Primary intestinal epithelial cells selectively transfer R5 HIV-1 to CCR5+ cells.
The upper gastrointestinal tract is a principal route of HIV-1 entry in vertical transmission and after oral-genital contact. The phenotype of the newly acquired virus is predominantly R5 (CCR5-tropic) and not X4 (CXCR4-tropic), although both R5 and X4 viruses are frequently inoculated onto the mucosa. Here we show that primary intestinal (jejunal) epithelial cells express galactosylceramide, an alternative primary receptor for HIV-1, and CCR5 but not CXCR4. Moreover, we show that intestinal epithelial cells transfer R5, but not X4, viruses to CCR5+ indicator cells, which can efficiently replicate and amplify virus expression. Transfer was remarkably efficient and was not inhibited by the fusion blocker T-20, but was substantially reduced by colchicine and low (4 degrees C) temperature, suggesting endocytotic uptake and microtubule-dependent transcytosis of HIV-1. Our finding that CCR5+ intestinal epithelial cells select and transfer exclusively R5 viruses indicates a mechanism for the selective transmission of R5 HIV-1 in primary infection acquired through the upper gastrointestinal tract.


Prion protein is a component of the multimolecular signaling complex involved in T cell activation.
In this study we analyzed the interaction of prion protein PrP(C) with components of glycosphingolipid-enriched microdomains in lymphoblastoid T cells. PrP(C) was distributed in small clusters on the plasma membrane, as revealed by immunoelectron microscopy. PrP(C) is present in microdomains, since it coimmunoprecipitates with GM3 and the raft marker GM1. A strict association between PrP(C) and Fyn was revealed by scanning confocal microscopy and coimmunoprecipitation experiments. The phosphorylation protein ZAP-70 was immunoprecipitated by anti-PrP after T cell activation. These results demonstrate that PrP(C) interacts with ZAP-70, suggesting that PrP(C) is a component of the multimolecular signaling complex within microdomains involved in T cell activation.


Prophylactic Negative-pressure Wound Therapy Prevents Surgical Site Infection in Abdominal Surgery: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials and Observational Studies.
Prevention of surgical site infection (SSI) is a public health challenge. Our objective was to determine if prophylactic negative-pressure wound therapy (pNPWT) allows preventing SSI after laparotomy. Medline, Embase, and Web of Science were searched on 6 October 2019 for original studies reporting the incidences of SSI in patients undergoing open abdominal surgery with and without pNPWT. Risk differences (RDs) between control and pNPWT patients and risk ratios (RRs) for SSI were obtained using random-effects models. Twenty-one studies (2930 patients, 5 randomized controlled trials [RCTs], 16 observational studies) were retained for the analysis. Pooled RD between patients with and without pNPWT was -12% (95% confidence interval [CI], -17% to -8%; I2 = 57%; P < .00001) in favor of pNPWT. That risk difference was -12% (95% CI, -22% to -1%; I2 = 69%; P = .03) when pooling only RCTs (792 patients). pNPWT was protective against the incidence of SSI with a RR of 0.53 (95% CI, .40-.71; I2 = 56%; P < .0001). The effect on pNPWT was more pronounced in studies with an incidence of SSI ≥20% in the control arm. The preventive effect of pNPWT on SSI remained after correction for potential publication bias. However, when pooling only high-quality observational studies (642 patients) or RCTs (527 patients), significance was lost. Existing studies suggest that pNPWT on closed wounds is protective against the occurrence of SSI in abdominal surgery, but these findings need to be confirmed by more high-quality evidence, preferentially in subgroups of patients with an incidence of SSI ≥20% in the control arm.


The structure of the lipopolysaccharide core region of Citrobacter 027.
The structure of Citrobacter 027 lipopolysaccharide core has been established using sugar and methylation analyses and 1H-NMR spectroscopy, and was shown to be identical to the core described recently in PCM 1487 strain which represents a separate serotype in Citrobacter genus.


Temporal bone carcinoma: testing the prognostic value of a novel clinical and histological scoring system.
Our group recently proposed the novel Padova prognostic scoring system for temporal bone carcinoma (TBSCC) that considers: the revised Pittsburgh staging system; radiological dura mater involvement; non-anterior spread (medial, inferior or posterior into the temporal bone and skull base) of T4 tumors; and histological grade. The aim of the present study was to validate this prognostic TBSCC scoring system in a case series selected from the literature. A search was run to identify studies on TBSCC reporting the variables included in our score for each patient. Then our system was applied to the data extracted. Only two published investigations reported all the clinical and pathological data required for our scoring system. In one series from the Gruppo Otologico in Piacenza (Italy), a significantly higher recurrence rate (p = 0.008), shorter disease-free survival (DFS) (p = 0.001), higher disease-specific mortality (DSM) (p = 0.006), and shorter disease-specific survival (DSS) (p = 0.004) were associated with scores ≥ 5. Receiver operating curve (ROC) analysis showed an AUC of 0.804 for TBSCC recurrence, and 0.832 for DSM. In a series from Kyushu University Hospital (Japan), a significantly higher DSM (p = 0.018) and shorter DSS (p = 0.021) were associated with scores ≥ 5. ROC analysis showed an AUC of 0.812 for tumor relapse and 0.790 for DSM. Our TBSCC Padova scoring system confirmed its validity when applied to the only two international TBSCC series providing the required data. These preliminary results need to be confirmed in a multi-center prospective setting.


Distinct Biological Phenotypes of Marburg and Ravn Virus Infection in Macaques.
Filoviruses are among the most pathogenic infectious agents known to human, with high destructive potential, as evidenced by the recent Ebola virus epidemic in West Africa. As members of the filovirus family, marburgviruses have caused similar devastating outbreaks, albeit with lower case numbers. In this study we compare the pathogenesis of Ravn virus (RAVV) and Marburg virus (MARV) strains Angola, Musoke, and Ozolin in rhesus and cynomolgus macaques, the 2 nonhuman primate species most commonly used in filovirus research. Our results reveal the most pathogenic MARV strain to be Angola, followed by Musoke, whereas Ozolin is the least pathogenic. We also demonstrate that RAVV is highly pathogenic in cynomolgus macaques but less pathogenic in rhesus macaques. Our results demonstrate a preferential infection of endothelial cells by MARVs; in addition, analysis of tissue samples suggests that lymphocyte and hepatocyte apoptosis might play a role in MARV pathogenicity. This information expands our knowledge about pathogenicity and virulence of marburgviruses.


Perichondrial wrist arthroplasty in rheumatoid patients.
A new method is proposed for reconstruction of the wrist joint in rheumatoid arthritis. Perichondrial arthroplasty done in four patients with severe deformity of the wrist from rheumatoid arthritis gave functionally improved results. In one case biopsy of the reconstructed joint showed newly formed cartilaginous tissue four months after initial surgery.


The lingering mysteries of metastatic recurrence in breast cancer.
Despite being the hallmark of cancer that is responsible for the highest number of deaths, very little is known about the biology of metastasis. Metastatic disease typically manifests after a protracted period of undetectable disease following surgery or systemic therapy, owing to relapse or recurrence. In the case of breast cancer, metastatic relapse can occur months to decades after initial diagnosis and treatment. In this review, we provide an overview of the known key factors that influence metastatic recurrence, with the goal of highlighting the critical unanswered questions that still need to be addressed to make a difference in the mortality of breast cancer patients.


The Association Between Triglyceride-Glucose Index as a Marker of Insulin Resistance and the Risk of Breast Cancer.
This study aims to evaluate the association and dose-response between triglyceride-glucose (TyG) index and breast cancer. This is a multicenter case-control study conducted in six public referral hospitals in Indonesia. Cases are individuals aged 19 years or above who were diagnosed with breast cancer within 1 year of diagnosis, based on histopathology and immunohistochemistry. Controls were recruited from corresponding hospitals. TyG index was determined by the formula: ln (fasting TG [mg/dl] × fasting glucose [mg/dl]). There were 212 participants in the breast cancer group and 212 participants in the control group. TyG index was higher in patients with breast cancer (median 8.65 [7.38, 10.9] vs. 8.30 [7.09, 10.84], p < 0.001). When compared with TyG quartile of Q1, Q4 was associated with an OR of 2.42 (1.77, 3.31), p < 0.001, Q3 was associated with an OR of 1.53 (1.21, 1.93), p < 0.001, Q2 was associated with an OR of 1.39 (1.12, 1.73), p = 0.002 for the risk of breast cancer. The dose-response relationship was nonlinear (p < 0.001). On univariate analysis, smoking (OR 2.15 [1.44, 3.22], p < 0.001), use of contraception (1.73 [1.15, 2.60], p = 0.008), alcohol consumption (OR 2.04 [0.96, 4.35], p = 0.064), and TyG Index >8.87 (OR 3.08 [1.93, 4.93], p < 0.001) were associated with risk of breast cancer. Independently associated with increased risk of breast cancer included smoking (OR 1.93 [1.23, 3.01], p = 0.004), use of contraception (OR 1.59 [1.02, 2.48], p = 0.039), and TyG Index >8.87 (OR 2.93 [1.72, 4.98], p < 0.001). TyG index was associated with breast cancer in a nonlinear dose-response fashion.


Thyrotropin Screening of Newborns: Before or After 72 Hours of Life? Before Discharge or at Home?
Objective: Until November 2019 in Belgium, dried blood spot (DBS) sampling was performed between 72 and 120 hours of life, when a majority of newborns had already been discharged from the maternity. In November 2019, the policy for newborn screening in South Belgium changed to allow sampling as soon as 48 hours of life, with the objective to accelerate the process and to allow more sampling during the hospital stay. Our objective was to evaluate the impact of this policy modification and, in particular, to assess the effectiveness of screening for hypothyroidism based on sampling before or after 72 hours of life, as well as to compare the effectiveness of DBS collection before discharge or at home. Methods: This retrospective study included live births ≥37 weeks of gestation, screened by the Université Libre de Bruxelles Newborn Screening Center between January 2019 and December 2021. To evaluate the efficiency of early sampling, we compared thyrotropin (TSH) results for screening <72 hours and screening ≥72 hours. We also compared TSH results of DBS performed before discharge with those performed at home. Results: A total of 53,794 newborns were included. The results of 24,816 healthy newborns screened before 72 hours of life and of 28,978 healthy newborns screened between 72 and 144 hours of life were compared. The median TSH level was similar (1.50 and 1.20 mU/L, respectively). The percentage of false positives was similar (0.08% and 0.07%, respectively). Earlier sampling, before 72 hours, allowed treatment of positive cases at 6 days rather than 8.5 days. DBS sampling at home resulted in longer delay for transferring the sample to the laboratory (a median of 3.0 days for hospital sampling vs. 5.0 days for home sampling). A poorer quality of home blood sampling was observed, with 0.27% unusable samples compared with 0.06% unusable samples for hospital sampling (p < 0.001). Conclusions: In term newborns, TSH screening before discharge, as early as 48 hours of life, is a valid strategy. It allows earlier treatment of positive cases, does not increase the percentage of false positives, and results in fewer unusable samples.


A new composite made from Luffa Cylindrica and ethylene vinyl acetate (EVA): Mechanical and structural characterization for its use as Mouthguard (MG).
The use of Mouthguards (MGs) in contact sports is an interesting biomedical topic. MGs are protective personal equipment made principally from the copolymer ethylene vinyl acetate (EVA). EVA is a thermoplastic whose thickness and rigidity are variables of concern for a good shock energy absorption capability in an MG. A natural fiber polymer composite is an interesting attempt for tackling these variables. Luffa cylindrica (luffa) is a sponge gourd that grows in 3D structure, which is used mainly as an ornament, a filling, or is trimmed for its use as a bathing product. In this work, a new EVA-luffa composite (EVLc) was made from commercial EVA sheets and luffa mat acting as reinforcement. FTIR, DSC, and TGA tests of EVA revealed its nature compared to literature data. A mechanical testing was applied to eight EVLc ASTM D-638 type V dumbbells (D1-D8) that showed low tensile strength values compared to EVA resistance ranges in literature. SEM images of EVLc's D1-D8 confirmed good adhesion between the reinforcement and matrix without surface treatment, and a descriptive statistical analysis indicated an intrinsic variation.


Methods for handling missing binary data in substance use disorder trials.
Missing data are a ubiquitous problem in longitudinal substance use disorder (SUD) clinical trials. In particular, the rates of missingness are often high and study participants often intermittently skip their scheduled outcome assessments, leading to so-called "non-monotone" missing data patterns. Moreover, when the primary outcome is a measure of substance use, study investigators often have strong prior beliefs based on their clinical experience that those participants with missing data are more likely to be using substances at those occasions, i.e., data are missing not at random (MNAR). Although approaches for handling missing data are well-developed when the missing data patterns are monotone, arising primarily from study participants withdrawing from the trial prematurely, fewer methods are available for non-monotone missingness. In this paper we review some conventional, as well as more novel, methods for handling non-monotone missingness in SUD trials when the repeatedly measured outcome variable is binary (e.g., denoting presence/absence of substance use). We compare and contrast the different approaches using data from a longitudinal clinical trial of four psychosocial treatments from the Collaborative Cocaine Treatment Study. We conclude by making some recommendations to the SUD research community concerning how more principled methods for handling missing data can be incorporated in the analysis and reporting of trial results.


Nanoparticle-induced platelet aggregation and vascular thrombosis.
Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet-nanoparticle interactions. We studied the effects of engineered and combustion-derived carbon nanoparticles on human platelet aggregation in vitro and rat vascular thrombosis in vivo. Multiplewall (MWNT), singlewall (SWNT) nanotubes, C60 fullerenes (C60CS) and mixed carbon nanoparticles (MCN) (0.2-300 microg ml(-1)) were investigated. Nanoparticles were compared with standard urban particulate matter (SRM1648, average size 1.4 microm). Platelet function was studied using lumi aggregometry, phase-contrast, immunofluorescence and transmission electron microscopy, flow cytometry, zymography and pharmacological inhibitors of platelet aggregation. Vascular thrombosis was induced by ferric chloride and the rate of thrombosis was measured, in the presence of carbon particles, with an ultrasonic flow probe. Carbon particles, except C60CS, stimulated platelet aggregation (MCN>or=SWNT>MWNT>SRM1648) and accelerated the rate of vascular thrombosis in rat carotid arteries with a similar rank order of efficacy. All particles resulted in upregulation of GPIIb/IIIa in platelets. In contrast, particles differentially affected the release of platelet granules, as well as the activity of thromboxane-, ADP, matrix metalloproteinase- and protein kinase C-dependent pathways of aggregation. Furthermore, particle-induced aggregation was inhibited by prostacyclin and S-nitroso-glutathione, but not by aspirin. Thus, some carbon nanoparticles and microparticles have the ability to activate platelets and enhance vascular thrombosis. These observations are of importance for the pharmacological use of carbon nanoparticles and pathology of urban particulate matter.


MRI-derived tumor volume as a predictor of biochemical recurrence and adverse pathology in patients after radical prostatectomy: a propensity score matching study.
To investigate the predictive value of MRI-derived tumor volume (TV) of biochemical recurrence (BCR) and adverse pathology (AP) in patients following radical prostatectomy (RP). The data of 565 patients receiving RP in a single institution between 2010 and 2021 were retrospectively analyzed. All suspicious tumor foci were delineated manually using ITK-SNAP software as the regions of interest (ROIs). The sum of the TV of all lesions was calculated automatically based on the voxel in the ROIs to acquire the final TV parameter. TV was categorized as low-volume (≤ 6.5 cm3) and high-volume (> 6.5 cm3) based on the cut-off value. Univariate and multivariate Cox and logistic regression analyses were performed to identify independent predictors of BCR and AP. The Kaplan-Meier with the log-rank test was conducted to compare the BCR-free survival (BFS) between the low and high-volume groups. All the included patients were divided into the low-volume group (n = 337) and the high-volume group (n = 228). The TV was an independent predictor of BFS in the multivariate Cox regression analysis (Hazard Ratio (HR) [95% CI]: 1.550 [1.066-2.256], P = 0.022). The Kaplan-Meier analysis demonstrated that low volume was associated with a better BFS than high volume before propensity score matching (PSM) (P < 0.001). One hundred and fifty-eight pairs were obtained by 1:1 PSM to balance the baseline parameters between the two groups. After the PSM, low-volume remained to be associated with a better BFS than high-volume (P = 0.006). TV as a categorical variable was an independent factor of AP in multivariate logistic regression analysis (Odd ratio (OR) [95% CI]: 1.821 [1.064-3.115], P = 0.029). After balancing the potential factors influencing AP by 1:1 PSM, 162 new pairs were identified. The high-volume group had a higher AP rate than the low-volume group after PSM (75.9 vs. 64.8%, P = 0.029). We adopted a novel approach to acquiring the TV on preoperative MRI. TV was significantly associated with BFS and AP of patients undergoing RP, which was further illustrated by PSM analysis. MRI-derived TV may serve as a predictive marker for assessing BFS and AP in further studies, which will facilitate clinical decision-making and patient counseling.


Protective effect of the methanolic leaf extract of Eclipta alba (L.) Hassk. (Asteraceae) against gentamicin-induced nephrotoxicity in Sprague Dawley rats.
Eclipta alba, also known as Eclipta prostrata, is a weed of the family Asteraceae found in tropical and subtropical regions widely used in herbal medicine, including treatment of renal diseases. This study aims to evaluate the protective effect of the methanolic leaf extract of Eclipta alba on gentamicin-induced nephrotoxicity in rats. Nephrotoxicity was induced in rats by subcutaneous injection of gentamicin (80mg/kg/day for seven days). Quercetin was used as a positive control. The nephroprotective activity was evaluated by determining blood urea nitrogen, serum creatinine, urinary microprotein, renal catalase and malondialdehyde levels. The extract protected the rat kidneys against gentamicin-induced renal tubular alterations and rises in blood urea nitrogen, serum creatinine, and microprotein levels. Lipid peroxidation and decrement in catalase levels were also ameliorated. The study revealed the protective effect of the methanolic leaf extract of E. alba and suggests that the probable mechanism for the nephroprotection by the extract may be due to its good radical scavenging activity and Fe(3+) ion-reducing ability.


Hydrogen sulfide maintains mesenchymal stem cell function and bone homeostasis via regulation of Ca(2+) channel sulfhydration.
Gaseous signaling molecules such as hydrogen sulfide (H2S) are produced endogenously and mediate effects through diverse mechanisms. H2S is one such gasotransmitters that regulates multiple signaling pathways in mammalian cells, and abnormal H2S metabolism has been linked to defects in bone homeostasis. Here, we demonstrate that bone marrow mesenchymal stem cells (BMMSCs) produce H2S in order to regulate their self-renewal and osteogenic differentiation, and H2S deficiency results in defects in BMMSC differentiation. H2S deficiency causes aberrant intracellular Ca(2+) influx because of reduced sulfhydration of cysteine residues on multiple Ca(2+) TRP channels. This decreased Ca(2+) flux downregulates PKC/Erk-mediated Wnt/β-catenin signaling which controls osteogenic differentiation of BMMSCs. Consistently, H2S-deficient mice display an osteoporotic phenotype that can be rescued by small molecules that release H2S. These results demonstrate that H2S regulates BMMSCs and that restoring H2S levels via nontoxic donors may provide treatments for diseases such as osteoporosis that can arise from H2S deficiencies.


Glycoproteomics Technologies in Glycobiotechnology.
Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity. As such, comprehensive information about glycosylation of biotherapeutics is critical to demonstrate similarity. Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars. Mass spectrometry has catalysed tremendous advancements in the characterisation of glycosylation CQAs of biotherapeutics. Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.


In vivo behavioral assessment of central nervous system purinergic receptors.
Administered intracisternally, adenosine (ADO), 2-chloroadenosine (CADO), adenosine-5'-cyclopropylcarboxamide (ACC) and adenosine-5'-ethylcarboxamide (AEC) caused dose-related increases in hot plate reaction times in mice. The rank order of potency was AEC=ACC greater than CADO greater than ADO and ACC exerted demonstrable effects with doses as low as 10 ng/mouse. ADO itself was more potent than AMP, ADP, ATP and several other related compounds of interest. Theophylline, caffeine and 8-phenyltheophylline antagonized the antinocisponsive effect of CADO or ACC. Papaverine (an adenosine uptake blocker) and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA: an adenosine deaminase inhibitor) potentiated the effect of ADO. EHNA did not potentiate the action of CADO in this procedure. The antinocisponsive effect of CADO was not antagonized by a host of neurally active agents including naloxone, clonidine and RO 20-1724. Time course studies indicated that the antinocisponsive effect of ADO was transient with the peak effect occurring 5 min after injection and disappearing by 60 min, whereas the effect of CADO persisted for at least 90 min. Intracisternally administered CADO also caused a pronounced hypothermia, loss of muscle tone and was active in the mouse writhing test. Taken together, these data demonstrate that purine exert potent in vivo behavioral effects and are consonant with the existence of a central purinergic P1-receptor which is amenable to selective pharmacological manipulation.


[Early human papillomavirus testing predicts residual/recurrent disease after LEEP risk factors for predicting residual disease in high-grade squamous cervical intraepithelial neoplasia following LEEP conization].
To explore the risk factors for residual/recurrent disease of cervical intraepithelial neoplasia (CIN) 2 or worse after loop electrosurgical excision procedure (LEEP) and the timing point for postoperative follow-up. 428 patients with CIN 2 or CIN 3 who were treated with LEEP were retrospectively reviewed. Postoperative follow-up was performed by Pap smear and human papillomavirus (HPV) hybrid capture 2 (HC2) testing. The definition of persistent/recurrent disease was biopsy-proven CIN 2 or worse. 296 patients were CIN 2 and 132 were CIN 3 among 428 patients. The positive rate of HPV HC2 before LEEP was 86.7% (371/428). During follow-up, 26 patients (6.1%) had residual/recurrent disease, the positive LEEP margin, especially the cone top status, was a significant risk factor for persistent/recurrent disease. Other factors such as age, HPV viral load [> or =100 relative light units (RLU)], and HPV typing (type 16/18 vs. other types) did not predict recurrence. HPV HC2 test at 3 months after LEEP can find all the residual/recurrent disease, the sensitivity and negative predictive value of the HPV HC2 test for residual/recurrent disease were both 100% at 3 and 6 months. The positive margin of LEEP specimen especially the cone top status was a significant risk factor for residual/recurrent disease after LEEP. HPV test at 3 months during follow-up can offer timely information about residual/recurrent disease and help for the risk control in treatment selection.


Time to first passage of meconium and defecation frequency preceding necrotizing enterocolitis in preterm infants: a case-control study.
Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality in preterm infants. Early recognition and treatment of NEC are critical to improving outcomes. Enteric nervous system (ENS) immaturity has been proposed as a key factor in NEC pathophysiology. Gastrointestinal dysmotility is associated with ENS immaturity and may serve as a predictive factor for the development of NEC. In this case-control study, preterm infants (gestational age (GA) < 30 weeks) were included in two level-IV neonatal intensive care units. Infants with NEC in the first month of life were 1:3 matched to controls based on GA (± 3 days). Odds ratios for NEC development were analyzed by logistic regression for time to first passage of meconium (TFPM), duration of meconial stool, and mean daily defecation frequency over the 72 h preceding clinical NEC onset (DF < T0). A total of 39 NEC cases and 117 matched controls (median GA 27 + 4 weeks) were included. Median TFPM was comparable in cases and controls (36 h [IQR 13-65] vs. 30 h [IQR 9-66], p = 0.83). In 21% of both cases and controls, TFPM was ≥ 72 h (p = 0.87). Duration of meconial stool and DF < T0 were comparable in the NEC and control group (median 4 and 3, resp. in both groups). Odds of NEC were not significantly associated with TFPM, duration of meconial stools, and DF < T0 (adjusted odds ratio [95% confidence interval]: 1.00 [0.99-1.03], 1.16 [0.86-1.55] and 0.97 [0.72-1.31], resp.). In this cohort, no association was found between TFPM, duration of meconium stool, and DF < T0 and the development of NEC. • Necrotizing enterocolitis (NEC) is a life-threatening acute intestinal inflammatory disease of the young preterm infant. Early clinical risk factors for NEC have been investigated in order to facilitate early diagnosis and treatment. • Signs of disrupted gastrointestinal mobility, such as gastric retention and paralytic ileus, have been established to support the diagnosis of NEC. Nevertheless, defecation patterns have insufficiently been studied in relation to the disease. • Defecation patterns in the three days preceding NEC did not differ from gestational age-matched controls of corresponding postnatal age. Additionally, the first passage of meconium and the duration of meconium passage were comparable between cases and controls. Currently, defecation patterns are not useful as early warning signs for NEC. It remains to be elucidated whether these parameters are different based on the location of intestinal necrosis.


Bioluminescence-mediated stimulation of photoreactivation in bacteria.
Although biochemistry and genetics of light emission by cells have been investigated in detail, a biological role for bacterial luminescence has remained obscure for a long time. It was proposed recently that luminescence may stimulate DNA repair, but the specific mechanism of this phenomenon was not investigated. Moreover, experiments showing decreased survival of UV-irradiated lux mutants relative to luminescent cells were performed previously using only one bacterial species, Vibrio harveyi. Here, we demonstrate that dark mutants of various strains of naturally luminescent bacteria (Photobacterium leiognathi, Photobacterium phosphoreum and Vibrio fischeri) are more sensitive to UV irradiation than wild-type cells. Thus, this phenomenon occurs not only in V. harveyi but also in other bacterial species. Using an artificial system of luminescent Escherichia coli in combination with phr mutants (defective in photolyase functions), we found that bacterial luminescence may stimulate photoreactivation, perhaps by providing photons that are necessary for photolyase activity.


Permanent reduction in heart and kidney organ growth in offspring of undernourished rat dams.
Maternal undernutrition affects fetal growth and development. We investigated whether maternal food restriction during pregnancy and/or lactation permanently alters organ growth among adult offspring. From 10 days to term gestation and through 21 days lactation, control pregnant rats received ad libitum food, whereas study rats were 50% food restricted. Cross-fostering techniques were used to examine the effects of food restriction during pregnancy and/or lactation periods. Organs were dissected and weighed (percentage of body weight) at ages 3 weeks and 9 months. Food restriction during pregnancy produced growth-restricted newborns that exhibited catch-up growth that resulted in markedly heavier adult offspring, although with relatively decreased weights of heart, kidney, lung, and brain as compared with controls. Conversely, food restriction during pregnancy/lactation or lactation alone resulted in adult offspring with similar body weights as controls, but with relatively decreased growth of heart and kidney. Males exhibited relatively smaller livers, whereas the females showed relatively smaller adrenal glands. Sex-dependent, selective, and permanent changes in relative growth of heart and kidney may increase risk of adult diseases.


Disruption of temporal processing in a subject with probable frontotemporal dementia.
Previous research suggests that the frontal lobes are essential for temporal processing. We report a patient, MN, with probable frontotemporal dementia (FTD) who was tested on a battery of timing tasks with stimuli in the sub- and supra-second range. MN demonstrated a substantial over-estimation and under-production of target intervals on estimation and production tasks respectively but was as accurate as controls on a reproduction task. Furthermore, this deficit was markedly different for auditory and visual stimuli on production and estimation tasks; estimates of the duration of auditory stimuli were three to four times longer than for comparable visual stimuli. She performed normally on a task requiring her to judge whether a stimulus was longer or shorter than a standard duration with both sub- and supra-second stimuli. She performed well on control tasks involving estimation, production and reproduction of line lengths suggesting that her deficits were not attributable to a generalized cognitive impairment or an inability to make magnitude judgments. These data suggest that bifrontal pathology disrupts the "clock" or memory for time.


The anti-cancer effect of series of strained photoactivatable Ru(II) polypyridyl complexes on non-small-cell lung cancer and triple negative breast cancer cells.
Ruthenium complexes have been recently reported as potential chemotherapeutic agents that offer tumor selectivity and low tumor resistance. This study investigates the photochemistry and the effect of four strained photoactivatable polypyridyl ruthenium(II) complexes on non-small-cell lung cancer (A549) and triple negative breast cancer (MDA-MB-231) cells. All four ruthenium(II) complexes, [Ru(bpy)2dmbpy]Cl2 (C1) where (bpy = 2,2'-bipyridine and dmbpy = 6,6'-dimethyl-2,2'-bipyridine), [Ru(phen)2dmbpy]Cl2 (C2) where (phen = 1,10-phenanthroline), [Ru(dpphen)2dmbpy]Cl2 (C3) (where dpphen = 4,7-diphenyl-1,10-phenanthroline) and [Ru(BPS)2dmbpy]Na2 (C4) where (BPS = bathophenanthroline disulfonate) eject the dmbpy ligand upon activation by blue light. Determination of the octanol-water partition coefficient (log P) revealed that C3 was the only lipophilic complex (log P = 0.42). LC-MS/MS studies showed that C3 presented the highest cellular uptake. The cytotoxic effect of the complexes was evaluated with and without blue light activation using WST-1 kit. Data indicated that C3 exhibited the highest cytotoxicity after 72 h (MDA-MB-231, IC50 = 0.73 µM; A549, IC50 = 1.26 µM) of treatment. The phototoxicity indices of C3 were 6.56 and 4.64 for MDA-MB-230 and A549, respectively. Upon light activation, C3 caused significant ROS production and induced apoptosis in MDA-MB-231 cells as shown by flow cytometry. It also significantly increased Bax/Bcl2 ratio and PERK levels without affecting caspase-3 expression. C3 exhibited poor dark toxicity (IC50 = 74 μM) on rat mesenchymal stem cells (MSCs). In conclusion, the physical property of the complexes dictated by the variable ancillary ligands influenced cellular uptake and cytotoxicity. C3 may be considered a promising selective photoactivatable chemotherapeutic agent that induces ROS production and apoptosis.


A randomised crossover trial: Exploring the dose-response effect of carbohydrate restriction on glycaemia in people with well-controlled type 2 diabetes.
Trials investigating the role of carbohydrate restriction in the management of glycaemia in type 2 diabetes (T2D) have been confounded by multiple factors, including degree of calorie restriction and dietary protein content, as well as by no clear definition of a low-carbohydrate diet. The present study aimed to provide insight into the relationship between carbohydrate restriction and glycaemia by testing the effect of varying doses of carbohydrate on continuous glucose concentrations within a range of intakes defined as low-carbohydrate at the same time as controlling for confounding factors. This was a randomised crossover trial in participants with T2D (HbA1c: 6.6 ± 0.6%, 49 ± 0.9 mmol mol-1 ) testing five different 6-day eucaloric dietary treatments with varying carbohydrate content (10%, 15%, 20%, 25%, and 30% kcal). Diets exchanged %kcal from carbohydrate with fat, keeping protein constant at 15% kcal. Daily self-weighing was employed to ensure weight stability throughout each treatment arm. Between dietary treatments, participants underwent a washout period of at least 7 days and were advised to maintain their habitual diet. Glycaemic control was assessed using a continuous glucose monitoring device. Twelve participants completed the study. There were no differences in 24-h and post-prandial sensor glucose concentrations between the 30 and 10%kcal doses (7.4 ± 1.1 mmol L-1 vs. 7.6 ± 1.3 mmol L-1 [p = 0.28] and 8.1 ± 1.5 mmol L-1 vs. 8.5 ± 1.4 mmol L-1 [p = 0.28], respectively). In our exploratory analyses, we did not find any dose-response relationship between carbohydrate intake and glycaemia. A small amount of weight loss occurred in each treatment arm (range: 0.4-1.1 kg over the 6 days) but adjusting for these differences did not influence the primary or secondary outcomes. Modest changes in dietary carbohydrate content in the absence of weight loss at the same time as keeping dietary protein intake constant do not appear to influence glucose concentrations in people with well-controlled T2D. This study randomised people with T2D to receive five different doses of carbohydrate from 10% to 30% of calories in random order to see what effect it had on their blood glucose.


[Finite element assisted study of the mechanical stability of 2 selected osteosynthesis systems for mandibular osteotomy].
The aim of this study was to use the finite element method (FEM) to compare the stability of 2.0 mm titanium screws in a triangular configuration with that of a 2.0 mm titanium miniplate as osteosynthesis material following bilateral sagittal split osteotomy. To this end, a model of the mandible was produced, consisting of 19,854 elements and 4285 nodes. The mechanical parameters of the materials investigated were taken from the literature or notified by the manufacturer. On condition that the materials were subjected only to their respective ultimate tensile stress, it was possible to neutralise the following masticatory force: 124.6 N with the miniplate and 167.5 N with the bicortical triangular screw configuration. The limitation of stress ensued from the peri-implant bone and not from the osteosynthesis material per se. The finite element method (FEM) appears to be suitable for simulating complex mechanical stress situations in the maxillofacial area, as also demonstrated by the fact that our data agree with those in the literature and with clinical experience. It will enable considerable savings to be made in terms of time and materials (animal experiments) in the future development of osteosynthesis materials and techniques.


Isolation and purification of a Clq-anti Clq precipitin ring enhancing protein from sera of patients with rheumatoid arthritis.
We have isolated and purified to apparent homogeneity a serum protein which appears to be a biological marker for active rheumatoid arthritis. The protein has been found in the sera in all 44 active rheumatoid arthritis patients thus far studied and is absent from, or present in undetected amounts, in sera from normal subjects or from patients with other arthritides. The protein has a molecular weight of 135,000 daltons, an isoelectric pH of 5.1-5.3, and it enhances the size of the C1q-anti C1q ring.


Term Familiarity to indicate Perceived and Actual Difficulty of Text in Medical Digital Libraries.
With increasing text digitization, digital libraries can personalize materials for individuals with different education levels and language skills. To this end, documents need meta-information describing their difficulty level. Previous attempts at such labeling used readability formulas but the formulas have not been validated with modern texts and their outcome is seldom associated with actual difficulty. We focus on medical texts and are developing new, evidence-based meta-tags that are associated with perceived and actual text difficulty. This work describes a first tag, term familiarity , which is based on term frequency in the Google corpus. We evaluated its feasibility to serve as a tag by looking at a document corpus (N=1,073) and found that terms in blogs or journal articles displayed unexpected but significantly different scores. Term familiarity was then applied to texts and results from a previous user study (N=86) and could better explain differences for perceived and actual difficulty.


A conceptual model for faculty development in academic medicine: the underrepresented minority faculty experience.
In May 2010, the Association of American Medical Colleges reported that nonwhite professors have a lower promotion rate than white professors. A cohort of 30 underrepresented minority (URM) junior faculty who participated in a structured faculty development program at a public, research-intensive, academic medical center were followed in a 10-year longitudinal study. This paper reports on the career status of 12 of the 30 URM faculty who were eligible for promotion during this period. Ninety-two percent (11/12) of URM faculty eligible for promotion were promoted to associate professor. When asked what factors contributed to their success, these URM faculty identified access and support of senior faculty mentors, peer networking, professional skill development, and knowledge of institutional culture. A faculty development program that addresses these components can promote the success of URM faculty in academic medicine.


Hsa_circ_0000437 upregulates and promotes disease progression in rheumatic valvular heart disease.
Currently, the diagnosis and outcome of rheumatic valvular heart disease (RVHD) are less than ideal, and there are no accurate biomarkers. Circular RNA (circRNA) might participate in the occurrence and development of RVHD. We use circRNA microarray to filter out the target has_circ_0000437. qRT-PCR was used to measure the expression levels of hsa_circ_0000437 in RVHD plasma samples. We assessed the diagnostic value of hsa_circ_0000437 in RVHD. Cell function in vitro experiment was to explore the effect of has_circ_0000437 on RVHD. Has_circ_0000437 is highly expressed in RVHD (p < 0.001). has_circ_0000437 has the diagnostic value in RVHD. In RVHD, hsa_circ_0000437 can promote cell proliferation and migration but inhibits its apoptosis. This may be due to the combination of has_circ_0000437 and target miRNA in the cytoplasm that affects the progress of RVHD. Has_circ_0000437 can promote the process of RVHD and may be a potential for the diagnosis and treatment of RVHD.


Studies on the glycosomal orotate phosphoribosyl transferase of Trypanosoma cruzi.
The orotate phosphoribosyltransferase of the epimastigote form of Trypanosoma cruzi was studied in its particulate state in preparations derived from glycosomes. Maximum activity was observed at pH 9. There was little activity in the absence of Mg2+; optimum [Mg2+] was related to [5'-phosphoribosyl-alpha-1-pyrophosphate]; Mn2+ could partially substitute for it. Kinetic analyses ruled out a substituted mechanism and suggested instead that the mechanism may be sequential. The apparent Km orotate was 2 microM; that for 5'-phosphoribosyl-alpha-1-pyrophosphate was 8 microM. The enzyme could not use uracil as substrate and was apparently not regulated by naturally-occurring nucleotides. It was, however, sensitive to inhibition by a wide range of pyrimidine analogues, the most active of which was 5-fluoroorotate. These inhibitors were as effective against the enzyme activity of intact glycosomes as broken preparations. This observation, when considered with an apparent lack of latency, suggests that the enzyme is located on the outside of the glycosome. The product of its reaction, orotidine 5'-phosphate, did not exchange readily with exogenous orotidine 5'-phosphate, suggesting that it is channeled directly to orotidine 5'-phosphate decarboxylase, the next enzyme in the pathway.


Differential 2-D protein gel electrophoresis analysis of Legionella pneumophila wild type and Tat secretion mutants.
The twin-arginine translocation (Tat) pathway is a secretory pathway for translocation of folded proteins with two arginines in their signal peptide across the cytoplasmic membrane. Recently, we showed the presence of the Tat secretion pathway in Legionella pneumophila Philadelphia-1 and its role in intracellular replication and biofilm formation. To analyse the importance of the Tat pathway in protein export and its role in L. pneumophila virulence, a comparative 2-D protein gel electrophoresis analysis was performed on supernatants of the wild type and two Tat secretion mutants in order to identify possible Tat substrates. Twenty proteins were identified as differential proteins, eight of which were present in a lower quantity in the supernatant of the tat mutants. Among these, one protein with a typical twin-arginine motif in its signal peptide was identified as the 3',5'-cyclic nucleotide phosphodiesterase. Two other proteins that resulted as differential proteins from this study were flagellin and LvrE, which were studied in more detail and their Tat-dependence was further confirmed with specific antibodies. LvrE was shown to play a role in intracellular growth in differentiated U937 cells.


Increased bleeding risk associated with concurrent vascular endothelial growth factor receptor tyrosine kinase inhibitors and low-molecular-weight heparin.
Some cancer patients who are diagnosed with thromboembolism may require dual treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors (low-molecular-weight heparin [LMWH] or direct oral anticoagulants [DOACs]). However, to the authors' knowledge, the safety of such combinations has not been well characterized. Patients with advanced cancer who were treated with concurrent VEGFR TKIs and factor Xa inhibitors between 2010 and 2018 at The Ohio State University Comprehensive Cancer Center were included. Charts were reviewed retrospectively for clinically significant bleeding events occurring during concurrent treatment compared with those occurring during factor Xa inhibitor therapy alone, using each patient as their own control. The Fisher exact test was used to compare distribution of bleeding severities. The Cox proportional hazards model was used to compare bleeding risk between groups. Among 86 patients, there were 29 clinically significant bleeding events (including 8 major bleeding events) reported during concurrent treatment and 17 events (including 4 major bleeding events) reported during factor Xa inhibitor therapy alone over a median follow-up of 63 days. Concurrent treatment was associated with significantly higher risks of overall bleeding (hazard ratio, 2.45; 95% confidence interval, 1.28-4.69 [P = .007]) and first-onset bleeding (hazard ratio, 2.23; 95% confidence interval, 1.13-4.42 [P = .02]). Analysis of 6-month bleeding risk and the subgroups of patients treated with concurrent TKIs and LMWH versus LMWH alone demonstrated a similar trend. The sample size was inadequate for comparisons between treatment with concurrent TKIs and DOACs versus DOACs alone. Concurrent treatment with VEGFR TKIs and LMWH was found to be associated with a significantly increased risk of bleeding events when compared with LMWH therapy alone.


Elaboration of systemic immunity following inner ear immunization.
The development of systemic humoral and cellular immunity following antigen presentation in the inner ear was compared with that seen following middle ear and peritoneal inoculation routes. Antibody developing against keyhole limpet hemocyanin was measured by a sensitive enzyme-linked immunofiltration assay, and cell-mediated immunity was measured by in vitro lymphocyte blastogenesis. The inner ear and peritoneal routes of antigen presentation resulted in a parallel rise in antibody over a 3-week period. In contrast, the middle ear route resulted in a weak, transient antibody response by 2 weeks. The acquisition of cell-mediated immunity occurred earliest (day 14) in the group receiving antigen intraperitoneally. A significant but smaller proliferative response was also seen in the group receiving antigen via the inner ear route on days 14 and 21. In contrast, the middle ear route failed to result in cell-mediated immunity. These studies indicate that the inner ear is an effective route of antigen processing which results in the acquisition of systemic humoral and cellular immunity. The development of systemic immunity, in turn, has been found to be protective of the inner ear.


The effects of norepinephrine on myocardial biology: implications for the therapy of heart failure.
Increased sympathetic nervous system (SNS) activity in patients with heart failure may help to support cardiovascular function. However, increased SNS activity, particularly if prolonged, may exert deleterious effects on cardiovascular structure and function by stimulating pathologic myocardial remodeling. In vitro, norepinephrine mimics many features of myocardial remodeling, including hypertrophy of individual myocytes and reinduction of fetal genes. Furthermore, stimulation of the beta-adrenergic pathway has been shown to stimulate apoptosis of cardiac myocytes in vitro, in rats infused with isoproterenol, and in mice that overexpress the stimulatory G-protein, Gs. Thus, increased SNS activity, acting via beta-adrenergic receptors, may play an important role in the progression of myocardial failure by acting directly on myocytes and other cell types in the heart to regulate fundamental biologic properties such as growth, apoptosis, and the composition of the extracellular matrix. This thesis provides a mechanism by which beta-adrenergic antagonists may inhibit or reverse pathologic remodeling, improve myocardial structure and function, and prolong patient survival.


The Spline implant interface: analysis and initial clinical experiences.
A new implant with a spline-shaped interface (Spline) was recently introduced. A common and preferred method of connecting two cylinders in many fields of industry, the Spline offers implant dentistry improved strength and precision compared to earlier and current implant connection designs. A comparative engineering analysis of the Spline and the major implant interfaces is offered, including the possible clinical implications. Initial surgical and restorative experiences with cement and screw-retained prostheses are presented in case reports.


Radius of curvature changes in spontaneous improvement of foveoschisis in highly myopic eyes.
Myopic foveoschisis is the splitting of retinal layers overlying staphyloma in highly myopic patients that can lead to vision loss. We assess possible contributing mechanisms to the formation of foveoschisis by examining two cases of spontaneous improvement of myopic foveoschisis and employ a radius of curvature (ROC) measure to track posterior scleral curvature over time. A retrospective, non-comparative case series was performed and optical coherence tomography images were analysed. Retinal pigment epithelial layer ROC was calculated from manually segmented images through the posterior scleral curvature apex. Two cases of myopic foveoschisis with foveal detachments in the left eye (OS) were studied. Both patients had high myopia (either <-10 D or >30 mm in axial length). One case occurred in a treatment-naive patient who improved after 4 months of observation. On initial presentation, OS posterior scleral ROC was 12.35 mm and decreased to 12.15 mm at the time of resolution. The other case occurred in a patient who was followed for 7 years, had previously underwent pars plana vitrectomy and removal of epiretinal membrane, experienced recurrence of foveoschisis and then spontaneously improved without further posterior segment surgery. There was an uncomplicated cataract extraction in the interim. Posterior scleral ROC was 4.05 mm on presentation, 4.10 during recurrence, 3.55 mm after cataract extraction and 3.75 mm at resolution. Spontaneous improvement of myopic foveoschisis may be due to changes in tractional forces from the internal limiting membrane, cortical vitreous or staphyloma or, alternatively, from a delayed or fluctuant recovery course after intervention.


Comparison of radiographic and clinical outcomes of revision reverse total shoulder arthroplasty with structural versus nonstructural bone graft.
Revision shoulder arthroplasty in the setting of glenoid bone loss poses substantial surgical challenges. This study's purpose was to compare radiographic and clinical results of patients requiring structural iliac crest bone autograft (ICBA) for severe bone loss versus patients with less severe bone loss treated with nonstructural bone allograft (NSBA) in the setting of revision reverse total shoulder arthroplasty (RSA). A retrospective cohort of 30 patients (70% of the 43 patients who met the inclusion criteria) undergoing revision RSA with ICBA (n = 15) or NSBA (n = 15) between 2007 and 2015 were analyzed at a minimum 2-year follow-up. Radiographic assessment included bone graft integration, bone graft resorption, glenosphere tilt, glenosphere version, and the presence of scapular notching. Clinical assessment included active range of motion, Penn Shoulder Score, Veterans RAND 12-item health survey, and need for revision surgery. No radiographic difference was found between the ICBA and NSBA groups with regard to implant position, graft integration, scapular notching, implant shift, or failure of fixation (P > .05). Of 15 patients with ICBA, 14 (93%) had at least partial integration of the bone graft. Some degree of resorption of the bone graft was noted in 6 of 15 patients (40%). There was no significant difference in postoperative active range of motion, Penn Shoulder Score, or Veterans RAND 12-item health survey score (P > .05 for all comparisons). One patient in the ICBA group underwent revision surgery for glenoid baseplate failure. Revision RSA with glenoid bone grafting resulted in good clinical and radiographic outcomes at short-term follow-up. Patients requiring structural ICBA were not at increased risk of component failure, radiographic or clinical complications, or inferior clinical outcomes.


Toxoplasmosis in Human and Animals Around the World. Diagnosis and Perspectives in the One Health Approach.
Toxoplasmosis is a unique health disease that significantly affects the health of humans, domestic animals, wildlife and is present in ecosystems, including water, soil and food. Toxoplasma gondii is one of the best-adapted parasites in the word. This parasite is able to persist for long periods in its hosts, in different geographic regions of the word. This review summarizes the current literature of these themes, focusing on: (1) toxoplasmosis, a zoonotic infection; (2) One health approach and toxoplasmosis; (3) human toxoplasmosis; (4) animal toxoplasmosis; (5) toxoplasmosis diagnosis, as immunological, parasitological and molecular diagnosis; (6) T. gondii outbreaks caused by infected meat, milk and dairy products, as well as, vegetables and water consume; (7) studies in experimental models; (8) genetic characterization of T. gondii strains; (9) extracellular vesicles and miRNA; and (10) future perspectives on T. gondii and toxoplasmosis. The vast prevalence of toxoplasmosis in both humans and animals and the dispersion and resistence of T. gondii parasites in environment highlight the importance of the one health approach in diagnostic and control of the disease. Here the different aspects of the one health approach are presented and discussed.


Fabrication of Custom Post-And-Core Using a Directly Fabricated Silicone Pattern and Digital Workflow.
This report introduces an alternative clinical and laboratory technique for the direct fabrication of a custom post-and-core pattern using poly (vinyl siloxane) (PVS) occlusal registration material, followed by a digital workflow. This technique decreases chairside time, eliminates the risk of locking the pattern into the postspace and improves accuracy of the custom post-and-core.


(137)Cs, (40)K and (210)Po in marine mammals from the southern Baltic Sea.
This study provides information on baseline concentrations of the radionuclides Cesium-137, Potassium-40 and Polonium-210 in sea mammals from the Baltic Sea. The radionuclides were analyzed in the liver, kidney and muscle of harbor porpoises, striped dolphins, and gray and ringed seals from the Polish coast by γ- and α-spectrometry. Median (137)Cs activities were 14.8, 13.2 and 23.2 Bq kg(-1) w.w. in the liver, kidney and muscles, respectively. Activities of (40)K and (210)Po in the respective tissues were found to be 79.1, 79.8 and 111 Bq kg(-1) for (40)K and 58.1, 59.2 and 32.9 Bq kg(-1) for (210)Po. The measured (137)Cs concentrations were extraordinarily high in comparison to those reported in sea mammals from other locations. However, dose assessments did not imply health effects from (137)Cs exposure in Baltic Sea mammals. Correlations between (137)Cs tissue activities and reported sea water concentrations highlight the potential use of marine mammals for biomonitoring purposes.


Enzymatic methods in food analysis: determination of ascorbic acid.
The feasibility and expediency of enzymatic methods application in food analysis is demonstrated by the example of ascorbic acid (AsA) determination in foods. Enzymatic determination of ascorbic acid is based on its action as a second substrate of horseradish (HRP) and peanut (PNP) peroxidases in the reactions of o-dianisidine (OD) and 3,3',5,5'-tetramethylbenzidine (TMB) oxidation with hydrogen peroxide. The rates of the reactions are monitored spectrophotometrically by measuring the duration of the induction period on kinetic curves plotted in coordinates absorption-time. The proposed procedures are sensitive (c(L)=0.1 microM), simple, and rapid. The procedure using horseradish peroxidase and the reaction of TMB oxidation was used to determine ascorbic acid in fruit juices, milk and sour-milk products for babies' nutrition.


Comparative sensitivity of CT scans, radiographs and radionuclide bone scans in detecting metastatic calvarial lesions.
CT scans of 100 patients with histologically diagnosed extracerebral neoplasms were reviewed and compared with either radionuclide bone images or skull radiographs. The results of this correlative study indicate that CT scans are more sensitive than skull radiographs in detecting corresponding calvarial lesions; conversely, radionuclide bone scans appear to be more sensitive than CT in detecting similar lesions.


Placebo and the Helsinki Declaration--what to do?
The Helsinki Declaration is the 'gold standard'--a directive, not a law, on how to conduct controlled studies in humans in conformity with ethical principles. In spite of many discussions about their unsuitability some articles have remained unchanged in the most recent (sixth) revision of the Declaration. The demand to use "the best treatment" excludes use of placebo in the control group and presents an obstacle to the scientific evaluation of a number of drugs and treatments in general. The use of placebo is justified whenever its use does not cause irreversible damage or considerable suffering to the well informed patient. It must be, is, and will be used in the controlled clinical trials of treatments of a great number of diseases especially those which have a tendency to spontaneous improvement, even healing, or have a pronounced psychological component.


Comparison of ephrin-A ligand and EphA receptor distribution in the developing inner ear.
Members of the recently discovered Eph family appear to play important roles in a variety of developmental processes including tissue segmentation, cell migration and axonal guidance. To begin to understand the functions of the EphA subclass of receptors and their corresponding GPI-linked (ephrin-A) ligands in the inner ear, a developmental immunohistochemical analysis was completed. The results indicated that the ligands ephrin-A1 and ephrin-A2 were localized mainly at cellular boundaries in the inner ear. Ephrin-A1 was detected mainly in the epithelial cells lining the fluid filled ducts of the inner ear, whereas ephrin-A2 was prominently expressed in connective tissue regions. The receptor EphA4 was detected in vestibular hair cells. EphA5 and EphA7 were detected mainly in cochlear and vestibular supporting cells. These results suggest that these Eph molecules play a role in establishing the formation and cellular organization of the complex inner ear labyrinth. Additionally, all of the ligands and receptors evaluated were expressed in vestibular and cochlear neurons at various developmental stages, suggesting they may play a role in establishing or maintaining innervation to the inner ear.


A review of recent developments based on chemiluminescence detection systems for pesticides analysis.
Chemiluminescence is one of the most coveted methods for sensitive determination of pesticides in food and environmental samples. To date, many methods have been developed for qualitative and quantitative analysis of pesticides, ranging from traditional to advanced methods. This study outlines the progress in the conventional and advanced analytical methods, coupled to a chemiluminescence detection system, that are employed for the determination of pesticides in food and environmental samples. Different analytical methods including chromatographic methods, flow-based systems, and paper-based systems are reviewed in this paper. As well, new advances in the application of nanomaterials, aptamer, and molecularly imprinted polymers are highlighted. We also address the challenges and difficulties associated with these methods. Finally, we highlight the future direction in this active field of research.


[Results of a phase I clinical trial of "theraphthal + ascorbic acid" catalytic system].
Phase-I clinical studies of teraphtal and a "teraphtal + ascorbic acid" catalytic system have been completed. The dose-limiting toxicity and maximum tolerable dose were not reached even at the end of maximal dose trials. No side-effects characteristic of antitumor cytostatic drugs were registered. The gravest side-effect ever recorded was a collapse which could not be linked to teraphtal dosage and was probably caused by hypersensitivity to the drug. The drug was recommended for phase II trials.


Assessment of a Peer Support Group Intervention for Undocumented Latinx Immigrants With Kidney Failure.
Most undocumented immigrants with kidney failure rely on emergency dialysis (defined as dialysis after a patient presents as critically ill) and experience significant depression and anxiety and high mortality. Culturally and language-concordant peer support group interventions may be associated with reduced depression and anxiety and may provide emotional support. To investigate the feasibility and acceptability of a single-group peer support group intervention. This qualitative and single-group prospective study for undocumented immigrants with kidney failure receiving emergency dialysis was conducted in Denver, Colorado, from December 2017 to July 2018. The 6-month intervention included peer support group meetings in the hospital while participants were hospitalized for emergency dialysis. Data were analyzed from March to June 2022. To assess feasibility, the recruitment, retention, implementation, and delivery for the intervention were tracked. To measure acceptability, interviews were conducted with participants using a structured format. To assess the value of the peer support group intervention, themes and subthemes were identified from interviews with participants and group meetings. Of 27 undocumented immigrants with kidney failure receiving emergency dialysis, 23 participants (9 females [39.1%] and 14 males [60.9%]; mean [SD] age, 47 [8] years) agreed to participate (recruitment rate, 85.2%). Among them, 5 individuals withdrew and did not attend meetings and 18 participants (retention rate, 78.3%) attended a mean of 6 of 12 meetings (50.0%). From interviews and meetings, 3 themes, with associated subthemes, were identified: camaraderie and emotional support from peers (subthemes: peer support is vital for people newly diagnosed with kidney failure, safe space to build relationships and share hardship with peers, hospital setting for peer support is ideal, solidarity to survive and change policy, and sustainability of the peer support group), solutions to improve care and resilience (subthemes: self-advocacy, self-motivation and optimism, kidney disease education, emotional support from peers caregivers, and faith), and emotional and physical aspects of receiving emergency dialysis (subthemes: psychosocial and physical distress, mixed experiences with language-concordant care, emotional exhaustion from end-of-life conversations, and gratitude for clinicians). This study found that peer support group intervention achieved feasibility and acceptability. The findings suggest that a peer support group may be a patient-centered strategy to build camaraderie and provide emotional support in kidney failure, especially for socially marginalized uninsured populations who report limited English proficiency.


Maternal-Infant interaction in women with unipoloar and bipolar depression.
One percent of women experience bipolar disorder and are likely to suffer from mood disorders during the postpartum period, potentially impacting interaction with their infants. The purpose of this study was to describe maternal-infant interactions in women with bipolar depression at 12 months postpartum and to compare interactions to women with unipolar depression and a control group. Using a descriptive design, maternal-infant interactions in women with bipolar disorder (n=40) were videotaped, coded, and analyzed for maternal sensitivity and maternal-infant reciprocity and compared to maternal-infant interaction in women with unipolar depression (n=50) and women without depression (n=40). Women with bipolar depression had lower scores on both maternal sensitivity and infant reciprocity, but differences were nonsignificant. This research is the first study to examine maternal-infant interaction in women with bipolar disorder, and important trends were noted. Future research should examine maternal-infant interaction at earlier time periods.


The Italian way to Continuing Education in Medicine.
Continuing education is a right and a duty for all professionals working in the healthcare system, and the Ministry of Health, has recently developed and introduced an experimental program for Continuing Education in Medicine (ECM) throughout Italy. The guiding principles and values of ECM are to assure the quality of educational events and to ensure that professionals can choose from among several opportunities for gaining credits. Although promoted by regional healthcare authorities, the educational program must be homogeneous throughout the national territory. Over the last few months, the National Commission for ECM has defined the role and responsibilities of different organisms and authorities involved in the ECM program. Each professional is expected to gain a total score of at least 150 credits over a 5-year timespan. Moreover, the Commission has established criteria for the accreditation of educational initiatives, the verification of their quality, and the evaluation of the educational benefit participants have from them. The ECM program in Italy is here to stay. It provides professionals with the opportunity to improve the quality of their knowledge, competence, and skills. Medical associations can now reevaluate their role and commitment to improving the quality of healthcare by providing all professionals with a better education and qualifications.


Higher immunoglobulin E antibody levels to recombinant Fel d 1 in cat-allergic children with asthma compared with rhinoconjunctivitis.
Current diagnosis of allergy and asthma to cat is confirmed using cat dander extract (CDE). We have previously engineered a recombinant major cat allergen, rFel d 1, with properties identical to the natural molecule. The aim of the study was to evaluate IgE and IgG4 antibodies to rFel d 1 among sera from cat-allergic children and adults suffering from asthma and/or rhinoconjunctivitis (RC) in populations from Sweden and Austria. Cat-allergic children and adults from Sweden (n=27 and 31, respectively) and Austria (n=41 and 41) with RC and/or asthma were selected. Sera were tested for IgE and IgG4 antibodies to CDE and rFel d 1 by CAP, and IgE to rFel d 1 by ELISA. Healthy subjects and non-cat-allergic patients (n=75) were included as controls. There was a high correlation between IgE responses to rFel d 1 and CDE among the 140 patients (r(s)=0.85, P<0.001); however, measured levels to rFel d 1 were on average 30% higher (P<0.0001). Ninety-eight percent of patients and none of the controls showed IgE to rFel d 1 and there was a threefold increased risk of asthma for half of the children with the highest IgE levels [odds ratio 3.23; 95% confidence interval (CI), 1.19-8.79] by ELISA. IgE responses to rFel d 1 among children with asthma were higher (median 19.4 kU/L) compared with children with RC (median 6.6 kU/L, P<0.05) and adults with asthma (median 3.0 kU/L, P<0.01). Furthermore, children with asthma displayed higher IgG4 levels than the asthmatic adults. A single recombinant molecule, rFel d 1, is at least as sensitive for in vitro diagnostics of cat allergy as the current extract-based test. Elevated IgE antibody levels to Fel d 1 are suggested to be a risk factor for asthma in cat-allergic children.


Cosyntropin-stimulated salivary cortisol in hospitalized patients with hypoproteinemia.
Analysis of adrenocortical function in acutely ill, hospitalized patients can be challenging due to changes in plasma binding proteins. This study used dynamic testing of salivary cortisol levels to evaluate adrenal function in hospitalized patients with low/low-normal plasma protein concentration in whom adrenal insufficiency was suspected. Twenty-eight patients with low serum albumin and proteins hospitalized for acute illness were evaluated for decreased adrenocortical function because of clinical presentations suspicious for adrenal insufficiency. Baseline and post cosyntropin-stimulated levels of serum total and salivary cortisol levels were assessed. Data were gathered by a retrospective analysis of medical records. Eight patients had normal peak serum total and salivary cortisol responses, consistent with intact adrenocortical function. Five patients had abnormal peak serum total and salivary cortisol responses indicating decreased adrenocortical function. Fifteen patients had subnormal peak serum total cortisol, but normal peak salivary cortisol responses indicating normal adrenal function. Salivary cortisol testing can identify hospitalized patients with apparently intact adrenal function in whom low serum protein confounded interpretation of serum total cortisol measurements. Salivary cortisol is a clinically useful surrogate for serum free cortisol in dynamic testing of adrenocortical function.


Characterization of hCG regulation in cultured human amniotic fluid cells: II. Mechanisms for stimulation.
We showed previously that sodium butyrate stimulated human chorionic gonadotropin (hCG) measured by radioimmunoassay of medium from human second trimester amniotic fluid cell cultures, termed AF cells. We now find that stimulation of hCG in the presence of sodium butyrate takes as long as 20 h. When AF cells are preincubated with sodium butyrate, hCG levels increase in direct relation to length of the preincubation period. These findings suggest that elevation of hCG is not due merely to a release of hormone from the cells. Addition of cycloheximide or Actinomycin D inhibited protein synthesis and RNA synthesis, respectively, and prevented the stimulation of hCG by sodium butyrate. These results lend support for a mechanism of regulation involving protein and RNA synthesis, the increase in hCG levels being due to new synthesis of the hormone. Other agents reported to influence hCG production by different types of cell cultures include dibutyryl cyclic AMP, epidermal growth factor (EGF), methotrexate, and hydroxyurea. Dibutyryl cyclic AMP and EGF have no effect on hCG production in our AF cells: methotrexate causes a minimal increase, hydroxyurea causes a further increase, but sodium butyrate has the strongest stimulatory effect. We conclude that amniotic fluid cells in culture are susceptible to environmental agents capable of modulating synthesis of hCG by mechanisms involving synthesis of RNA and protein.


Monolithic lithium niobate photonic circuits for Kerr frequency comb generation and modulation.
Microresonator Kerr frequency combs could provide miniaturised solutions for a wide range of applications. Many of these applications however require further manipulation of the generated frequency comb signal using photonic elements with strong second-order nonlinearity (χ(2)). To date these functionalities have largely been implemented as discrete components due to material limitations, which comes at the expense of extra system complexity and increased optical losses. Here we demonstrate the generation, filtering and electro-optic modulation of a frequency comb on a single monolithic integrated chip, using a nanophotonic lithium-niobate platform that simultaneously possesses large electro-optic (χ(2)) and Kerr (χ(3)) nonlinearities, and low optical losses. We generate broadband Kerr frequency combs using a dispersion-engineered high-Q lithium-niobate microresonator, select a single comb line using an electrically programmable add-drop filter, and modulate the intensity of the selected line. Our results pave the way towards monolithic integrated frequency comb solutions for spectroscopy, data communication, ranging and quantum photonics.


The perseveration of checking thoughts and mood-as-input hypothesis.
This paper describes two experiments designed to investigate how a current model of task perseveration, the mood-as-input hypothesis, might be applied to activities relevant to compulsive checking. The mood-as-input hypothesis predicts that perseveration at an open-ended task will be determined by a combination of the "stop rules" adopted for the task, and the valency of the mood state in which the task is conducted. Experiment 1 required participants to generate items that should be checked for safety/security if they were leaving their home unattended. Experiment 2 used an analogue recall task, in which participants were asked to recall items from a comprehensive list of items that should be checked if they were to leave their home safe/secure. Both experiments found that perseveration at the tasks was determined by particular configurations of mood and stop rules for the task. Of most relevance to compulsive checking was the fact that facilitated perseveration occurred when participants were asked to undertake the tasks in a negative mood using "as many as can" stop rules. Implications for the factors that develop and maintain compulsive checking are discussed.


Chromatin Scanning by Dynamic Binding of Pioneer Factors.
Pioneer factors such as FoxA target nucleosomal DNA and initiate cooperative interactions at silent genes during development, cellular reprogramming, and steroid hormone induction. Biophysical studies previously showed that the nuclear mobility of FoxA1 is slower than for many other transcription factors, whereas a new single molecule study (Swinstead et al., 2016, Cell) shows comparable chromatin residence times for FoxA1 and steroid receptors. Despite that steroid receptors engage nucleosome-remodeling complexes, the vast majority of co-bound sites with FoxA are dependent upon FoxA, not vice versa. Taken together, the distinguishing feature of pioneer factors remains nucleosomal access rather than an exceptional residence time in chromatin.


Labdane conjugates protect cardiomyocytes from doxorubicin-induced cardiotoxicity.
The cardiovascular side effects associated with doxorubicin (DOX), a wide spectrum anticancer drug, have limited its clinical application. Therefore, to explore novel strategies with cardioprotective effects, a series of new labdane conjugates were prepared (6a-6c and 8a-8d) from the natural diterpene labdanodiol (1). These hybrid compounds contain anti-inflammatory privileged structures such as naphthalimide, naphthoquinone, and furanonaphthoquinone. Biological activity of these conjugates against DOX-induced cardiotoxicity was tested in vitro and the potential molecular mechanisms of protective effects were explored in H9c2 cardiomyocytes. Three compounds 6c, 8a, and 8b significantly improved cardiomyocyte survival, via inhibition of reactive oxygen species-mediated mitogen-activated protein kinase signaling pathways (extracellular signal-regulated kinase and c-Jun N-terminal kinase) and autophagy mediated by Akt activation. Some structure-activity relationships were outlined, and the best activity was achieved with the labdane-furonaphthoquinone conjugate 8a having an N-cyclohexyl substituent. The findings of this study pave the way for further investigations to obtain more compounds with potential cardioprotective activity.


Correlation of saphenous vein bypass graft angiograms with histologic changes at necropsy.
Previous studies of saphenous vein (SV) bypass grafts have been either angiographic or morphologic, and few have correlated angiograms with histology. Nine necropsy patients who had received 21 SV implants 12 to 120 months (mean 67 +/- 42) before death were studied. All patients had severe coronary artery disease. Three types of histologic changes were found: atherosclerosis in 9 grafts, fibrointimal proliferation in 8 and total occlusion with fibrosis in 4. All patients had premortem angiograms 0 to 3 months (mean 0.7 +/- 1.1) before death. In 14 of 21 grafts, premortem angiograms accurately reflected the postmortem findings. In 7 grafts, the premortem angiograms either overestimated (4 grafts) or underestimated (3 grafts) the extent of luminal narrowing. Six of the 7 SV implants incorrectly assessed by angiography had fibrointimal proliferation and 1 had atherosclerosis. The presence of smooth muscle in SV implants with fibrointimal proliferation may be a mechanism of spasm or relaxation during angiography, which could cause errors in estimating the degree of stenosis. Nitrates or calcium antagonists may be useful in both assessing the degree of underlying vasomotion in SV grafts and as a therapeutic modality.


Use of mixed cultures of biocontrol agents to control sheep nematodes.
Biological control is a promising non-chemical approach for the control of gastrointestinal nematodes of sheep. Use of combinations of biocontrol agents have been reported to be an effective method to increase the efficacy of biological control effects. In this study, combinations of either two Bacillus thuringiensis (Bt) or Clonostachys rosea (C. rosea) isolates and Bt+C. rosea isolates were evaluated in vitro in microtitre plates for their biocontrol activity on sheep nematodes. The Baermann technique was used to extract the surviving L3 larval stages of intestinal nematodes and counted under a dissecting microscope to determine the larval counts. Results indicate that there was a significant reduction of nematode counts due to combination of biocontrol agents (P<0.001). Combinations of Bt isolates reduced nematodes counts by 72.8%, 64% and 29.8%. The results revealed a control level of 57% when C. rosea isolates P3+P8 were combined. Combination of Bt and C. rosea isolates B10+P8 caused the greatest mortality of 76.7%. Most combinations were antagonistic, with only a few combinations showing an additive effect. None were synergistic. The isolate combinations were more effective than when isolates were used alone.


[Endoscopic transforaminal lumbar decompression, bone graft fusion and pedicle screw fixation under X-tube system: report of 42 cases].
To evaluate the surgical procedure of unilateral transforaminal discectomy, bone grafting, cage (Telamon) insertion and Dylanok pedicle screw fixation using X-tube operation system for the treatment of lumbar disc herniation combined with segmental instability and Spondylolysis with pars defect. From 2004 to 2006, 42 patients including 17 male and 25 female were treated in our department. The age range from 22 to 77 (mean: 51.6). Etiologies including lumbar disc herniation combined with segmental instability and Spondylolysis with pars defect. Of these 42 patients, the mean operation time was 240 min (110 - 320 min), the average blood loss was 140 ml (80 - 420 ml), the average incision length was 3 cm (2.8 - 3.2 cm) and the average hospitalization time was 12.5 days (5 - 25 days). Nakai criteria, Excellent in 23 cases (62.2%), good in 11 cases (29.2%) and fair in 3 cases (8.6%). 5 patients had postoperative complication (complication rate: 16.3%). The surgical procedure has shown predominant benefits: small incision, less stripping of paraspinal muscles, minimal blood loss and rapid postoperative recovery which makes it a valuable alternative to conventional surgical procedures.


Interval training in the boundaries of severe domain: effects on aerobic parameters.
Although time spent at VO2max (t@VO2max) has been suggested as an optimal stimulus for the promotion of greater VO2max improvements, scientific findings supporting this notion are surprisingly still lacking. To investigate this, the present study described t@VO2max in two different severe-intensity interval training regimens and compared its effects on aerobic indexes after a 4-week intervention. Twenty-one recreational cyclists performed an incremental exercise test and six time-to-exhaustion tests on four different days to determine VO2max, lactate threshold (LT), critical power (CP) and the highest intensity (IHIGH) and lowest exercise duration (TLOW) at which VO2max was attained. Subjects were assigned to the lower (LO, n = 11, 4 × 5 min at 105% CP, 1 min recovery) or the upper severe-intensity training groups (UP, n = 10, 8 × 60% TLOW at 100% IHIGH, 1:2 work:recovery ratio). t@VO2max was measured during the first and last training sessions. A significantly higher t@VO2max was elicited in the UP during training sessions in comparison with the LO group (P < 0.05), and superior improvements were observed in VO2max (change in measure ± 95% confidence interval) (6.3 ± 1.9 vs. 3.3 ± 1.8%, P = 0.034 for interaction terms) and LT (54.8 ± 11.8 vs. 27.9 ± 11.3%, P = 0.023 for interaction terms). The other aerobic indexes were similarly improved between the groups. The present results demonstrated that UP training produced superior gains in VO2max and LT in comparison with LO training, which may be associated with the higher t@VO2max.


[Survey of contamination of food by 3, 4-benzopyrene. I. Demonstration of a universal method of determination. Application to the determination in complete meals in food emporia].
A versatile spectrofluorimetric method is proposed for the determination of 3,4-benzopyrene in foods and biological material. Recording the emission spectrum allows a reliable identification, and determination at a 0,2 ppb level, with 85 p. 100 recovery and good reproductibility. The time required for analysis is decreased, if compared to existing methods. As a test of its reliability, results of a survey on 3,4-benzopyrene content in canteen meals are presented. The values obtain are very low, generally below 1 ppb; their significance is discussed.


Categorization of interictal epileptiform potentials using a graph-theoretic method.
In patients with epileptic seizures, localization of the source of interictal epileptiform activity is of interest. For correct source localization, a favorable signal to noise ratio is important, and to achieve this, averaging of several epileptiform potentials is often necessary. Before averaging, a careful categorization of epileptiform potentials with different potential distributions is crucial. The aim of this study was to investigate whether a a hierarchic, graph-theoretic algorithm could be used for this categorization. In 4 patients, 50-100 sharp waves with different surface distributions were categorized independently with the algorithm, and by visual inspection of the traces. As an independent evaluation of the algorithm, a dipole reconstruction was performed for each sharp wave, and the dipole results for the sharp waves from the different automatically obtained categories were compared. All patients showed a high degree of correspondence between the results of the automatic analysis and the visual estimation. There were clear differences in dipole results between the sharp waves of the different categories obtained from the automatic categorization. The results indicate that the graph-theoretic categorization algorithm provides a reliable clustering of interictal epileptiform potentials, and that the method may become a useful tool in the pre-averaging categorization of interictal epileptiform potentials prior to source localization.


Two cases of a perforated duodenal diverticulum after gastrectomy with Roux-en-Y reconstruction.
What type of reconstruction procedure should be applied is one of the important issues in surgery for gastric cancer. We have several options for reconstruction procedure after distal gastrectomy. The Billroth II and Roux-en-Y reconstruction have a duodenal stump while the Billroth I does not have it, which is the biggest structural difference in these procedures. An increase in intraduodenal pressure due to the formation of duodenum stump occasionally causes severe complication such as duodenal stump leakage; however, a duodenal diverticulum perforation after the Roux-en-Y reconstruction has not yet been reported. Herein, we report two cases of a perforated duodenal diverticulum after gastrectomy with the Roux-en-Y reconstruction. The first case was a 66-year-old man who presented to our hospital with an acute onset right-upper-quadrant abdominal pain. He had undergone laparoscopic distal gastrectomy with the Roux-en-Y reconstruction for the early gastric cancer 15 months before. A large periampullary diverticulum had been detected during the checkup before the gastrectomy. Abdominal contrast-enhanced CT showed a retroperitoneal fluid collection with gas present at the second part of the duodenum. Therefore, a perforated duodenal diverticulum with abdominal abscess was diagnosed, and an emergency laparotomy was performed. Pancreaticoduodenectomy was performed because of severe duodenal inflammation and surrounding tissue damage. The second case was a 52-year-old man who had undergone open distal gastrectomy for locally advanced gastric cancer. Multiple non-ampullary duodenal diverticula had also been identified during the preoperative checkup. On the 2nd postoperative day, he presented with a sudden-onset abdominal pain with peritoneal irritation signs, and intestinal fluid was identified through the intraperitoneal drainage tube placed in a suprapancreatic site during his previous gastrectomy. Therefore, an emergency laparotomy was performed. During laparotomy, a perforated diverticulum at the second part of the duodenum was detected. The perforated duodenum diverticulum was directly sutured with drainage of the retroperitoneal space. It is necessary to recognize that the Roux-en-Y reconstruction after gastrectomy for gastric cancer patients with duodenal diverticulum might cause a perforation of the diverticulum.


[The use of sorption detoxification methods for the prevention of dynamic intestinal obstruction in peritonitis].
The effect of hemosorption on motor-evacuatory intestinal function was studied in 169 patients with different forms of peritonitis of appendicular genesis. Early inclusion of hemosorption into the complex of treatment contributed to restoration of motor-evacuatory function of the intestine in 2-3 days, as well as to prevention of development of early commissural ileus.


Etiologic diagnosis of pneumonia by antigen detection: crossreactions between pneumococcal C-polysaccharide and oral microorganisms.
Crossreactions between bacteria occurring more or less frequently in the respiratory tract were investigated using an enzyme-linked immunosorbent assay (ELISA) developed for the detection of pneumococcal C-polysaccharide. A collection of 218 strains was investigated: 30 Streptococcus pneumoniae, 120 alpha-streptococci, and 68 strains representing other species. Strong crossreactions were observed with 36% of the alpha-streptococci and with two of 11 Staphylococcus aureus strains. The collection of alpha-streptococci consisted of 90 fresh clinical isolates and 30 stock strains. Almost all crossreactions of alpha-streptococci were found among the clinical isolates. Among the stock strains only one of four Streptococcus mitis strains was positive. Pneumococcal C-polysaccharide and phosphorylcholine inhibited the reactions in ELISA with monoclonal antibodies against pneumococcal C-polysaccharide, as well as with a polyclonal antiserum against pneumococcal C-polysaccharide. We suggest that the cross reactions between alpha-streptococci and pneumococci depend on the presence of phosphorylcholine as a common antigenic determinant. The crossreaction in the ELISA with some Staphylococcus aureus strains may be explained by the presence of protein A binding to the Fc portion of the antibodies. When the 10 alpha-streptococci that showed the strongest crossreactions and ten pneumococci representing different types were tested in different concentrations the absorbance values were lower for most alpha-streptococci compared with the pneumococci. This explains that false positive results with alpha-streptococci do not seem to constitute a practical problem in this ELISA developed for detection of pneumococcal C-polysaccharide in samples from patients with pneumonia.


Nitrate leaching, direct and indirect nitrous oxide fluxes from sloping cropland in the purple soil area, southwestern China.
This study provides a combined dataset on N loss pathways and fluxes from sloping cropland in the purple soil area, southwestern China. A lysimeter experiment was conducted to quantify nitrate leaching (May 2004-May 2010) and N(2)O emission (May 2009-May 2010) losses. Nitrate leaching was the dominant N loss pathway and annual leaching fluxes ranged from 19.2 to 53.4 kg N ha(-1), with significant differences between individual observation years (P < 0.05). Direct N(2)O emissions due to N fertilizer use were 1.72 ± 0.34 kg N ha(-1) yr(-1), which corresponds to an emission factor of 0.58 ± 0.12%. However, indirect N(2)O emissions caused by nitrate leaching and surface runoff N losses, may contribute another 0.15-0.42 kg N ha(-1) yr(-1). Our study shows that nitrate leaching lowered direct N(2)O emissions, highlighting the importance for a better understanding of the tradeoff between direct and indirect N(2)O emissions for the development of meaningful N(2)O emission strategies.


Aggregation behaviour and interspecific relationships in Dermaptera.
The rate of gregariousness and intra- and inter-specific attractivity were evaluated under laboratory conditions in five species of Dermaptera. The three species of the genus Forficula (Forficula auricularia L., F. decipiens Gené and F. pubescens Gené) showed distinctly gregarious behaviour in old larvae and adults in the pre-reproductive phase. This gregariousness was seen at the intraspecific level and also among individuals of different species. The other two species, Labidura riparia Pallas and Euborellia moesta Gené, were randomly distributed over the available shelters, with no distinct tendency for aggregation or isolation. In individual tests, insects of all five species were attracted by shelters previously visited by conspecifics in preference to control shelters. For the two non-gregarious species, this phenomenon might function as a burrow marker. The same tests showed an interattractivity for four of the species studied. Only L. riparia did not respond to the trails of the four other species, although its trails were attractive to the other species. The pheromonal nature of the substances involved in the interspecific relationships and the involvement of behaviour in the biology and speciation of Dermaptera are discussed.


Occurrence of microfilariae in various hollow organs and in the peritoneal cavity after treatment of Litomosoides carinii infected Mastomys natalensis with diethylcarbamazine and haloxon.
Treatment of Litomosoides carinii infected Mastomys natalensis with diethylcarbamazine (DEC: 500 mg/kg p.o.) was followed by increased occurrence of microfilariae in the bronchi of the host after 40 min and lasting at least until 6 h after treatment. After 4 h, increased levels of larvae were observed in the gut. Only a few microfilariae occurred in the bladder and sputum. Accumulations of microfilariae were found furthermore in the Lnn. hepaticae whereas no changes were observed in the inguinal or jejunal and lung and pleura associated lymph nodes. Increased numbers of microfilariae were found in the peritoneal cavity only after 8 and continuing until at least 48 h after treatment. In contrast, after haloxon treatment (100 mg/kg p.o.) an accumulation of microfilariae was found in the peritoneal cavity only, following a time course similar to that after DEC.


[Milta-F: a magnetic infrared laser therapeutic apparatus with a photorecorder for diagnosis, prognostication and treatment of inflammatory diseases of the adnexa uteri].
Laser biophotometry is an objective method to diagnose and to predict the course of inflammatory diseases of the uterine appendages. By taking into account its simplicity, reliability, and validity of findings, a MILTA apparatus should be recommended in additional studies of patients.


Giant papillary conjunctivitis in contact lens wearers.
A syndrome that occurred in both hard and soft contact lens wearers was characterized by increased mucus, itching, decreased lens tolerance, and giant papillae in the upper tarsal conjunctiva. It developed in as few as three weeks with soft lens wearers but also occurred after months or even years of successful wear. The histology was characterized by basophils, eosinophils, and mast cells in the epithelium, and these cells as well as increased numbers of lymphocytes, plasma cells, and polymorphonuclear leukocytes in the stroma. The syndrome may be immunologic in origin with deposits on the lenses as the antigen, and the syndrome may be a major cause of difficulty in wearing contact lenses once they have been successfully fit.


Relationships between risk factors and morphological patterns of human carotid atherosclerotic plaques. A multivariate discriminant analysis.
The histological characterization of the fibroatheromatous plaques and their histogenesis are still to be defined. Factors responsible for the evolution of intimal components and the mechanisms and stages of fibroatheromatous plaque formation are still largely obscure. Focusing on symptomatic plaques, the aim of this study is to determine whether plaque heterogeneity is the result of a haphazard clustering of various components or an organized pattern in response to risk factors. To this end, 180 carotid plaques from patients affected by transient ischemic attacks (TIA) or by stroke, with angiographic stenosis greater than 50%, were studied after endoarterectomy. Clinical and morphological data were collected by means of a pre-defined protocol, quantified and correlated, by using the discriminant analysis, with age, sex, hypertension, diabetes, hypercholesterolemia and smoking habit. Our results show that the relationships between plaque components are non-random and consistent with the knowledge derived from studies on human and experimental plaques. Moreover, some plaque patterns can be significantly correlated with single risk factors. The fibrous plaque was correlated with aging and diabetes; the granulomatous plaque, rich in giant cells, with the female sex and hypertension; the xanthomatous plaque, rich in foam cells and with extensive alcianophilia, with hypercholesterolemia. In the smokers, finally, the plaques were frequently complicated by mural thrombosis.


Nerve injury associated with orthognathic surgery. Part 1: UK practice and motor nerve injuries.
The head and neck is anatomically complex, and several nerves are at risk during orthognathic operations. Some injuries to nerves are reported more commonly than others. To find out what consultant surgeons tell their patients about the prevalence of common nerve injuries before orthognathic operations, we did a postal survey of fellows of the British Association of Oral and Maxillofacial Surgeons (BAOMS). We also reviewed published papers to find out the reported incidence of injuries to cranial motor nerves during orthognathic operations. Only injuries to the facial nerve were commonly reported, and we found only case reports about injuries to the oculomotor, abducens, and trochlear nerves. The risk of temporary facial nerve palsy reported was 0.30/100 nerves (95% CI 0.23 to 0.50) and permanent facial nerve palsy was 0.06/100 nerves (95% CI 0.02 to 0.15).


Reactivity to pseudorandom environmental patterns in woodlice: Effects of hydric deprivation and light exposure.
Exploratory activity is an essential component of animal behavior, including among invertebrate species. This study examined the effects of hydric deprivation and their possible modulation by light exposure on locomotion and rearing-up behavior in two woodlice species, Porcellio scaber (Latreille 1804) and Armadillidium vulgare (Latreille 1804). It was also an attempt to replicate previous findings on the stimulation of these behaviors in P. scaber, exposed to (pseudo)random vs. regular visual and tactile patterns in a small enclosure. In Experiment 1, two groups of P. scaber and two groups of A. vulgare were exposed to randomly vs. regularly distributed visual (black and white) and tactile (grained and smooth) patterns for approximately 20 min. No rewards were present in the environment and the woodlice were tested without preliminary hydric deprivation. In Experiment 2, the same procedure was used but the woodlice were tested following a 20-min hydric deprivation under a bottle cap (darkness). Experiment 3 replicated this procedure with the 20-min hydric deprivation spent in a plastic cup (light exposure). The results of Experiments 1 and 3 provide partial replication with A. vulgare, but not P. scaber, of the previous findings: Random patterns stimulate rearing-up behavior on the apparatus' vertical walls more than regular patterns. Also, a more aversive stimulation in Experiment 3 compared to Experiment 2, increased locomotion, especially in the random environment. The role of hydric deprivation and light exposure in the process of escaping from a hostile environment is discussed, as well as the effects of the treatments used in these experiments.