Ratio of FEV1/Slow Vital Capacity of < 0.7 Is Associated With Clinical, Functional, and Radiologic Features of Obstructive Lung Disease in Smokers With Preserved Lung Function.
Mild expiratory flow limitation may not be recognized using traditional spirometric criteria based on the ratio of FEV1/FVC. Does slow vital capacity (SVC) instead of FVC increase the sensitivity of spirometry to identify patients with early or mild obstructive lung disease? We included 854 current and former smokers from the Subpopulations and Intermediate Outcome Measures in COPD Study cohort with a postbronchodilator FEV1/FVC ≥ 0.7 and FEV1 % predicted of ≥ 80% at enrollment. We compared baseline characteristics, chest CT scan features, exacerbations, and progression to COPD (postbronchodilator FEV1/FVC, < 0.7) during the follow-up period between 734 participants with postbronchodilator FEV1/SVC of ≥ 0.7 and 120 with postbronchodilator FEV1/SVC < 0.7 at the enrollment. We performed multivariate linear and logistic regression models and negative binomial and interval-censored proportion hazards regression models adjusted for demographics and smoking exposure to examine the association of FEV1/SVC < 0.7 with those characteristics and outcomes. Participants with FEV1/SVC < 0.7 were older and had lower FEV1 and more emphysema than those with FEV1/SVC ≥ 0.7. In adjusted analysis, individuals with postbronchodilator FEV1/SVC < 0.7 showed a greater percentage of emphysema by 0.45% (95% CI, 0.09%-0.82%), percentage of gas trapping by 2.52% (95% CI, 0.59%-4.44%), and percentage of functional small airways disease based on parametric response mapping by 2.78% (95% CI, 0.72%-4.83%) at baseline than those with FEV1/SVC ≥ 0.7. During a median follow-up time of 1,500 days, an FEV1/SVC < 0.7 was not associated with total exacerbations (incident rate ratio [IRR], 1.61; 95% CI, 0.97-2.64), but was associated with severe exacerbations (IRR, 2.60; 95% CI, 1.04-4.89). An FEV1/SVC < 0.7 was associated with progression to COPD during a 3-year follow-up even after adjustment for demographics and smoking exposure (hazard ratio, 3.93; 95% CI, 2.71-5.72). We found similar results when we examined the association of prebronchodilator FEV1/SVC < 0.7 or FEV1/SVC less than the lower limit of normal with chest CT scan features and progression to COPD. Low FEV1 to SVC in current and former smokers with normal spirometry results can identify individuals with CT scan features of COPD who are at risk for severe exacerbations and is associated with progression to COPD in the future. ClinicalTrials.gov; No.: NCT01969344T4; URL: www.clinicaltrials.gov.


An effective strategy for development of docetaxel encapsulated gold nanoformulations for treatment of prostate cancer.
Nanoformulation based drug delivery is one of the most important research areas in the field of nanomedicine, which provides promising alternatives to the limitations of conventional chemotherapy. Nano drug delivery enables improved pharmacokinetic profile, bioavailability and therapeutic efficiency compared to the regular chemotherapeutic drugs. Herein, we have established a simple method for the synthesis of docetaxel (Dtx) encapsulated poly (ethylene glycol) (PEG) functionalized gold nanoparticles (AuNPs) for targeted drug delivery to prostate cancer. AuNPs were synthesized by the citrate ion reduction method followed by functionalization with thiol-PEG-amine (SH-PEG-NH2). SH-PEG-NH2 functionalized AuNPs were conjugated with the targeting vehicle, folic acid (FA). The anticancer drug, Dtx was encapsulated within AuNPs by the non-covalent linkage method. The physicochemical characteristics of the synthesized nanoformulations were extensively characterized by various spectral and microscopic studies. HR-TEM indicates the average size of the AuNPs is 16 nm and the nanoformulations is 18 nm. The encapsulation efficiency of the Dtx is ~ 96% which is confirmed by the elemental mapping analysis. The in vitro drug release profile of Dtx and AuNPs nanoformulations were studied by the dialysis membrane method. The anticancer activity of docetaxel encapsulated AuNPs were evaluated with prostate cancer cell lines (PC3). The drug encapsulated nanoformulations reduced the cell viability to about 40% (40 µM concentration at 24, 48 and 72 h of treatment). The optical microscopy observation reveals that the damage of prostate cancer cells after exposure to Dtx encapsulated AuNPs. The good cytotoxic activity of the present nanoformulation against prostate cancer cell lines enables its application for targeted drug delivery to prostate cancer.


Management of nutritional alterations and issues concerning quality of life.
Malnutrition is common in human immunodeficiency virus (HIV) infection and plays an important role in morbidity and mortality. Malnutrition can affect hospitalizations, disease complications, quality of life, and survival, and has adverse clinical consequences that may be independent of CD4 lymphocyte count. There have been recent advances in knowledge concerning the pathogenesis of malnutrition and the nature of weight loss in HIV patients. The onset of body cell mass depletion may occur early in the infection and predate significant immune deficiency, implying that the virus itself may be involved. Hypogonadism, a common finding in HIV patients, is associated with body composition changes and is involved in body cell mass depletion. In addition, intestinal dysfunction and malabsorption contribute to weight loss in HIV patients. Several studies have evaluated the use of appetite stimulants, enteral and parenteral nutritional support, anabolic agents, and other agents in the management of weight loss and malnutrition in HIV patients. Results of a randomized trial comparing total parenteral nutrition (TPN) and an oral semi-elemental diet (SED) in AIDS patients with malabsorption indicate that the TPN group consumed more calories and gained more weight than the SED group, but the gain was due to increased body fat. The effect of nutritional support on malnutrition and weight loss in HIV patients and potential secondary benefits to quality of life, physical and mental performance, immune function, and disease progression require further study.


Changing the culture of clinical education in massage therapy.
Much within the profession of massage therapy is done according to tradition. From an epistemological viewpoint, tradition is a way of knowing or, by extension, being, that is based upon both tenacity and authority and not always in best practices. As the profession of massage therapy moves in the direction of evidence-based medicine, or evidence-informed practice, the opportunity to re-evaluate massage therapy education presents itself.


Diverse immunological and hematological effects of interleukin 7: implications for clinical application.
Interleukin-7 (IL-7) was originally discovered to be a pre-B cell growth factor. Soon thereafter, a broader role for IL-7 in leukocyte development and function began to be identified. IL-7 now has been shown to be a critical cytokine for normal T and B lymphopoiesis and a mobilizer of pluripotent stem cells and myeloid progenitors. IL-7 has been demonstrated to enhance T cell function and induce cytokine expression in monocytes. Preclinical studies have already found that IL-7 could accelerate murine lymphocyte regeneration following chemotherapy and bone marrow transplantation, induce antitumor effects in mice, and expand anti-HIV-specific human T cells. Thus it is essential that further preclinical and clinical research be performed to evaluate IL-7 as a potential therapy for leukopenia, bone marrow/stem cell transplantation, cancer, and HIV/AIDS.


Comparison of the Proximate Composition and Nutritional Profile of Byproducts and Edible Parts of Five Species of Shrimp.
The nutritional components of different parts (meat, head, shell and tail) of Litopenaeus vannamei (L.v), Macrobrachium rosenbergii (M.r), Penaeus monodon (P.m), Fenneropenaeus chinensis (F.c), and Penaeus japonicus (P.j) were analyzed and their nutritional values were evaluated. For the five species of shrimp, the meat yield was 37.47-55.94%, and the byproduct yield was 44.06-62.53%. The meat yields of L.v and F.c were the highest (55.94 and 55.92%, respectively), and the meat yield of M.r was the lowest (37.47%). The shrimp contain high amounts of crude protein, and the values of the amino acid score (AAS), chemical score (CS), and essential amino index (EAAI) were greater than or close to 1.00, indicating that shrimp protein had higher nutritional value. The shrimp head was rich in polyunsaturated fatty acids and the ratio of n-6 to n-3 PUFAs was from 0.37 to 1.68, indicating that the shrimp head is rich in n-3 PUFAs and is a good source of n-3 PUFAs. The five species of shrimp were rich in macro- and micro-minerals, especially in shrimp byproducts. The shrimp byproducts were also rich in other bioactive ingredients (astaxanthin), which are also very valuable for developing biological resources. Therefore, shrimp have many nutritional benefits, and their byproducts can also be used to develop natural nutraceuticals, which are considered to be one of the healthiest foods.


[Vibrio cholera (Vibrio cholerae non-01) isolated in Poland from the Bug river].
Non-01 cholera vibrios for the first time has been isolated from freshwater in Poland. In October 1994 during bacteriological examination of Bug water by a two-step enrichment method in alkaline peptone water at pH 8.6 and TCBS. Repeated examination in November, December and January in the same and other locations among the polish-ukrainian borderline revealed persistence of V. cholerae in the river; 22 strains were isolated. All 22 strains were identical to V. cholerae E1 Tor 01 Ogawa reference strain except to antigens 0. The strains isolated from water were no agglutinable by standard 01 serum neither by 0139 serum. Determination of their antigens 0 is under investigations. They might be pathogenic for people as it could be judged by their high resistance to bile, proteolytic and haemolytic activity. No cholera-like cases were notified on the polish side of the river.


Effect of photogenerated charge transfer on the photocatalysis in high-performance hybrid Pt-Co:ZnO nanostructure photocatalyst.
Hybrid Pt-Co:ZnO nanostructure photocatalysts were prepared via a facile two-step synthetic strategy. SPS and TPV investigations demonstrate the existence of the synergetic effect between Pt and Co dopants. Such synergetic effect could make use of visible photons as well as facilitates the separation of photogenerated charges to prevent recombination, effectively prolongating the charges lifetime to participate photocatalytic reaction. The synergetic effect exist in Pt-Co:ZnO inducing as high as 7.7-fold in photovoltaic response and 10-fold in the photo-activity for hybrids compared to Co:ZnO.


Views of older adults on patient participation in medication-related decision making.
Medication decision making is complex, particularly for older patients with multiple conditions for whom benefits may be uncertain and health priorities may be variable. While patient input would seem important in the face of this uncertainty and variability, little is known about older patients' views of involvement in medication decision making. To explore the views of older adults regarding participation in medication decision making. Qualitative study. Fifty-one persons at least 65 years old who consumed at least one medication were recruited from 3 senior centers and 4 physicians' offices. One-on-one interviews were conducted to uncover participants' perceptions of medication-related decision making through semistructured, open-ended questions. Themes were compared according to the constant comparative method of analysis. The predominant theme that emerged was the variability in perceptions concerning whether it was possible or desirable for patients to participate in prescribing decisions. For some participants, involvement was limited to sharing information. Physician and system factors that were felt to facilitate or impede patient participation included communication skills, the expanding number of medications available, multiple physicians prescribing for the same patient, and a focus on treating numbers. Perceived lack of knowledge, low self-efficacy, and fear were the patient factors mentioned. Both the presence and absence of trust in the prescribing physician were seen as alternatively impeding and enhancing patient participation. Only 1 participant explicitly mentioned patient preference, a cornerstone of shared decision making. While evolution to greater patient involvement in medication decision making may be possible, and desirable to some older patients, findings suggest that the transition will be challenging.


Occupational stress and health risk of employees working in the garments sector of Bangladesh: An empirical study.
The present study was conducted with a view to examining the impact of occupational stress on employees' health risk. A total number of 350 garment employees (114 supervisors and 236 workers) were selected from 25 readymade garment factories of Dhaka, Narayanganj, and Gazipur industrial areas of Bangladesh on a random sampling basis. Occupational stress was estimated using an ERIs modified questionnaire; when self-reported health problems, work related information and socio-demographic information were obtained using face-to-face interviews using a pre-formed questionnaire. The survey was conducted for 2 years from January 2020 to December 2021 in Dhaka, Narayanganj and Gazipur districts where most of the garment industries in Bangladesh are located. All data were processed by using Statistical Package for Social Sciences (SPSS) and Decision Analyst Stats, Version 2.0. For analyzing data, suitable statistical tools such as two-way ANOVA, z-test, chi-square test, Pearson's product-moment correlation, stepwise multiple regressions, and descriptive statistics were used. The results of the present study reveal that the occupational stress had a significant positive influence on health risk. The findings also reveal that both the male and female employees perceived garment job highly stressful and risky for their health causes many dies and sickness, but it was higher among the female employees than their counterparts. Study suggests that due to major illness and diseases garments' employees are lacks of sound health that have to consider remedying for reducing occupational stress and health risk.


High sugar content and body mass index: modelling pathways around the first 1000 d of life, BRISA cohort.
Few studies are focused on sugar consumption around the first 1000 d of life. Thus, this work modelled the pathways linking the consumption of sugary drinks in pregnancy and maternal pre-gestational BMI to early child's exposure to products with high sugar content and to BMI z-score in the second year of life. BRISA cohort, São Luís, Brazil was used from the baseline to the follow-up at the second year of life. A theoretical model was constructed to analyse associations between variables from prenatal period (socio-economic status, age, frequency of sugary drinks consumption during pregnancy and pre-gestational BMI), birth weight, exclusive breast-feeding and two outcomes: higher calories from products with added sugar as a percentage of the total daily energy intake and BMI z-score at follow-up at the first 2 years of life, using structural equation modelling. Data of pregnant women (n 1136) and their offspring. Higher pre-gestational BMI (standardised coefficient (SC) = 0·100; P = 0·008) and higher frequency of sugary drinks consumption during pregnancy (SC = 0·134; P < 0·001) resulted in high percentage of daily calories from products with added sugar in the second year of child, although no yet effect was observed on offspring weight at that time. Maternal obesity and sugary drinks consumption in pregnancy increased the risk of early exposure (before to 2 years) and high exposure of child to added sugar, showing perpetuation of the unhealthy dietary behaviours in the first 1000 d of life.


A reaction-diffusion model of the receptor-toxin-antibody interaction.
It was recently shown that the treatment effect of an antibody can be described by a consolidated parameter which includes the reaction rates of the receptor-toxin-antibody kinetics and the relative concentration of reacting species. As a result, any given value of this parameter determines an associated range of antibody kinetic properties and its relative concentration in order to achieve a desirable therapeutic effect. In the current study we generalize the existing kinetic model by explicitly taking into account the diffusion fluxes of the species. A refined model of receptor-toxin-antibody (RTA) interaction is studied numerically. The protective properties of an antibody against a given toxin are evaluated for a spherical cell placed into a toxin-antibody solution. The selection of parameters for numerical simulation approximately corresponds to the practically relevant values reported in the literature with the significant ranges in variation to allow demonstration of different regimes of intracellular transport. The proposed refinement of the RTA model may become important for the consistent evaluation of protective potential of an antibody and for the estimation of the time period during which the application of this antibody becomes the most effective. It can be a useful tool for in vitro selection of potential protective antibodies for progression to in vivo evaluation.


Prognostic model of patients with liver cancer based on tumor stem cell content and immune process.
Globally, liver hepatocellular carcinoma (LIHC) has a high mortality and recurrence rate, leading to poor prognosis. The recurrence of LIHC is closely related to two aspects: degree of immune infiltration and content of tumor stem cells. Hence, this study aimed to used RNA-seq and clinical data of LIHC from The Cancer Genome Atlas, Estimation of Stromal and Immune cells in Malignant Tumours, mRNA stemness index score, and weighted gene correlation network analysis methods to find genes significantly linked to the aforementioned two aspects. Key genes and clinical factors were used as input. Lasso regression and multivariate Cox regression were conducted to build an effective prognostic model for patients with liver cancer. Finally, four key genes (KLHL30, PLN, LYVE1, and TIMD4) and four clinical factors (Asian, age, grade, and bilirubin) were included in the prognostic model, namely Immunity and Cancer-stem-cell Related Prognosis (ICRP) score. The ICRP score achieved a great performance in test set. The area under the curve value of the ICRP score in test set for 1, 3, and 5 years was 0.708, 0.723, and 0.765, respectively, which was better than that of other prognostic prediction methods for LIHC. The C-index evaluation method also reached the same conclusion.


The Irukandji syndrome. A devastating syndrome caused by a north Australian jellyfish.
The Irukandji syndrome is a group of delayed (10-40 mins, mean 30 mins) severe systemic symptoms occurring after an initial mild skin sting by small carybdeid (box) jellyfish including Carukia barnesi, known colloquially as the 'Irukandji'. Although the syndrome is well known in tropical Australian waters, the 1998-1999 season in north Queensland was notable for the unusually high number of victims with severe toxic heart failure who needed admission to intensive care facilities for more complex investigations and treatment. There have also been other severe and unusual symptoms reported this year, which leads to the conclusion that there may be more than one species of jellyfish causing the Irukandji syndrome, or a seasonal variation in the symptoms and/or severity of symptoms caused by Carukia spp. This article describes the updated current state of information on the ecology of jellyfish causing the Irukandji syndrome, introduces the new symptoms, and discusses some treatment regimens that may be effective. Problems associated with inappropriate treatment are also discussed. To date there have been no reported deaths from Irukandji envenomation but there have been a number of patients who were probably only saved by high quality intensive care treatment. Research into the cause and treatment of this potentially devastating syndrome is hampered by lack of funding, although there are large costs to the taxpayers for retrieval and medical treatment of victims. These costs are analysed and presented.


Inhaled 1,8-cineole reduces inflammatory parameters in airways of ovalbumin-challenged Guinea pigs.
Eucalyptol, also known as 1,8-cineole, is a monoterpene traditionally used to treat respiratory disorders due to its secretolytic properties. In addition to its myorelaxant effects, it also has anti-inflammatory actions in vitro. In this study, we aimed to evaluate the efficacy of acute treatment with 1,8-cineole on reducing airway inflammatory parameters. Ovalbumin (OVA)-sensitized guinea pigs were submitted to antigenic challenge (OVA) with or without pre-treatment with a single dose of 1,8-cineole administered by inhalation. Airway inflammatory parameters were reduced or absent in 1,8-cineole-treated animals as compared with untreated guinea pigs. Acute treatment with 1,8-cineole impaired the development of airway hyperresponsiveness to carbachol in isolated tracheal rings. Levels of the pro-inflammatory cytokines TNFα and IL-1β was lower in bronchoalveolar lavage fluid (BALF) of 1,8-cineol-treated guinea pigs than in untreated animals. 1,8-Cineole impaired the OVA-induced increase of the myeloperoxidase activity in BALF. 1,8-Cineole also prevented the reduction of the mucociliary clearance induced by the antigen presentation. The present investigation provides evidence that inhaled 1,8-cineole prevents hyperresponsiveness and inhibits inflammation in airways of ovalbumin-challenged guinea pigs.


Eleven cases of intraosseous lipoma of the calcaneus.
Intraosseous lipomas are rare benign primary bone tumors, with an incidence of one per thousand bone tumors. We studied eleven cases of intraosseous lipoma of the calcaneus. All the patients received radiographic examinations and MRI with T1-and T2-weighted images with Gd-DTPA enhancement. Seven patients received tumor curettage. Plain radiographs demonstrated that all of the lesions showed clear osteolysis surrounded by a sclerotic margin in the central body of the calcaneus. MRI revealed that all the lesions had demarcated homogenous high signal intensity lesions on both T1- and T2-weighted images, which strongly suggested adipose tissue. In 5 cases, the center of the lesion showed low signal intensity lesions on T1-weighted images, suggesting the existence of central necrosis or cyst formation. After excising the tumors of 7 patients, there was no local tumor recurrence. Surgical intervention was considered unnecessary in all cases after the diagnosis of an intraosseous lipoma was determined by MRI.


Investigation of cervical patency and uterine appearance in domestic cats by fluoroscopy and scintigraphy.
The cervical patency of six domestic female cats was monitored under sedation by infusion of contrast medium (Omnipaque) into the cranial vagina during early oestrus, mid-oestrus, late oestrus and interoestrus or a radiopharmaceutical ((99m)Tc-HSA) during mid- and interoestrus in a non-ovulatory oestrous cycle. The transport of the contrast medium or the radiopharmaceutical through the cervix and within the uterine horns was observed under fluoroscopy and with the aid of scintigraphy. In three of the queens, transcervical transport of contrast medium was demonstrated in all stages of oestrus, in one queen during mid-oestrus, late oestrus and 1 day after oestrus, and in two queens only during late oestrus. The relations between the cervical patency to the contrast medium and the oestrous behaviour, cornification of the vaginal cells and the serum oestradiol-17beta concentration were evaluated, and a relationship was found between the cervical patency and the degree of vaginal cornification. Transcervical transport of the radiopharmaceutical was observed in three queens during mid-oestrus. When the cervix was open, hysterography under a fluoroscope and hysteroscintigraphy were performed. The fluoroscopic and scintigraphic recordings revealed the patterns of the uterine contractions during oestrus in both ascending and descending directions, and the movement of the uterine contents back and forth between the uterine horns. The hysterograms were classified according to the shape of the uterine horns and the appearance of the endometrial lining. Spiral-shaped uterine horns with a smooth inner contour were observed in two queens, and a corkscrew appearance with irregular filling defects in the uterine lumen was shown in two queens that had developed subclinical cystic endometrial hyperplasia. These findings demonstrated that fluids or particles deposited in the cranial vagina of the cat can be transported into the uterus during some stages of the oestrous cycle. The fluoroscopic and scintigraphic techniques developed in this study may be further modified to permit more detailed studies of uterine contractile patterns and sperm transport in the feline female reproductive tract. Hysterography proved useful to diagnose uterine disease. The information on cervical patency is of value also for the development of techniques for artificial insemination in this species, and should be studied also in the ovulatory cycle.


Identification of a Novel Pathogen Using Family-Wide PCR: Initial Confirmation of COVID-19 in Thailand.
In resource-limited countries, early detection of novel pathogens is often challenging, due to financial and technical constraints. This study reports the efficacy of family-wide polymerase chain reaction (PCR) in screening, detecting, and identifying initial cases of the novel SARS-CoV-2 in Thailand. Respiratory secretions were collected from suspected individuals traveling from Wuhan, China to Thailand at the beginning of January 2020. Family-wide PCR assays yielded positive results for coronavirus in one traveler within 12 h on January 8, 2020. Nucleotide sequences (290 bp) showed 100% similarity to SARS-CoV-2. The whole genome sequence was further characterized by Next Generation Sequencing (NGS) for confirmation. Combining family-wide PCR, as a rapid screening tool, with NGS, for full genome characterization, could facilitate early detection and confirmation of a novel pathogen and enable early containment of a disease outbreak.


[Effect of arnebia root oil in promoting the tissue recovery of surface of wound and basic fibroblast growth factor (bFGF) mRNA expression].
To explore the molecular biological mechanism of Arnebia Root oil (AO) in promoting the recovery of surface of wound by observing basic fibroblast growth factor (bFGF) mRNA expression in the wound tissue and healing rate of the wound. Patients in the observed group with their wound treated by AO and those in the control group treated by petrolatum gauze. The wound surface healing rate was estimated and bFGF mRNA expression was observed by RT-PCR. Endogenous bFGF mRNA expression existed in the wound surface of both groups, but its level in the observed group at any time point was obviously higher than that in the control group respectively, with significant difference in comparison of the gray density between the two groups (P < 0.05). The wound surface healing rate kept abreast with bFGF mRNA expression in wound tissues, so it was significantly higher in the observed group than that in the control group (P < 0.05). GAPDH gene, which was taken as a parameter for internal reference, expressed with a certain amount unchanged in different periods of healing (P > 0.05 ). AO shows obviously promotive action on bFGF, an important regulatory factor on wound healing, it might complete the recovery process by stimulating the increase of bFGF.


Low cefpirome levels during twice daily dosing in critically ill septic patients: pharmacokinetic modelling calls for more frequent dosing.
To measure plasma levels and pharmacokinetics of cefpirome in critically ill septic patients with normal renal function. To use the pharmacokinetic model to simulate alternate dosing regimens and identify those that predict sustained levels. A prospective, open-label, descriptive study in a 22-bed, multidisciplinary, adult ICU in a university-affiliated, tertiary referral hospital. Twelve adults with normal renal function on enrollment and with suspected or documented sepsis in whom cefpirome was judged to be the appropriate therapy by the managing clinician. Cefpirome 2 g was infused intravenously over 3 min every 12 h. Timed blood samples were taken prior to and during two dosing intervals. Urine was collected for creatinine clearance determination. Two patients were non-evaluable due to renal dysfunction post-enrollment. The median cefpirome trough level was 1.1 mg/l (range 0.5-8.1 mg/l) after the initial dose and 1.4 mg/l (range < 0.5-15.9 mg/l) at 'steady state'. The volumes of distribution and elimination half-lives were greater and more variable than in healthy volunteers. Pharmacokinetic simulation predicted that more frequent bolus dosing, increased doses and continuous infusions would result in concentrations greater than 4 mg/l for over 60% of the dosing interval for all patients. Cefpirome 2 g twice daily produced low plasma troughs in a number of patients. Our data suggest that this drug regimen may be inadequate for successful treatment of difficult-to-treat infections in critically ill patients with normal renal function.


Novel perspectives on the bioaccumulation of PFCs--the concentration dependency.
The effects of exposure concentration on the bioaccumulation of four perfluorinated chemicals (PFCs): perfluorooctanesulfonate (PFOS), perfluoroocanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), was investigated using green mussels, Perna viridis. Mussels were exposed to concentrations of 1 μgL(-1) and 10 μgL(-1) of each PFC for 56 days, and the bioaccumulation factors (BAF) were found to range from 15 to 859 L/kg and from 12 to 473 L/kg at 1 μgL(-1) and 10 μgL(-1), respectively. For all compounds, the BAF was larger at the lower dosage. Results suggest that the bioaccumulation of PFCs is concentration dependent. This concentration dependency can be explained by a nonlinear adsorption mechanism, which was further supported by the experimental results. The sensitivity of BAF to exposure concentration was found to be positively related to perfluorinated chain length and the binding affinity of the compounds. Bioaccumulation of long chain carboxylates and sulfonates are more easily affected by concentration changes. The validity of the conventional kinetic method was examined by comparing the results with the fundamental steady-state method: in addition to the above-mentioned batch test, mussels were also subject to 24-day exposure (1 μgL(-1) and 10 μgL(-1)) followed by 24-day depuration. Contradictions were found in the resulting kinetic BAF and model curving fittings. A new kinetic model based on adsorption mechanism was proposed, which potentially provide more accurate description of the bioaccumulation process of PFCs.


Effects of aerobic conditioning on cardiovascular sympathetic response to and recovery from challenge.
Exercise has widely documented cardioprotective effects, but the mechanisms behind these effects are still poorly understood. Here, we test the hypothesis that aerobic training lowers cardiovascular sympathetic responses to and speeds recovery from challenge. We conducted a randomized, controlled trial contrasting aerobic versus strength training on indices of cardiac (pre-ejection period, PEP) and vascular (low-frequency blood pressure variability, LF-BPV) sympathetic responses to and recovery from psychological and orthostatic challenge in 149 young, healthy, sedentary adults. Aerobic and strength training did not alter PEP or LF-BPV reactivity to or recovery from challenge. These findings, from a large randomized, controlled trial using an intent-to-treat design, show that moderate aerobic exercise training has no effect on PEP and LF-BPV reactivity to or recovery from psychological or orthostatic challenge. In healthy young adults, the cardioprotective effects of exercise training are unlikely to be mediated by changes in sympathetic activity.


Functional characterization of phosphoinositide-specific phospholipase C-beta 1 and -beta 3 in intestinal smooth muscle.
Soluble and membrane phosphoinositide-specific phospholipases obtained separately from dispersed circular and longitudinal intestinal muscle cells were characterized for substrate specificity and G protein dependence using selective antibodies to various isoforms of phospholipase C (PLC) and G protein subunits. Western blot analysis disclosed the presence of the main PLC isozymes, PLC-gamma 1, PLC-delta 1, and PLC-beta 1. Soluble PLC from circular and longitudinal muscle was stimulated by guanosine 5'-O-(3-thiophosphate) and inhibited by PLC-beta 1 antibody (80-90%) and PLC-beta 3 antibody (approximately 25%) but not by G protein antibodies. Membrane PLC from circular and longitudinal muscle was stimulated by cholecystokinin octapeptide (CCK-8) and inhibited selectively by PLC-beta 1 antibody (85%), PLC-beta 3 antibody (15%), and G alpha q/11 antibody (90%). CCK-8-induced contraction in permeabilized circular muscle cells was also selectively inhibited by PLC-beta 1 antibody (76%), PLC-beta 3 antibody (24%), and G alpha q/11 antibody (86%). The combined effects of PLC-beta 1 and PLC-beta 3 antibodies on PLC activity and muscle contraction were additive, causing complete inhibition. Soluble and membrane PLC from circular and longitudinal muscle were immunologically similar but functionally different. The enzymes from circular muscle preferentially hydrolyzed endogenous and exogenous phosphatidylinositol 4,5-biphosphate (PIP2), confirming previous findings of preferential hydrolysis of PIP2 in dispersed intestinal circular muscle cells.


Use of Nitrogen-Doped Carbon Nanodots for the Photocatalytic Fluoroalkylation of Organic Compounds.
The use of amine-rich N-doped carbon nanodots (NCNDs) for the photochemical radical perfluoroalkylation of organic compounds is reported. This operationally simple approach occurs under mild conditions producing valuable new C-C bonds. The chemistry is driven by the ability of NCNDs to directly reach an electronically excited state upon light absorption, thereby successively triggering the formation of reactive radical species from simple perfluoroalkyl iodides. Preliminary mechanistic studies are also reported.


MOF-Derived AlCuSe2 Embedded in a Carbon Matrix for an Economical Anode of Lithium-Ion Battery.
Binary metal chalcogenides (TMCs) have emerged as a potential candidate for lithium-ion batteries due to their availability, abundance, chemical properties, and high theoretical capacities. Despite these characteristics, they suffer from significant volume change, limited life cycle, and inferior rate capabilities which hinder their practical applications. These issues can be addressed by selecting low-cost nanostructure metal combinations coupled with a carbon matrix, which tackles significant volume change to give prolonged cycle life and high-rate capabilities. Herein, novel MOF-derived aluminum copper selenide (ACSe@C) nanospheres embedded in a carbon matrix are synthesized via a facile solvothermal route. Owing to their uniform porous structure, ACSe@C nanospheres exhibit excellent electrochemical performance as an anode material for Li-ion batteries. ACSe@C delivers a high specific capacity of 633.6 mAh g-1 at 0.1 A g-1 and a good rate capability of 532 mAh g-1 at 0.1 A g-1 and 400 mAh g-1 at 8 A g-1. This study demonstrates that ACSe@C is a good candidate for next-generation energy-storage devices.


Immunology and homeopathy. 1. Historical background.
Homeopathy was born as an experimental discipline, as can be seen from the enormous amount of homeopathic data collected over more than two centuries. However, the medical tradition of homeopathy has been separated from that of conventional science for a long time. Conventional scientific wisdom dictates that homeopathy should have no effect above placebo but experiments on ultra-high dilutions of solutes together with some clinical data suggest the intriguing possibility that it might do in some circumstances. Today, an osmotic process between disciplines, previously seen as in conflict, is facilitated because over the last few decades homeopathy has initiated the methods of current medical science and a substantial number of experimental studies-at molecular, cellular and clinical levels-are available. One area of dialogue and of common progress is that of inflammation and immunity, probably because these are closely related to the traditional 'vital force' of the body's self-healing power. In a series of papers we review the historical origins of homeopathy, the laboratory and animal models related to the field of immunopharmacology, the clinical evidence in favor and against the use of homeopathy in the inflammatory diseases and the hypotheses regarding its action mechanism(s). Finally, we will enlighten the specific characteristics of the homeopathic approach, which places great emphasis on identifying a cure for the whole organism.


Accuracy of Demirjian's and Cameriere's Methods for Age Estimation in 6- to 10-Year-Old Iranian Children Using Panoramic Radiographs.
This study assessed the accuracy of Demirjian's and Cameriere's methods for age estimation in Iranian children using panoramic radiographs. This cross-sectional study evaluated 212 panoramic radiographs of 6- to 10-year-old children retrieved from the archives of an oral and maxillofacial radiology department from 2011 to 2017. The chronological age of children at the time of radiography was determined by subtracting the date of radiography from their birth date. The developmental stage of 7 permanent left mandibular teeth was determined according to Demirjian's method. The stage of dental maturation was determined according to Cameriere's method by using the normalized values for 7 permanent left mandibular teeth and the number of teeth with complete root development. The error value of the two methods was calculated by comparing them with the actual chronological age of male and female children, and the absolute error values of the two methods were compared with paired t-tests. The mean error value of Demirjian's and Cameriere's methods was found to be 0.84 and -0.06 in girls and 0.93 and 0.04 in boys, respectively. Significant differences were noted in the absolute error of the two methods compared with the chronological age of male and female children (both Ps < 0.001). In conclusion, this study indicated that Cameriere's method was more accurate than Demirjian's method for age estimation in Iranian children.


(-)-Epigallocatechin-3-Gallate Inhibits the Life Cycle of Pseudorabies Virus In Vitro and Protects Mice Against Fatal Infection.
A newly emerged pseudorabies virus (PRV) variant with enhanced pathogenicity has been identified in many PRV-vaccinated swine in China since 2011. The PRV variant has caused great economic cost to the swine industry, and measures for the effective prevention and treatment of this PRV variant are still lacking. (-)-Epigallocatechin-3-gallate (EGCG) exhibits antiviral activity against diverse viruses and thus in this study, we investigated the anti-PRV activity of EGCG in vitro and in vivo. EGCG significantly inhibited infectivity of PRV Ra and PRV XJ5 strains in PK15 B6 cells and Vero cells. The anti-PRV activity of EGCG was dose-dependent, and 50 μM EGCG could completely block viral infection at different multiplicities of infection. We next revealed that EGCG blocked PRV adsorption and entry to PK15 B6 cells in a dose-dependent manner, but inhibition of PRV entry by EGCG was not as efficient as its inhibition of PRV adsorption. PRV replication was suppressed in PK15 B6 cells treated with EGCG post-infection. However, EGCG did not affect PRV assembly and could promote PRV release. Furthermore, 40 mg/kg EGCG provided 100% protection in BALB/c mice challenged with PRV XJ5, when EGCG was administrated both pre- and post-challenge. These results revealed that EGCG exhibits antiviral activity against PRV mainly by inhibiting virus adsorption, entry and replication in vitro. Meanwhile, EGCG increased the survival of mice challenged with PRV. Therefore, EGCG might be a potential antiviral agent against PRV infection.


Isolation and characterization of the protein body membrane of castor beans.
Intact protein bodies were isolated from dry castor bean seeds (Ricinus communis L.) after homogenization in nonaqueous medium. After repeated washing with glycerol to remove trapped lipid globules, the soluble matrix proteins were removed by the addition of aqueous buffer. The membrane remained attached to the insoluble protein crystalloids and was subsequently released by sonication. Purification of the membrane vesicles in a sucrose gradient produced a single band at a density of 1.21 grams per cubic centimeter. Treatment with 6 molar urea, 1 molar KCl, or 0.25 molar galactose had no effect on the equilibrium density of the membrane. Electron microscopy revealed a highly pure and uniform collection of membrane vesicles. No enzyme activity was specifically associated with the membrane. Sodium dodecyl sulfate gel electrophoresis of the protein body fractions showed that the membrane contained unique proteins, two of which were glycosylated. The membrane contained 153 nanomoles of phospholipid per milligram of protein. The composition of the phosphoglycerides was 51% ethanolamine, 41% choline, 8% inositol, and a trace of serine.


Pulling chromatin fibers: computer simulations of direct physical micromanipulations.
A low-resolution molecular model, which combines the known mechanical properties of protein-free DNA with the accumulating picture of chromatosome structure, has been developed to account for the stretching of single chromatin fibers by an imposed external force. Force-extension characteristics of sets of chains accumulated by Monte Carlo sampling are consistent with recently observed findings in the non-destructive regime (<20 pN imposed force), where the structure of the chromatosome remains intact. The correspondence between simulation and the relaxation phase of the experiment limits the equilibrium entry-exit angle of linker DNA on the chromatosome to W=50(+/-10) degrees and the effective DNA linker length to L(eff)=40(+/-5) bp. The computed force-extension characteristics are relatively insensitive to other parameters of the model, precluding their accurate estimation. The introduction of an attractive potential between closely spaced nucleosomes reproduces the added initial resistance of single fibers to extension at high salt conditions. The consideration of elastic linkers also improves the fitting of assorted classical measurements of unstressed chromatin structure in solution. The overall picture of chromatin that emerges is an irregular, fluctuating, three-dimensional, zig-zag structure with intact, mechanically stable chromatosome units and deformable linkers. The modeled fiber undergoes large-scale configurational rearrangements without significant perturbation of the constituent chromatosome beads, collapsing into a highly condensed form in response to small (<2kT) inter-nucleosomal attractions.


Modelling of polysomnographic respiratory measurements for artefact detection and signal restoration.
Polysomnography (PSG), which incorporates measures of sleep with measures of EEG arousal, air flow, respiratory movement and oxygenation, is universally regarded as the reference standard in diagnosing sleep-related respiratory diseases such as obstructive sleep apnoea syndrome. Over 15 channels of physiological signals are measured from a subject undergoing a typical overnight PSG session. The signals often suffer from data losses, interferences and artefacts. In a typical sleep scoring session, artefact-corrupted signal segments are visually detected and removed from further consideration. This is a highly time-consuming process, and subjective judgement is required for the job. During typical sleep scoring sessions, the target is the detection of segments of diagnostic interest, and signal restoration is not utilized for distorted segments. In this paper, we propose a novel framework for artefact detection and signal restoration based on the redundancy among respiratory flow signals. We focus on the air flow (thermistor sensors) and nasal pressure signals which are clinically significant in detecting respiratory disturbances. The method treats the respiratory system and other organs that provide respiratory-related inputs/outputs to it (e.g., cardiovascular, brain) as a possibly nonlinear coupled-dynamical system, and uses the celebrated Takens embedding theorem as the theoretical basis for signal prediction. Nonlinear prediction across time (self-prediction) and signals (cross-prediction) provides us with a mechanism to detect artefacts as unexplained deviations. In addition to detection, the proposed method carries the potential to correct certain classes of artefacts and restore the signal. In this study, we categorize commonly occurring artefacts and distortions in air flow and nasal pressure measurements into several groups and explore the efficacy of the proposed technique in detecting/recovering them. The results we obtained from a database of clinical PSG signals indicated that the proposed technique can detect artefacts/distortions with a sensitivity>88.3% and specificity>92.4%. This work has the potential to simplify the work done by sleep scoring technicians, and also to improve automated sleep scoring methods.


Autologous or allogeneic bone marrow transplantation for acute myeloblastic leukemia in second complete remission. Importance of duration of first complete remission in final outcome.
Between May 1983 and March 1994, 31 patients with AML in second CR underwent BMT. Fifteen underwent allogeneic BMT from an HLA-identical sibling donor and 16 without a donor, unpurged ABMT. Two different preparative regimens were used: CY (120 mg/kg) and 12 Gy of fractioned TBI (19 patients), and Bu (16 mg/kg) and Cy (120 mg/kg) (BuCy2) in 12 patients. Main clinical characteristics including age, sex, length of first remission, FAB type, and number of leukocytes at diagnosis were similar in both groups. A combination of MTX and CsA was used in 13 cases whereas either CsA or MTX alone was employed in the other two patients. With a median follow-up of 5 years the actuarial 5 year probability of disease-free survival (DFS) for the whole group was 39.8% (95% CI: 29.5-50.1%). The 5 year DFS was equivalent for those who received either ABMT (41.6 +/- 14.2%) or allogeneic BMT (40 +/- 15%). Probabilities of relapse and non-relapse mortality for ABMT and allo BMT patients were 48.7 +/- 16.1 and 18.7 +/- 14.3, and 30.1 +/- 19.2 and 40.7 +/- 16.9, respectively. DFS was better in those patients with a longer duration of first CR (> 18 months) 62.5 +/- 14.4 vs 30.4 +/- 17.9%, attributable to a significantly lower relapse rate in this group of patients 16.6 +/- 12.8 vs 57.8 +/- 22.7 (P 0.05). In conclusion, similar results were observed when ABMT and allo BMT were compared for AML in CR2. A higher antileukemic effect associated with the allo BMT is balanced by an increase in transplant-related mortality. Duration of first remission was the most important factor affecting DFS and better outcome was observed for patients with longer CR1.


Diagnosis and treatment of solid pseudopapillary neoplasm of the pancreas in children: A report of 18 cases.
To explore the incidence, imaging and treatment of solid pseudopapillary tumor of pancreas in children, and Summarize the experience of treatment. The clinical data of 18 children with a solid pseudopapillary tumor of the pancreas treated in our hospital from January 2012 to June 2021 were analyzed retrospectively. The age range was 8-16 years old, the average age was 11.67 years old, and the median age was 11.5 years old, namely, three boys with an average age of 10 years old and 15 girls with an average age of 12 years old. In total, two cases were admitted to the hospital because of trauma, seven cases were found in physical examination, and nine cases were admitted with the abdominal pain as the main complaint. Enhanced CT examination was performed before operation, nuclear magnetic resonance examination and abdominal ultrasound examination were performed in some children, and plain CT scan was performed after operation. Solid pseudopapillary tumor of the pancreas can occur in all parts of the pancreas, especially in the body and tail of the pancreas. Among the 18 cases, SPN occurred in the head of pancreas in 5 cases (27.78%), the neck of pancreas in 2 cases (11.11%), and the body and tail of pancreas in 11 cases (61.11%). All the 18 children were treated by operation. among them, 4 cases underwent choledochal pancreatico duodenectomy (1 case), 4 cases underwent pancreaticoduodenectomy combined with splenectomy (3 cases), 6 cases underwent spleen-preserving pancreatectomy / tail pancreatectomy (1 case), 3 cases underwent enucleation of pancreatic tumor due to exogenous growth, 1 case underwent laparoscopic partial pancreatectomy and pancreaticoenterostomy. Laparotomy was performed in 12 cases and endoscopic surgery in 6 cases. Postoperative pathology confirmed solid pseudopapillary tumor of the pancreas. None of the patients received radiotherapy and chemotherapy after operation and were followed up for 6 months to 2 years. There was no recurrence, metastasis or pancreatic dysfunction. Solid pseudopapillary tumor of pancreas in children is a rare, low-grade malignant solid tumor with no specific clinical manifestations and laboratory examinations. Preoperative diagnosis mainly depends on enhanced CT. Surgical resection of tumor is a reliable treatment, and the specific operation is mainly based on the experience of the chief surgeon, the location of the tumor and the invasion of surrounding tissue. At present, there is no evidence of the effectiveness of other treatment options, and surgical resection of the tumor has a good prognosis.


Effects of extracellular calcium on the subcellular translocation of bovine parathyroid PKC isozymes.
The release of parathyroid hormone is regulated by the extracellular concentration of Ca2+ through a sensor(s) on the surface of the parathyroid cells, but few details are known on the further relay of the signal inside the cell. Activation of protein kinase C (PKC) isozymes is associated with their translocation from the cell soluble fraction to the particulate fraction of the cell. Therefore, identification of a subcellular localization of a PKC isozyme in parathyroid cells as a response to changes in extracellular Ca2+ should be an indication for its putative role in signal transduction coupled to the Ca2+ sensor. We have determined the subcellular localization of six PKC isozymes (alpha, betaI, betaII, epsilon, zeta, and iota) in nonstimulated parathyroid cells and in those treated with low (0.5 mM) and high (3.0 mM) extracellular Ca2+ by confocal microscopy. At the physiological concentration of serum Ca2+, all PKC isozymes studied were localized mainly to the cytosol, although to different extents. Low extracellular Ca2+ caused a redistribution of PKCalpha to the periphery of the cells. In contrast, PKCbetaI, -epsilon, -zeta, and -iota were translocated to the periphery of the cells at high extracellular Ca2+. These results indicate that PKCalpha, -betaI, -epsilon, -zeta, and -iota are involved in the response of parathyroid cells to changes in extracellular Ca2+.


Self-monitoring and close relationships.
Three types of close relationships have received attention from theorists and researchers interested in self-monitoring: friendships, romantic relationships, and marriage. Our review of this literature was organized around three phases of relationships: initiation, maintenance, and dissolution. Across the three types of relationships, consistent differences between high self-monitors and low self-monitors emerged concerning the structure of their social relationships (segmented vs. integrated), the basis for choosing friends and romantic partners (activity-based vs. person-based), and the orientation taken to romantic and marital partners (uncommitted vs. committed). Across all three types of relationships, however, little is known about the processes and consequences involved in the dissolution of close relationships for high self-monitors and low self-monitors. Relatively little is also known about the processes used by high self-monitors and low self-monitors to maintain their friendships and marriages. In addition to addressing these deficiencies in the literature, theorists and researchers interested in self-monitoring and close relationships need to develop sophisticated, causal models that can account for (a) interaction exchanges in the relationships, (b) dyadic as well as individual levels of analysis, and (c) temporal and situational changes in the course of close relationships.


[Influence of ergometric parameters on the results of myocardial perfusion tomographic scintigraphy].
The percentage of peak predicted heart rate that is accepted to consider as sufficient a given exercise test is 85%. However, the optimal value of such rate and other exercise parameters for the purposes of myocardial single-photon emission tomography is not well established. With the aim of establishing the minimal levels of maximal heart rate, product heart rate x systolic blood pressure and ventilatory oxygen uptake to obtain an adequate diagnostic efficacy of myocardial perfusion scintigraphy, 159 patients with coronary artery disease or suspicion of this without previous myocardial infarction were studied with stress test single photon emission tomography with 99mTc-methoxi-isobutil-isonitrile. All the patients were coronary angiography tested. Sensitivity and negative predictive value were significantly higher at levels of heart rate > 80% (93 vs 78%; p = 0.002 and 94 vs 56%; p = 0.0004), product heart rate x systolic blood pressure > 18,000 (88 vs 78%; p = 0.04 and 84 vs 52%; p = 0.004) and > 5 METs (85 vs 77%; p = 0.002 and 74 vs 69%; p = 0.03). Sensitivity and negative predictive value of stress test single photon emission tomography with 99mTc-methoxi-isobutil-isonitrile are low if levels higher than 80% of heart rate, 18,000 of product of heart rate x systolic blood pressure and 5 METs have not been achieved.


Diversity and dynamics in larval digenean assemblages parasitizing Heleobia parchappii in a freshwater shallow lake from the Southeastern Pampa plain, Argentina.
Digeneans have important roles within ecosystems; however, it is estimated that only 14% of the species have been described. Therefore, before being able to detail their role, digenean species' identification and the diversity present in the ecosystems must be known. In this study, the diversity and the temporal-spatial dynamics of larval digeneans in the freshwater snail Heleobia parchappii were analysed in a shallow lake. Specimens of H. parchappii were collected seasonally at three points during one year and a total of 2871 molluscs were analysed. A total of 23 species of digenea were registered and both the overall prevalence and the composition of the assemblages presented temporal and spatial variations, responding to the differential environmental conditions characteristics (anthropic effect, presence of native forests, and differential use of the habitat by the definitive hosts) of three sampled sites. The assemblages of larval digenean in their first intermediate host support the idea that this area is of great importance in biodiversity, and could be endemic areas of some species of digenean that use reptiles, amphibians and bats as hosts, groups that are at risk of conservation. Protection of these environments is a fundamental pillar in the policies for the conservation of wild flora and fauna.


Continuous Observation of Serum Total Magnesium Level in Patients Undergoing Hemodialysis.
Magnesium is an indispensable cation and plays an important physiological role in the body. Most previous studies focused on the single measurement of serum magnesium in patients undergoing hemodialysis. However, scant studies focused on continuous observations of serum magnesium levels. To provide continuous observations of serum magnesium levels in patients on maintenance hemodialysis (MHD). The levels of magnesium in patients initiating hemodialysis are also recorded and analyzed in the present study. In this retrospective study, we serially investigated the measurements of serum total magnesium in MHD patients and patients initiating hemodialysis. Our data were followed up for one year. We provided real-time update on the levels of serum magnesium in patients on hemodialysis. On January 1, 2019, a total of 356 end-stage renal disease patients were receiving hemodialysis in our hospital. On December 31, 2019, the number had increased to 383. We found that serum total magnesium levels were in the normal range before initiating hemodialysis. With the initiation of hemodialysis, the levels of serum total magnesium increased. In patients on MHD, hypermagnesemia was very common. Hypomagnesemia was rare when 0.5 mmol/L magnesium dialysate was used. We did not find proton pump inhibitor associated hypomagnesemia. We find that serum total magnesium levels are in the normal range before initiating hemodialysis. However, in patients on MHD, hypermagnesemia is common when 0.5 mmol/L magnesium dialysate is used. Hypomagnesemia is very rare. Hypomagnesemia in patients on MHD is an indicator of poor condition.


Exaggerated pain behavior: by what standard?
This paper provides a philosophical, historical, and clinical analysis of exaggerated pain behavior, focusing on the nature of the standards used to judge behavior as exaggerated. Malingering is understood as a special case of exaggerated pain behavior. Drawing upon the work of philosopher Ludwig Wittgenstein and psychiatrist-anthropologist Horacio Fabrega, I argue that these standards are primarily moral rather than scientific in nature. Pain behavior is not validated by matching public pain behavior with private pain experience. If this pain experience is truly private, it is not available to scientific investigation. Rather, pain behavior is judged as appropriate or exaggerated through complex assessments of the function of this behavior in its social context. As human social contexts have become more complex through history, so have the accommodations made for sick and disabled members of the group. Criteria for legitimate entry to the sick role have evolved with society, with only modern industrial society placing heavy emphasis on tissue damage demonstrated on medical tests. The highly variable relation between clinical pain and tissue damage, as well as the common problem of medically unexplained physical symptoms in primary care, pose serious challenges to this strategy of illness behavior validation. It will remain necessary to triage suffering presented to health care providers into that which should be addressed in the medical setting and that which is better addressed elsewhere. But we need to discard pseudoscientific reliance on medical tests and develop new standards that are openly acknowledged to be moral and social in nature.


Characterization and localization of the ATPase associated with pea chloroplast envelope membranes.
Chloroplast envelope membranes isolated from Pisum sativum seedlings have been found to contain a Mg-ATPase activity (specific activity 50-175 nanomoles per minute per milligram protein). The ATPase had a broad pH optimum between 7.0 and 9.5. The activity was not inhibited by oligomycin, N,N'-dicyclohexylcarbodiimide, ouabain, or antibodies directed against chloroplast coupling factor 1; nor was the activity stimulated by monovalent cations. However, the ATPase was inhibited by vanadate, molybdate, and adenylyl imidodiphosphate.The ATPase hydrolyzed a broad range of nucleoside triphosphates, but did not hydrolyze ADP, AMP, or pyrophosphate. The K(m) for Mg-ATP was determined to be 0.2 millimolar. The ATPase was found to be distinct from ADPase and pyrophosphatase activities also present in pea envelope membranes.The ATPase was determined to be located on the inner membrane of the envelope after resolution of inner and outer membranes by sucrose density gradient centrifugation.


Attenuation of atherosclerosis in apolipoprotein E-deficient mice by ramipril is dissociated from its antihypertensive effect and from potentiation of bradykinin.
We investigated the mechanism of the antiatherosclerotic effect of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, in the apolipoprotein (apo) E-deficient mice. Mice that received a high dose (5 mg/kg/day) of ramipril supplemented in their drinking water for 10 weeks showed reduced aortic lesion size by 75% compared with placebo-treated mice. At this dosage, ramipril significantly reduced blood pressure from 95+/-5 mm Hg before treatment to 68+/-4 mm Hg at the end of the treatment period. Ramipril also increased the resistance of the mouse low-density lipoprotein (LDL) to CuSO4-induced oxidation, as shown by a prolongation of the lag time required for the initiation of LDL oxidation from 90 min in the placebo-treated mice to >180 min in the ramipril-treated mice. Similarly, a reduction in the maximal LDL-associated conjugated dienes after 180 min of oxidation by 250% in comparison with placebo-treated mice was noted. Ramipril (1 mg/kg/day) that was still adequate to reduce their plasma ACE activity and LDL propensity to lipid peroxidation was insufficient to reduce their blood pressure. This dosage also inhibited the progression of atherosclerosis in the apo E-deficient mice by 74%. The contribution of bradykinin potentiation to the ACE-inhibitor action was assessed by cotreatment of ramipril with the bradykinin B2-receptor antagonist, icatibant (HOE-140, 0.5 mg/kg given subcutaneously twice a day) for a period of 10 weeks. HOE-140 had no effects on ACE activity, LDL lipid peroxidation, blood pressure, or atherosclerosis. In combination with ramipril, no additional effect of HOE-140 on LDL oxidation or on atherosclerosis was noted in comparison with ramipril treatment alone. We thus conclude that the antiatherogenic effect of ramipril in E(0) mice is independent of blood pressure reduction and is not mediated by bradykinin. It seems, therefore, that most of its antiatherosclerotic and antioxidative effects are mediated through the inhibition of angiotensin II production.


N-Terminal Domain Mediated Regulation of RORα1 Inhibits Invasive Growth in Prostate Cancer.
Four members of the retinoic acid-related orphan receptor α (RORα) family (RORα1, RORα2, RORα3 and RORα4) are transcription factors that regulate several processes including circadian rhythm, lipid metabolism, cerebellar development, immune function, and cancer. Only two isoforms, RORα1 and 4, are specifically co-expressed in the murine and human. In the present study, we identified a specific N-terminal domain (NTD) of RORα1 that potentiated the downregulation of target genes involved in tumor progression and proliferation, based on results from RORα-deficient mouse embryonic fibroblasts and prostate carcinoma tissues. The hyperactivation of proliferative target genes were observed in RORα-deficient embryonic fibroblasts, and reconstitution of RORα1 inhibited this activation by a NTD dependent manner. Downregulation of RORα1 and upregulation of Wnt/β-catenin target genes were correlated in prostate cancer patients. These findings revealed the control of invasive growth by NTD-mediated RORα1 signaling, suggesting advanced approaches for the development of therapeutic drugs.


Neutral sphingomyelinase increases the binding, internalization, and degradation of low density lipoproteins and synthesis of cholesteryl ester in cultured human fibroblasts.
I have investigated the effects of human urinary neutral sphingomyelinase (N-SMase) (Chatterjee, S., and Ghosh, N. (1989) J. Biol. Chem. 264, 12554-12561) on the cell-surface binding, internalization, and degradation of 125I-low density lipoprotein (LDL) and on cholesteryl ester synthesis in cultured human fibroblasts. N-SMase exerted a concentration-dependent continuous stimulation of 125I-LDL cell-surface binding, internalization, and degradation in normal human fibroblasts. A 3-fold increase in binding, internalization, and degradation was observed at the maximum amount (600 units of N-SMase/ml) examined. This phenomenon was accompanied by a continuous stimulation of cholesteryl ester synthesis. A 5-fold increase in cholesteryl ester synthesis was observed after incubation for 4 h with N-SMase. Antibody against N-SMase and heat inactivation of N-SMase compromised the stimulatory effects of N-SMase on 125I-LDL metabolism and cholesteryl ester synthesis in these cells. Incubation of cells with phospholipase D and phospholipase C did not alter 125I-LDL binding, internalization, or degradation. This finding suggests that the stimulatory effects of N-SMase on LDL metabolism and on cholesteryl ester synthesis in fibroblasts is specific. Moreover, unlabeled LDL competitively displaced 125I-LDL from binding to N-SMase-treated cells. None of the precursors of sphingomyelin could mimic the stimulatory effects of N-SMase on 125I-LDL metabolism in these cells. Taken together, these studies suggest that one of the biological roles of N-SMase involves modulating LDL metabolism and cholesterol metabolism in fibroblasts.


Processing of form stimuli presented unilaterally in humans, chimpanzees (Pan troglodytes), and monkeys (Macaca mulatta).
Visual forms were unilaterally presented using a video-task paradigm to 10 humans, 3 chimpanzees, and 2 rhesus monkeys to determine whether hemispheric advantages existed in the processing of these stimuli. Both accuracy and reaction time served as dependent measures. For the chimpanzees, a significant right hemisphere advantage was found within the first 3 test sessions. The humans and monkeys failed to show a hemispheric advantage as determined by accuracy scores. Analysis of reaction time data revealed a significant left hemisphere advantage for the monkeys. A Visual Half-Field x Block interaction was found for the chimpanzees, with a significant left visual field advantage in Block 2, whereas a right visual field advantage was found in Block 4. In the human subjects, a left visual field advantage was found in Block 3 when they used their right hands to respond. The results are discussed in relation to recent reports of hemispheric advantages for nonhuman primates.


Cardiac arrest during cornea transplant surgery.
This paper describes a case of cardiac arrest during femtosecond laser enabled penetrating keratoplasty (FLEK) in a young, healthy patient with no known cardiac risk factors and discusses the risk of cardiac arrest during intraocular surgery. A healthy 22-year-old man who underwent repeat FLEK under general anaesthesia developed bradycardia and subsequent cardiac arrest while open sky during surgery. After resuscitation and completion of the transplant surgery, the patient recovered and the graft has survived with excellent uncorrected visual acuity over 1 year after surgery. Understanding the risks of cardiac arrest and death during intraocular surgery is imperative to discussing the systemic risks of surgery during the preoperative informed consent.


A comparison of autogenous patellar tendon and hamstring tendon grafts for anterior cruciate ligament reconstruction.
Several graft options exist for reconstruction of the deficient ACL. The most commonly used grafts are the BPTB and quadrupled hamstring tendon autografts. Based on a comprehensive review of the literature, one graft is not superior to the other. Advantages and disadvantages are associated with the use of each graft. Surgeons who perform ACL reconstruction should be familiar with the use of both grafts.


Secondary ion mass spectra of tryptic peptides of human hemoglobin chains.
Secondary ion mass spectra of tryptic peptides of human globin alpha-, beta-, gamma and delta-chains were studied. Almost all mass peaks of protonated molecular ions of tryptic peptides were observed and they were very stable and abundant. The present results show the possibilities for quantitative analysis of two gamma-globin species: A gamma and G gamma chains, and for structural analysis of unknown abnormal hemoglobins.


The behavioral and cognitive effects of two benzodiazepines associated with drug-facilitated sexual assault.
Recently, sexual assaults have included the use of benzodiazepines to impair the victim. Our aim was to examine the physiological, cognitive, and behavioral effects of flunitrazepam (FN) and clonazepam (CLO). In the first study, ten healthy volunteers received a single oral dose of 2 mg of FN. Mini Mental State Examination (MMSE), behavioral reports and staff observations were then collected. In the second study, ten healthy volunteers received a single oral dose of 3 mg of CLO. Vital signs, performance on the MMSE and Digit Symbol Substitution Test, and behavioral changes were examined. FN significantly decreased systolic and diastolic blood pressure 4 h post drug ingestion with diastolic remaining low at 6 h. CLO was associated with changes in temperature and decreased systolic pressure. FN affected memory and attention 4 h following ingestion. CLO affected memory and attention throughout the study (6 h), and psychomotor performance was decreased 2 h post ingestion. In both studies, subjects were disinhibited and did not perceive their own impairment.


RNA-mediated gene silencing of ToxB in Pyrenophora tritici-repentis.
The fungus Pyrenophora tritici-repentis causes tan spot, a wheat leaf disease of worldwide importance. The pathogen produces three host-selective toxins, including Ptr ToxB, which causes chlorophyll degradation and foliar chlorosis on toxin-sensitive wheat genotypes. The ToxB gene, which codes for Ptr ToxB, was silenced in a wild-type race 5 isolate of the fungus thorough a sense- and antisense-mediated silencing mechanism. Toxin production by the silenced strains was evaluated in culture filtrates of the fungus via Western blotting analysis, and plant bioassays were conducted to test the virulence of the transformants in planta. The chlorosis-inducing ability of the silenced strains was correlated with the quantity of Ptr ToxB, and transformants in which toxin production was strongly decreased also caused very little disease on toxin-sensitive wheat genotypes. Cytological analysis of the infection process revealed that, in addition to a reduced capacity to induce chlorosis, the silenced strains with the greatest decrease in the levels of Ptr ToxB produced significantly fewer appressoria than the wild-type isolate, 12 and 24 h after inoculation onto wheat leaves. The results provide strong support for the suggestion that the amount of Ptr ToxB protein produced by fungal isolates plays a significant role in the quantitative variation in the virulence of P. tritici-repentis.


Challenges and Advances in Diagnosis and Treatment of Leptomeningeal Disease (LMD).
Leptomeningeal disease (LMD) is a devastating category of CNS metastasis with a very poor prognosis and limited treatment options. With maximal aggressive therapy, survival times remain short and, without treatment, prognosis is measured in weeks. Both LMD diagnosis and treatment are challenging topics within neuro-oncology. In this review, we discuss the advances in LMD diagnosis with a focus on the role of circulating tumor DNA (ctDNA) and discuss the role of targeted and immunotherapy in LMD treatment.


Noninvasive beam-wave reflectometric instrumentation for measuring complex permittivity of dielectric materials at microwave frequencies.
A noncontact and nondestructive method of measuring at microwave frequencies the complex permittivity of a selected region in a dielectric slab is described. For this purpose the test dielectric sample is irradiated with a focused (gaussian) microwave beam by means of a suitable applicator. From the characteristics of the reflected beam wave measured at a reflectometric bridge arrangement, the complex permittivity of the exposed region is determined. Some theoretical and experimental results analysing the test conditions are presented. Application of this method to biological in vivo (or in vitro) measurements of dielectric properties of bones and tissues, with selective partial-body microwave irradiation, is discussed.


Total Hip Arthroplasty With Subtrochanteric Shortening Osteotomy in Patients With High Hip Dislocation Secondary to Childhood Septic Arthritis: A Matched Comparative Study With Crowe IV Developmental Dysplasia.
Total hip arthroplasty (THA) with subtrochanteric shortening osteotomy (SSO) is performed to manage hips with high dislocations. We compared outcomes of THA with SSO in patients with high hip dislocation resulting from childhood septic arthritis and Crowe IV developmental dysplasia of the hip (DDH). We reviewed 60 THAs with SSO performed between May 1996 and December 2013. Thirty-one cases were classified as sequelae of childhood infection and 29 as DDH. Twenty-five hips were selected for each group after the propensity score was matched with preoperative demographics and leg length discrepancy (LLD). Clinical scores, complication and reoperation rates, radiographic results, and survivorships were compared. The mean duration of follow-up was 12.3 (range 5-22) years. The average correction in LLD was 2.5 cm for childhood infection and 3.6 cm for DDH (P = .002). The infection group received more transfusions (mean 3.3 vs 2.0 units, P = .002), required more time for union of osteotomy site (mean 6.8 vs 5.2 months, P = .042), and reported lower Harris Hip Score (mean 85.1 vs 91.3, P = .017). Reoperations were performed in 11 (44%) previously infected hips and 3 (12%) DDHs (P = .012). Kaplan-Meier survivorship with an endpoint of revision for any reason was lower in the infection group (83.6%) than in the DDH group (100%) at 10 years (log rank, P = .040). THA with SSO in high hip dislocation secondary to childhood septic arthritis demonstrated less favorable clinical outcomes with increased risks of complication, compared with those performed in Crowe IV DDH with similar degree of chronic dislocation.


Genetically engineered human cancer models utilizing mammalian transgene expression.
Cancer models are vital to cancer biology research, and multiple cancer models are currently available that utilize either murine or human cells, each with particular strengths and weaknesses. The ability to transform primary human cells into tumors through the expression of specific transgenes offers many advantages as a cancer model, including genetic malleability and the ability to transform specific cell types. Until recently, the conversion of primary human cells into tumors through transgene expression required the use of viral genetic elements, which unfortunately adds uncertainty regarding which cancer pathways are affected and how they are affected. In recent years multiple reports have described the transformation of primary human cells into tumors using only mammalian transgenes. This review focuses on these five cancer models, comparing the different cell types which were transformed into tumors and which transgenes were expressed, as well as the cancer pathways affected in the disparate models. These genetically-engineered human cancer models offer a valuable tool to complement existing cancer models and further cancer research.


Dual epicardial ventricular tachycardia: a tale of two VTs.
A young female with isolated ventricular noncompaction and acute myocarditis presented with incessant dual epicardial ventricular tachycardia consisting of a manifest reentrant circuit and a shorter cycle length concealed circuit. A single radiofrequency terminated both tachycardias.


Mean-Field Effects on the Phosphorescence of Dinuclear Re(I) Complex Polymorphs.
A computational study rationalizes the different phosphorescence colors of two highly emitting crystal polymorphs of a dinuclear Re(I) complex, [Re2(μ-Cl)2(CO)6(μ-4,5-(Me3Si)2pyridazine)]. The electrostatic interactions between the charge distributions on neighboring molecules inside the crystal are responsible for the different stabilization of the emitting triplet state because of the different molecular packing. These self-consistent effects play a major role in the phosphorescence of crystals made of polar and polarizable molecular units, offering a powerful handle to tune the luminescence wavelength in the solid state through supramolecular engineering.


Association between Serum Zinc Levels and Clinical Index or the Body Composition in Incident Hemodialysis Patients.
The relationships between serum zinc levels and body composition or clinical outcomes of incident hemodialysis (HD) patients remain unclear. This prospective observational study examined the relationships between serum zinc levels and clinical indexes, including body composition, in 142 incident HD patients using a bioelectrical impedance analysis. Patients were divided into three groups according to baseline serum zinc levels: tertile, <45, 45-59, and ≥60 µg/dL. The reference group was set as ≥60 µg/dL. Cox's regression analysis was performed to investigate the relationships between serum zinc categories and cardiovascular events and all-cause mortality after adjustments for potential confounders. Serum zinc levels positively correlated with the nutritional index and negatively correlated with fluid volume markers. In a mean follow-up of 2.5 years, there were 20 cases of cardiovascular events and 15 of all-cause mortality. In the Cox's regression analysis for cardiovascular events and all-cause mortality, the hazard ratio increased with a decrease in serum zinc levels, but was not significant. Serum zinc levels were associated with nutritional and fluid volume markers in incident HD patients. To clarify the relationship between serum zinc levels and cardiovascular events or mortality, further studies with a larger number of cases will be necessary.


Reactivity of NH4H2PO4 toward LaCl3 in LiCl-KCl melt flux. Step by step formation of monazite-like LaPO4.
The synthesis of lanthanum phosphates in molten LiCl-KCL eutectic was chosen to address the preliminary treatment of chlorinated wastes containing fission products that are already present in a Li/Cl eutectic. The obtained monazite compound shows interesting properties to be considered as a good candidate to trap lanthanum for a long-time. The synthesis route based on LaCl(3) reaction with NH(4)H(2)PO(4) in a stoichiometric amount is a key point to obtain monazite as a pure phase. Hence, the salt composition is not modified during the synthesis reaction. The chemical reactivity of ammonium dihydrogenphosphate (NH(4)H(2)PO(4), hereafter abbreviated ADP) toward lanthanum chloride (LaCl(3)) in molten LiCl-KCl eutectic is probed by NMR spectroscopy to follow the formation of LaPO(4). Formally, a direct transformation of the two aforementioned precursors into LaPO(4), NH(4)Cl and HCl can be discarded on the basis of the low thermal stability of ADP. To shed some light on the formation of LaPO(4), in situ and ex situ NMR experiments were carried out on LiCl-KCl/LaCl(3)/ADP, as well as LiCl-KCl/ADP, KCl/ADP, and LiCl/ADP mixtures. First, the reactivity of the precursors in contact with the eutectic was studied from room temperature to 600 degrees C by means of (31)P, (35)Cl, and (139)La high temperature NMR. Second, ex situ room temperature magic angle spinning (MAS) and RadioFrequency driven recoupling (RFDR) (31)P solid-state NMR experiments were carried out on solid samples prepared in different conditions (i.e., temperature and atmosphere) and quenched at room temperature to identify frozen intermediate species in their metastable state. On the basis of this approach, we propose a model for the LaPO(4) formation based on a multistep mechanism which highlights the strong reactivity of ADP toward the alkaline salts but without final change in the composition of the solvent.


The role of tumor necrosis factor, interferon-gamma, transforming growth factor-beta, and nitric oxide in the expression of immunosuppressive functions of splenic macrophages induced by Mycobacterium avium complex infection.
In order to verify the participation of some cytokines in the expression of the suppressor activity of splenic macrophages (M phi s) induced by Mycobacterium avium complex (MAC) infection, we studied whether anticytokine antibodies were capable of blocking their suppressor activity against concanavalin A (ConA)-induced mitogenesis of splenocytes (SPCs). When either anti-tumor necrosis factor (TNF), anti-transforming growth factor-beta (TGF-beta), or anti-interferon-gamma (IFN-gamma) antibody was added to culture medium, suppressor activity was markedly reduced, in the order of anti-TNF, anti-IFN-gamma, and anti-TGF-beta antibodies. By contrast, neither anti-interleukin-6 (IL-6) nor anti-IL-10 antibody exerted such a blocking effect. Therefore, TNF, IFN-gamma, and TGF-beta seem to be related to the full display of the suppressor function of MAC-induced M phi s. However, TNF-alpha and IFN-gamma but not TGF-beta were substantially lacking in inhibitory action against SPC mitogenesis, when added exogenously. Hence, it is unlikely that TNF-alpha and INF-gamma directly modulated the proliferative response of T cells. On the other hand, both TNF-alpha and IFN-gamma potentiated the effector function of the suppressor M phi s. Because their suppressor activity was severely reduced by NG-monomethyl-L-arginine and aminoguanidine, nitric oxide (NO) synthase inhibitors, an NO-dependent mechanism is important for the expression of the immunosuppressive function of MAC-induced M phi s. Moreover, because these M phi s seem to produce a substantial amount of TNF-alpha in membrane-bound form, cell-to-cell contact might be needed for efficient expression of their suppressor action on target T cells.


High-surface-area TiO2 and TiN as catalysts for the C-C coupling of alcohols and ketones.
To design more sustainable processes for the alkylation of ketones, the use of both atom-ineffective leaving groups such as halides and boron as well as noble-metal-based catalysts should be avoided. For that purpose, high-surface-area titanium nitride was prepared from high-surface-area titanium dioxide using cyanamide as a transcription agent. The resulting nitride as well as the initial oxide proved to be effective and versatile catalysts for the alkylation of ketones with alcohols. Interestingly, the TiN catalyst yields unsaturated compounds, while the oxide-based catalyst mainly yields saturated coupling products. As a result of its metallic properties, TiN shows a strong tendency to catalyse the dehydrogenation of alcohols, which then undergo aldol condensation with ketones. In contrast, TiO(2) promotes the direct nucleophilic attack of ketones on alcohols.


Joint Probabilistic Analysis of Risk for Aquatic Species and Exceedence Frequency for the Agricultural Use of Chlorpyrifos in the Pampean Region, Argentina.
The Pampa Húmeda region in Argentina is characterized by soybean, wheat, and maize production, with intensive application of agrochemicals such as herbicides and insecticides. We used a joint probabilistic approach to analyze the probabilities for environmental chlorpyrifos concentrations measured in the Pampa Húmeda to exceed acute or chronic hazardous concentration for 5% of the species (HC5) values estimated from species sensitivity distributions for aquatic species. Chlorpyrifos concentrations in water ranged from 0.0005 to 10.8 µg/L, with a median of 0.013 µg/L. The HC5 limits were 0.0637 µg/L for acute and 0.0007 µg/L for chronic effects. The probabilities for chlorpyrifos environmental concentrations to exceed the HC5 values ranged from 35% (acute effects) to 96% (chronic effects). Water quality criteria (WQC) for the protection of aquatic life were also frequently exceeded (by 48-87%) for both acute and chronic effects. Together with published threshold limit values from mesocosm studies, these data suggest that macroinvertebrate communities can be severely affected by the reported environmental concentrations of chlorpyrifos. Indeed, changes in the macroinvertebrate assemblage in the Pampa Húmeda have been correlated with chlorpyrifos levels in sediments. Nevertheless, the actual impact needs to be ascertained by assessing the recovery rate of macroinvertebrate populations in this region. Considering the HC5 for chronic effects and the threshold limits for macroinvertebrate community level effects, we propose 0.7 ng/L as a new WQC to effectively protect aquatic life from long-term exposure to chlorpyrifos. Environ Toxicol Chem 2019;38:1748-1755. © 2019 SETAC.


Pirenzepine and propantheline effects on esophageal pressure responses to bethanechol.
Pirenzepine is an antisecretory anticholinergic type drug that has recently been shown to be relatively free of usual anticholinergic side effects on esophageal smooth muscle. It has also been suggested that this drug might release some of the inhibitory control of the esophagus and allow increased muscle contractions. To test this hypothesis, we compared the response of the lower esophageal sphincter (LES) and esophageal peristaltic contractions to bethanechol in 12 healthy controls after background oral doses of placebo, pirenzepine (50 mg), and propantheline (30 mg). After baseline placebo, bethanechol (40 micrograms/kg subcutaneously) produced the expected significant increases in LES pressure and amplitude of peristaltic contractions. Maximal increases were 51.9 +/- 14.9 and 29.5 +/- 7.0%, respectively. Also as expected, propantheline inhibited the cholinergic stimulation from bethanechol, allowing only a 10.1 +/- 13.6% increase in LES pressure and a decrease in peristaltic contraction amplitudes (-44.1 +/- 5.0%) after bethanechol. After background pirenzepine, the responses to bethanechol were intermediate between the other two drugs. A significant increase (44.2 +/- 16.4%) in LES pressure occurred after bethanechol while no significant changes (6.9 +/- 5.8%) were noted in peristaltic amplitudes with this drug. Typical side effects of dry mouth were noted in six of the 12 subjects with propantheline and in only three subjects after pirenzepine. These studies once again confirm the absence of usual anticholinergic side effects with oral pirenzepine compared to oral propantheline in the doses studied. We could find no evidence for a release of cholinergic inhibition after pirenzepine administration.


Molecular epidemiology of tuberculosis among HIV-infected persons in Switzerland: a countrywide 9-year cohort study. Swiss HIV Cohort Study.
We investigated tuberculosis transmission during a nine-year period (1988-1996) in a countrywide community-based cohort of HIV-infected persons in Switzerland (the Swiss HIV Cohort Study [SHCS]). We estimated the proportion of tuberculosis cases due to reinfection and relapse, and assessed factors which may increase the risk of tuberculosis transmission. HIV-infected persons were followed prospectively and molecular fingerprinting with insertion sequence (IS) 6110, 36-bp direct repeat, and IS6110-PCR was used to determine M. tuberculosis case clustering. Out of 7999 SHCS participants, 267 persons developed tuberculosis. 158 M. tuberculosis isolates from 138 patients were available for study. Molecular analysis identified 33 (24%) episodes of tuberculosis associated with 12 clusters including 2 to 8 patients. Two patients experienced reinfection, and nine had a relapse. Detailed contact investigation identified definite or possible epidemiological links between 21 of 33 cluster patients (64%). Multivariate logistic regression analysis did not identify any risk marker significantly associated with clustering. During a nine-year period, one fourth of tuberculosis cases were grouped in clusters within a selection of 138 HIV-infected patients. This may represent the lowest estimation of recently acquired tuberculosis infection. There were no large institutional or community outbreaks among HIV-infected participants of the Swiss HIV Cohort Study.


The Nepali-speaking Bhutanese Immigrants: A Population Overlooked amidst the COVID-19 Crisis.
The Nepali-speaking Bhutanese (NSB) community living in Central Pennsylvania has been significantly affected by COVID-19 due to various biopsychosocial determinants of health. In this paper, we discuss interventions developed by a tertiary care health system in Central Pennsylvania to provide immediate support to the NSB community.


Dental students' familiarity with the medical management of dental patients at Brazilian dental schools.
Drug therapy in dentistry is essential for patients' treatment and requires special care by dentists, so it must be part of a well-grounded education for predoctoral dental students. The aim of this study was to evaluate the knowledge of undergraduate students at dental schools in Brazil about the use of drugs in dental practice. The sample universe was comprised of all undergraduates enrolled in the last year of the dentistry course in three universities in 2010 (n=253). Inclusion criteria were students in their last year of enrollment and who agreed to participate in the research. The results were analyzed on Epi Info 3.5.1 software. Analyses were conducted with chi-square, Friedman, and Wilcoxon tests. Slightly more than half of the participants (51.9 percent) reported the ideal dose of anesthetic for a normal patient. However, their difficulties increased when asked about the relationship between the anesthetic and patients with systemic disease or those needing special care. Regarding drugs that usually cause allergic attack, only 29.2 percent and 36.6 percent, respectively, cited methyl methacrylate and latex. This study found that the knowledge of these undergraduates about the questions was deficient, so dental education should include more theoretical and clinical practice in recognizing the patient's medical needs.


Syringocystadenoma papilliferum associated with apocrine poroma.
A 65-year-old Japanese man presented with a gradually enlarging mass on the right side of the abdomen, which he had first noticed about 4 years previously. He was otherwise asymptomatic. Histopathological examination of the mass revealed an aggregation of neoplastic cells (tumor cell nests) with cellular proliferation extending from the epidermis to the dermis. The tumor consisted of two histologically distinct parts. One part was composed of uniformly small cells with a cuboidal appearance. Some ductal structures were visualized, and some of the cells lining the ductal lumina contained decapitation secretions. These histological changes were consistent with the diagnosis of apocrine poroma. The remaining part of the tumor was composed of cystic invaginations with numerous projections oriented toward the lumen. There were two rows of cells in the projections; the cells on the luminal side were columnar, and those at the apical aspect were small cuboidal cells. These histological changes were characteristic of syringocystadenoma papilliferum (SCAP). Based on these findings, a diagnosis of SCAP associated with apocrine poroma was made. To the best of our knowledge, there have been no previous reports of such a case in the published work.


[Association between Distigmine-induced Adverse Events and Serum Butyrylcholinesterase Level: A Multicenter Retrospective Study].
Distigmine sometimes causes severe adverse events, and the serum butyrylcholinesterase (BChE) level is reduced by distigmine. However, limited data are available on the association between serum BChE level and the risk of distigmine-induced adverse events. To clarify the association between the risk of distigmine-induced adverse events and serum BChE level, we retrospectively reviewed 371 patients with 2199 measurements of serum BChE levels at three hospitals, of whom 24 (6.5%) had adverse events. Multivariate logistic regression analysis was performed to identify risk factors associated with adverse events of distigmine. The risk of adverse events was associated with distigmine dose>0.15 mg/kg/d [odds ratio (OR) 3.55, 95% confidence interval (CI) 1.07-11.70, p=0.04], serum BChE level 80-112 U/L (OR 3.13, 95% CI 1.03-9.52, p=0.04), and serum BChE level <80 U/L (OR 13.70, 95% CI 5.14-36.50, p<0.01). Serum BChE might be a useful biomarker for estimating the risk of distigmine-induced adverse events. The risk of adverse events might be decreased by closely monitoring serum BChE and assessing distigmine dose in patients with high risk factors.


Chronic lithium prevents REM sleep deprivation-induced increased responsiveness to apomorphine.
REM sleep deprivation of rats induces an increased responsiveness to dopaminergic agonists. Chronic lithium (Li) has been reported to prevent the development of dopamine receptor supersensitivity induced by other agents. The effects of chronic dietary Li administration (producing a mean serum level of 0.96 mequiv. litre-1) and 96 h REM sleep deprivation were studied. Chronic Li completely blocked the increased stereotypy, and partially prevented the aggressive behaviour induced, respectively, by 0.6 and 5 mg kg-1 of apomorphine in REM sleep deprived rats compared with the appropriate control groups. This study constitutes the first attempt to evaluate chronic lithium effects on rats undergoing REM sleep deprivation, chosen as another method of inducing alteration of dopaminergic sensitivity.


Aerosol extinction contribution to atmospheric attenuation in infrared wavelengths.
Atmospheric attenuation in several good transmission windows is estimated for long sea-level paths using relatively unsophisticated techniques. The estimates consist of separate estimates of gas and water vapor absorption, aerosol extinction, and aerosol liquid absorption. The contribution of aerosol extinction and aerosol liquid absorption to total atmospheric attenuation is explored. Estimated spectral aerosol extinction and absorption coefficients between the wavelengths of 2 microm and 14 micron are plotted for a wide variety of relative humidities and aerosol nucleation particle distributions. Total attenuation estimates are compared to accepted field measurement data. The agreement is sufficiently good to provide a base for estimating infrared instrument performance under similar conditions.


Street Clinics and the Healthcare of Vulnerable Homeless Communities in Brazil: A Qualitative Study.
(1) Background: homeless people are characterized by serious social vulnerability and difficulty in accessing health services worldwide. In Brazil, this population is supported by the Street Clinic teams who are challenged to establish intersectoral networks to expand access and promote unique and humanized care from the perspective of harm reduction. The study aimed to analyze the practices of professionals working at the Street Clinic in a city in the interior of São Paulo, Brazil, to tackle the vulnerabilities of the homeless population and expand access to the health care network. (2) Methods: a qualitative study was conducted with a social approach in which we interviewed eight workers from the Street Clinic. Data were analyzed using the thematic content analysis tool. (3) Results: three nuclei of meaning were built: stigma and prejudice as the main barriers to accessing services, harm reduction as a humanized care practice and valuing autonomy, and Street Clinic as a gateway to the health system and main interlocutor with other services. (4) Conclusions: the articulation with network services is marked by contradictory relationships, of conflict and trust, signaling the need for greater investment in educational qualifications and working conditions for professionals at all levels of care to expand access to health care.


A density functional theory study of the zero-field splitting in high-spin nitrenes.
This work presents a detailed evaluation of the performance of density functional theory (DFT) for the prediction of zero-field splittings (ZFSs) in high-spin nitrenes. A number of well experimentally characterized triplet mononitrenes, quartet nitrenoradicals, quintet dinitrenes, and septet trinitrenes have been considered. Several DFT-based approaches for the prediction of ZFSs have been compared. It is shown that the unrestricted Kohn-Sham and the Pederson-Khanna approaches are the most successful for the estimation of the direct spin-spin (SS) interaction and the spin-orbit coupling (SOC) parts, respectively, to the final ZFS parameters. The most accurate theoretical predictions (within 10%) are achieved by using the PBE density functional in combination with the DZ, EPR-II, and TZV basis sets. For high-spin nitrenes constituted from light atoms, the contribution of the SOC part to ZFS parameters is quite small (7%-12%). By contrast, for chlorine-substituted septet trinitrenes, the contribution of the SOC part is small only to D value but, in the case of E value, it is as large as the SS part and has opposite sign. Due to this partial cancellation of two different contributions, SS and SOC, the resulting values of E in heavy molecules are almost two times smaller than those predicted by analysis of the widely used semiempirical one-center spin-spin interaction model. The decomposition of D(SS) into n-center (n=1-4) interactions shows that the major contribution to D(SS) results from the one-center spin-spin interactions. This fact indicates that the semiempirical SS interaction model accurately predicts the ZFS parameters for all types of high-spin nitrenes with total spin S=2 and 3, if their molecules are constructed from the first-row atoms.