[The value of medical imaging in the diagnosis and assessment of local and regional extension of cancers of the cavum at Yaounde].
In this work, we aimed to provide a clear description of the contribution to and role of major imaging techniques in the diagnosis of cancers of the cavum and assessment of their local and regional expansion. This should provide doctors with a useful guide for decisions concerning the imaging technique to be used. This is a retrospective analysis of 41 cases of cavum cancer, all confirmed by histology. The series consisted of 29 male patients (70%) and 12 female patients (30%), giving a sex ratio of 2.4. The mean age of the patients was 42 years (range: 11 to 71 years). All patients were examined and treated in the Radiology and Oncological Radiotherapy Department of Yaounde General Hospital over a period of eight years (December 1988 to November 1996 inclusive). All data relating to diagnosis, assessment of local and regional expansion and the response of the tumor to treatment were retrieved from the medical files and analyzed. We found that clinical diagnosis of cancer of the cavum was difficult and this cancer was often diagnosed late. It was therefore often necessary to resort to paraclinical means of diagnosis and assessment of expansion, such as endoscopy, conventional X rays and tomography. Endoscopy and conventional X rays give poor results but may be used if there is a lack of equipment or for an initial examination, to be followed by assessment using other methods. Tomography remains the most effective technique and is recommended for the diagnosis of cancers of the cavum and for assessment of their local and regional expansion.


U.S. census data uses.
"This article examines the principal applications of the statistics yielded by the 1990 U.S. Census of Population and Housing. Before doing so, however, a framework of census policy and operational features that directly influenced the content of the questionnaires will be outlined.... Having established this background, the uses of census data will be addressed, citing case examples in some instances, for...major groups of data users."


Staged total cavopulmonary connection: serial comparison of intra-atrial lateral tunnel and extracardiac conduit taking account of current surgical adaptations.
Our goals were to compare the outcome of the intra-atrial lateral tunnel (ILT) and the extracardiac conduit (ECC) techniques for staged total cavopulmonary connection (TCPC) and to compare the current modifications of the TCPC technique, i.e. the prosthetic ILT technique with the current ECC technique with a ≥18-mm conduit. We included patients who had undergone a staged TCPC between 1988 and 2008. Records were reviewed for patient demographics, operative details and events during follow-up (death, surgical and catheter-based reinterventions and arrhythmias). Of the 208 patients included, 103 had the ILT (51 baffle, 52 prosthetic) technique and 105 had the ECC technique. Median follow-up duration was 13.2 years (interquartile range 9.5-16.3). At 15 years after the TCPC, the overall survival rate was comparable (81% ILT vs 89% ECC; P = 0.12). Freedom from late surgical and catheter-based reintervention was higher for patients who had ILT than for those who had ECC (63% vs 44%; P = 0.016). However, freedom from late arrhythmia was lower for patients who had ILT than for those who had ECC (71% vs 85%, P = 0.034). In a subgroup of patients who had the current TCPC technique, when we compared the use of a prosthetic ILT with ≥18-mm ECC, we found no differences in freedom from late arrhythmias (82% vs 86%, P = 0.64) or in freedom from late reinterventions (70% vs 52%, P = 0.14). A comparison between the updated prosthetic ILT and current ≥18-mm ECC techniques revealed no differences in late arrhythmia-free survival or late reintervention-free survival. Overall, outcomes after the staged TCPC were relatively good and reinterventions occurred more frequently in the ECC group, whereas late arrhythmias were more common in the ILT group.


A Comprehensive Review of Outcome Predictors in Low MELD Patients.
Risk scoring for patients with cirrhosis has evolved greatly over the past several decades. However, patients with low Model for End-Stage Liver Disease-Sodium scores still suffer from liver-related morbidity and mortality. Unfortunately, it is not clear which of these low Model for End-Stage Liver Disease-Sodium score patients would benefit from earlier consideration of liver transplantation. This article reviews the literature of risk prediction in patients with cirrhosis, identifies which patients may benefit from earlier interventions, such as transplantation, and proposes directions for future research.


Acute Ischemic Stroke Due to Basilar Artery Occlusion with Coronavirus Disease 2019: A Case Report.
Although it is increasingly recognized that coronavirus disease 2019 (COVID-19) can cause multi-organ disease, including acute ischemic stroke, the incidence of coagulation disorder is reported to be lower in Asian countries. We report a case of a 47-year-old Asian man with mild COVID-19 respiratory symptoms who had acute basilar artery occlusion. Despite successful recanalization with mechanical thrombectomy, the patient developed extensive cerebral infarction in the posterior circulation, necessitating decompressive craniotomy. Our findings suggest that severe large vessel occlusion (LVO) can occur even in young Asian patients with mild COVID-19 respiratory symptoms and that its outcome can be extremely severe despite successful recanalization. The management of COVID-19-related LVO can be very challenging, as both the prevention of possible nosocomial infection and early recanalization are required simultaneously.


Establishing content for a digital educational support group for new adolescent mothers in the Dominican Republic: a user-centered design approach.
As digital interventions to improve health become widespread globally, it is critical to include target end-users in their design. This can help ensure interventions are maximally beneficial among intended populations. To generate the content of a digital educational support group, administered through WhatsApp, for new adolescent mothers and establish participants' cellular access and WhatsApp use. Adolescent mothers with new babies. We completed a two-phase user-centered design process. In phase I design sessions, participants discussed their postpartum experiences and completed an activity to elucidate their health and wellbeing information needs. In phase II sessions, participants individually identified which health information topics were important to them, then all topics were prioritized as a group. Phase II participants also completed a brief survey on cell phone access and WhatsApp use. Phase I included 24 participants, 21 of whom completed phase II. Priority health and wellbeing information topics in the postpartum period were identified as: child growth and development, understanding your baby, common childhood illnesses, breastfeeding, childhood nutrition, family planning, and self-care. Of phase II participants, 45% had cellular phone access and none had a data plan. Cellular service was inconsistently obtained with data packages or Wi-Fi. 30% of participants had no experience using WhatsApp. Participants identified numerous health information needs, which will serve as the content for our planned digital support group and provides valuable insight for health care providers globally. Less than half of participants had consistent cellular phone access, and none had reliable access to cellular service.


Investigation of random lasing from all-inorganic halide perovskite quantum dots prepared under ambient conditions.
Random lasing from CsPbBr3 quantum dots (QDs) prepared by the hot injection method under ambient conditions has been investigated. The lasing characteristics and performance were related to the thickness and aggregation of the QDs film on a glass substrate. The perovskite emitted linear polarized ASE from the edge of the prepared sample as pump energy above a certain threshold, owing to the gain guiding effect. In comparison to the Q-switched Nd:YAG laser, the prepared perovskite random lasers produced a speckle reduced image with a lower contrast of around 0.051. Through temperature-dependent measurements under a surface normal emission configuration, the photon energy of ASE revealed a red shift as the temperature increased and showed a larger characteristic temperature of around 230 K. This result illustrates that the perovskite prepared under ambient conditions can be a promising material for a microcavity laser in the near future.


Demonstration in yeast of the function of BP-80, a putative plant vacuolar sorting receptor.
BP-80, later renamed VSR(PS-1), is a putative receptor involved in sorting proteins such as proaleurain to the lytic vacuole, with its N-terminal domain recognizing the vacuolar sorting determinant. Although all VSR(PS-1) characteristics and in vitro binding properties described so far favored its receptor function, this function remained to be demonstrated. Here, we used green fluorescent protein (GFP) as a reporter in a yeast mutant strain defective for its own vacuolar receptor, Vps10p. By expressing VSR(PS-1) together with GFP fused to the vacuolar sorting determinant of petunia proaleurain, we were able to efficiently redirect the reporter to the yeast vacuole. VSR(PS-1) is ineffective on GFP either alone or when fused with another type of plant vacuolar sorting determinant from a chitinase. The plant VSR(PS-1) therefore interacts specifically with the proaleurain vacuolar sorting determinant in vivo, and this interaction leads to the transport of the reporter protein through the yeast secretory pathway to the vacuole. This finding demonstrates VSR(PS-1) receptor function but also emphasizes the differences in the spectrum of ligands between Vps10p and its plant equivalent.


Fetal-maternal HLA-A and -B discordance is associated with placental RNase expression and anti-HIV-1 activity.
The incidence of maternal-to-fetal human immunodeficiency virus type 1 (HIV-1) transmission is 25-30% in absence of antiretroviral therapy, and is inversely associated with Human leukocyte antigens (HLA) class-I discordance. Based on our earlier report that mixed lymphocyte reactions (MLR) induce a ribonuclease (RNase) that inhibits HIV-1 replication, we proposed that maternal-fetal alloantigen stimulation activates factors that protect the fetus against vertically-transmitted infections. We investigate here whether the degree of mother-infant HLA discordance associates with the ability to produce anti-HIV-1 alloantigen-stimulated factor (ASF), and affects placental RNases. We also determine whether such HLA association is influenced by the mother's HIV-1 status. Paired maternal and cord blood leukocytes were tested for the induction of ASF by MLR, and typed for HLA-A and -B. The placentas were tested for mRNA expression of three RNases. Neonate anti-mother, but not mother anti-neonate MLR generated supernatants with anti-HIV-1 activity, that was associated with HLA class I discordance. This HLA association was not seen in the HIV-infected cohort. HLA class I discordance was also associated with expression of placental RNase 1. Our findings are consistent with the hypothesis that HLA class I discordance induces expression of RNases in the placenta that contribute to innate host resistance to HIV-1 and other viral infections.


Angiopoietin-like 4 Is a Wnt Signaling Antagonist that Promotes LRP6 Turnover.
Angiopoietin-like 4 (ANGPTL4) is a secreted signaling protein that is implicated in cardiovascular disease, metabolic disorder, and cancer. Outside of its role in lipid metabolism, ANGPTL4 signaling remains poorly understood. Here, we identify ANGPTL4 as a Wnt signaling antagonist that binds to syndecans and forms a ternary complex with the Wnt co-receptor Lipoprotein receptor-related protein 6 (LRP6). This protein complex is internalized via clathrin-mediated endocytosis and degraded in lysosomes, leading to attenuation of Wnt/β-catenin signaling. Angptl4 is expressed in the Spemann organizer of Xenopus embryos and acts as a Wnt antagonist to promote notochord formation and prevent muscle differentiation. This unexpected function of ANGPTL4 invites re-interpretation of its diverse physiological effects in light of Wnt signaling and may open therapeutic avenues for human disease.


Effects of Echis carinatus Venom on the Haemodynamy and Contractility of Vascular and Visceral Smooth Muscle of Rats.
Abstract Echis carinatus is considered to be one of the most dangerous snakes in the world because of its venom toxicity and high population densities in rural agriculture areas. However, little information is available on the pharmacological effects of venom from this snake on haemodynamy and vasculature smooth muscle contractility. The haemodynamic alterations induced by the intravenous administration of Echis carinatus venom was investigated in anaesthetized rats. Injection of several doses of venom (1, 3, 5, and 7 mu g kg (- 1)) decreased the arterial blood pressure. For instance, injection of 3 mu g kg(-1) of Echis carinatus venom reduced the mean arterial blood pressure from 107 +/- 4 to 71 +/- 4 mmHg (p < 0.05). Exposure of the rat isolated vas deferens preparations to Echis carinatus venom (1 mu g ml(-1)) significantly reduced the contractile responses to epinephrine (10 mu g ml(- 1)) without changing the response to KCl (50 mM). To investigate the effects of venom on peripheral vascular resistance, mesenteric bed was removed and perfused with Krebs solution. Addition of different concentrations of venom (1, 3, and 10 mu g ml(-1)) to the precontracted mesenteric bed (with phenylephrine, 5 x 10(- 4) M) decreased the contraction in a concentration-dependent manner. However, preincubation of mesenteric bed with atropine (0.1 mu M), L-NAME (10 (-5) M) or indomethacin (10(-5) M) prevented this effect of the venom. These results may suggest that the inhibitory effect of the venom on nonvascular smooth muscle (such as vas deferens) contractions is a postsynaptic phenomenon. Furthermore, it could be suggested that the cardiovascular effects of Echis carinatus venom are mediated through multiple mechanisms such as activation of muscarinic receptors as well as production of nitric oxide and prostaglandins.


Effects of ethanol on experimental hepatocarcinogenesis.
Although primary hepatoma is not very frequent in alcoholics, the incidence of hepatoma in cases of hepatitis B infection combined with heavy alcohol drinking is high. In the present study, the effects of chronic alcohol administration on the development of chemical-induced hepatic cancer in rats were analyzed. In 70% hepatectomized Wistar strain male rats, a single dose (1 mg per 100 gm body weight) of diethylnitrosamine was injected intraperitoneally. Eight weeks after the injection, 20% alcohol-10% sucrose solution (diethylnitrosamine-alcohol group), 0.1% sodium phenobarbital solution (diethylnitrosamine-phenobarbital group), 10% sucrose solution (diethylnitrosamine-sucrose group) or tap water (diethylnitrosamine-alone group) was given as drinking water for 32 weeks. The numbers of visible nodules per liver were significantly greater in the diethylnitrosamine-alcohol and diethylnitrosamine-phenobarbital groups compared to the diethylnitrosamine-alone and diethylnitrosamine-sucrose groups. The numbers of enzyme-altered foci which were positive to gamma-glutamyl transpeptidase staining per square centimeter of liver section were also greater in the diethylnitrosamine-alcohol and diethylnitrosamine-phenobarbital groups than in the diethylnitrosamine-alone and diethylnitrosamine-sucrose groups, although the numbers of nodules and enzyme-altered foci were significantly larger in the diethylnitrosamine-phenobarbital group than in the diethylnitrosamine-alcohol group. The enzyme-altered foci areas calculated by gamma-glutamyl transpeptidase staining were significantly larger in the diethylnitrosamine-alcohol and diethylnitrosamine-phenobarbital groups than in the diethylnitrosamine-alone and diethylnitrosamine-sucrose groups. Histologically, visible nodules observed in diethylnitrosamine-phenobarbital and diethylnitrosamine-alcohol groups showed characteristic features of neoplastic nodules. These results indicate that alcohol has a promoter action on the development of chemically induced hepatic cancer like phenobarbital.


[THE PROBLEM OF CHOOSING A METHOD FOR RECURRENT INGUINAL HERNIA REPAIR].
Inguinal hernia repair is the most popular surgery performed by general surgeons around the world. The recurrence rate with various inguinal hernia repair techniques is 15%. The use of laparoscopic techniques in the treatment of inguinal hernias has significant advantages over open surgery, since it can significantly reduce pain, achieve excellent cosmetic results and shorten the duration of hospitalizations. At the same time, the recurrence rate after using laparoscopic techniques reaches 8.9%. The aim of this work is to determine the optimal method of surgical intervention for recurrent inguinal hernias. In the period from 2007 to 2011, a comparative randomized study was conducted, included 82 patients with recurrent inguinal hernias. Initially, all 82 patients were operated using Liechtenstein method with polypropylene mesh. All 82 patients with recurrent inguinal hernias were divided into two groups, patients in group I were operated on using laparoscopic methods (TAPP), in group II, repeated hernioplasty was performed using a modified Lichtenstein technique. In group I, the duration of the operation was 87±12 minutes. There were no serious intraoperative complications in group I. In group II, the average duration of the operation was 112±15 minutes. Complications in group II: severe pain syndrome was observed in 29 patients (69%), seroma developed in 15 patients (35.7%), in 4 patients (9.5%) hernia recurrence was revealed. Thus, patients who have been operated on using laparoscopic methods have certain advantages in terms of the duration of the operation, the number of postoperative complications, the presence of pain syndrome, and most importantly, these patients do not have a recurrent hernia. The results of repeated interventions in patients with recurrent inguinal hernias who did not use mesh implants were analyzed. The results obtained show the advantage of laparoscopic methods in reoperations, which was accompanied by fewer complications and reccurences. A rather difficult problem of choosing the optimal method of re-interventions in patients with relapses after laparoscopic hernioplasty. In 16.7% of patients, repeated laparoscopic hernioplasty turned out to be impossible due to technical difficulties and they had to switch to open Lichtenstein plasty. At the same time, in almost half of patients with recurrent inguinal hernias, it was possible to successfully perform repeated laparoscopic hernioplasty with good immediate and long-term results.


Long-term clinical outcome of patients treated with beta-brachytherapy in routine clinical practice.
Only limited data exist regarding the long-term efficacy of beta-brachytherapy (beta-VBT) in routine clinical practice and the impact of the prolonged (>6 months) combined antiplatelet therapy after beta-VBT. Our aim is to examine the long-term clinical efficacy of routine beta brachytherapy (beta-VBT) followed by indefinite administration of combined antiplatelet therapy in patients at high restenotic risk. Sixty-one patients with 65 lesions [de novo: 41, in-stent restenotic (ISR): 24] underwent intracoronary beta-VBT and were followed prospectively. All patients received indefinite administration of aspirin and clopidogrel, underwent routine angiography 6 months later and were followed-up clinically for 43.7 months (range: 32 to 52 months). Acute success was achieved in 60/61 (98.4%) patients. Lesion length was 36.1 (+/-17.6) mm for the de novo and 22.0 (+/-9.8) mm for the ISR (p=0.001). Stents were implanted in 35/41 de novo and 7/24 ISR lesions (p<0.01). Six-month binary restenosis after successful beta-VBT was 35.9% (23/64). During follow-up patients with de-novo lesions who received a new stent during index procedure had a higher incidence of major cardiac events than patients with ISR lesions without a new stent (log rank test, p=0.02). Acute and late thrombotic events were reported at 6 patients, all with de novo lesions and stent implantation. Beta-VBT plus stenting in de novo lesions is related to an unacceptable high rate of thrombotic complications and clinical restenosis despite prolonged administration of combined antiplatelet therapy. Brachytherapy remains a reasonable option for patients with ISR lesions until full data from large randomized trials comparing drug eluting stents with brachytherapy are available.


Squamous cell carcinoma of the oral tongue in patients over 75 years old.
Squamous cell carcinoma (SCC) of the oral tongue is one of the most frequent head and neck cancers. The over-70-year age group is the fastest growing segment of the population. Age, however, is not considered a prognostic factor in oral tongue SCC. This study investigated the clinical and histopathological characteristics, disease course, and outcome of SCC of the oral tongue in patients over 75 years old compared with younger patients. We reviewed the files of 85 patients with histologically proven SCC of the oral tongue who were treated in our department in 1992-2007 and followed for a minimum of 2 years. Findings were compared between those aged 75 years or more and younger patients. Twenty-eight patients (33%) were aged 75 to 94 years (average 80.5±4.5 yrs), including 14 who were over 80 years old, and 57 patients were aged 15-74 years (average 51.1±18.2 yrs). No statistically significant differences were found between the groups in clinical or histopathological characteristics or patient outcome. The 5-year disease-free survival rate was 65% for patients over 75 and 58% for younger patients. Corresponding rates for 5-year disease-specific survival were 69% and 70%. These differences were not statistically significant. Patients over 75 with oral tongue SCC should be managed like younger patients in terms of clinical staging and co-morbidities. They should be given a chance for treatment, as their prognosis is no different from that of younger patients.


Extensive Metastases on 18F-FDG PET/CT in Primary Lymphoepithelioma-Like Carcinoma of the Ovary.
We describe extensive metastatic lesions of very rare lymphoepithelioma-like carcinoma originating from the ovary assessed by F-FDG PET/CT. A 59-year-old woman presented with abdominal distention. Pelvis MRI demonstrated a large right ovarian malignant lesion with massive lymphadenopathy suggesting lymphoma. Patient underwent surgical removal. The lymphoepithelioma-like carcinoma arising from the ovary based on immunohistochemistry was pathologically confirmed. Multiple metastases including peritoneum, omentum, and lymph nodes were confirmed. F-FDG PET/CT for staging and evaluation of metastasis after operation showed multiple lymph node metastases. F-FDG PET/CT revealed hepatic metastasis in the dome region of the right liver besides multiple skeletal metastases.


Brownian dynamics of cylindrical capsule-like particles in a nanopore in an electrically biased solid-state membrane.
We use Brownian dynamics simulations to study the motion of cylindrical capsule-like particles (capsules) as they translocate through nanopores of various radii in an electrically biased silicon membrane. We find that for all pore sizes the electrostatic interaction between the particle and the pore results in the particle localization towards the pore 's center when the membrane and the particle have charges of the same sign (case 1) while in case of the opposite sign charges, the capsule prefers to stay near and along the nanopore wall (case 2). The preferential localization leads to all capsules rotating less while inside the pore compared to the bulk solution, with a larger net charge and/or particle length resulting in a smaller range of rotational movement. It also strongly affects the whole translocation process: in the first case, the translocation is due to the free diffusion along the pore axis and is weakly dependent on the particle charge and the nanopore radius while in the second case, the translocation time dramatically increases with the particle size and charge as the capsule gets "stuck" to the nanopore surface.


Identification of patients with non-metastatic colorectal cancer in primary care: a case-control study.
Colorectal cancer is the third most common cancer worldwide and second most common in Europe. Despite screening, it is often diagnosed at an unfavourable stage. To identify and quantify features of non-metastatic colorectal cancer in primary care to enable earlier diagnosis by GPs. A case-control study was conducted using diagnostic codes from national and regional healthcare databases in Sweden. A total of 542 patients diagnosed with non-metastatic colorectal cancer in 2011 and 2139 matched controls were selected from the Swedish Cancer Register (SCR) and a regional healthcare database respectively. All diagnostic codes (according to ICD-10) from primary care consultations registered the year before the date of cancer diagnosis (according to the SCR) were collected from the regional database. Odds ratios were calculated for variables independently associated with non-metastatic colorectal cancer using multivariable conditional logistic regressions. Positive predictive values (PPVs) of these variables were calculated, both individually and in combination with each other. Five features were associated with colorectal cancer before diagnosis: bleeding, including rectal bleeding, melaena, and gastrointestinal bleeding (PPV 3.9%, 95% confidence interval [CI] = 2.3 to 6.3); anaemia (PPV 1.4%, 95% CI = 1.1 to 1.8); change in bowel habit (PPV 1.1%, 95% CI = 0.9 to 1.5; abdominal pain (PPV 0.9%, 95% CI = 0.7 to 1.1); and weight loss (PPV 1.0%, 95% CI = 0.3 to 3.0); all P-value <0.05. The combination of bleeding and change in bowel habit had a PPV of 13.7% (95% CI = 2.1 to 54.4); for bleeding combined with abdominal pain this was 12.2% (95% CI = 1.8 to 51.2). A risk assessment tool for non-metastatic colorectal cancer was designed. Bleeding combined with either diarrhoea, constipation, change in bowel habit, or abdominal pain are the most powerful predictors of non-metastatic colorectal cancer and should result in prompt referral for colorectal investigation.


Comparative evaluation of shear bond strength of three resin based dual-cure core build-up materials: An In-vitro study.
The in-vitro study compared the shear bond strength (SBS) of three recently introduced dual-cure resin based core build-up materials namely ParaCore, FluoroCore, and MultiCore. One hundred twenty extracted permanent human mandibular molar teeth were taken and sectioned horizontally beneath the dentinoenamel junction to expose the coronal dentin. The specimens obtained were divided into three main groups based on the materials used and then further divided into four sub-groups based on time interval with ten samples each. The dentin surface was treated with the respective adhesives of the groups and then bulk filled with core build-up materials. The attained samples were than subjected to shear loading in Instron Universal Testing Machine. The data were tabulated and statistically analyzed using analysis of variance (ANOVA), Tukey's HSD, and Levene's test. The mean SBS was highest in MultiCore at all time periods as compared to FluoroCore and ParaCore and was also higher at 48 h thermocycling in all three groups studied. MultiCore dual-cure resin based core build-up material showed the highest mean SBS as compared to FluoroCore and ParaCore. SBS was not negatively affected by thermocycling.


Deoxyguanosine forms a bis-adduct with E,E-muconaldehyde, an oxidative metabolite of benzene: implications for the carcinogenicity of benzene.
Benzene is employed in large quantities in the chemical industry and is an ubiquitous contaminant in the environment. There is strong epidemiological evidence that benzene exposure induces hematopoietic malignancies, especially acute myeloid leukemia, in humans, but the chemical mechanisms remain obscure. E,E-Muconaldehyde is one of the products of metabolic oxidation of benzene. This paper explores the proposition that E,E-muconaldehyde is capable of forming Gua-Gua cross-links. If formed in DNA, the replication and repair of such cross-links might introduce structural defects that could be the origin of the carcinogenicity. We have investigated the reaction of E,E-muconaldehyde with dGuo and found that the reaction yields two pairs of interconverting diastereomers of a novel heptacyclic bis-adduct having a spiro ring system linking the two Gua residues. The structures of the four diastereomers have been established by NMR spectroscopy and their absolute configurations by comparison of CD spectra with those of model compounds having known configurations. The final two steps in the formation of the bis-nucleoside (5-ring → 6-ring → 7-ring) have significant reversibility, which is the basis for the observed epimerization. The 6-ring precursor was trapped from the equilibrating mixture by reduction with NaBH(4). The anti relationship of the two Gua residues in the heptacyclic bis-adduct precludes it from being formed in B DNA, but the 6-ring precursor could readily be accommodated as an interchain or intrachain cross-link. It should be possible to form similar cross-links of dCyt, dAdo, the ε-amino group of lysine, the imidazole NH of histidine, and N termini of peptides with the dGuo-muconaldehyde monoadduct.


Evaluation of the RNA-dependence of PRC2 binding to chromatin in human pluripotent stem cells.
Polycomb Repressive Complex 2 (PRC2), an important histone modifier and epigenetic repressor, has been known to interact with RNA for almost two decades. In our previous publication (Long, Hwang et al. 2020), we presented data supporting the functional importance of RNA interaction in maintaining PRC2 occupancy on chromatin, using comprehensive approaches including an RNA-binding mutant of PRC2 and an rChIP-seq assay. Recently, concerns have been expressed regarding whether the RNA-binding mutant has impaired histone methyltransferase activity and whether the rChIP-seq assay can potentially generate artifacts. Here we provide new data that support a number of our original findings. First, we found the RNA-binding mutant to be fully capable of maintaining H3K27me3 levels in human induced pluripotent stem cells. The mutant had reduced methyltransferase activity in vitro, but only on some substrates at early time points. Second, we found that our rChIP-seq method gave consistent data across antibodies and cell lines. Third, we further optimized rChIP-seq by using lower concentrations of RNase A and incorporating a catalytically inactive mutant RNase A as a control, as well as using an alternative RNase (RNase T1). The EZH2 rChIP-seq results using the optimized protocols supported our original finding that RNA interaction contributes to the chromatin occupancy of PRC2.


Probing the Strong Nonadiabatic Interactions in the Triazolyl Radical Using Photodetachment Spectroscopy and Resonant Photoelectron Imaging of Cryogenically Cooled Anions.
Although the adiabatic potential energy surfaces defined by the Born-Oppenheimer approximation are the cornerstones for understanding the electronic structure and spectroscopy of molecular systems, nonadiabatic effects due to the coupling of electronic states by nuclear motions are common in complex molecular systems. The nonadiabatic effects were so strong in the 1,2,3-triazolyl radical (C2H2N3) that the photoelectron spectrum of the triazolide anion was rendered unassignable and could only be understood using nonadiabatic calculations, involving the four low-lying electronic states of triazolyl. Using photodetachment spectroscopy and resonant photoelectron imaging of cryogenically cooled anions, we are able to completely unravel the complex vibronic levels of the triazolyl radical. Photodetachment spectroscopy reveals a dipole-bound state for the triazolide anion at 172 cm-1 below the detachment threshold and 32 vibrational Feshbach resonances. Resonant photoelectron imaging is conducted by tuning the detachment laser to each of the Feshbach resonances. Combining the photodetachment spectrum and the resonant photoelectron spectra, we are able to assign all 28 vibronic peaks resolved for the triazolyl radical. Fundamental frequencies for 12 vibrational modes of the ground state of the triazolyl radical are measured experimentally. The current study provides unprecedented experimental vibronic information, which will be valuable to verify theoretical models to treat nonadiabatic effects involving multiple electronic states.


Separating genuine cases of reading disability from reading deficits caused by predominantly inattentive ADHD behavior.
Conventional methods of differentiating reading disability (RD) caused by deficits in decoding skills or comprehension from poor reading performance caused by inconsistent attention associated with attention-deficit/hyperactivity disorder (ADHD) have produced equivocal results. This study presents a model of differential diagnosis of attentional problems and RD that differs from these conventional approaches. The new diagnostic procedure uses intraindividual differences seen in the performance of at-risk learners on tasks related to reading that vary in their sensitivity to the sustained attention required for successful performance. The hypothesis is that children with inconsistent attention would perform more poorly on tests that require sustained attention, such as listening comprehension, than on tests that are more tolerant of inattention, such as reading comprehension. Such differences would not be seen in the test scores of children who have only RD, because their performance is determined more by the difficulty level of the reading tests than by the degree of sensitivity of the task to attention. The validity of this new model was evaluated by determining the capability of the differences seen in the scores of tests that differ in their sensitivity to sustained attention to predict the degree of inconsistency in sustained attention as measured by a continuous performance test. The data obtained from 39 children who are at risk for RD suggest that this is a viable model.


Repeated glucose spikes and insulin resistance synergistically deteriorate endothelial function and bardoxolone methyl ameliorates endothelial dysfunction.
Both insulin resistance and postprandial glucose spikes are known for their potential to induce vascular endothelial dysfunction in individuals with metabolic syndrome. However, these factors are inextricable, and therefore, their relative contributions to inducing endothelial dysfunction remain elusive. In this study, we aimed to disentangle the effects of these factors and clarify whether bardoxolone methyl (CDDO-Me), a novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator, protects against glucose spike-induced endothelial dysfunction. We induced glucose spikes twice daily for a duration of 1 week to rats fed a standard/control diet (CD) and Western-type diet (WTD). Endothelium-dependent relaxation (EDR) was evaluated using isolated thoracic aortas. Gene expression and dihydroethidium (DHE)-fluorescence studies were carried out; the effect of CDDO-Me on aortic endothelial dysfunction in vivo was also evaluated. Neither WTD-induced insulin resistance nor pure glucose spikes significantly deteriorated EDR. However, under high-glucose (20 mM) conditions, the EDR of thoracic aortas of WTD-fed rats subjected to glucose spikes was significantly impaired. In this group of rats, we observed significantly enhanced DHE fluorescence as a marker of reactive oxygen species, upregulation of an oxidative stress-related gene (NOX2), and downregulation of an antioxidant gene (SOD2) in the thoracic aortas. As expected, treatment of the thoracic aorta of this group of rats with antioxidant agents significantly improved EDR. We also noted that pretreatment of aortas from the same group with CDDO-Me attenuated endothelial dysfunction, accompanied by a correction of the redox imbalance, as observed in gene expression and DHE fluorescence studies. For the first time, we showed that insulin resistance and glucose spikes exert a synergistic effect on aortic endothelial dysfunction. Furthermore, our study reveals that CDDO-Me ameliorates endothelial dysfunction caused by glucose spikes in a rat model of metabolic syndrome.


Alterations in growth-associated protein (GAP-43) expression in lower urinary tract pathways following chronic spinal cord injury.
Alterations in the expression of growth-associated protein 43 (GAP-43) were examined in lower urinary tract micturition reflex pathways 6 or 8 weeks following complete spinal cord transection (approximately T9). In control animals, expression of GAP-43 was present in specific regions of the gray matter in the rostral lumbar and caudal lumbosacral spinal cord, including: (1) the dorsal commissure; (2) the corticospinal tract; (3) the dorsal horn; and (4) the regions of the intermediolateral cell column (L1-L2) and the sacral parasympathetic nucleus (L6-S1); and (5) in the lateral collateral pathway of Lissauer in L6-S1 spinal segments. Densitometry analysis has demonstrated significant increases (p < or =0.001; 1.3-6.4-fold increase) in GAP-43-immunoreactivity (IR) in these regions of the rostral lumbar (L1-L2) and caudal lumbosacral (L6-S1) spinal cord 6 weeks following spinal cord injury. Changes in GAP-43-IR were restricted to the L1-L2 and L6-S1 segments that are involved in lower urinary tract reflexes. Changes in GAP-43-IR were not observed at the L5 segmental level except for an increase in GAP-43-IR in the superficial, dorsal horn at 6 weeks post-injury. In all segments examined, GAP-43-IR was decreased (2-5-fold) in the corticospinal tract (dorsal division) 6 and 8 weeks following spinal cord injury. Eight weeks following spinal cord injury, changes in GAP-43-IR had returned to control levels except for the persistence of increased GAP-43-IR in the region of the sacral parasympathetic nucleus and the lateral collateral pathway in the S1 spinal segment. Alterations in GAP-43-IR following chronic spinal cord injury may suggest a reorganization of bladder afferent projections and spinal elements involved in urinary bladder reflexes consistent with alterations in urinary bladder function (hyperreflexia) observed in animals following spinal cord injury above the lumbosacral spinal cord.


Emergency oxygen delivery in adults 1: updating nursing practice.
The first in this two-part unit discusses new British Thoracic Society guidance on using emergency oxygen in adults. This is the first national guidance on this area and the implications for possible changes to practice are highlighted here. This part outlines the philosophy behind the guideline, the differences between hypoxaemic and hypercapnic patients and essential assessments for critically ill patients who need emergency oxygen. It also discusses using this therapy for patients with lung cancer in acute situations.


Deterioration of Basic Properties of the Materials in FRP-Strengthening RC Structures under Ultraviolet Exposure.
This paper presents an experimental study of the basic properties of the main materials found in reinforced concrete (RC) structures strengthened by fibre reinforced polymer (FRP) sheets with scope to investigate the effect of ultraviolet (UV) exposure on the degradation of FRP, resin adhesive materials and concrete. The comparison studies focused on the physical change and mechanical properties of FRP sheet, and resin adhesive materials and concrete before and after UV exposure. However, the degradation mechanisms of the materials under UV exposure were not analyzed. The results show that the ultimate tensile strength and modulus of FRP sheets decrease with UV exposure time and the main degradation of FRP-strengthened RC structures is dependent on the degradation of resin adhesive materials. The increase in the number of FRP layers cannot help to reduce the effect of UV exposure on the performance of these materials. However, it was verified that carbon FRP materials have a relatively stable strength and elastic modulus, and the improvement of the compression strength of concrete was also observed after UV exposure.


Alveolar ridge preservation using xenogeneic collagen matrix and bone allograft.
Alveolar ridge preservation (ARP) has been shown to prevent postextraction bone loss. The aim of this report is to highlight the clinical, radiographic, and histological outcomes following use of a bilayer xenogeneic collagen matrix (XCM) in combination with freeze-dried bone allograft (FDBA) for ARP. Nine patients were treated after extraction of 18 teeth. Following minimal flap elevation and atraumatic extraction, sockets were filled with FDBA. The XCM was adapted to cover the defect and 2-3 mm of adjacent bone and flaps were repositioned. Healing was uneventful in all cases, the XCM remained in place, and any matrix exposure was devoid of further complications. Exposed matrix portions were slowly vascularized and replaced by mature keratinized tissue within 2-3 months. Radiographic and clinical assessment indicated adequate volume of bone for implant placement, with all planned implants placed in acceptable positions. When fixed partial dentures were placed, restorations fulfilled aesthetic demands without requiring further augmentation procedures. Histological and immunohistochemical analysis from 9 sites (4 patients) indicated normal mucosa with complete incorporation of the matrix and absence of inflammatory response. The XCM + FDBA combination resulted in minimal complications and desirable soft and hard tissue therapeutic outcomes, suggesting the feasibility of this approach for ARP.


[Documented and suspected risk factors for childhood cancer aetiology].
We present an updated summary on risk factors for childhood malignancies, following to previous reviews published on Epidemiologia&Prevenzione and largely based on the monographs of the International Agency for Research on Cancer (IARC). Ionizing radiations are certain carcinogens, with evidence in humans, from studies both on children and on adults. Evidence specifically regarding childhood cancers is available also for other carcinogens, such as tobacco smoking, some solvents, some occupational activities of parents, and some viruses (HIV and EBV). For most carcinogens, information specifically regarding childhood cancer risks is limited, but it is enough to suggest the reduction of exposure, according to a precautionary approach. Available evidence can be helpful in evaluating reports of possible clusters of disease and the association with putative causes.


The potential of wastewater-source heat pump in decarbonising buildings sector of China.
As China's economy and society continue to advance, there has been a notable enhancement in the quality of life for its people. However, the escalating energy consumption in buildings, particularly for heating and cooling purposes, has emerged as a pressing concern, accounting for nearly 60% of the overall energy consumption. In response to this challenge, heat pumps have emerged as a promising solution by efficiently meeting the demand for heating and cooling. Among these options, wastewater-source heat pumps (WWSHP) have garnered attention as an innovative choice, harnessing the waste heat in available wastewater resources in China to provide efficient heating and cooling services. The objective of this study was to comprehensively investigate the decarbonisation potential associated with sewage source heat pumps in China. By employing both techno-economic analysis and life cycle assessment methods, we conducted a thorough comparison between conventional heating and cooling systems and various heat pump systems. The results of our analysis demonstrate that WWSHPs not only exhibit the lowest greenhouse gas (GHG) emissions but also yield the lowest production costs. Our findings reveal that the potential capacity of WWSHPs amounted to a total of 2.4 EJ in 2020, with the capability to mitigate 99 Mt CO2-eq emissions and achieve cost savings of 24 billion RMB. Importantly, WWSHPs' maximum potential cannot be fully realised by replacing heating alone. However, by replacing both heating and cooling options, WWSHPs unlock substantial decarbonisation potential and cost savings.


Influence of rheological parameters on the velocity of erythrocytes passing nailfold capillaries in humans.
One thousand two hundred and fifty-six subjects (apparently healthy subjects and patients with cardiovascular diseases) were registered in a prospective study including demographical and clinical data, rheological parameters (hematocrit, plasma viscosity, erythrocyte aggregation, erythrocyte deformability) as well as the erythrocyte velocity in human nailfold capillaries under resting and postischemic conditions. A multivariate regression analysis showed that under resting conditions there was no correlation between rheological parameters and erythrocyte velocity in capillaries. The blood flow regulation seemed to be so effective, that pathological changes of the blood fluidity showed no effect on the velocity of an erythrocyte passing the capillaries. During vessel paralysis in the early phase of the postischemic hyperemia following a stasis of three minutes in the vasculature distal to a pressure cuff at the upper arm a very clear correlation between the plasma viscosity and the maximum postischemic erythrocyte velocity in ipsilateral cutaneous capillaries could be observed (p < 0.0001) while none of the other rheological parameters seemed to play a role. In a subgroup of diabetic patients the erythrocyte aggregation (measured during stasis) also correlated with the erythrocyte velocity (p = 0.0175) besides the plasma viscosity. This shows that a correlation of rheological parameters with the capillary perfusion could only be found during vessel paralysis. In of diabetic patients besides the plasma viscosity also the erythrocyte aggregation correlated with the mean capillary erythrocyte velocity. Theses results are in agreement with the hypothesis from Barras that plasma viscosity determines the perfusion of microvessels. Under certain conditions e.g. diabetic disorder, also the erythrocyte aggregation plays a role.


The role of social risk in an early preventative care programme for infants born very preterm: a randomized controlled trial.
To examine the differential effects of an early intervention programme for infants born preterm on neurodevelopment and parental mental health according to family social risk. One hundred and twenty infants born earlier than 30 weeks' gestation were randomized to early intervention (n=61) or control groups (n=59). Cognitive, language, and motor outcomes were assessed by blinded assessors at 2 years, 4 years, and 8 years, and primary caregivers completed questionnaires on their anxiety and depression. Outcomes at each time point were compared between groups using linear regression with an interaction term for social risk (higher/lower). There was evidence of interactions between intervention group and social risk for cognition at 2 years and 4 years, motor function at 4 years, and language at 8 years, with a greater intervention effect in children from higher social risk environments. In contrast, the impact of early intervention on parental depressive symptoms was greater for parents of lower social risk than for those of higher social risk. Effects of early intervention on outcomes for children born preterm and their caregivers varied according to family social risk. Family social risk should be considered when implementing early intervention programmes for children born preterm and their families. Intervention is associated with better early cognitive functioning for children in higher social risk families. Positive effects of intervention for the high risk group were not sustained at school-age. Intervention has a greater effect on primary caregiver mental health in the lower social risk group compared with higher social risk.


Defining normal pouch function in patients with ileal pouch-anal anastomosis: a pilot study.
Most patients experience good functional outcomes following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis. We aimed to determine if asymptomatic patients with an IPAA had findings consistent with normal defecation on standard objective anorectal tests. Patients 18-65 years old with IPAA and self-reported healthy pouch function were recruited. Patients with chronic pouchitis, Crohn's disease, anastomotic stricture, or indication for IPAA other than ulcerative or indeterminate colitis were excluded. Patients underwent an interview with an abbreviated Rome Questionnaire followed by high-resolution ano-pouch manometry, balloon expulsion test, pouch barostat, and magnetic resonance (MR) defecography. Twenty patients completed all testing. Six patients were excluded from the final analysis due to symptoms suggestive of pouch evacuation disorder on the abbreviated Rome Questionnaire (n = 2), structural abnormality on MR imaging (n = 3), or both (n = 1). Of the remaining 14 patients, mean anal resting pressure during high-resolution manometry was 72 ± 16 mmHg, mean anal squeeze pressure was 247 ± 69 mmHg, and mean pouch-anal gradient during the simulated evacuation was -27 ± 37 mmHg. The meantime to balloon expulsion was 54 seconds. During dynamic MR defecography, the mean descent of ano-pouch junction was 2.6 cm, and mean pouch evacuation was 44.5% and 74.2% pre- and posttoilet phase, respectively. A substantial proportion of patients with IPAA and self-reported healthy pouch function have anatomic and/or functional abnormalities of the pouch. In asymptomatic IPAA patients with an anatomically normal pouch, we have proposed normal parameters for high-resolution ano-pouch manometry, time to balloon expulsion, pouch barostat, and MR defecography.


Update on Acrylic Resins Used in Dentistry.
Acrylic resins are the most commonly used materials in prosthetics and orthodontics until now. They have a well-documented history of use as biomaterials in the manufacturing of different types of dental appliances. The objective of this study was to describe the properties of acrylic resins and the processing methods used for these materials in dentistry. The review depicts the most important achievements in this area, indicating that the resin technology evolved in different directions. The mechanical and biological properties of acrylic resins were improved by the addition of mineral or natural fibers, and/or fillers, including nanofillers, as well as by poly(methyl methacrylate) surface modification. The presence of residual monomer was reduced as a result of postpolymerization activity. New types of acrylic resins were developed for processing Computer-Aided Design/Computer- Aided Manufacturing systems and three-dimensional printing.


Co-existence of intramuscular spindle cell lipoma with an intramuscular ordinary lipoma:report of a case.
Spindle cell lipoma is a relatively rare adipocytic neoplasm, which usually occurs in the posterior neck, shoulder or upper back of male patients aged 45-65 years. We report here an unusual coexistence of ordinary and spindle cell lipoma. The patient presented with a painless mass in the area of the right scapula. Imaging was suggestive of a lipomatous mass, possibly liposarcoma. Histological examination revealed the concurrent existence of an intramuscular spindle cell lipoma and an ordinary lipoma. In the literature there are only fourteen cases of intramuscular spindle cell lipoma and only in four cases there was a coexisting mature lipoma. As exclusion of malignancy remains clinicians main concern,diagnosis and treatment of deep seated lipomatous tumors remains challenging.


Prophylactic vaccination targeting ERBB3 decreases polyp burden in a mouse model of human colorectal cancer.
Prophylactic vaccination is typically utilized for the prevention of communicable diseases such as measles and influenza but, with the exception of vaccines to prevent cervical cancer, is not widely used as a means of preventing or reducing the incidence of cancer. Here, we utilize a peptide-based immunotherapeutic approach targeting ERBB3, a pseudo-kinase member of the EGFR/ERBB family of receptor tyrosine kinases, as a means of preventing occurrence of colon polyps. Administration of the peptide resulted in a significant decrease in the development of intestinal polyps in C57BL/6J-ApcMin mice, a model of familial adenomatous polyposis (FAP). In addition, even though they were not vaccinated, ApcMin offspring born to vaccinated females developed significantly fewer polyps than offspring born to control females. Lastly, to validate ERBB as a valid target for vaccination, we found no overt toxicity, increases in apoptosis, or morphological changes in tissues where Erbb3 was ablated in adult mice. These results indicate that prophylactic vaccination targeting ERBB3 could prevent the development of colon polyps in an at-risk patient population.


The bees (Hymenoptera: Apoidea) of the Maltese Islands.
This study presents the first checklist of the bees of the Maltese Islands and includes notes on the distribution of each species. A total of 95 species belonging to five bee families are recorded: Andrenidae (17 species), Apidae (34 species), Colletidae (6 species), Halictidae (15 species) and Megachilidae (23 species). Lasioglossum callizonium (Pérez, 1896) is recorded for the first time from the Maltese Islands. Records of three previously reported species are listed as dubious. The bee fauna of the Maltese Archipelago is dominated by widespread West-Palaearctic species, and most of the species recorded are also found in the Western Mediterranean Basin. Bees that have been recorded from Malta are also known from Southern Europe. The study provides a biogeographical analysis of the Maltese bee fauna, and discusses the conservation of this group and their important role in the delivery of ecosystem services in the Maltese Islands.


Fatal toxic effect of bleomycin on brain tissue after intracystic chemotherapy for a craniopharyngioma: case report.
Craniopharyngiomas are benign neoplasms of epithelial origin that arise from the remnants of Rathke's pouch and are located in the sellar, parasellar, and third ventricular regions. Despite major advances in microsurgical techniques, total removal of these tumors is associated with a high risk of death, long-term endocrinological dependence, cognitive dysfunction, and behavioral disorders. For patients with monocystic craniopharyngiomas, encouraging postoperative survival rates and high rates of cyst regression after intracavitary administration of bleomycin have been reported. Moreover, only a few side effects have been reported for this treatment method. We report a patient with a cystic craniopharyngioma who was treated using intracavitary bleomycin administration and died as a result of the direct toxic effects of bleomycin on deep brain structures and the brainstem. A 47-year-old woman with a cystic craniopharyngioma underwent stereotactic insertion of a catheter attached to a subcutaneous reservoir. Five months after the procedure, positive-contrast computed tomographic cystography was performed to confirm the absence of fluid leakage. Daily intracavitary injections of bleomycin were administered through the reservoir into the cyst, until a total dose of 56 mg had been administered in 8 days. After the treatment, the cystic cavity regressed but the patient exhibited neurological deterioration; magnetic resonance imaging scans revealed diffuse edema in the diencephalon and brainstem. The patient died 45 days after completion of the treatment. Intracavitary administration of bleomycin is not a treatment protocol without risks or side effects, even if there is no fluid leakage into the cerebrospinal fluid. Although this is known to be an effective treatment for cystic craniopharyngiomas, previous reports cannot be used to establish a standard treatment method, and more research is needed to yield a safer effective protocol.


Highly Specific and Wide Range NO2 Sensor with Color Readout.
We present a simple and inexpensive method to implement a Griess-Saltzman-type reaction that combines the advantages of the liquid phase method (high specificity and fast response time) with the benefits of a solid implementation (easy to handle). We demonstrate that the measurements can be carried out using conventional RGB sensors; circumventing all the limitations around the measurement of the samples with spectrometers. We also present a method to optimize the measurement protocol and target a specific range of NO2 concentrations. We demonstrate that it is possible to measure the concentration of NO2 from 50 ppb to 300 ppm with high specificity and without modifying the Griess-Saltzman reagent.


The significance of CUX1 and chromosome 7 in myeloid malignancies.
Loss of chromosome 7 has long been associated with adverse-risk myeloid malignancy. In the last decade, CUX1 has been identified as a critical tumor suppressor gene (TSG) located within a commonly deleted segment of chromosome arm 7q. Additional genes encoded on 7q have also been identified as bona fide myeloid tumor suppressors, further implicating chromosome 7 deletions in disease pathogenesis. This review will discuss the clinical implications of del(7q) and CUX1 mutations, both in disease and clonal hematopoiesis, and synthesize recent literature on CUX1 and other chromosome 7 TSGs. Two major studies, including a new mouse model, have been published that support a role for CUX1 inactivation in the development of myeloid neoplasms. Additional recent studies describe the cellular and hematopoietic effects from loss of the 7q genes LUC7L2 and KMT2C/MLL3, and the implications of chromosome 7 deletions in clonal hematopoiesis. Mounting evidence supports CUX1 as being a key chromosome 7 TSG. As 7q encodes additional myeloid regulators and tumor suppressors, improved models of chromosome loss are needed to interrogate combinatorial loss of these critical 7q genes.


Not just a spring fever... Information and advice to help families with hay fever sufferers.
Hay fever is an allergy to pollen or spores presenting as an allergic inflammatory response in all mucous membranes of the upper airway. The UK has one of the highest rates (it's estimated one in four of us have hay fever) and symptoms are often trivialised, even though the socio-economic and health costs are huge. If left treated, for example, a hay fever sufferer risks developing asthma. Also paediatric allergists now consider the combination of eczema and hay fever to be a significant marker, indicating an atopic child's propensity to develop more serious allergic disease. Unfortunately childhood hay fever is often poorly treated, but a combination of sensible allergen avoidance measures and appropriate medication or treatments is usually sufficient to control symptoms.


Mathematical models of proprioceptors. II. Structure and function of the Golgi tendon organ.
We developed a physiologically realistic mathematical model of the Golgi tendon organ (GTO) whose elements correspond to anatomical features of the biological receptor. The mechanical interactions of these elements enable it to capture all salient aspects of GTO afferent behavior reported in the literature. The model accurately describes the GTO's static and dynamic responses to activation of single motor units whose muscle fibers insert into the GTO, including the different static and dynamic sensitivities that exist for different types of muscle fibers (S, FR, and FF). Furthermore, it captures the phenomena of self- and cross-adaptation wherein the GTO dynamic response during motor unit activation is reduced by prior activation of the same or a different motor unit, respectively. The model demonstrates various degrees of nonlinear summation of GTO responses resulting from simultaneous activation of multiple motor units. Similarly to the biological GTO, the model suggests that the activation of every additional motor unit to already active motor units that influence the receptor will have a progressively weaker incremental effect on the GTO afferent activity. Finally, the proportional relationship between the cross-adaptation and summation recorded for various pairs of motor units was captured by the model, but only by incorporating a particular type of occlusion between multiple transduction regions that were previously suggested. This occlusion mechanism is consistent with the anatomy of the afferent innervation and its arrangement with respect to the collagen strands inserting into the GTO.


Uncemented total hip arthroplasty in patients with rheumatoid arthritis.
Total hip arthroplasty has become a successful way of treating the painful and destroyed hip joint in the patient with rheumatoid arthritis. Because of the underlying disease, it still is controversial whether the implants selected should be used with bone cement, or whether uncemented devices will give equally good results in this population. Fifteen patients suffering from rheumatoid arthritis underwent 21 hip arthroplasties. The followup period averaged 3.3 years (range, 2.5-6.8 years). All but one patient were taking medication at the time of surgery for their underlying disease. Clinical evaluation was based on a modified Harris hip score that showed significant improvement in pain and function preoperatively compared with pain and function at the most recent followup. Radiographic analysis revealed five cases of minor migration of the acetabular components, and three cases of distal migration of 2 mm or less in the femoral components. Complications consisted of heterotopic ossifications in one patient, and an intraoperative femoral fracture in one patient. There were no infections, and there were no deep vein thromboses. The results in these patients suggest that cementless total hip arthroplasty might become a successful way of treating the destroyed hip joint in the patient with rheumatoid arthritis.


Improving clinical outcomes using adoptively transferred immune cells from umbilical cord blood.
Because of the necessary immunodepletion prior to cord blood transplantation as well as the immaturity of cord blood immune cells, recipients experience a high incidence of viral infection in addition to complications observed after hematopoietic stem cell transplantation, such as relapse and graft-versus-host disease. We describe current immunotherapeutic approaches to treating these complications, including the generation of antigen-specific T cells from cord blood, redirecting cord blood T cells using chimeric antigen receptors, and generating cord blood-derived natural killer cells and regulatory T cells.


Preterm birth, neonatal therapies and the risk of childhood cancer.
Our aim was to study the impact of preterm birth and neonatal therapies on the risk of childhood cancer using a nationwide, registry-based, case-control design. Combining population-based data from Finnish Medical Birth Registry (MBR) and Finnish Cancer Registry, we identified a total of 2029 patients diagnosed with cancer under the age of 20 years and 10 103 age- and sex-matched controls over the years 1996 to 2014. Information on the prenatal and perinatal conditions was obtained from the MBR. Gestational age was categorized into early (<32) and late preterm (32-36) and term (≥37 weeks). Cancer risk among the preterm compared to term neonates was evaluated using conditional logistic regression. We identified 141 cancers among the preterm (20.8% of 678) vs 1888 cancers in the term children (16.5% of 11 454). The risk of any cancer was increased for the preterm (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.06-1.57), especially for the early preterm (OR 1.84, 95% CI 1.16-2.92). The risk of acute myeloid leukemia (AML; OR 2.33, 95% CI 1.25-4.37), retinoblastoma (OR 3.21, 95% CI 1.22-8.41) and germ cell tumors (OR 5.89, 95% CI 2.29-15.18) was increased among the preterm compared to term. Germ cell tumors were diagnosed at a significantly younger age among the preterm. Neonatal therapies, for example, mechanical ventilation, were associated with an increased risk of childhood cancer independent of gestational age. Preterm, especially early preterm birth, is associated with an increased risk of childhood cancer, especially germ cell tumors and AML. Respiratory distress requiring neonatal intervention also appears to be associated with an increased risk.


Interaction of Sedlin with PAM14.
Sedlin is an evolutionarily conserved and ubiquitously expressed protein that is encoded by the gene SEDL. Mutations in the latter are known to be causative for spondyloepiphyseal dysplasia tarda. However, the mechanism underlying this remains unclear. We have previously shown that Sedlin interacts with the intracellular chloride channel proteins CLIC1 and CLIC2 in the cytoplasm. In this report we show that Sedlin is also physically associated with protein associated with MRG 14 kDa (PAM14), a nuclear protein that interacts with the transcription factor MORF4-related gene on chromosome 15 (MRG15). This was suggested by yeast two-hybrid screening and was confirmed with GST pull-down and immunoprecipitation assays. Moreover, we demonstrate that the C-terminus of Sedlin and the N-terminus of PAM14 are critical for their interaction. Together, these results suggest that nucleus-localized Sedlin may play a role in regulation of transcriptional activities of the MRG family of transcription factors via binding to PAM14.


[[Effects of fertility and mortality change on aspects of aging in Japan]].
"The purpose of the present paper is to review the recent trends in population age structure in Japan and to assess the demographic determinants of those trends relating to the impacts of fertility and mortality change on aging." A decline in cohort mortality and a significant decrease in the birth rate since 1973 have increased the proportion of the aged population. (SUMMARY IN ENG)


Endogenous levels of auxin and tumorigenesis in a Nicotiana amphiploid.
Young seedlings of the tumor-prone amphiploid Nicotiana suaveolens X N. langsdorffii were grown aseptically on nutrient medium in a controlled environment chamber. At regular intervals after the seeds had been sown, the incidence of tumor formation was scored and plants were harvested. Indole-3-acetic acid was extracted, purified, and assayed spectrofluorometrically. A close correlation in time between onset of tumor formation and decline in endogenous level of indole-3-acetic acid was demonstrated.


The Phenion full-thickness skin model for percutaneous absorption testing.
In recent years many efforts have been made to replace dermal toxicity testing of chemicals in the animal by in vitro assays. As a member of a German research consortium, we have previously contributed to the validation of an in vitro test protocol for percutaneous absorption studies on the basis of reconstructed human epidermis and both human and pig skin ex vivo. Aiming to assess the barrier properties of a newly developed reconstructed skin model, this protocol has now been transferred to the Phenion Full-Thickness Skin Model (FT model). The permeation of testosterone and caffeine was quantified in parallel to that of pig skin using Franz-type diffusion cells. In addition, the permeation of benzoic acid and nicotine was studied. As expected, the FT model is more permeable than pig skin, yet its barrier properties are well in accordance with those of reconstructed human epidermis when compared to previous data. In fact, the FT model most efficiently retards testosterone as the compound of highest lipophilicity, which can be explained by an additional uptake by a reservoir formed by the dermis equivalent. Thus, the structure closely parallels human skin. In consequence, the Phenion FT model appears to be suitable for percutaneous absorption studies in hazard analysis and should be subjected to a catch-up validation study.


Long-term stability of periodontal conditions achieved following guided tissue regeneration with bioresorbable membranes: case series results after 6-7 years.
To evaluate the results of guided tissue regeneration (GTR) treatment of intrabony defects with bioresorbable membranes after 6-7 years, and to disclose factors that may influence the long-term outcome of the treatment. Twenty-five defects in 19 patients were treated by means of polylactic acid/citric acid ester copolymer bioresorbable membranes. At baseline and after 1 and 6-7 years, the following parameters were recorded: (1) probing pocket depth (PPD), (2) gingival recession (REC), (3) probing attachment level (PAL)=PPD+REC, (4) presence/absence of plaque (PI), (5) presence/absence of bleeding on probing (BOP). Smoking habits and frequency of dental-control visits were also recorded. Significance of differences between categorical variables was evaluated with McNemar's test, and between numerical variables with the t-test for paired observations. Generalized linear models were constructed to evaluate the influence of various factors on PAL gain and PPD changes from 1 to 6-7 years. Association of smoking, frequency of dental controls, oral hygiene, and BOP with sites losing > or =2 mm in PAL was evaluated with Fisher's exact test. At baseline, a mean PPD of 8.7+/-1.1 mm and a mean PAL of 9.8+/-1.5 mm was recorded. Statistically significant clinical improvements were observed at 1 and 6-7 years after GTR treatment. An average residual PPD of 3.8+/-1.1 mm and a mean PAL gain of 3.8+/-1.4 mm were observed after 1 year. After 6-7 years the corresponding values were 4.7+/-1.3 and 3.6+/-1.4 mm, respectively. There were no statistically significant differences between the 1- and the 6-7-year values. At the 6-7-year control, only 16% of the sites had lost > or =2 mm (maximum 3 mm), of the PAL gain obtained 1 year after GTR treatment. None of the sites had lost all of the attachment gained 1 year after treatment. Smoking, frequency of dental controls, oral hygiene, and BOP did not seem to influence the change of PPD and PAL gain, or the stability of PAL gain (i.e. losing PAL or not) from 1 to 6-7 years from treatment. Clinical improvements achieved by GTR treatment of intrabony defects by means of bioresorbable membranes can be maintained on a long-term basis.


Employment and Occupational Productivity Among Women Living With HIV: A Conceptual Framework.
Women living with HIV (WLWH) have lower employment rates and more difficulty finding and keeping employment compared with their counterparts without HIV. These disparities affect physical, psychological, and socioeconomic outcomes, and they may compound the disadvantages associated with living with HIV. Although historical literature has emphasized the impact of clinical factors on employment, current evidence suggests that socioeconomic and psychosocial factors associated with HIV should be included for a more comprehensive view. Based on this broader inclusion, a conceptual framework is presented describing how socioeconomic and psychosocial characteristics influence employment acquisition and maintenance among WLWH. The framework posits that there is a reciprocal relationship between employment acquisition and occupational productivity, and psychological health, physical health, social support, and empowerment. Implications for future research and interventions include (a) an extended conceptualization of vocational rehabilitation and (b) the use of peer support groups to increase social capital, empowerment, knowledge, and resources among WLWH.


Infection Prevention and Control Challenges With First Pregnant Woman Diagnosed With COVID-19: A Case Report in Al Ahssa, Saudi Arabia.
This study report focuses on facts on a pregnant woman of COVID-19 who admitted to Al Ahsa Maternity and Children Hospital on March 2020, with suspicion of COVID-19 infection. The patient was complaining of labor pain prior to presentation. The objective of this study is to report the case and to describe the challenges that are faced while dealing with a case of COVID-19 pregnant patient, during labor, delivery, and surgical intervention. This case reports a patient in labor pain with suspicion of COVID-19 infection due to contact with a positive COVID-19 family member. With no clinical signs or symptoms consistent with the disease, and positive polymerase chain reaction (PCR) outcome for COVID-19 later on, the hospital main departments conducted an active contact tracing and reviewed the preparation and infection prevention control precautions. The most common problem with COVID-19 is the low level of awareness between healthcare workers related to infection prevention and transmission of the COVID-19 virus. The illness can be better handled and the medical team can be more secure by enhancing the education, case triage, proper guideline and protocols to be implemented appropriately.


[Molecular biology aspects of neuroblastoma].
Neuroblastoma is one of the most frequent malignant tumors in childhood. Molecular and cytogenetic methods have led to important advances in our understanding of the biology of this tumor. Amplification and increased expression of the gene N-myc is correlated with the clinical stage. This may be a useful marker for monitoring tumor activity during therapy. In addition, karyotyping and flow cytometric DNA analysis may be useful diagnostic tools for staging and predicting the clinical outcome.


Violence and threats of violence within psychiatric care--a comparison of staff and patient experience of the same incident.
This study compared staff members' and psychotic patients' experiences of one and the same violent incident. The staff exposed to the violence completed the Staff Observation Aggression Scale (SOAS). The patients who had exhibited the violent behaviour were interviewed prior to discharge from the ward. When comparing the SOAS data with the patient interviews, it was found that the staff members were able to identify less than 50% of the provocations that the patient experienced. According to the patient interviews, giving the patient medication was far more often experienced as a provocation, resulting in violence, than the staff perceived. Knowledge about how to interpret the patients' body language and other signals, and how patients perceive the staff's behaviour, must be understood for an efficient prevention of violence in psychiatric care.


Impact of pulmonary vein isolation on fractionated atrial potentials and ganglionated plexi in patients with persistent atrial fibrillation.
Some patients with persistent atrial fibrillation (AF) acquire long-term freedom from AF by pulmonary vein (PV) isolation alone. The aim of the present study was to evaluate the characteristics of their atrial substrate.We studied 20 patients with persistent AF to examine the distribution of fractionated atrial potentials (FAP) and that of the anatomic sites of ganglionated plexi (GPs) with vagal reflexes elicited by high frequency stimulation (HFS) with the use of the CARTO system before and after the PV isolation.Both the %FAP area defined as a proportion of the FAP area to the total left atrial area (34.3 ± 10.3 to 21.5 ± 10.2%; P < 0.0001) and number of GP sites with vagal reflexes (4.0 [3.0, 5.0] to 2.0 [1.0, 2.8]; P < 0.0001) were markedly decreased after the PV isolation. Seven (35%) patients had AF recurrences, and they had a greater %FAP area after the PV isolation than those without (32.8 [22.1, 37.3] versus 13.8 [10.9, 19.9]%; P = 0.0049). A %FAP area after the PV isolation of > 20% was significantly associated with an AF recurrence (odds ratio 20.0, 95% confidence interval 2.26470.34; P = 0.018). No significant difference was found between the patients with and without AF recurrence in the reduction rate of anatomic sites of GPs with a vagal reflex induced by the HFS.A more marked reduction in the FAP area by the PV isolation was significantly associated with a better outcome in patients with persistent AF.


Cell detachment triggers p38 mitogen-activated protein kinase-dependent overexpression of Fas ligand. A novel mechanism of Anoikis of intestinal epithelial cells.
Many cell types undergo apoptosis when they are detached from the extracellular matrix (ECM). This phenomenon has been termed anoikis. Most epithelial cells, which are normally attached to a type of ECM called basement membrane, are particularly sensitive to anoikis. Conversely, carcinoma cells tend to be resistant to anoikis, and this resistance plays a critical role in tumor invasion and metastasis. We reported previously that detachment-induced down-regulation of the anti-apoptotic molecule Bcl-X(L) makes a significant contribution to anoikis of intestinal epithelial cells. Here we demonstrate that exogenous Bcl-X(L), no matter how highly expressed in these cells, can significantly attenuate anoikis but cannot completely prevent it, suggesting that at least another pro-apoptotic event is activated by the loss of cell-ECM contacts. Indeed, in this study we identified a novel mechanism of anoikis in intestinal epithelial cells that involves detachment-induced overexpression of Fas ligand. We also demonstrated that this elevation in Fas ligand expression requires a detachment-induced increase of p38 mitogen-activated protein kinase activity. We conclude that the activation of at least two different pro-apoptotic events is required for anoikis of intestinal epithelial cells.


Systematic review with meta-analysis: rifaximin for the prophylaxis of spontaneous bacterial peritonitis.
The primary and secondary prevention of spontaneous bacterial peritonitis (SBP) is recommended in high-risk patients with cirrhosis. Several studies evaluating the efficacy of rifaximin for SBP prophylaxis have yielded conflicting results. Rifaximin has the potential advantage of preventing bacterial overgrowth and translocation without the systemic side effects of broad-spectrum antibiotics. To evaluate the efficacy of rifaximin in the primary and secondary prevention of SBP. A literature search using five databases was performed to identify studies on the association between rifaximin and SBP. We performed two meta-analyses: (1) rifaximin compared to systemic antibiotics and (2) rifaximin compared to no antibiotics. Random-effect modelling was conducted to determine overall pooled estimates and 95% confidence intervals (CIs). Five studies with 555 patients (295 rifaximin, 260 systemic antibiotics) compared rifaximin with systemic antibiotics. The pooled odds ratio (OR) for SBP was 0.45 (95% CI 0.16-1.27; P = .13) in patients receiving rifaximin and strengthened on sensitivity analysis (OR 0.38, 95% CI 0.19-0.76, P = .01). In the analysis comparing rifaximin with no antibiotics, there were five studies with 784 patients (186 rifaximin, 598 no antibiotics). The OR for SBP was 0.34 (95% CI 0.11-0.99; P < .05) in patients receiving rifaximin. In subgroup analysis, rifaximin reduced the risk of SBP by 47% compared to no antibiotics for primary prophylaxis and by 74% compared to systemic antibiotics for secondary prophylaxis. Rifaximin may be effective in preventing SBP in patients with cirrhosis and ascites compared to systemically absorbed antibiotics and compared to placebo.


ZnO/CuO nanocomposites from recycled printed circuit board: preparation and photocatalytic properties.
Cost-effective recycling of e-waste (from computer printed circuit boards, PCB's) for the synthesis of metal oxide nanocomposites is demonstrated. Metals in electronic components of waste memory slots were leached out using nitric acid (HNO3). Compositional analyses of the filtrate obtained after leaching were 66 wt.% Cu, 27.7 wt.% Zn, and 6.2 wt.% Ni. The leached out metal salt solutions were subjected to alkaline hydrothermal treatment to synthesize nanocomposites. Two nanoparticle samples were prepared, one without any stabilizing agent and another sample with PVP as a stabilizing agent. XRD, HR-XRD, HR-TEM, UV-DRS, UV-visible spectroscopy was used to characterize the as-prepared metal oxide nanoparticles. The analysis showed the formation of ZnO/CuO nanocomposites only. No nickel oxide component was precipitated under the studied hydrothermal experimental conditions. Most of the ZnO/CuO nanocomposite particles obtained by this route consisted of fine ZnO nanostructures precipitated on CuO cores. The ZnO and CuO components exhibit both direct and indirect band gaps in the visible range. The nanocomposites demonstrate good visible light photo-Fenton methyl orange (MO) degradation by pseudo-zero order kinetics.


Direction observation of the grain boundary segregation in molybdenum substituted lanthanum tungstate membranes.
Molybdenum substituted lanthanum tungstate membranes (LWO-Mo) offer a good alternative for the separation of hydrogen from gas mixtures. During several essential steps of the membrane processing, an intensive employment of ZrO2 milling balls is usually inevitable. However, how these milling balls affect the final LWO-Mo membranes, is still largely unknown. Employing comprehensive transmission electron microscopy (TEM) techniques, the residual Zr was found to segregate to the grain boundaries (GBs) of the LWO-Mo, either as thin layers or as individual nanograins. At atomic scale, structural and chemical analyses on these GB features were carried out quantitatively. The segregated Zr took more than half of the W sites of the LWO-Mo, resulting in a strained LWO structure and locally concentrated oxygen vacancies. To minimize any Zr contamination, either a competent alternative for ZrO2 or a careful introduction of certain secondary phases (SPs) was proposed. Our results unravel the processing-induced GB behaviors in LWO-Mo, which pave the way towards further optimized processing for various types of functional membranes.


iNKT Cells Induce FGF21 for Thermogenesis and Are Required for Maximal Weight Loss in GLP1 Therapy.
Adipose-resident invariant natural killer T (iNKT) cells are key players in metabolic regulation. iNKT cells are innate lipid sensors, and their activation, using their prototypic ligand α-galactosylceramide (αGalCer), induces weight loss and restores glycemic control in obesity. Here, iNKT activation induced fibroblast growth factor 21 (FGF21) production and thermogenic browning of white fat. Complete metabolic analysis revealed that iNKT cell activation induced increased body temperature, V02, VC02, and fatty acid oxidation, without affecting food intake or activity. FGF21 induction played a major role in iNKT cell-induced weight loss, as FGF21 null mice lost significantly less weight after αGalCer treatment. The glucagon-like peptide 1 (GLP-1) receptor agonist, liraglutide, also activated iNKT cells in humans and mice. In iNKT-deficient mice, liraglutide promoted satiety but failed to induce FGF21, resulting in less weight loss. These findings reveal an iNKT cell-FGF21 axis that defines a new immune-mediated pathway that could be targeted for glycemic control and weight regulation.


Race performance following epiglottic entrapment surgery in Thoroughbred yearlings.
Epiglottic entrapment can occur in yearling Thoroughbreds (TB); however, race performance following surgical correction is unknown. To determine the race performance of horses treated surgically for epiglottic entrapment as yearlings as compared to an untreated cohort. A second objective was to identify risk factors for treated horses not racing post-operatively. Retrospective cohort and case-control studies. Medical (1989-2014) and race records of 66 treated TB racehorses were reviewed. Observed abnormalities on pre- and post-operative endoscopic images and surgical method were recorded. Race records (EquineLine) were recorded. Racing performance of treated yearling TBs and two of their maternal half-siblings, which were used as the untreated cohort, was evaluated in a cohort study. A case-control study was used to investigate risk factors for not racing post-operatively among treated horses. Quarterly starts and earnings were compared to an untreated cohort. Survival analysis was used to assess career longevity. Rates of racing and earnings were compared between groups using Poisson and negative binomial regression respectively. Associations between clinical variables and not racing post-surgery were evaluated using logistic regression. Sixty-six treated horses were identified, 65 of which had at least one half-sibling. Proportions of horses that raced were similar for treated and maternal cohorts (70.0 vs. 70.8%, P = 0.9). Treated horses performed similarly to untreated horses. In treated horses, epiglottic entrapment with abnormal right arytenoid movement was associated with never racing (OR 15.40, 95% CI 1.64-144.23, P = 0.02). More females were affected by epiglottic entrapment than males (47/66 vs. 19/66 respectively, P<0.001). The retrospective design over a prolonged period of time with cases obtained from a single hospital population. Low case numbers likely influenced the outcome of the multivariable analysis. Thoroughbred racehorses treated in their yearling year for epiglottic entrapment had no differences in performance variables compared to their untreated cohort. Epiglottic entrapment with abnormal right arytenoid movement might decrease odds of racing post-operatively.


[Distribution of immunocompetent cells small intestine transplantation in rats].
Heterotopic small bowel transplantation was performed in allogeneic rats with and without cyclosporine. Syngeneic animals served as controls. Small bowel allografts, lymphoid tissues and small bowel of the host were investigated by immunohistochemistry using antibodies against T-cells and macrophages. During rejection, increasing numbers of macrophages infiltrated preferentially the deep layers of the small bowel wall, whereas only a slight T-cell infiltration was observed. No histological changes were noted in the organs of the host. Cyclosporine prevented lymphoid as well as macrophage infiltration of the transplant. Rejection monitoring of small bowel transplants is possible by investigation of macrophage infiltration in deep biopsies including the submucosa.


Do Health Technology Assessment organisations consider manufacturers' costs in relation to drug price? A study of reimbursement reports.
Drug reimbursement decisions are often made based on a price set by the manufacturer. In some cases, this price leads to public and scientific debates about whether its level can be justified in relation to its costs, including those related to research and development (R&D) and manufacturing. Such considerations could enter the decision process in collectively financed health care systems. This paper investigates whether manufacturers' costs in relation to drug prices, or profit margins, are explicitly mentioned and considered by health technology assessment (HTA) organisations. An analysis of reimbursement reports for cancer drugs was performed. All relevant Dutch HTA-reports, published between 2017 and 2019, were selected and matched with HTA-reports from three other jurisdictions (England, Canada, Australia). Information was extracted. Additionally, reimbursement reports for three cases of expensive non-oncolytic orphan drugs prominent in pricing debates in the Netherlands were investigated in depth to examine consideration of profit margins. A total of 66 HTA-reports concerning 15 cancer drugs were included. None of these reports contained information on manufacturer's costs or profit margins. Some reports contained general considerations of the HTA organisation which related prices to manufacturers' costs: six contained a statement on the lack of price setting transparency, one mentioned recouping R&D costs as a potential argument to justify a high price. For the case studies, 21 HTA-reports were selected. One contained a cost-based price justification provided by the manufacturer. None of the other reports contained information on manufacturer's costs or profit margins. Six reports contained a discussion about lack of transparency. Reports from two jurisdictions contained invitations to justify high prices by demonstrating high costs. Despite the attention given to manufacturers' costs in relation to price in public debates and in the literature, this issue does not seem to get explicit systematic consideration in the reimbursement reports of expensive drugs.


Quantitative intradermal terbutaline sweat test in horses.
The aim of the current study was to quantify sweating responses to intradermal terbutaline in normal horses. Seven Thoroughbred horses were used. Terbutaline (10-fold dilutions from 1000-0.001 mg/l) and a saline control were injected intradermally (0.1 ml/site) and sweat collected for 30 min into absorbent pads taped over each injection site. Tests were performed monthly for 11 successive months and temperature, relative humidity and dewpoint were measured at the time of testing. There was no significant effect (P<or=0.05) of environmental variables or time of year on sweat responses at any dose. There was significant effect (P<0.001) of terbutaline concentration on sweat weight, with significant increases at every concentration from 0.1-1000 mg/l. This quantitative intradermal terbutaline sweat test should be a useful aid to the study of equine sweating and anhidrosis.


The clinical application of PET/CT: a contemporary review.
The combination of positron emission tomography (PET) scanners and x-ray computed tomography (CT) scanners into a single PET/CT scanner has resulted in significant improvements in the diagnosis and staging of disease, particularly in the field of oncology. A decade on from the publication of the details of the first PET/CT scanner, we review the technology and applications of the modality. We examine the design aspects of combining two different imaging types into a single scanner, and the artefacts produced such as attenuation correction, motion and CT truncation artefacts. The article also provides a discussion and literature review of the applications of PET/CT to date, covering detection of tumours, radiotherapy treatment planning, patient management, and applications external to the field of oncology.


Third generation P2Y12 antagonists inhibit platelet aggregation more effectively than clopidogrel in a myocardial infarction registry.
The current standard of antiplatelet therapy of patients after myocardial infarction includes the P2Y12 receptor antagonists clopidogrel, prasugrel or ticagrelor. This study aimed to compare the antiplatelet effect of clopidogrel, prasugrel and ticagrelor in patients after myocardial infarction. In a single-centre registry the antiplatelet effect of clopidogrel, prasugrel and ticagrelor was investigated by aggregometry in patients after myocardial infarction. To assess the overall capacity of platelet aggregation whole blood was induced with thrombin receptor activating peptide (TRAP; 32 µM). To specifically quantify the effect of P2Y12 antagonists, whole blood was stimulated with 6.4 µM adenosine diphophosphate (ADP). Relative ADP induced aggregation (r-ADP-agg) was defined as the ADP-TRAP ratio to reflect an individual degree of P2Y12-dependent platelet inhibition.Platelet function of 238 patients was analysed [clopidogrel (n=58), prasugrel (n=65), ticagrelor (n=115)]. The r-ADP-agg was 35 ± 14% for patients receiving clopidogrel, 28 ± 10% for patients receiving prasugrel and 26 ± 11% for patients receiving ticagrelor. The r-ADP-agg was significantly lower in patients treated with prasugrel (p=0.0024) or ticagrelor (p<0.0001) compared to clopidogrel. There was no significant difference between patients receiving prasugrel or ticagrelor (p=0.2559). In conclusion, prasugrel and ticagrelor provide a stronger platelet inhibition compared to clopidogrel in patients after myocardial infarction. No significant difference in platelet inhibition was detected between prasugrel and ticagrelor. (registry for patients after Myocardial Infarction Treated with AntiPlatelet agents; DRKS00003146).


Hollow-fiber dialyzers and their pyrogenicity testing by Limulus amebocyte lysate.
Aqueous extracts of cellulose hollow fibers (CHF) exhibit positive reactions in some Limulus amebocyte lysate (LAL) tests. However, in spite of LAL activity, the extracts produce no fever reaction in rabbits. A comparison of lysates from different suppliers shows pronounced activity differences when extracts of cuprammonium-derived CHF are tested. One of the lysates, which is fully reactive against standard endotoxin, shows no reaction with such extracts, nor do CHF extracts diminish its sensitivity to standard endotoxin. Investigations of the cuprammonium process have shown that endotoxins introduced by the linters are degraded and washed out. Other endotoxin introduction, particularly by the process water, has been excluded. Oxidative or acidic degradation of cellulose does not result in the formation of LAL-reactive material (LAL-RM). On the other hand, sterile cotton wool shows LAL reactivity, and cellulose acetate regains LAL reactivity when it is saponified. Thus, it appears likely that the LAL-RM found in CHF is of purely cellulosic origin and crossreacts with a number of commercially available lysates.


A spectrophotometric coupled enzyme assay to measure the activity of succinate dehydrogenase.
Respiratory complex II (succinate:ubiquinone oxidoreductase) connects the tricarboxylic acid cycle to the electron transport chain in mitochondria and many prokaryotes. Complex II mutations have been linked to neurodegenerative diseases and metabolic defects in cancer. However, there is no convenient stoichiometric assay for the catalytic activity of complex II. Here, we present a simple, quantitative, real-time method to detect the production of fumarate from succinate by complex II that is easy to implement and applicable to the isolated enzyme, membrane preparations, and tissue homogenates. Our assay uses fumarate hydratase to convert fumarate to malate and uses oxaloacetate decarboxylating malic dehydrogenase to convert malate to pyruvate and to convert NADP(+) to NADPH; the NADPH is detected spectrometrically. Simple protocols for the high-yield production of the two enzymes required are described; oxaloacetate decarboxylating malic dehydrogenase is also suitable for accurate determination of the activity of fumarate hydratase. Unlike existing spectrometric assay methods for complex II that rely on artificial electron acceptors (e.g., 2,6-dichlorophenolindophenol), our coupled assay is specific and stoichiometric (1:1 for succinate oxidation to NADPH formation), so it is suitable for comprehensive analyses of the catalysis and inhibition of succinate dehydrogenase activities in samples with both simple and complex compositions.


The situation of children affected by HIV/AIDS in Southwest China: Schooling, physical health, and interpersonal relationships.
To investigate the schooling, physical health and interpersonal relationships of children affected by HIV/AIDS in rural areas of southwest China. Using a structured survey, quantitative data were collected on a total of 116 children and 114 of their caregivers. Parental illness or death adversely affected children's school attendance and school performance. Over one-third (36.2%) of children reported being ill for more than 3 days during the previous 6 months; more orphans were hospitalized during the latest illness than nonorphans, although the difference was not statistically significant. One-third (33.6%) of children were aware that their parents were HIV positive. Ten percent of orphans reported that their relationships with peers became worse after parental illness or death, which was significantly higher than nonorphans. Twenty-five percent of orphans reported they were teased by others compared with 1.9% of nonorphans. HIV infection has impacted negatively on the children in terms of education, health, and peer association. These findings can be used as preliminary data supporting intervention strategies and activities to improve the general welfare of children affected by HIV/AIDS in China.


Carbon Dioxide Capture Chemistry of Amino Acid Functionalized Metal-Organic Frameworks in Humid Flue Gas.
Metal-organic framework-808 has been functionalized with 11 amino acids (AA) to produce a series of MOF-808-AA structures. The adsorption of CO2 under flue gas conditions revealed that glycine- and dl-lysine-functionalized MOF-808 (MOF-808-Gly and -dl-Lys) have the highest uptake capacities. Enhanced CO2 capture performance in the presence of water was observed and studied by using single-component sorption isotherms, CO2/H2O binary isotherm, and dynamic breakthrough measurements. The key to the favorable performance was uncovered by deciphering the mechanism of CO2 capture in the pores and attributed to the formation of bicarbonate as evidenced by 13C and 15N solid-state nuclear magnetic resonance spectroscopy studies. On the basis of these results, we examined the performance of MOF-808-Gly in simulated coal flue gas conditions and found that it is possible to capture and release CO2 by vacuum swing adsorption. MOF-808-Gly was cycled at least 80 times with full retention of performance. This study significantly advances our understanding of CO2 chemistry in MOFs by revealing how strongly bound amine moieties to the MOF backbone create the chemistry and environment within the pores, leading to the binding and release of CO2 under mild conditions without application of heat.