affected by contrast balancing or by shifts of attention between local and global forms, suggesting that it does not result from inhibitory interactions between spatial frequency channels or from temporal precedence of low versus high spatial frequency information. Finally, shifts of attention between local and global forms were also little affected by contrast balancing, suggesting that they were not based on spatial frequency.


Understanding the impact of heatwave on urban heat in greater Sydney: Temporal surface energy budget change with land types.
The impact of heatwaves (HWs) on urban heat island (UHI) is a contentious topic with contradictory research findings. A comprehensive understanding of the response of urban and rural areas to HWs, considering the underlying cause of surface energy budget changes, remains elusive. This study attempts to address this gap by investigating a 2020 HW event in the Greater Sydney Area using the Advanced Weather Research and Forecasting (WRF) model with 250-m high resolution. Findings indicate that the HW intensifies the nighttime surface UHI by approximately 4 °C. An analysis of surface energy budgets reveals that urban areas store more heat during the HW due to receiving more solar radiation and less evapotranspiration compared to rural areas. The maximum heat storage flux in urban during the HW can be around 200 W/m2 higher than that during post-HW. The stored heat is released at nightime, raising the air temperature in the urban areas. Forests and savannas have relatively lower storage heat fluxes due to high transpiration and albedo, and the maximum heat storage flux is only around 50 W/m2 higher than that during post-HW. In contrast, a negative synergistic effect is detected between the 2-m UHI and HW. This may be because other meteorological conditions including wind have substantial impacts on the air temperature pattern. The strong hot and dry winds coming from the west resulted in a higher air temperature in the western urban district, and intra-city disparities are higher. Meanwhile, the western forest area also experiences higher temperatures due to the westward winds. In addition, changes in wind direction alter the temperature distribution in the northern rural region. The findings of the present study may provide some insights into urban heat mitigation during HW.


Behavioral Health in Prevention and Chronic Illness Management: Motivational Interviewing.
This article reviews the history, methodology, and evidence related to the effective use of motivational interviewing (MI) in the primary care setting. MI has been shown to have a positive effect in promotion and modification of health habits and to increase treatment engagement. MI is also effective when used in conjunction with other treatment modalities, such as educational programs and cognitive behavioral therapy. Practical application of MI can be accomplished in a variety of primary care settings by a wide range of practitioners, incorporates nicely into new health care delivery models, and may improve the patient-provider relationship.


N-acylethanolamines in seeds of selected legumes.
Seven molecular species of N-acylethanolamines were quantified in seeds from selected members of the legume family. Total concentrations for the 14 taxa studied ranged over approximately three orders of magnitude with no consistent overall relationship to phylogeny. Elevated concentrations observed in some species make them good candidates for natural sources of these compounds which are of increasing therapeutic interest in the modulation of the mammalian endocannabinoid system.


Altered substrate metabolism in neurodegenerative disease: new insights from metabolic imaging.
Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD) and multiple sclerosis (MS), are relatively common and devastating neurological disorders. For example, there are 6 million individuals living with AD in the United States, a number that is projected to grow to 14 million by the year 2030. Importantly, AD, PD and MS are all characterized by the lack of a true disease-modifying therapy that is able to reverse or halt disease progression. In addition, the existing standard of care for most NDs only addresses the symptoms of the disease. Therefore, alternative strategies that target mechanisms underlying the neuropathogenesis of disease are much needed. Recent studies have indicated that metabolic alterations in neurons and glia are commonly observed in AD, PD and MS and lead to changes in cell function that can either precede or protect against disease onset and progression. Specifically, single-cell RNAseq studies have shown that AD progression is tightly linked to the metabolic phenotype of microglia, the key immune effector cells of the brain. However, these analyses involve removing cells from their native environment and performing measurements in vitro, influencing metabolic status. Therefore, technical approaches that can accurately assess cell-specific metabolism in situ have the potential to be transformative to our understanding of the mechanisms driving AD. Here, we review our current understanding of metabolism in both neurons and glia during homeostasis and disease. We also evaluate recent advances in metabolic imaging, and discuss how emerging modalities, such as fluorescence lifetime imaging microscopy (FLIM) have the potential to determine how metabolic perturbations may drive the progression of NDs. Finally, we propose that the temporal, regional, and cell-specific characterization of brain metabolism afforded by FLIM will be a critical first step in the rational design of metabolism-focused interventions that delay or even prevent NDs.


Interleukin-2 production and bone-resorption activity in vitro by unstimulated lymphocytes extracted from chronically-inflamed human periodontal tissues.
Lymphocytes isolated from chronically-inflamed tissues were assessed for their ability to produce lymphokines without further stimulation in vitro. Cells were extracted from tissue obtained from 42 patients undergoing periodontal surgery. Cultures were set up in triplicate and supernatants collected after 48 h were assayed for interleukin-2 (IL-2) or bone-resorptive activity. IL-2 was assayed in the cultured supernatants from 20 patients using a previously-standardized T-cell growth assay, with maximally-stimulated peripheral blood-lymphocytes as a positive control. Bone-resorptive activity (BRA) was assessed in culture supernatants from another 22 patients using an in-vitro mouse-calvaria culture-system in which calcium release was measured with a calcium analyser. IL-2 was detected in 12 out of the 20 unstimulated cultures; BRA was detected in 14 of the 22 unstimulated cultures. There appeared to be no relationship between IL-2 production and BRA and the severity of the disease as assessed by loss of attachment. Nevertheless, it seems that most of the cells extracted from chronically-inflamed tissue were producing lymphokines which may indicate stimulation in vivo prior to cell extraction.


Assessment of soft tissue changes after LeFort I advancement.
The aim of this retrospective study was to investigate the soft tissue changes after maxillary advancement in class III patients. Pre- and post-operative lateral cephalometric radiographs of 20 patients treated with maxillary advancement surgery were included in our study. Skeletal, dental and soft tissue measurements were performed by a single researcher using Dolphin Imaging software version 11.95 (Dolphin Imaging, Chatsworth, CA, USA). Paired t test was used for statistical evaluation and p < 0.05 was considered statistically significant. The amount of motion in soft tissues, respectively, are UL-E: 2.05 mm, ST.A: 0.65 mm, ST.B: - 5 mm, ST.Pog: - 5.73 mm, ST.Conv: - 3.95 mm, nasal prominence: - 1.58 mm, nasal height: 2.76 mm and upper lip length: 2.22 mm. The change of distance to horizontal and vertical reference planes are, respectively, Prn-HRL: 3.02 mm Prn-VRL: 1.76 mm Sn-HRL: 2.76 mm Sn-VRL: 2.94 mm ST. 3.74 mm ST. 3.81 mm UL-HL: 3.93 mm UL-VRL: 4.57 mm LL-HRL: 2.29 mm LL-VRL: 5.31 mm. It can be concluded that soft tissues related to maxilla moved anteriorly due to maxillary advancement.


A way forward for fundamental physics in space.
Space-based research can provide a major leap forward in the study of key open questions in the fundamental physics domain. They include the validity of Einstein's Equivalence principle, the origin and the nature of dark matter and dark energy, decoherence and collapse models in quantum mechanics, and the physics of quantum many-body systems. Cold-atom sensors and quantum technologies have drastically changed the approach to precision measurements. Atomic clocks and atom interferometers as well as classical and quantum links can be used to measure tiny variations of the space-time metric, elusive accelerations, and faint forces to test our knowledge of the physical laws ruling the Universe. In space, such instruments can benefit from unique conditions that allow improving both their precision and the signal to be measured. In this paper, we discuss the scientific priorities of a space-based research program in fundamental physics.


Effects of confinement on static and dynamical properties of water.
Molecular-dynamics results on water confined in a silica pore are reviewed and discussed in connection with experiments performed on water in Vycor and with studies of water in contact with proteins. The properties of confined water are studied as a function of both temperature and hydration level. The interaction of water in the film close to the substrate with the silica atoms induces a strong distortion of the hydrogen bond network. At high hydration levels a double dynamical regime is observed. At low hydration an anomalous diffusion is found upon supercooling with a transition from a Brownian to a non-Brownian regime on approaching the substrate in agreement with results found in studies of water in contact with globular proteins.


A quantum chemical study on the mechanism of glycinamide ribonucleotide transformylase inhibitor: 10-Formyl-5,8,10-trideazafolic acid.
A density functional theory (DFT) study is presented on the reaction mechanism of glycinamide ribonucleotide (GAR) with 10-formyl-5,8,10-trideazafolic acid (10f-TDAF), which is an inhibitor designed for GAR transformylase (GAR Tfase). There are three different paths for this system and the results indicate that inhibitor 10f-TDAF can form a very stable intermediate with the substrate GAR or generate an imine bond with GAR by elimination of water. The results have verified the presumption from available experiments and implied that 10f-TDAF would be an important target for anti-neoplastic intervention.


Flap survival and functional outcomes in elbow soft tissue reconstruction: A 25-year systematic review.
Different elbow flap reconstructions have been described in the literature. We aim to define the optimal flap technique based on defect size and etiology. A systematic review was undertaken using the terms "(Elbow reconstruction) AND ((Soft tissue) OR (flap))". Flaps were grouped under fasciocutaneous (FCF), muscular (MF), distant pedicled (DPF), and free flaps (FF). The primary outcome was flap survival. The secondary outcomes were postoperative complications and range of motion (pROM). Twenty articles with 224 patients were included. Defect sizes were small (<10 cm2) (18%), medium (10-30 cm2) (23%), large (30-100 cm2) (43%), and massive (>100 cm2) (16%). Etiologies included trauma (26%), burn contractures (26%), infection (26%), hardware coverage (16%), and others (6%). FCF (54%) was the preferred flap followed by MF (28%), DPF (13%), and FF (5%). The rate of flap necrosis was 4% and that of other complications was 10%. The postoperative range of motion (pROM) (reported in 154 patients) was >100°, 50-100°, and <50° in 82%, 17%, and 1% of the cases, respectively. Small defects were most commonly reconstructed with MFs (83%), medium defects were reconstructed with MFs (52%) or FCFs (46%), and large defects were reconstructed with FCFs (91%). Massive defects predominantly required DPFs (60%) and FFs (26%). FCFs were the most common reconstruction method for burn contractures (84%), infections (55%), and traumatic defects (51%). Hardware coverage was predominantly performed using MFs (86%). No difference in complications and pROM was found between flap techniques. Elbow flap reconstruction can be performed using different techniques. FCFs are the most commonly used reconstruction method. MFs are useful for smaller defects and hardware coverage. DPFs and FFs are needed for massive injuries.


Correction: A hybrid GaN/Ga2O3 structure anchored on carbon cloth as a high-performance electrode of supercapacitors.
Correction for 'A hybrid GaN/Ga2O3 structure anchored on carbon cloth as a high-performance electrode of supercapacitors' by Yan-Ling Hu, et al., Dalton Trans., 2022, https://doi.org/10.1039/d2dt02904a.


Results of Mannerfelt wrist arthrodesis for rheumatoid arthritis in relation to the position of the fused wrist.
The wrist is involved early in rheumatoid arthritis and is often severely affected. A stable wrist is crucial to good hand function, which often necessitates a fusion. One of the most commonly used techniques in rheumatoid patients is the Mannerfelt arthrodesis. In this retrospective study the outcome and the patient's subjective satisfaction are presented and compared to other techniques. Also the influence of the position of the wrist following a fusion procedure is analysed. Thirty-four wrists were retrospectively analysed using radiological measurements, functional scores such as the Disabilities of the Arm, Shoulder and Hand (DASH) and a pain assessment. The objective function of the hand with the fused wrist was assessed. In 92.6% of wrists the patients rated their satisfaction as good or excellent. The mean DASH score post-operatively was 63.3. Of the wrists, 17 were fixed in a median flexed position of 13° and 17 wrists in a median extended position of 8°. There was no statistically significant correlation between the position of the wrist and the satisfaction or objective function. The rate of fusion was 94.1%. The Mannerfelt arthrodesis achieves good results and provides a high rate of satisfaction and pain relief in our study. It has major advantages compared to other wrist fusion techniques in the rheumatoid patient. We could not show clear statistical evidence for better results in either a flexed or an extended position, but the ratings of the patients indicated better subjective results with a slightly extended position of the arthrodesis.


Assessing food web dynamics and relative importance of organic matter sources for fish species in two Portuguese estuaries: a stable isotope approach.
Stable carbon and nitrogen isotopes (δ¹³C, δ¹⁵N) were used to analyse food web dynamics of two of the main estuaries of the Portuguese coast: Tejo and Mira. The ultimate sources of organic matter supporting production of some of the most abundant and commercially important fish species were determined; and seasonal, inter- and intra- estuarine differences in the trophic relations among producers and consumers were identified. Stable isotope analysis was performed in different producers, primary consumers (main prey items for fish) and fish species (Solea solea, Solea senegalensis, Pomatoschistus microps, Dicentrarchus labrax, Liza ramada, Diplodus vulgaris and Atherina presbyter) of two areas in each estuary, in July and October 2009. Model calculations showed that the main prey for the fish species in the Tejo estuary used mostly salt marsh-derived organic matter as nutritional sources, with no marked differences between the sampled months. Trophic levels of fish species from the same estuary differed at multiple scales: inter-species, seasonally and spatially (both between and within estuaries). Significant differences in isotopic composition of fish species were more pronounced spatially (between the two sampled areas in the estuary) than seasonally (between sampled months). Trophic relationships in both estuaries demonstrated that organic matter is transferred to higher trophic positions mainly through benthic pathways. This shows the flexibility of these species to share resources and to exploit temporary peaks in prey populations. The present results showed that extensive disturbance in intertidal habitats from both estuaries may potentially change the balance of organic matter in the base of these complex food webs.


Pre-induction of labour: comparing dinoprostone vaginal insert to repeated prostaglandin administration: a systematic review and meta-analysis.
To assess the efficacy and safety of the dinoprostone vaginal insert compared to repeated prostaglandin administration (including dinoprostone and misoprostol) in women at term. Electronic databases and additional handsearching were used to identify randomized controlled trial (RCT). We included studies reporting data separately for nulliparous and/or multiparous in women with unfavourable cervix (Bishop <5) and intact membranes. The primary efficacy outcome was caesarean section (CS) rate. Primary safety outcome was uterine hyperstimulation requiring immediate delivery. Eighteen RCTs were eligible and seven studies were included (totally 911 patients). The dinoprostone vaginal insert reduces CS rate in nulliparous women of 24% compared to the other ways of administration (RR = 0.76, 95% CI = 0.59, 0.98). The risk of oxytocin use is reduced with the use of vaginal insert (RR = 0.64, 95% CI = 0.42, 0.99). The risk of hyperstimulation is statistically higher in nulliparous women using vaginal insert than the other ways of administration with RR = 2.17, 95% CI = 1.08,4.33. In nulliparous women with unprepared cervix and intact membranes vaginal insert perform better than repeated vaginal doses since it is associated with more vaginal deliveries and less oxytocin use. Although vaginal insert is associated with more uterine hyperstimulation, it shows a protective effect toward caesarean section.


[Beclobrate and eniclobrate hydrochloride, new diphenylmethane derivatives as agents for lowering cholesterol and triglyceride levels. Part I: Synthesis and consideration of structure-activity relationships (author's transl)].
Within the course of a research project for finding new lipid-lowering substances with better therapeutic indices than the standard agent in use, various diphenylmethane derivatives were synthesized and tested with respect to their activity and toxicity. On the basis of these results Sgd 24774 (beclobrate) and Sgd 33374 (eniclobrate-hydrochloride) were selected for further investigation and clinical studies.


Comparison between two thermoplastic root canal obturation techniques regarding extrusion of root canal filling--a retrospective in vivo study.
The aim of this study was to compare two different thermoplastic techniques--a core-carrier technique (Thermafil) and warm vertical compaction--in terms of overextension of root canal filling in vivo. Flaring of 88 teeth was conducted using Pro Files .04 as finishing files, and the teeth were obturated using Thermafil. Flaring of 74 teeth was performed using Pro Files .06 as finishing files, and the teeth were obturated using warm vertical compaction. Seventy (80 %) of the teeth obturated using Thermafil and 31 (42 %) teeth obturated using warm vertical compaction show extruded root canal filling. In contrast to Thermafil, there is a higher rate of extruded root canal filling of teeth with more than one root canal using warm vertical compaction. Thermafil demonstrated a higher rate of extruded root canal filling compared to warm vertical compaction. Warm vertical compaction is a more predictable method of filling compared to Thermafil. Root canal filling extrusion will cause irritation of the surrounding tissue and impair repair processes. In the present in vivo study, there was a higher rate of root canal filling extrusion using Thermafil compared to warm vertical compaction.


Identification of P-glycoprotein substrates using open tubular chromatography on an immobilized P-glycoprotein column: Comparison of chromatographic results with Caco-2 permeability.
The Caco-2 cell monolayer model was used to classify 13 compounds as P-glycoprotein (Pgp) substrates or non-substrates. The apparent permeability coefficients (Papp) in the basal-to-apical direction (Papp(B-A)) and in the apical-to-basal direction (Papp(A-B)) were determined for each compound and a compound was designated as a Pgp substrate if Papp(B-A)/Papp(A-B), the permeability ratio, exceeded 2.0. The same compounds were chromatographed on open tubular glass columns containing membranes from cell lines that either expressed Pgp (Pgp+-OT column) or did not express Pgp (Pgp(-)-OT column). The differential retentions in min, Deltat values, of the compounds were determined using the following relationship Deltat=t((Pgp(+)-OT))-t((Pgp(-)-OT)). A statistically significant correlation was observed between the Deltat values and the permeability ratios, r2=0.7749 (p=0.0063), indicating that the differential chromatography approach could be used to quantitatively assess permeability ratios. The results also indicated that a Deltat value > or =0.5 min was a reliable measure of a permeability ratios >2 and could be used as a rapid qualitative determination of whether a test compound was a Pgp substrate. The chromatographic study took 1h to complete and a single pair of columns could be used to screen at least 150 compounds a week and 600 compounds during the 4-week lifetime of the columns.


Current practice of thoracic anaesthesia in Europe - a survey by the European Society of Anaesthesiology Part I - airway management and regional anaesthesia techniques.
The scientific working group for "Anaesthesia in thoracic surgery" of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) has performed an online survey to assess the current standards of care and structural properties of anaesthesia workstations in thoracic surgery. All members of the European Society of Anaesthesiology (ESA) were invited to participate in the study. Thoracic anaesthesia was most commonly performed by specialists/board-certified anaesthetists and/or senior/attending physicians. Across Europe, the double lumen tube (DLT) was most commonly chosen as the primary device for lung separation (461/ 97.3%). Bronchial blockers were chosen less frequently (9/ 1.9%). Throughout Europe, bronchoscopy was not consistently used to confirm correct double lumen tube positioning. Respondents from Eastern Europe (32/ 57.1%) frequently stated that there were not enough bronchoscopes available for every intrathoracic operation. A specific algorithm for difficult airway management in thoracic anaesthesia was available to only 18.6% (n = 88) of the respondents. Thoracic epidural analgesia (TEA) is the most commonly used form of regional analgesia for thoracic surgery in Europe. Ultrasonography was widely available 93,8% (n = 412) throughout Europe and was predominantly used for central line placement and lung diagnostics. While certain "gold standards "are widely met, there are also aspects of care requiring substantial improvement in thoracic anaesthesia throughout Europe. Our data suggest that algorithms and standard operating procedures for difficult airway management in thoracic anaesthesia need to be established. A European recommendation for the basic requirements of an anaesthesia workstation for thoracic anaesthesia is expedient and desirable, to improve structural quality and patient safety.


Bacterial second messenger 3',5'-cyclic diguanylate attracts Caenorhabditis elegans and suppresses its immunity.
Cyclic di-nucleotides are important secondary signaling molecules in bacteria that regulate a wide range of processes. In this study, we found that Caenorhabditis elegans can detect and are attracted to multiple signal molecules produced by Vibrio cholerae, specifically the 3',5'-cyclic diguanylate (c-di-GMP), even though this bacterium kills the host at a high rate. C-di-GMP is sensed through C. elegans olfactory AWC neurons, which then evokes a series of signal transduction pathways that lead to reduced activity of two key stress response transcription factors, SKN-1 and HSF-1, and weakened innate immunity. Taken together, our study elucidates the role of c-di-GMP in interkingdom communication. For C. elegans, bacterial c-di-GMP may serve as a cue that they can use to detect food. On the other hand, preexposure to low concentrations of c-di-GMP may impair their immune response, which could facilitate bacterial invasion and survival.


Biosensors: A novel approach to and recent discovery in detection of cytokines.
Cytokines in tissues and physiological fluids can function as potentially suitable biomarkers. Cytokines are involved in stimulating different body responses including inflammatory response to external pathogens, regulating cell-to-cell communication, and maintaining tissue homeostasis. Consequently, cytokines are extensively used to monitor and predict disease progression and to track the outcome of patient treatment. The critical diagnosis of cytokine and chemokine biomarkers has been the focus of attention and it has been continuously directing the trajectory of related research to developing a novel sensing platform. Given the major challenges and constraints of the older identification methods including their high costs, low sensitivity, and high specificity, the development of biosensor technology as a simple and inexpensive tool with high sensitivity is quite attractive and interesting. The fundamental aim of this study is to present the state-of-the-art biosensor systems in order to detect different types of cytokines and to emphasize the role of these systems in the prevention, monitoring, and treatment of various cytokine-associated diseases.


Management of older adults with multiple myeloma.
Two-thirds of patients with multiple myeloma are aged 65 years or more and the prevalence of multiple myeloma in elderly patients is expected to rise in the next future. Patients older than 65 years are usually considered ineligible for transplantation. The introduction of novel agents, such as the immunomodulatory drugs thalidomide and lenalidomide and the proteasome inhibitor bortezomib, combined with conventional chemotherapy, has radically changed the treatment paradigm of elderly patients and improved outcome. A sequential approach, consisting of an induction regimen associated with a high rate of complete response, followed by consolidation/maintenance therapy, induces a profound cytoreduction and delays relapse, thus improving survival. Novel agents associated with reduced-intensity autologous transplant showed to be safe and effective in fit elderly patients. Patients older than 75 years or vulnerable ones are more susceptible to adverse events that negatively affect treatment adherence and outcome. In this setting, less toxic regimens and appropriate dose reductions should be adopted. Here we provide an overview of novel agent-based treatment strategies for elderly patients with multiple myeloma.


Retracted: The Application of Pattern Recognition System in Design Field Based on Aesthetic Principles.
[This retracts the article DOI: 10.1155/2022/8581900.].


Bandages for backslabs: an experimental study.
Five types of bandage commonly used to support plaster backslabs were subject to static and dynamic performance tests. Dry and wet samples were studied. The performance of wet bandage is inferior. Attention is drawn to possible hazards caused by the shrinkage exhibited by 2 types of wet bandage.


[Prevalence of dyslipidemia and its phenotypes in recently diagnosed essential arterial hypertension].
To know the prevalence of phenotypic dyslipidemias and their clinical and metabolic characteristics in recently diagnosed hypertensive patients. Consecutive study of 158 essential hypertensive patients without previous pharmacological treatment. 69.6% of the patients had some kind of dyslipidemia, being the isolated increase of Lp(a) (27.3%) the most prevalent and the hyperapobetalipoproteinemia the less (10.0%). Age, sex, smoking, alcohol consumption, uric acid, systolic and pulse pressure and serum glucose were different among phenotypes. Essential hypertensive patients have high and heterogeneous prevalence of dyslipidemias.


Effect of COVID-19 pandemic on inpatient service utilization and patient outcomes in Uganda.
COVID-19 has had devastating effects on health systems but reports from sub-Saharan Africa are few. We compared inpatient admissions, diagnostic tests performed, clinical characteristics and inpatient mortality before and during the COVID-19 pandemic at an urban tertiary facility in Uganda. We conducted a retrospective chart review of patients admitted at Kiruddu National Referral Hospital in Uganda between January-July 2019 (before the pandemic) and January-July 2020 (during the pandemic). Of 3749 inpatients, 2014 (53.7%) were female, and 1582 (42.2%) had HIV. There was a 6.1% decline in admissions from 1932 in 2019 to 1817 in 2020. There were significantly fewer diagnostic tests performed in 2020 for malaria, tuberculosis, and diabetes. Overall, 649 (17.3%) patients died. Patients admitted during the COVID-19 pandemic (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.04-1.5, p = 0.018), patients aged ≥ 60 years (aOR 1.6, 95% CI 1.2-2.1, p = 0.001), HIV co-infected (aOR 1.5, 95% CI 1.2-1.9, p < 0.001), and those admitted as referrals (aOR 1.5, 95% CI 1.2-1.9, p < 0.001) had higher odds of dying. The COVID-19 pandemic disrupted inpatient service utilization and was associated with inpatient mortality. Policy makers need to build resilience in health systems in Africa to cope with future pandemics.


Prevalence of elevated serum transferrin saturation in adults in the United States.
A population-based hemochromatosis screening program that uses serum transferrin saturation has been proposed, but few data exist on the number of U.S. adults that such a program would identify for further testing. To determine the prevalence of an initially elevated serum transferrin saturation and the prevalence of concurrently elevated serum transferrin saturation and serum ferritin levels in the adult population of the United States. Nationally representative cross-sectional survey of the noninstitutionalized U.S. civilian population. 15 839 men and nonpregnant women 20 years of age and older who were examined in the third National Health and Nutrition Examination Survey (1988-1994). Single measurements of serum transferrin saturations and serum ferritin levels. Cut-off values used to define elevated serum transferrin saturation ranged from greater than 45% to greater than 62%. The prevalence of initially elevated serum transferrin saturation ranged from 1% to 6%. Approximately 11% to 22% of those with elevated serum transferrin saturation had concurrently elevated serum ferritin levels. The prevalence of elevated serum transferrin saturation was lower in women than in men when the same cut-off value was used to define elevated serum transferrin saturation. The prevalence of elevated serum transferrin saturation in non-Hispanic black persons and Mexican-Americans was similar to or slightly less than that in non-Hispanic white persons. The prevalence of elevated serum transferrin saturation in persons 20 to 49 years of age was as high as or higher than that in older adults. A hemochromatosis screening program that uses a cut-off value of greater than 60% to define elevated serum transferrin saturation would identify an estimated 1.4 to 2.5 million U.S. adults for further testing.


Diagnosis and management of the thyroid nodule. An overview.
The traditional approach to evaluation of patients with thyroid nodules is being replaced by more cost-effective methods of diagnosis. The author describes a rational approach to the evaluation of thyroid nodules that takes into consideration patient factors, minimizes false-positive diagnoses of cancer, and balances the competing responsibilities of cost-effective management and identifying all patients with thyroid carcinoma.


Comparative immune responses in Japanese flounder, Paralichthys olivaceus after vaccination with viral hemorrhagic septicemia virus (VHSV) recombinant glycoprotein and DNA vaccine using a microarray analysis.
A viral hemorrhagic septicemia virus (VHSV), recombinant glycoprotein vaccine (VHSVg) and a DNA vaccine (pCMV-VHSg) were injected in Japanese flounder (Paralichthys olivaceus). Each fish was injected with 10 microg vaccine dissolved in 50 microl phosphate buffer saline (PBS). One month after the vaccination, the fish were challenged intraperitoneally with either 1 x 10(2) or 1 x 10(3) TCID(50) of virus. Fish that received the VHSg DNA vaccine were highly protected against virus infection over a 21-day observation period, with cumulative mortalities ranging from 4 to 10%. However, the recombinant protein vaccine group appeared to have low survival rates. Using microarray analysis, humoral defense-related genes such as complement component C3, complement regulatory plasma proteins, IgM, IgD, MHC class II-associated invariant chain and CD20 receptor were observed to be up-regulated by the VHSg recombinant protein vaccine at 1 or 21 days post vaccination. On the other hand, cellular defense-related genes such as CD8 alpha chain, T-cell immune regulator, MIP1-alpha and apoptosis-associated protein were not detected. Specific antibodies against VHSVg protein were detected in both vaccinated groups at a titer of 1:40 at 28 days post vaccination.


Role of MIF-173G/C and Mbl2 Codon 54A/B Variants in the Risk of Multiple Myeloma: An Association Study.
Multiple myeloma (MM) is a malignant disease manifested by the clonal proliferation of atypical plasma cells. Macrophage inhibitory factor (MIF) is one of the pleiotropic regulators in various biological and cellular processes. Mannose-binding lectin (MBL) is a crucial protein involved in the lectin pathway of the immune system. We aimed to assess whether variants of MIF and MBL2 genes are associated with MM among a Turkish population. We analyzed the MIF-173G/C (rs755622) and MBL2 codon 54A/B (rs1800450) variants in 200 patients with MM and 200 healthy control subjects using a polymerase chain reaction (PCR) followed by restriction endonuclease digestion. There was also an evaluation of the patients undergoing autologous stem-cell transplantation (ASCT) for these variants. AA and BB genotypes of MBL2 codon 54A/B increased in the patients as compared to the controls (p=0.008, p=0.001, respectively). The subjects carrying AA and BB genotypes of MBL2 were at high risk of development of susceptibility to MM by 7.377 and 8.812 times, respectively. The distribution of MBL2 codon 54A/B alleles was similar between the groups (p>0 .05). There was no statistical difference between the patients and controls in the genotype and allele frequencies of the MIF- 173G/C variant (p>0 .05). The patients undergoing ASCT, MBL2 codon 54A/B AA and BB genotypes also showed association with increased risk for MM (p=0.004, p=0.001, respectively). As far as we know, this is the first report of the study on an association between these variants and MM in our population. Our results indicate that the MBL2 codon 54A/B variant may be associated with susceptibility to MM.


The emerging role of gut microbial metabolism on cardiovascular disease.
The gut microbiome has been implicated in the progression of cardiovascular diseases (CVD) including hypertension, dyslipidemia, atherosclerosis, thrombosis, heart failure, and ischemic stroke. Metabolomics studies in humans and diverse mouse populations have revealed associations between diet-derived gut bacterial metabolites, including trimethylamine-N-oxide, short-chain fatty acids, and intermediates of aromatic amino acid breakdown, with progression of CVD. Functional studies in animals fed diets of defined composition have been instrumental for establishing causal links between these metabolites, the microbes that produce them, dietary substrates and disease. The purpose of this review is to discuss recent progress in our understanding of how gut microbial metabolism of food influences the development of CVD and to outline experimental approaches that can be useful for addressing crucial knowledge gaps in the field. Together, this body of work supports the notion that the gut microbiomes mediate many of the effects of diet.


Magnetic resonance imaging examination of denervated muscle.
Denervated muscles due to lumbar radiculopathy, peroneal axonal neuropathy and hypoglossal neuropathy were studied with magnetic resonance imaging (MRI). Denervated muscle was clearly distinguished from normal muscle by its higher intensity signal. Comparison of the resulting signal intensity of the muscle using various imaging parameters suggests an alteration in water macromolecular binding. These preliminary findings indicate that MRI may be useful in the noninvasive in vivo diagnosis and study of the effects of denervation on muscle.


The combined effects of N-3 fatty acids and aspirin on hemostatic parameters in man.
Both fish oils and aspirin are readily available to the consumer as over-the-counter preparations. Since both of these products have been shown to prolong bleeding times, it is possible that hemostasis might be adversely affected in subjects taking them in combination. This study was undertaken to examine the effects of n-3 fatty acids and aspirin on platelet function. Eight healthy men took a total of 485 mg of aspirin over 3 days before beginning two weeks of fish oil supplementation (4.5 g of n-3 fatty acids/day). Subjects continued with fish oil while resuming aspirin treatment for 3 days. Aspirin alone prolonged bleeding times by 34% (p less than 0.05). Fish oil alone raised bleeding times only slightly (9%; N.S.), but aspirin plus fish oil raised them by 78% (p less than 0.01). The increase in bleeding times with the combination (78%) was not significantly different than the sum of the individual increases (43%). The effects of fish oil and aspirin on platelet aggregation were investigated using single and dual agonists. Although fish oil alone did not significantly raise aggregation thresholds for collagen, arachidonic acid, or PAF, it did reduce the extent of aggregation with collagen. When challenged by single or dual agonists, the combination of fish oil and aspirin did not make platelets less sensitive than did aspirin alone. Since fish oil and aspirin had synergistic effects on bleeding times, but not on platelet aggregation, these two substances appear to affect hemostasis by different mechanisms.


A cytotoxic agent can be generated selectively at cancer sites.
Attempts to improve the selectivity of anti-cancer agents by conjugating them to antibodies directed at tumour associated antigens have demonstrated tumour localisation but only limited therapeutic success. We report here the advantage of a 2-stage approach in which the first component combines the selective delivery of antibody with a capability to generate a cytotoxic agent from a second subsequently administered component. A bacterial enzyme, carboxypeptidase G2 (CPG2) was conjugated with F(ab')2 fragment of a monoclonal antibody directed at beta subunit of human chorionic gonadotrophin (beta-hCG) and injected into nude mice bearing hCG producing CC3 xenografts of human choriocarcinoma. Time was allowed for the conjugate to localise at tumour sites and clear from blood before injecting para-N-bis (2-chloroethyl) aminobenzoylglutamic acid. Cleavage of the glutamic acid moiety from this molecule by CPG2 released a benzoic acid mustard. Growth of the tumour which is resistant to conventional chemotherapy was markedly depressed by a single course of treatment. This demonstrates for the first time the potential of an antibody directed enzyme to activate an alkylating agent and to eradicate an established human cancer xenograft.


Amylin reduces food intake more potently than calcitonin gene-related peptide (CGRP) when injected into the lateral brain ventricle in rats.
Amylin and the structurally and functionally related peptide calcitonin gene-related peptide (CGRP) have been shown to reduce food intake in rats. The aim of the present study was to compare the anorectic potency of both peptides over a wide dose range when administered into the lateral brain ventricle (ICV). Furthermore, we also tested the influence of a lesion in the area postrema/nucleus of the solitary tract (AP/NTS) region on the anorectic effects of amylin and CGRP after ICV administration because AP/NTS lesion has been shown to reduce the anorectic effects of both peptides when injected intraperitoneally (IP). Amylin [1-510 pmol/rat (0.004-2 microg/rat) ICV] and CGRP [1-131 pmol/rat (0.004-0.5 microg/rat) ICV] dose-dependently reduced food intake in food-deprived rats. At a dose of 26 pmol/rat (0.1 microg/rat), amylin almost completely suppressed food intake for 1 h after injection. Amylin [EC50 = 2 pmol/rat (0.007 microg/rat)] was markedly more potent than CGRP [57 pmol/rat (0.215 microg/rat)] with regard to its anorectic effect. A lesion in the AP/NTS region did not influence the anorectic effects of amylin and CGRP after administration into the lateral ventricle. It is concluded that amylin is more potent than CGRP in reducing food intake after administration into the lateral brain ventricle. Receptors in the forebrain may mediate the anorectic effects of both peptides when administered via this route.


Expression and gene doses changes of the p53-regulator PPM1D in meningiomas: a role in meningioma progression?
The aim of our study was to clarify the expression and gene copy number levels of protein phosphatase 1D magnesium-dependent, delta isoform (PPM1D), which is thought to be a regulator of the p53 protein in meningiomas of all three different WHO grades. Genomic DNA and mRNA were extracted from frozen tissues of meningiomas (WHO grade I, 20 cases; grade II, 17 cases; grade III, 20 cases). For analysis of the mRNA expression and gene dosage level of PPM1D, semiquantitative duplex RT-PCR, real-time RT-PCR, and semiquantitative duplex PCR were performed. We also analyzed several genes which locate near PPM1D in the genomic locus 17q22-24 using semiquantitative duplex RT-PCR. We found that the mean mRNA expression of PPM1D is higher in WHO grade II and III meningiomas than in grade I tumors. This finding is accompanied by moderate gene dosage increases for PPM1D in meningiomas of higher grades. Other genes located in the vicinity of PPM1D also showed mRNA overexpression in single meningioma cases. For these genes, however, no significant expression differences between meningioma grades could be observed. Thus, PPM1D in the chromosomal location 17q22-24 might be the most relevant candidate gene with respect to a potential functional implication in meningioma progression.


The absence of voiding symptoms in men with a prostate-specific antigen (PSA) concentration of ≥3.0 ng/mL is an independent risk factor for prostate cancer: results from the Gothenburg Randomized Screening Trial.
What's known on the subject? and What does the study add? There are only a few studies and no consensus concerning the relationship between LUTS and prostate cancer. This paper focuses on 2353 men with an elevated PSA level within the Gothenburg Randomized Screening Trial who underwent biopsy and answered questions regarding LUTS. The main conclusion was that the absence of voiding symptoms is an independent risk factor for prostate cancer detection. To investigate whether men with obstructive voiding symptoms are at increased risk for being diagnosed with prostate cancer within the Gothenburg randomized population-based prostate cancer screening trial. In 1995, 20 000 men born between 1930 and 1944 were randomly selected from the population register and randomized to either a screening group (10 000), invited for total prostate-specific antigen (tPSA) testing every second year until they reached an upper age-limit pending between 67 and 71 years, or to a control group not invited (10 000). Men with a PSA concentration of ≥3.0 ng/mL were offered further examination with prostate biopsies. Immediately before the physician's examination a self-administered, study-specific questionnaire was completed including one question concerning obstructive voiding symptoms. Multivariate logistic regression modelling was used to estimate odds ratios (ORs) for associations of age, tPSA, free/total PSA (f/tPSA) ratio, prostate volume and the presence of voiding symptoms in prostate cancer risk. A P < 0.05 was considered statistically significant. Between 1995 and 2010 there were 2590 men who had an elevated PSA concentration (≥3.0 ng/mL) at least once during the study. Of these, 2353 men (91%) accepted further clinical examination with transrectal ultrasonography (TRUS) and prostate biopsies. In all, 633/2353 men had prostate cancer (27%) on biopsy and 1720/2353 men (73%) had a benign pathology. Men with prostate cancer reported a lower frequency of voiding symptoms (24% vs 31%, P < 0.001), independent of age and locally advanced tumours (T2b-T4). In the multivariate logistic regression model increasing age and tPSA were positively associated with prostate cancer while prostate volume, f/tPSA ratio and the presence of voiding symptoms were all inversely associated with the risk of detecting prostate cancer in a screening setting. This inverse association of voiding symptoms and prostate cancer detection was restricted to men with large prostates (>37.8 mL); 15% in men with voiding symptoms vs 22% in asymptomatic men (P < 0.001). The presence of voiding symptoms should not be a decision tool for deciding which men with an elevated PSA concentration should be offered biopsies of the prostate.


Adalimumab dose escalation and dose de-escalation success rate and predictors in a large national cohort of Crohn's patients.
Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30-40% after 1 year. Attempts for dose de-escalation have not been studied. This study aimed to assess the need for, predictors, and outcome of dose escalation and de-escalation in a large cohort of adalimumab treated Crohn's patients. All consecutive patients treated with open label adalimumab for active Crohn's disease from the participating centres were included in this cohort study. A detailed retrospective chart review was performed to look for possible factors predicting outcome. Eighty four percent of 720 patients had a primary response and were followed up for a median of 14 months. Thirty four percent needed escalation after a median of 7 months (0-55 months). Multivariate predictors for dose escalation were the following: prior anti-TNF use (p<0.0001), no concomitant azathioprine or <3 m (p<0.02) and abnormal CRP at start (p<0.05). Dose escalation re-induced response for at least 6 months in 67%. Only abnormal CRP at start correlated with failure of dose escalation (p=0.02). Dose de-escalation was attempted in 54% and was successful in 63%. After a median follow-up of 14 m adalimumab was discontinued in 29% of patients. In this study real life nationwide cohort of Crohn's patients treated with adalimumab dose escalation was needed in 34% and was successful in 67%. Dose de-escalation was attempted in 54% and was successful in 63%. Overall 71% of patients maintained long term response on adalimumab.


Propranolol unmasks class III like electrophysiological properties of norepinephrine.
Isolated perfused spontaneously beating rabbit hearts were treated with increasing concentrations of norepinephrine (0.01, 0.1, 0.5 mumol/l) either alone or in presence of propranolol (0.1 mumol/l). For analysis of the epicardial activation and repolarization process and epicardial mapping (256 unipolar leads) was performed. For each electrode the activation and repolarization time was determined. From these data the "breakthrough-points" (BTP) of epicardial activation were determined. At each electrode an activation vector (VEC) was calculated giving direction and velocity of the local excitation wave. The beat similarity of various heart beats (under NE) compared to control was evaluated by determination of the percentage of identical BTP and of similar VEC (deviation < or = 5 degrees). Moreover at each electrode the local activation recovery interval (ARI) and its standard deviation (of 256 leads, dispersion, DISP) were determined. Norepinephrine alone (0.01, 0.1, 0.5 mumol/l) led to an increase in left ventricular pressure, heart rate and DISP with concomitant frequency dependent reduction in ARI, and to changes in the epicardial activation pattern (reduction in BTP, VEC). We found that in the presence of propranolol (0.1 mumol/l) norepinephrine prolonged ARI and reduced ARI-dispersion. This effect was not due to changes in heart rate. The disturbing effects on the activation pattern were diminished. These effects could be prevented by pretreatment with 1 mumol/l prazosin. From these results we conclude, that norepinephrine prolongs the relative action potential duration via stimulation of alpha 1-adrenoceptor and enhances cellular coupling.(ABSTRACT TRUNCATED AT 250 WORDS)


Investigation and diagnosis of diarrhea caused by sodium phosphate.
Because there are no published reference values for fecal phosphate concentration or output, diagnosing surreptitious use of phosphate laxatives has been difficult. The purposes of this study were to determine normal fecal phosphate levels and to quantitate and chemically analyze diarrhea produced by sodium phosphate. Timed stool collections were obtained from 20 normal subjects during 25 study periods (normal controls), from 27 normal subjects with diarrhea induced by a variety of laxatives not containing phosphate during 234 study periods (diarrhea controls), and from 10 normal subjects during 14 periods after ingestion of 45 or 22.5 ml of a commercially available 66% sodium phosphate solution (Fleet Phospho-Soda). All stools were analyzed for soluble phosphate concentration, and daily output was calculated. The upper limits of normal for soluble fecal phosphate concentration and output, derived from the normal controls and diarrhea controls, respectively, were 33 mmol/liter and 15 mmol/day. Diarrhea produced by 45 ml of sodium phosphate was watery and voluminous, with fecal weights averaging 1078 g/day (range 601-1713 g/day). Measured fecal phosphate concentrations and outputs averaged 85 mmol/liter and 92 mmol/day, respectively, and all values were significantly elevated. Soft, less voluminous stools were produced with 22.5 ml of sodium phosphate but all had an abnormally high soluble phosphate concentration and 24-hr output. In conclusion, the upper limits of normal for soluble fecal phosphate concentration and output established in this study should be useful in the chemical diagnosis of phosphate-induced diarrhea.


Transient deformation measurement with electronic speckle pattern interferometry by use of a holographic optical element for spatial phase stepping.
We have used a computer-generated holographic optical element (HOE) with electronic speckle pattern interferometry to calculate the interference phase corresponding to the deformation of a test object from a single TV frame. The HOE is a modified crossed phase grating that introduces a known phase change between the +/-1 diffracted orders, without being translated. The progressive propagation of transient mechanical waves was measured with an rms precision of 2pi/30.


The prevalence of post-traumatic stress disorder (PTSD) in US combat soldiers: a head-to-head comparison of DSM-5 versus DSM-IV-TR symptom criteria with the PTSD checklist.
The definition of post-traumatic stress disorder (PTSD) underwent substantial changes in the 2013 edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). How this will affect estimates of prevalence, whether clinical utility has been improved, and how many individuals who meet symptom criteria according to the previous definition will not meet new criteria is unknown. Updated screening instruments, including the PTSD checklist (PCL), have not been compared with previously validated methods through head-to-head comparisons. We compared the new 20-item PCL, mapped to DSM-5 (PCL-5), with the original validated 17-item specific stressor version (PCL-S) in 1822 US infantry soldiers, including 946 soldiers who had been deployed to Iraq or Afghanistan. Surveys were administered in November, 2013. Soldiers alternately received either of two surveys that were identical except for the order of the two PCL versions (911 per group). Standardised scales measured major depression, generalised anxiety, alcohol misuse, and functional impairment. In analysis of all soldiers, 224 (13%) screened positive for PTSD by DSM-IV-TR criteria and 216 (12%) screened positive by DSM-5 criteria (κ 0·67). In soldiers exposed to combat, 177 (19%) screened positive by DSM-IV-TR and 165 (18%) screened positive by DSM-5 criteria (0·66). However, of 221 soldiers with complete data who met DSM-IV-TR criteria, 67 (30%) did not meet DSM-5 criteria, and 59 additional soldiers met only DSM-5 criteria. PCL-5 scores from 15-38 performed similarly to PCL-S scores of 30-50; a PCL-5 score of 38 gave optimum agreement with a PCL-S of 50. The two definitions showed nearly identical association with other psychiatric disorders and functional impairment. Our findings showed the PCL-5 to be equivalent to the validated PCL-S. However, the new PTSD symptom criteria do not seem to have greater clinical utility, and a high percentage of soldiers who met criteria by one definition did not meet the other criteria. Clinicians need to consider how to manage discordant outcomes, particularly for service members and veterans with PTSD who no longer meet criteria under DSM-5. US Army Military Operational Medicine Research Program (MOMRP), Fort Detrick, MD.


The prognostic impact of uric acid in patients with severely decompensated acute heart failure.
The serum level of uric acid (UA) is a well-known prognostic factor for heart failure (HF) patients. However, the prognostic impact of hyperuricemia and the factors that induce hyperuricemia in acute HF (AHF) patients are not well understood. Eight hundred eighty-nine AHF patients were enrolled in this study. The patients were assigned into a low UA group (UA≤7.0mg/dl, n=495) or a high UA group (UA>7.0mg/dl, n=394) according to their UA level on admission. A Kaplan-Meier curve showed that the survival rate of the low UA group was significantly higher than that of the high UA group. A multivariate Cox regression model identified that a high UA level (HR: 1.192, 95%CI 1.112-1.277) was an independent predictor of 180-day mortality. A multivariate logistic regression model for a high serum UA level on admission indicated that chronic kidney disease (CKD) (OR: 2.030, 95%CI: 1.298-3.176, p=0.002) and the administration of loop diuretics before admission (OR: 1.556, 95%CI: 1.010-2.397, p=0.045) were independent factors. The prognosis, including all-cause death and HF events, was significantly poorer among patients who had a high UA level who had previously used loop diuretics and among CKD patients with a high UA level than among other patients. The serum UA level was an independent predictor in patients who were hospitalized during an emergent situation for AHF. An elevated serum UA level on admission was associated with the presence of CKD and the use of loop diuretics. These factors were also associated with adverse outcomes in hyperuricemic patients with AHF.


Impact of the COVID-19 pandemic on patients with myasthenia gravis: A survey of the Myasthenia Gravis Foundation of America MG patient registry.
Factors associated with coronavirus disease 2019 (COVID-19) infection among the myasthenia gravis (MG) population are incompletely understood. This study aimed to characterize the behavior of MG patients during the pandemic and to examine risk factors associated with COVID-19 infection. A "COVID-19 Survey" was sent to MG Patient Registry participants in the summer of 2020 (CSS20) and winter of 2021 (CWS21). Survey results were summarized descriptively. Demographics, disease characteristics, medication use, and survey results were compared between those reporting COVID-19 diagnosis (COVID), COVID-19 like symptoms without diagnosis (COVID-Like), and asymptomatic participants. A total of 454 and 665 participants completed the CSS20 and CWS21 surveys respectively; 326 participants completed both. Most continued follow-up visits and MG treatments. The frequency of COVID-like symptoms was similar between CSS20 and CWS21, while COVID-19 exposure (6% vs. 27%), COVID-19 testing among symptomatic individuals (35% vs. 78%), and COVID-19 diagnosis (0.2% vs. 6%) were higher in the CWS21. Cough, fever, fatigue, myalgia, anosmia/ageusia, and hospital and intensive care unit (ICU) admissions were more frequent in the COVID compared to the COVID-Like group. COVID-19 exposure (odds ratio [OR] 7.88), number of people in the household (OR 1.31), and report of MG exacerbation before the pandemic (OR 2.6) were independently associated with COVID-19 infection. COVID-19 affected MG patients increasingly through the early pandemic. While face-to-face contact with a COVID-19 infected individual was an obvious risk factor, MG patients who had more people in the household and unstable disease were at elevated risk for COVID-19 infection.


Rebamipide enema is effective for treatment of experimental dextran sulfate sodium induced colitis in rats.
We investigated therapeutic efficacy of rebamipide using dextran sulfate sodium (DSS) induced colitis model in rats. Three percent DSS solution was given to rats for 9 days. After that, we evaluated the drug efficacy on colitis sustained with continuous drinking of 1% DSS. Twice-daily treatment with 0.3% or 1% rebamipide for 14 days significantly ameliorated the stool abnormality in the colitis model, preferentially suppressed hematochezia. The colonic mucosal lesion, determined by Alcian blue staining on day 24, was significantly reduced by rebamipide enema in a dose-dependent manner. Either rebamipide or 5-aminosalycilic acid (5-ASA) enema treated once daily significantly ameliorated colitis. The minimum effective dose of rebamipide was 0.3% in once-daily treatment, and that of 5-ASA was 10%. In a mechanistic study, the epithelial cell sheet formation of the T84 colon cancer cell was measured as an increase in generation of trans-epithelial electrical resistance in vitro. Rebamipide accelerated the increase, while 5-ASA conversely suppressed it. These results suggest that rebamipide enema is effective for treatment of experimental ulcerative colitis (UC).


First confirmed case of infant botulism in Africa, caused by a dual-toxin-producing Clostridium botulinum strain.
Botulism, a rare life-threatening toxemia, is probably underdiagnosed in all of its forms in Africa. This study reports the first laboratory-supported case of infant botulism on the African continent. A 10-week-old, previously well infant presented with progressive global weakness, feeding difficulty, and aspiration pneumonia. During a lengthy hospitalization, a rare bivalent Clostridium botulinum strain, producing subtype B3 and F8 toxins and with a new multilocus sequence type, was isolated from stool. The infant was successfully treated with a heptavalent botulinum antitoxin infusion and pyridostigmine. Despite the relative rarity of infant botulism, this case illustrates the importance of maintaining a high level of clinical suspicion when assessing hypotonic infants. The value of modern diagnostic modalities in identifying and characterizing this under-recognized condition is also demonstrated.


Educators Countering the Impact of Structural Racism on Health Equity.
Health equity endorses that all persons are respected equally, and society must exert intentional efforts to eradicate inequities. Race, frequently taught as an impartial risk factor for disease, is a facilitator of structural inequities stemming from racist policies. Nursing educators must help students understand the impact of structural racism on patient populations, communities, and society at large. This article illustrates the face of structural racism, highlights how structural racism impacts health care outcomes, and provides meaningful ways for educators to unmute racism and facilitate race-related discourse in the classroom to counter the impact of structural racism on health equity.


Use of an appendicitis medical information sheet in the pediatric primary care system.
Accurate and prompt diagnosis is required for the primary evaluation of pediatric appendicitis. Among pediatricians and surgeons working in Yamanashi Prefecture, the pediatric appendicitis medical information (PAMI) sheet was edited in April 2011 to reflect the diagnostic results of the pediatric primary and emergency medical service and used as a referral document for surgical consultation to secondary hospitals. The PAMI sheet consisted of sections for history taking, symptoms, physical signs and laboratory findings without a scoring system. For 32 consecutive months starting in April 2011, 59 patients hospitalized for suspected appendicitis were retrospectively reviewed. In particular, a total of 17 referral patients evaluated with the PAMI sheet were assessed in order to evaluate the utility of the form. The pediatric surgeons were able to easily determine patient condition from the PAMI sheet. In total, 13 of 17 patients had appendicitis. According to the physical findings of the 17 studied patients, the judgment of right lower quadrant tenderness (κ = 0.63) and guarding (κ = 1.00) was consistent between the pediatric surgeons and primary attending pediatricians. The PAMI sheet aids in the collection of detailed history and objective data with a high level of accuracy, and provides useful referral diagnostic information to the secondary-level hospitals.


Regulation of pathways of extramitochondrial fatty acid oxidation and liver fatty acid-binding protein by long-chain monocarboxylic fatty acids in hepatocytes. Effect of inhibition of carnitine palmitoyltransferase I.
The regulation of the extramitochondrial fatty acid oxidation pathways located in the peroxisomes and the endoplasmic reticulum is not fully understood. Although both long-chain dicarboxylic fatty acids, which are poorly metabolized in hepatocytes, and non-beta-oxidizable fatty acid analogs induce peroxisomal beta-oxidation and liver fatty acid-binding protein (L-FABP) by a pretranslational mechanism, monocarboxylic long-chain fatty acids, which are rapidly esterified and oxidized, do not. To establish whether impaired utilization and, hence, sustained intracellular levels of monocarboxylic long-chain fatty acids increase their efficacy as inducers, the effect of oleic acid on cytochrome P-450 4A1, peroxisomal beta-oxidation, and L-FABP during inhibition of mitochondrial beta-oxidation was determined. In primary hepatocyte cultures, oleic acid had no inducing effect, but in the presence of 2-tetradecylglycidic acid (TDGA), an inhibitor of carnitine palmitoyltransferase I, it induced P-450 4A1, peroxisomal beta-oxidation, and L-FABP pretranslationally. An increase in peroxisomal beta-oxidation was also noted in the presence of etomoxir, another inhibitor of carnitine palmitoyltransferase I. Exposure of hepatocytes to TDGA for 1 h led to an expected decrease in incorporation of radiolabel from [1-14C]oleate into CO2 and water-soluble products. In contrast, long-term exposure to TDGA increased incorporation of [1-14C]oleate into oxidation products, most likely due to an adaptive induction of peroxisomal beta-oxidation. Both acute and long-term exposure of hepatocytes to TDGA decreased incorporation of oleic acid into triglycerides, an effect that may have contributed to the intracellular accumulation of fatty acids. These results provide support for a mechanism by which long-chain fatty acids or specific metabolites, including long-chain acyl-CoA esters and long-chain dicarboxylic acids, act as signals in the induction of P-450 4A1, peroxisomal beta-oxidation, and L-FABP under conditions in which long-chain fatty acids accumulate due to impaired entry into the mitochondrial beta-oxidation pathway.


Validity of the copper/zinc ratio as a diagnostic marker for taste disorders associated with zinc deficiency.
Although zinc (Zn) deficiency is often suspected in patients with taste disorders, it may be difficult to diagnose Zn deficiency, especially in patients without any clear risk factors. Accordingly, the aim of the present study was to detect possible markers for taste disorders or zinc deficiency. To achieve this aim, we analyzed data obtained from 122 Japanese men who were not using medicines and had no diseases requiring treatment. We evaluated the following factors: awareness of dysgeusia; salty taste recognition threshold (SRT); the serum concentrations of Zn, copper (Cu), iron, alkaline phosphatase, and albumin; and the Cu/Zn ratio. The serum Cu/Zn ratio was positively correlated with the both the SRT and the awareness of dysgeusia. The serum Zn concentration was not correlated with the SRT or the awareness of dysgeusia in univariate analyses. However, in multivariate logistic regression, the serum Zn concentration was associated with the awareness of dysgeusia. In conclusion, the serum Cu/Zn ratio is a good diagnostic marker for taste disorders and the value of 1.1 may be a threshold level for detecting taste disorders.


Blood and saliva-derived exomes from healthy Caucasian subjects do not display overt evidence of somatic mosaicism.
Somatic mosaicism is a normal occurrence during development in the tissues and organs. As part of establishing a "healthy population "(HP) background or base-line, we investigated whether such mosaicism can be routinely detected in the circulating DNA secured from a rigorously designed healthy human liquid biopsy clinical trial (saliva, blood). We deployed next generation (NG) whole exome sequencing (WES) at median exome coverage rates of 97.2 % (-to-30x) and 70.0 % (-to-100x). We found that somatic mosaicism is not detectable by such standard bulk WES sequencing assays in saliva and blood DNA in 24 normal healthy Caucasians of both sexes from 18 to 60 years of age. We conclude that for circulating DNA using standard WES no novel somatic mutational variants can be detected in protein-coding regions of normal healthy subjects. This implies that the extent within normal tissues of somatic mosaicism must be at a lower level, below the detection threshold, for these circulating DNA WES read depths.


Diagnostic effect of artificial intelligence solution for referable thoracic abnormalities on chest radiography: a multicenter respiratory outpatient diagnostic cohort study.
We aim ed to evaluate a commercial artificial intelligence (AI) solution on a multicenter cohort of chest radiographs and to compare physicians' ability to detect and localize referable thoracic abnormalities with and without AI assistance. In this retrospective diagnostic cohort study, we investigated 6,006 consecutive patients who underwent both chest radiography and CT. We evaluated a commercially available AI solution intended to facilitate the detection of three chest abnormalities (nodule/masses, consolidation, and pneumothorax) against a reference standard to measure its diagnostic performance. Moreover, twelve physicians, including thoracic radiologists, board-certified radiologists, radiology residents, and pulmonologists, assessed a dataset of 230 randomly sampled chest radiographic images. The images were reviewed twice per physician, with and without AI, with a 4-week washout period. We measured the impact of AI assistance on observer's AUC, sensitivity, specificity, and the area under the alternative free-response ROC (AUAFROC). In the entire set (n = 6,006), the AI solution showed average sensitivity, specificity, and AUC of 0.885, 0.723, and 0.867, respectively. In the test dataset (n = 230), the average AUC and AUAFROC across observers significantly increased with AI assistance (from 0.861 to 0.886; p = 0.003 and from 0.797 to 0.822; p = 0.003, respectively). The diagnostic performance of the AI solution was found to be acceptable for the images from respiratory outpatient clinics. The diagnostic performance of physicians marginally improved with the use of AI solutions. Further evaluation of AI assistance for chest radiographs using a prospective design is required to prove the efficacy of AI assistance. • AI assistance for chest radiographs marginally improved physicians' performance in detecting and localizing referable thoracic abnormalities on chest radiographs. • The detection or localization of referable thoracic abnormalities by pulmonologists and radiology residents improved with the use of AI assistance.


Nasal Reconstruction in 4-years-old Child Affected by Nasal wing Cleft.
Congenital and pediatric nasal lesion resection and their reconstructive outcomes are not well studied. A surgeon must consider the site, depth, size, age, etiology and effect on future function (including growth). The path of total reconstruction or of portions of the cartilaginous / cutaneous nasal structure in the pediatric patient must undergo a series of totally different needs with respect to the management of the adult. First of all, it is essential to understand at what age to intervene, given that the child in the growth phase up to adolescence sees the nasal skeleton change significantly and in relation to the possible psychological repercussions that the tissue deficit can cause. This path will often require serious interventions in order to recreate a structure that is aesthetically ideal, functionally effective and finally suitable for the growth phase of the rest of the body and facial structures. The online version contains supplementary material available at 10.1007/s12070-022-03364-y.


Synthesis of natural product-like polyprenylated phenols and quinones: Evaluation of their neuroprotective activities.
Twenty-seven natural product-like polyprenylated phenols and quinones were synthesized and their neuroprotective activity was tested using human monoamine oxidase B (MAO-B) and SH-SY5Y cells. Eight compounds inhibited MAO-B (IC50 values < 25 μM) and the inhibition mode and molecular docking of two (8c and 16c) were investigated. Compounds inhibiting MAO-B activity were additionally tested for their ability to protect SH-SY5Y cells from peroxide injury. Three derivatives (3c, 8c and 16c) exhibited both MAO-B inhibitory and neuroprotective activity. A structure activity-relationship study showed that a phenolic hydroxyl group and a longer side chain are important for both activities.